LUMINIDE AND MACROLUMINIDE CLASS OF PHARMACEUTICALS

Abstract: A broad class of pharmaceutical agents which react directly with electron carriers or with reactive species produced by electron transport to release a pharmacologically active molecule to effect a therapeutic functional change in the organism by a receptor or nonreceptor mediated action.

Description: LUMINIDE AND MACROLUMINIDE CLASS OF PHARMACEUTICALS FIELD OF THE INVENTION The present invention relates to therapeutic pharmaceutical agents which are activated intracellularly by reaction with cellular electron carriers or free radicals to cause release of a free and active drug molecule. CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation in part of my co-pending U.S. Patent Application Serial No. 948,326, entitled LUMINIDE CLASS OF PHARMACEUTICALS, filed December 31, 1986. BACKGROUND OF THE INVENTION The effects of the preponderance of drugs result from their interaction with functional macromolecular components of the organism. Such interaction alters the function of the pertinent cellular component and thereby initiates the series of biochemical and physiological changes that are characteristic of the response to the drug. The term receptor denotes the component of the organism with which the chemical agent interacts. There are fundamental corollaries to the statement that the receptor for a drug can be any functional macromolecular component of the organism. One is that a drug is potentially capable of altering the rate at which any bodily function proceeds; a second is that, by virtue of interactions with specific receptors, drugs do not create effects but merely modulate the rates of ongoing functions. A simple pharmacological dictum thus states that a drug cannot impart a new function to a cell. Functional changes due to a drug result from either enhancement or inhibition of the unperturbed rate. Furthermore, a drug that has no direct action can cause a functional change by competition for a binding site with another, active regulatory ligand of the receptor. Drugs are termed agonists when they cause effects as a result of direct alteration of the fundamental properties of the receptor with which they interact. Compounds that are themselves devoid of intrinsic pharmacological activity but cause effects by inhibition of the action of a specific agonist (eg. by competition for agonist binding sites) are designated as antagonists. At least from a numerical standpoint, the proteins of the cell form the most important class of drug receptors. Obvious examples are the enzymes of crucial metabolic or regulatory pathways (eg., tyrosine hydroxylase; 3-hydroxy-3-methylglutaryl CoA reductase) , but of equal interest are proteins involved in transport processes (eg. Ca + - ATPase; Na K + ATPase) or those that are protein kinases which activate other proteins as a consequence of their binding a secondary messenger such as cAMP. Specific binding properties of other cellular constituents can be exploited. Thus, nucleic acids are important drug receptors, particularly for chemotherapeutic approaches to the control of malignancy, and plant lectins shown remarkable specificity for recognition of specific carbohydrate residues in polysaccharides and glycoproteins. Small ions such as Ca + which can function as a regulatory ion or Fe + which can serve as an essential enazmatic cofactor can be exploited as drug receptors. And, drugs can also produce a functional change by a nonreceptor-rnediated action. Certain drugs that are structural analogues of normal biological constituents may be incorporated into cellular components and thereby alter their function. This has been termed a "counterfeit incorporation mechanism" and has been implemented with analogues of purines and pyrimidines that can be incorporated into nucleir acids and that have utility in cancer chemotherapy and that have antiviral activity. Also, specific constituents of pathogens can be exploited as receptors. For example, the electron carriers of bacterial can serve as receptors as described in my previous U.S. Patent Application Serial No. 948,326, and the replicative enzymes of viruses can be serve as receptors as described below for the virus HIV. Many compounds are known which have receptor or nonreceptor mediated in vitro activity as appears in Handbook of Enzyme Inhibitors, Mahendra Kumor Jain, 1982, Wiley Interscience, New York, hereby incorporated by reference. However, only a small percentage produce the desired functional change in vivo or have a high therapeutic ratio because they are toxic in their free form; they are rapidly inactivated or excreted; or, they cannot obtain access to their target receptor or site of action because they are impermeant to cells or biological barriers such as the blood brain barrier due to unfavorable energetics due, for example, to the possession of polar or charge groups; or, they are toxic as a consequence of being nonselective with regards to their access to and action with receptors in one biological environment or compartment relative to another. In these cases, compounds which demonstrate in vitro efficacy are ineffective therapeutics. SUMMARY OF THE INVENTION A broad class of pharmaceutical agents is disclosed herein as the Luminide class of pharmaceuicals. Luminide agents are three part or four part molecules where each part is a functionality with a defined purpose. Exemplary Luminides are A-B-C , D-A-B-C, A-D-B-C, and A-B-C D where A represents a functionality which is activatable by the environment and capable of transferring energy from its own excited state to the B functionality which is an energy acceptor. Upon receiving energy from A, B achieves an excited state which relaxes through the heterolytic cleavage of the covalent bond of B with C where C is a drug moiety which is released into the intracellular compartment where activation of A occured. Released C can act locally or at a distant site. D serves as an electron transfer functionality which gains (loses) electrons from (to) the environment and donates (accepts) electrons to (from) A to activate it so that the energy of excited A is transferred to B with release of C as occurs for the three functionality case. In both cases, free C is a drug molecule. The released drug molecule effects a therapeutic functional change by a mechanism which comprises receptor mediated mechanisms including reversible or irreversible competitve agonism or antagonism including a suicide substrate or transition state analogue mechanism or a noncompetitive or uncompetitve agonism or antagonism or the action is by a nonreceptor mediated mechanism including a "counterfeit incorporation mechanism". The chemical and physical properties of the Luminide agents such as permeance and reactivity to different oxidoreductase enzymes, electron carriers, or different free radicals including those of oxygen are exploited to control the environment into which C is released. Permeance of the Luminide agent to the blood brain barrier or cell membranes, or affinity of the Luminide agent to plasma proteins which results in a decreased excretion rate relative to free C, or lack of reactivity of extracellular enzymes with the Luminide agent relative to free C are exemplary mechanism where by Luminides provide for the release of active free C in the proper biological compartment or in the presence of the target receptor so that the desired therapeutic change is achieved. Thus, Luminides serve as therapeutic drugs. And, the present invention, Luminides, a broad class of pharmaceutical agents comprises antilipidemic drugs, anticholesterol drugs, contraceptive agents, anticoagulants, anti-inflamatory agents, immuno-suppressive drugs, antiarrhythmic agents, antineoplastic drugs, antihypertensive drugs, epinephrine blocking agents, cardiac inotropic drugs, antidepressant drugs, diuretics, antifungal agents, antibacterial drugs, anxiolytic agents, sedatives, muscle relaxants, anticonvulsants, agents for the treatment of ulcer disease, agents for the treatment of asthma and hypersensitivity reactions, antithroboembolic agents, agents for the treatment of muscular dystrophy, agents to effect a therapeutic abortion, agents for the treatment of anemia, agents to improve allograft survival, agents for the treatment of disorders of purine metabolism, agents for the treatment of ischemic heart disease, agents for the treatment of opiate withdrawal, agents which activate the effects of secondary messenger inositol triphosphate, agents to block spinal reflexes, and antiviral agents including a drug for the treatment of AIDS. DETAILED DESCRIPTION OF THE INVENTION Electron transferring and transporting elements are ubiquitous and are necessary for life. All eukaryotic and prokaryotic organisms depend on electron transferring and transporting elements which include metal containing hemes and nonmetal containing molecules such as flavins to convert the energy stored in the chemical bonds of foodstuffs into a form utilizable for the maintenance of the highly negative entropic state of life. The chemical energy conversion process generally involves a coupled series of electron carriers which is called an electron transport chain. Free radicals of oxygen are produced during aerobic respiration in mitochondria as electrons are carried by electron carriers of the electron transport chain to the ultimate electron acceptor, oxygen, and superoxide and peroxide, partial reduction products of oxygen, are continuously produced during cytosolic hydroxylation and oxygenation reactions as well as during other reactions which involve enzymatic reduction of oxygen. The cytosol as well as mitochondria of aerobic cells contain high concentrations of the enzyme superoxide dismutase which converts superoxide into hydrogen peroxide and molecular oxygen. Oxygen radicals which include hydrogen peroxide and superoxide are found in greater concentration in the mitochondria relative to the cytosol because reduction of oxygen occurs to a greater extent in the former compartment; however, appreciable concentration are found in both compartments. Luminides are agents which are permeant to the desired biological compartment which undergo an oxidation reduction reaction with the target cell's electron carriers or react with free radicals produced as a consequence of electron transport and release a drug moiety into the desired compartment in active form to effect a greater therapeutic effect or therapeutic ratio relative to the free C agent as a consequence of altered pharmacokinetics or pharmacodynamics such as a desirable kinetics of release, a resistance to inactivation or excretion, greater solubility, enhanced absorption, a diminished toxicity, or greater access to the cellular or biological compartment which is the site of action of C. Luminide agents are three or four part molecules where each part is a functionality with a defined purpose. Exemplary Luminides are A-B-C, D-A-B-C, A-D-B-C and A-B-C I D where A represents a functionality which undergoes an oxidation reduction reaction where electrons are transferred directly between A and the target cell's electron carriers or the electrons are transferred indirectly through an electron transfer functionality, D, which is described in more detail below. Alternatively, A represents a functionality which undergoes a reaction with free radicals of oxygen which are produced as a consequence of electron transport. An excited state is produced in A as a consequence of its participation in one of these reactions. Then A undergoes intramolecular energy transfer from its own excited state to the B functionality which is an energy acceptor. Upon receiving energy from A, B achieves an excited state which relaxes through heterolytic cleavage of the covalent bond of B with C where C is a drug moiety which is released into the environment. D serves as an electron transfer functionality which gains (loses) electrons from (to) the environment and donates (accepts) electrons to (from) A to activate it so that the energy of excited A is transferred to B with release of C as occurs for the 'three functionality case. In both cases, free C is a drug molecule. The released drug molecule effects a therapeutic functional change by a mechanism which comprises receptor mediated mechanisms including reversible and irrereversible competitive agonism or antagonism including a molecle known as a suicide substrate or a transition state analogue mechanism or a noncompetitive or uncompetitive agonism or antagonism or the action is by a nonreceptor mediated mechanism including a "counterfeit incorporation mechanism" . The energy donating funtionality, A, is a molecule which reacts as previously described to form an excited state of high enough energy so that this subsequently transferred energy is of sufficient magnitude to break the covalent bond between the drug functionality, C, and the energy acceptor functionality, B. Chemiluminescent molecules can form highly excited states of the proper magnitude of energy, can undergo oxidation reduction reactions or react with free radicals, and possess a metastable excited state from which intramolecular energy transfer can occur; thus, they can serve as the A functionality. In general, chemiluminescent molecules relevant to this invention can be placed into three categories: 1) molecules undergoing reaction involving peroxides and oxygen free radicals; 2) molecules undergoing reaction involving oxidation or reduction and 3) molecules undergoing both reaction with peroxides and oxygen free radicals followed by an oxidation or reduction reaction. Molecules of the first category include Lophine and its derivatives, acridinium esters and acridans, tetraphenylpyrrole, phthalhydrazides, acyloins, biacridinium salts, vinylcarbonyls, vinylnitriles, tetrakis (dimethylamino) ethylene, acylperoxides, indoles, tetracarbazoles and active oxalates. Molecules belonging to the second category include ruthenium chelates 2, 6-diaminopyrene, or cation radicals and molecules which follow a Chemically Initiated Electron Exchange Luminescence mechanism such as certain dioxetans and dioxetanones. Dioxene derivatives belong to the third category. They form a dioxetan by reation with superoxide and then produce efficient chemiluminescence by a CIEEL mechanism. As an example from the first category, the chemiluminescent compound, luminol, has a chemiluminescent maximum in the region 390-400 nm in an aqueous solution. Chemiluminescence is produced by the reaction of luminol with oxygen free radicals where a large fraction of the product molecules are formed in their excited state. The nature of the excited state is electronic, and it has a mean lifetime of the order of 10 —8 seconds which is typically ten thousand times the period of a > molecular vibration. Emission involves a quantum mechanically allowed singlet to singlet transition with energy of the order of 75 Kcal/mole. The quantum yield for forming the excited electronic state is 0.5. Because luminol undergoes a chemiluminescent reaction with oxygen radicals, this compound has been used as a molecular probe for these radicals by linkage to a molecule which directs the probe to a cellular compartment. For example, when luminol is attached to carnitine, the probe is transported into mitochondria and the intensity of chemiluminescence produced is proportional to the magnitude of electron transport activity which produces oxygen radicals. The chemiluminescent molecule, lucigenin, is also used as a probe for oxygen free radicals. As for members of the second category, chemiluminescent molecules which undergo a redox reaction to produce an excited state react directly with electron carriers of the cell or undergo a redox reaction with the electron transfer functionality D. As for the third category, a D functionality is optional. A chemiluminescent molecule of this category reacts with oxygen free radicals and forms an excited state, and chemiluminescence is produced but properties such as quantum yield or the relative ratio of singlet to triplet excited state can be altered by the transfer of electrons involving for example a D functionality. See Table 1 below for chemiluminescent molecules. Table 1 Representative Chemiluminescent Molecules Name Structure 2 , 6-di aminopyrene Arninoph halhydrazide Dioxene Imidazole derivaties Sulfonyloxamides Indole derivatives Tetrakis(dialkylamino)ethylene R R R-N N- .C = C R-N' N-R I R R 2,5, 7,8-tetraoxabicyclo-[4.2.0.] octane Dioxetan Lucigenin Lophine Acridinium esters Active oxalate / / Jj.L ' Tris-2 , 2 ' -bipyridinedichlororuthenium (II) CI CI Dioxetanone Dipheyl peroxide Exemplary energy acceptor molecules include those which demonstrate photochromic behavior with electromagnetic radiation and bleaching agents. If the A functionality is chemiluminescent, then the B functionality is such that the photodissociative drug release spectrum of B overlaps the chemiluminescence spectrum of A. Triarylmethane dyes react with cyanide to form nitriles called leucocyanides which liberate cyanide ion with a quantum yield of approximately one when irradiated with UV light in the wavelength range of 250 to 320 nm. c_» The spectrum of the photorelease reaction of cyanide ion can be extended to longer wavelengths in the case of triarylmethane dyes by substitutions of a naphthylene for an aryl group and also by using cationic polymethine dyes. The latter form nitriles, which are thermally stable, by the reaction of the carbonium ion of the dye with cyanide. The formation of the nitrile causes the colored dye to be bleached as is the case with triarylmethane dyes, and cyanide is released as the dye becomes colored upon absorption of 320-415 nm. Reversible bleaching by an agent and coloration by light is photochromic behavior. Cationic dyes demonstrate this behavior and include di and triarylmethane dyes, triarylmethane lactones and cyclic ether dyes, cationic indoles, pyronines, phthaleins, oxazines, thiazines, acridines, phenazines, and anthocyanidins, and cationic polymethine dyes and azo and diazopolymethines, styryls, cyanines, hemicyanines, dialkylaminopolyenes, and other related dyes. See Table 2 below for structures for salt isomerism-type photochromic dyes. These photochromic molecules form covalent bonds with a number of agents called bleaching agents because they convert the compounds from colored to colorless form during bond formation. Bleaching agents are diverse and include hydroxide, cyanide, azide, bisulfide, and sulfite compounds, thiocyanate, ferrocyanide, chromate, tetraborate, acetate, nitrite, carbonate, citrate, aluminate, tungstate, molybdate, methoxide, 2-methoxyethoxide, cinnamate, and p-methoxycinnamate salts, and thiols and amines. TABLE I I Visible Spectrum Dye Name or Struc ture; CI Name and Nominal Notes Referring Number; Oilier Names Aiiion"- " to Solvent'' λ,„ a . (nm) Solvent Malachite Green 42000 CN, SOj N, OH c ee 622 lit ha no I 61 7 Water Helvetia Green 42020 CN d, ee Basic Blue I 42025 CN, SOjl I r, //, aa 640 Iithanol Brilliant Blue 628 Water Seloglaucine Basic Green 1 ■ 42040 CN, SO3H t , fl, Ii, 633 Iithanol Brilliant Green //_ - .. ,. ./ 622 Water Acid Blue 1 42045 CN d , ee 628 Ethanol X lenc Blue VS 636 Water Patent Blue V Alpha/urine 2G Acitl Blue 3 42051 CN s, dd, ee 632 Water Brilliant Blue V Patent Blue V l : oo Green 3 42053 CN dd, ee I DC Green 3 Λcid Green 6 42075 CN, SO3 H dd, ee 629 lithano Light Green SF Bluish 628 Water Λcid Blue 7 42080 CN s, dd, ee 628 lithano Xj lene Blue AS 633 Water Patent Blue Λ Acid Green 3 42085 CN, SO . , 11 dd lilt 626 lithano Λcid Blue 9 42090 CN ,v, dd, ee 626 Water Erioglaucine Acid G een 5 42095 CN, SO.- H dd, ee, hh 634 Ethanol Light Green SF Yellowish 634 Water Λcid Green 9 42100 CN, S0 3 H ff hh 640 Ethanol lirioviridene B 635 Water Λcid Blue 147 42135 CN dd, ee Xylene Cyanol W Basic Red 9 42500 CN, SO 3 N, OH <- ' (J, lι. 550 Ethanol P ai'osaniline n, 0, 11, 543 Water ff- ii Basic Violet 14 42510 CN, SO.,M ff-hh 545 Water Fuchsin Magenta Basic Fuchsin 425 I B SO , I I hh 539 Water Basic Violet 2 42520 CN, SO3H ff-hh 544 Water New Fuchsin New Magenta Moll ' nian Violet 42530 SO ,1 1 584 Water Iodine Violet Basic Violet 1 42535 CN, SO.,11 , e, , k , 588 Ethanol Methyl Violet 11, jj, ι</< 584 Water Basic Violet 13 42536 SO3I I 585 Water Methyl Violet 6B Basic Violet 3 42555 CN, SO3I I. OH c, d, g, h, 595 Ethanol Crystal Violet n-p, 11, Gentian Violet ff ii, kk 00 Iodine reen 42556 SO . ,1 1 Visible Sf H'ctrum Dye Name or Structure; CI Name and Nominal Notes Referring Number; Other t ames Anion"-" Solvent" ,,, a * (nm) Solvent Basic Blue 8 42563 CN aa 594, 538 Water Victoria Blue 4R Λcid Blue 13 42571 CN s, dd, ee 611 Water last Λcid Violet I0B Λcid Blue 75 42576 SO, II 626 Ethanol Eriocya i e Λ 614 Water Methyl Green 42585 CN e, j, dd 640 Ethanol 634 Water Ethyl Green 42590 CN Λ, dd hh Basic Violet 4 42600 CN, SO 3 H s 597, 546 Water Ethyl Violet Λcid Violet 49 42640 CN, SO 3 II dd, ee 608, 544 Water Wool Violet 5BN Λcid Blue 15 42645 SO.,11 554 Water Brilliant Milling Blue B Λcid Violet 17 42650 CN, SO3II s, dd- hh 591, 548 Ethanol Λcid Violet 6B 592, 539 Water Wool Violet 4BN Formyl Violet Λcid Violet 5 S Cone. Λcid Violet 19 42685 CN, SO3H ff-hh, 545 Water Λcid Fuchsin PP-rr 287, 291 , 305 Red Violet 5R 42690 SO.,H 281 Λcid Blue 22 42755 CN, SO.,11 dd, ee, hh 590 Ethanol 281 , 284, 286, Aniline Blue 607 Water 292, 293 Soluble Blue Solvent Blue 3 42775 SO.,1 1 hh 595 Ethanol 284 590 Methanol Λcid Blue 93 42780 CN, SO, 11 ff hh 606 Ethanol 284, 287 Methyl Blue 586 Water Λurin 43800 CN, OH S, tt 306, 307 Mordant Blue 3 43820 SO, I I 588 aq. ON - 281 1 Eriochromc Cyanine R Λcid Green 16 44025 CN ee, tt 638 Ethanol 303, 307, 310 1 Naphthalene Green V 639 Water Pontacyl Green NV Extra Basic Blue 1 1 44040 CN, SO.,11 .', uu 615, 558 Water 280, 281 Victoria Blue R Basic Blue 15 44085 SO.,11 628, 568 Water 281 Night Blue Λcid Green 50 44090 CN ee, tt 628 Ethanol 303, 31 1 Wool Green S 632 Water iton Green S Cone. Basic Green 3 SOj l l, OH hh, pp 609 9: 1 284, 286 Sevron een B π>, 'I Methanol - Water Brilliant Blue F & R Extra O., 1 1 281 Brilliant Green Sulfonatc CN 288 Visible Spectrum Dye Name or Structure; CI Name and Nominal Notes Referring Number; Other Names Anion"- 1 ' to Solvent h Λ ma χ ( |lm ) Solvent Hexak is{ hy d roxyet y 1 ) Pararosaniline CN 600 -.thanol (IIOCH 2 CH 2 ) N- Λ ■ c * New Green CN 615 Ethanol Phenolphthalein CN A ' Λ ' Malachite Green Ethiodide CN (CH,) 2 N-^^-C + -H^ - + N(CH 3 )_C 2 H 5 C„Hr I lylroxyalkylatcd Pararosanilines CN dd Hydroxyalkylaled New I ' uchsins CN dd I a_ above New Yellow CN 463 Ethanol (C lj N- Doc-oner's Violet CN 575 Ethanol anol New Red CN 507 Eth < II,),N ■ ( " ) • Visible Spectrum Dye Name or Structure; CI Name and Nominal Notes Referring Numbe ; Other Names Aι on a ' b to Solvent 1 " λ maj (nm) Solvent βw(hydroxyethyl) Doebner's Violet CN 597 Ethanol |l_OCI_ 2 CI_ 2 NI.- -C'C Ij New Magenta CN 547 Ethanol CH,O- lrtA ■ N(CH,)j 7 r«A:/.v(hydroxyethyl) Doebner's Violet CN 632 Ethanol Trichloro Crystal Violet CN z υ o en O C O O O oo oo en oo 00 O I isible Spectrum Dye Name or Structure; CI Name and Nominal Noh Rcjerriinj Number; Other Names Aiiion"-" to Solvent' " Only the cyanide, bisulfite, and hydroxide ions are considered, regardless of the other anions present in the solution. '' More detailed descriptions of the compositions of photochromic materials tested are given in Macnair's review [255 ; tables I - 4], r Hthanol. * Dielhyl ether. c 1 ,2-Dichloroethane. 1 1 ,1-1. ichloroethane, cyclohexane l ,l-diehloroethane, or cyclohexane- l .2-diehloroethane mixtures, 9 Benzene. Λ D imcthylsulfoxide, neat and aqueous. ' Acetone, ■ * Acetic acid, λ Ethyl acetate. ' Ethyl bromide. '" 2-Melhoxyelhanol. " Chloroform. " Ethanol with KCN. " Ethanol with KOI I. '' Carboxylic acids— acetic to stcaric; hydrocinnamic acid ; ethyl and butyl acid phtlialates. ' Ocladccylnitrilc, Iributyl phosphate, aniline, 2-( ?-/c(7-bulylphenoxy)elhanol, tetraethj lenegljcol dimethy l ether, or poly(elhylene gly cols). * Amides - forma ide to stearamide; melliylfor amide or methylacetamide; dimethyl- or dielhyl-formamide or acetamide, ' Three-lo-one solutions of cellulose acetate with any of the following iive-to-one plaslici/cr mixtures : Polyethylene Glycol 600" 1 - buly I slearate, Polyethylene Glycol 600 butyl acetoxysteaiate, I) owanol EP'" butyl stearale, or I ) ovvanol EP butyl acotoxystearate. " Water containing S0 2 . " Water containing bisulfite and papain. " Po|y(vinyl alcohol) with dimethylsulfoxide (5 : 1 ), x Films, containing residual solvent, cast from the following solutions: ethanol-acetone solutions of vinyl acetate-vinyl alcohol copolymer; aqueous poly(vinyl alcohol); aqueous poly(vinyl pyrrol idone); or aqueous methyl vinylether-maleic acid copolymer. " Methanol-dioxane with aqueous NH 4 HSO 3 . z Paper impregnated with a toluene solution of poly(methyl methacrylate), stearic acid, and 2-(/7-/<?r/-butylphenoxy)ethanol, then dried. "" Inlramiccllar impregnation of cellulose with the following swelling agents: M-propylamine, //-butylamine, . i-hexylamine, 2-aminoethanol, dimethylformamide, acetic acid, dimethylsulfoxide, methylacetamide, dimethylacetamide, or formamide. bh F τ ilms cast from an approximately 4 : 3 mixture of a 20% solution of cellulose acetate butyratc in toluene-ethyl acetate (1 : l )and Iriallycyanurate in dioxane. * " * " I inis cast from a 2 : 1 mixture of a 25 %, solution of cellulose acetate butyratc in toluene ethyl acetate (1 : l) and the titanium esters of N,N,N', N'-_. ./.. _. (2-hydroxypropyI) ethylenediamine. dd Pure water. "' Films cast from aqueous gelatin or other hydrocolloids. fS Dimethylsulfoxide with melhanolic KCN. 99 2-Methoxyethanol with melhanolic KCN. ** Water or aqueous methanol containing bisulfite. " Paper impregnated with /π-dimethoxybenzene, acetonitrile, acetic acid, or phenyl methyl carbinol. JJ Ethanol- benzene. ** Aqueous ethanol, methanol, aqueous methanol, aqueous acetone, benzcne-methanol, carbon tetrachloride-methanol, cycIohexane-methanol, or chlorofoπn-mcthanol. " Films cast from 3 : I solutions of cellulose acetate and either Polyethylene Glycol 6 0^ or ethylcne glycol phenyl ether as plasticizer. """ Films, containing residual solvent, cast from solutions of cither cellulose acetate in 2-methoxyethanol or poly(vinyl alcohol) in aqueous ethanol. "" Films, containing residual solvent, cast from solutions of either cellulose acetate butyratc in 2-methoxycthanol orpoly(vinyl acetatc) in methanol. "" Ethanol containing ammonia. pp Aqueous methanol containing NH 4 HSO 3 and urease. qq Aqueous methanol containing NH 4 HSO 3 , with or without sodium dithionite. " Aqueous acid at pll 1. " Aqueous ammonia containing KCN. " Paper impregnated with aqueous solutions with or without hydrocolloids. "" 2-Methoxyethanol containing HC1. "" Aqueous methanol containing NH 4 I ISO 3 , and glucose oxidase. ww 9 : I Methanol -water. * ** Aqueous NaOl I. u 176 Photochromic Polymethine Dyes α, ω-bis(p- Dimβthylaminophenyl)polyenes Ar n C 6 H 5 0, 1, 2 4-(CH 3 ) 2 NC 6 H 4 0, 1, 2 4-(CH 3 )2CHC 6 H, 0, 1, 2, 3, 4 4-CH 3 OC 6 H 4 0, 1, 2 4-C*.H 9 OC 6 H 4 0, 1 , 2 3-CH 3 C 6 H 4 1, 2 4-F 3 CC 6 H 4 1 3,4-H 2 N(OCH 3 )C 6 H 3 1 2-Naphthyl 1, 2 2,4-Cl->C 6 H 3 2 1-Naphthyl 2 12 - , cc-bis(p-dimethylaminophenyl)polyenes R Miscellaneous polyenes Basic Red 13 Basic Violet 7 Basic Red 14 Basic Red 15 Basic Violet 15 CH, 8 - 39 - © s e K TABU V (Cont'd) r»oτocH___ • ♦lie rowtiruπoHs or t tusnτKτvt . nirHEi fLMETHAHe ores TABU V (Cont'd) rnoTDCHKOMic rowi AtiOMS or _zrusεκτAτrvc Txirϊ MT trrHΛΛS DIES Identi ication efface TABU V (Cont 'd) rifcrroαiitcHic ΓORHULΛΠOHS or βnxseMTATivt TI-irKtffϊLMeTHAHK DYES IdadC lf icacton efface 49 >- SO " - " SALT-ISOMERISM TYPE PHOTOTROPIC DYES Night Blue Victoria Blue R Brilliant Milling Blue B Brilliant Blue F & R Ex. Eriocyanine A Methyl Blue Aniline Blue Eriochrome Cyanine R Methyl Violet 6B Iodine Green Aniline Blue Wool Violet 5 BN Wool Violet EM Light Green SF Yellowish Iodine Violet Methvl violet Crystal Violet Ethyl Violet Acid Green L Extra Victoria Green (Malachite Green) Red-Violet 5R Brilliant Green "B" Di- [ 4 ( N , N-diethy larnine ) phenyl ] - [ 4-( N , N-άiethy 1- amine-2-methyI) phenyl] methyl carbonium Tri-i 4 (N, -άipropylamino) phenyl] methyl carbonium Di-[4 (N, -άiethy 1 amino) phenyl] - [4 (ethylamino) phenyl] methyl carbonium Di-[ (N,N-dieth lamino)phenyl]-[4(N, -dieth l■ amino)naphthyl] methyl carbonium Di-[4(N, -dimethylamino)phenyl]-[4(hydroxy)phenyl] methyl carbonium Tri-[4 (N-ρropylamino)phenyl] methyl carbonium -> Hectolene Blue DS-1398 Hectolene Blue DS-1823 Sevron Brilliant Reά 4G Di-[4 (N, N-άimethyl amino) phenyl] -[4 (hyάroxy) henyl] methvi carbonium Tri- [4 (N-propylamino) phenyl] methyl carbonium Hectolene Blue DS-1398 Hectolene Blue DS-1823 Sevron Brilliant Red 4G Genacrvl Red 6B Genacryl Pink G Sevron Brilliant - Red B Sevron Brilliant - Red 3B l,5-bis-[ (N,N-dimethylamino)phenyl] -1,5-bis- (phenyl) ivinyl carbonium trifluoroacetate CFiCOO- 1,1,3,3-tetrakis[4(N, -dimethylamino)phenyl] vinyl carbonium perchlorate IO.- 1,5-bis-[4(I.,N-dimehtylamino)phenyl]-1,5-bis- (phenyl) divinyl carbonium p-toluenesulfonate j l,7-bis-[4 (N,N-dimethylamino)phenyl] -1, 7-bis- (2 , 4-dichlorophenyl) trivinyl carbonium per¬ chlorate Di-[ (N, N-dimethylamino)phenyl vinyl] -[2 , 4-di- ρhenyl-6-methane thiopyran] methyl carbonium perchlorate 1, 7-bis- [ 4- (N, N-dimethyl amino) phenyl] -1, 7-bis - (4-chlorophenyl) trivinyl carbonium trifluoro- acetate 1,1, 3-tris-t4-(N,N-dimethylamino)phenyl] divinyl carbonium perchlorate 1,1,7, 7-tetrakis-[4-(N,N-dimethylamino) phenyl] trivinyl carbonium perchlorate 1, 3-bis- [4-(N, -dimethylamino) henyl] -1,3-bis- (phenyl) vinyl carbonium perchlorate 1,1,5, 5-tetrakis-[4-(N,N-diemthylamino)phenyl] άivinyl carbonium perchlorate 1, 5-bis- [ -(N,N-άimethylamino)phenyl] -1, 5-bis- (phenyl) άivinyl carbonium perchlorate C10 4 - 1, 7-bis- [ -(N,N-άimethylamino) phenyl] -1, 7-bis- (phenyl) trivinyl carbonium trifluoroacetate 1,1, 5- ris-[4-(N,N-άimethylamino)phenyl] divinyl carbonium perchlorate C10 4 - 1(1,3, 3-trimethyl inάoline)-2-[4-(N,N-άimethyl- amino)phenyl] ethylene carbonium perchlorate 1(1,3, 3-trimethyl indoline)-4-[4-(N,N-άimethyl- amino) henyl] butylene carbonium perchlorate 1,1,3, 3-tetrakis-[4(N,N-diethylamino)phenyl] vinyl carbonium perchlorate 1, 1-bis-[4-(N, -diethylamino)phenyl]-3,3-bis- [4-(N,N-dimethylamino)phenyl] vinyl carbonium perchlorate 1,1,5, 5-tetrakis-[4-(N,N-άiethylamino)phenyi] άivinyl carbonium perchlorate iInO,..-' 1, 1-bis-[4-(N,N-άimethylamino)phenyl] -3-[4-(amino) phenyl] -3-methylvinyl carbonium perchlorate Tris- [ 1, 1-bis-[ (N,N-dimethylamino)phenyl] ethylene] methyl carbonium perchlorate Tris- [1, 1-bis- [4-(N,N-diethylamino)phenyl] ethylene] methyl carbonium perchlorate 1, l,5-tris-[4-(N, -άimethylamino)phenyl] άivinyl carbonium perchlorate [4-(N,N-άimethylamino) cinnamyliάene] auramine (CH,). / D 1, 1-bis-[4-(N,N-dimethylamino)phenyl-3 ,4-bis* (phenyl) ]-3,4-άiazo butene carbonium 1,1,5, 5-tetrakis-[4-(N,N-άimethylamino)phenyl] ,3-άiazo pentene carbonium N-(N' ,N'-dimethylamino cinnamylidene)-N,N-diphenyl ammonium Azo Polymethines Dyes of the general structural type Photochromic diazopolymethmes 1,1,5,5-tetrakis-[4-(N,Np-άimethylamino)phenyl] 2,3-άiazo pentene carbonium ,l-bis-[4-(N,N-άimethylamino)phenyl-3,4-bis- (phenyl) ]-3,4-άiazo butene carbonium The drug functionality, C, incluάes any molecule which exhibits bleaching behavior with the B functionality anά has an increaseά therapeutic effect or therapeutic ratio as a consequence of its delivery as part of a Luminide agent. For example, Foscarnet, a viral reverse transcriptase inhibitor possesses both a carboxylate and phosphate group which will bleach photochromic compounds; 4-bromocrotonyl-CoA, an acetoacetyl -CoA thiolase inhibitor, possesses a thiol group which will bleach photochromic compounds; L-3-iodo-α- methyltyrosine, a tyrosine hyάroxylase inhibitor, possesses a carboxylate group which will bleach photochromic compounάs, and captopril, an antihypertensive pharmaceutical, possesses both a sulfide anά carboxylate group which will bleach photochromic compounάs. Furthermore, the pharmacokinetics anά/or pharmacoάynamics of these agents are altered via delivery to the site of action by way of a luminide agent such that the therapeutic effect or therapeutic ratio is enhanced. Other drugs which are not inherently photochromic bleaches in that they lack a nucleophilic group which will form a reversible covalent bond with the B functionality can be derivatized with a known bleaching nucleophilic group such as cinnamate, sulfite, phosphate, carboxylate, thiol, or amine group to transform them into bleaching agents of the B functionality such as a cationic dye. See Table 3 below for the structure of a exemplary drug molecules. Table 3. Representative Drug Molecules Name Structure Captopril Prostaglanάin E_ 2 , 3-άichloro-α-methylbenzylamine Sinef ungin 3 , 5-άiiodo-4-hydroxybenzoic aciά 6,6'-άithiobis ( 9-B-D-ribof ranosylpurine) γ-aminobutyric acid H 2 NCH 2 CH 2 CH-C00H Gabaculine OH N-(5'-phosphopyriάoxyl)-4-aminobutyric aciά 4-amino-hex-5-enoic aciά CH 2 =CHCHCH 2 C:-i 2 C00H NH. Baclofen Aάenosine 3-hyάroxy-3-methylglutarate OH 1 :H 7 CH. ,CCH COOH I CH Compactin But-3-ynoyl-CoA HC≡CCH 2 Suramin L-3-iodotyrosine L-3-ioάo-α-methyl tyro sine Disoάium cromoglycate Adenosine 3', 5 '-cyclic monophosphate 36 - D,L-B-(5-hyάroxy-3-inάolyl) -α-hyάrazinopropionic aciά D , L-α-hyάr az ino-α-meth lάopa α-meth ldopa 5-(3,4-άihyάroxycinnamoyl)salicylic acid N-(phosphonacetyl)-L-aspartate P-glycolohyάroxamate o- 5-(p-s lfamylphenylazo)salicylic aciά Cof ormycin Thioinosinate Phosphonoformate 0 0 II II OP-CO ' _0 Phosphonoacetate Riάavirin Sotalol . 2 Cimetidine Fuscaric acid 2-mercaρtoethylamine HSCH 2 CH 2 NH 3 + Iproniaziά .CH 3 '2 Trans-4-aminocrotonic aciά H 2 NCH 2 CH=CHC00H NSD 1055 NH- Nicotinic aciά Kynurenic acid Lentysine C00H Orotic acid lyoxin D Cephalosporin Penicillin - » - -. . ., .. . The electron transfer functionality, D, includes molecules which undergo a redox reaction which transfers electrons between the electron carriers and the A functionality where a redox reaction of A results in its * activation to an excited energy state. The D functionality can be a natural electron carrier such as ubiquinone or a synthetic electron carrier such as methylene blue, phenazine methosulfate, or 2, 6-dichlorophenolindophenol. Structures of electron transfer molecules appear below in Table 4. Table 4. Representative Electron Transfer Molecules Name Structure Methylene Blue Ubiquinone 2, 6 - άichlorophenolinάophenol Phenazine methosulfate Ferricyanide > A Representative Luminiάe A representative luminide is the product of the covalent linkage of the polymethine άye with a bleaching άrug such as Foscarnet anά with a chemiluminescent reactive molecule such as luminol. This conjugate represents a molecule which releases Foscarnet in the presence of oxygen free radicals. The energy of the reaction of luminol with oxygen raάicals unάergoes intramolecular electronic energy transfer by raάiative anά nonraάiative mechanisms. The latter άominate anά incluάe coulombic interactions, άipole-άipole resonance, anά exchange interaction. These processes increase the quantum yielά for άrug release above that which woulά be produceά by luminescence transfer alone. For example, Forster, in a quantum mechanical treatment of resonance transfer, in the region of spectral overlap involving alloweά transitions of two well separateά molecules has only consiάereά άipole-άipole interactions in άeriving an experimentally verifieά formula which preάicts a distance of 5-10 nm as the άistance at which transfer anά spontaneous άecay of the exciteά άonor are equally probable. The formula preάicts the transfer probability is inversely proportional to the separation distance raiseά to the sixth power. However, the άonor and accepter functionalities of a Luminide are covalently linked; thus, since the separation distance is of the order of angstroms, the transfer probability is great. In fact, the efficiency of transfer has been studieά in certain molecules which consist of two independent chromophores separated by one or more saturateά bonάs. In such cases, energy transfer over large distances has been observed to be in agreement with preάictions from Forster's Theory. The Luminiάes can be prepareά by known reactions where necessary, appropriate άerivatives of the subunits are formed before coupling. Representative examples of appropriate derivatization anά coupling reactions are given in the following examples, illustrating the preparation of representative Luminiάes. These examples are not to be taken as an exhaustive listing, but only illustrative of the possibilities accorάing to the present invention. Representative Luminiάes with Outline of Synthetic Pathway. Luminiάes synthesis involves the chemical joining of three or four functionalities. A representative luminiάe of three functionalities comprises an energy άonor molecule such as a chemiluminescent molecule, an energy acceptor molecule such as a photochromic molecule, and a drug. A representative luminide of four functionalities comprises the mentioneά three functionalities and also an electron transfer functionality which can undergo an oxiάation reάuction reaction. A three group Luminάe can be formed by condensing a photochromic dye functionalized as an acid chloride with a chemiluminescent molecule possessing an alcoholic or amino group to form an ester or amide. The luminide pharmaceutical is then formed by adάition of the drug bleaching agent. An exemplary pathway of this type appears in example 1. Alternatively, the chemiluminescent or/and electron transfer functionality can be linked to the energy acceptor functionality by formation of an ester or amide where the former functionality/functionalities is/are an aciά halide as άemonstrateά in example 15. Also, functionalities of the electron transfer anά energy άonor type can be linked to the energy acceptor part by an acylation reaction as άemonstrateά in examples 2, 3 anά 8; by nucleophillic substitution as άemonstrateά in examples 4, 5, 6, 7, 9, 10, 12 anά 17; by a carbanion mechanism as άemonstrated in example 11; by a Grignard reaction as άemonstrateά in example 14, by a tosylate mechanism as άemonstrateά in example 13, or by a Wittig reaction as άemonstrateά in example 16. Similar reaction pathways can be useά to link chemiluminescent molecules to energy άonor molecules. The list of examples of reaction pathways is intenάeά to be examplary and other pathways can be deviseά by one skilleά in the art. Furthermore, only a representative number of luminiάes are shown anά a vast number of other novel luminiάes can be maάe by one skilleά in the art following the guiάelines herein άiscloseά. . Anά, the άiscloseά exemplary luminiάes, anά components: chemiluminescent molecules, photochromic molecules, energy transfer molecules, anά άrug molecules can be moάifieά to further canάiάate components by aάάition of functional groups by one skilleά in the art. Representitive groups include aklyl, cycloalkl, alkoxycarbonyl, cyano, carbamoyl, heterocyclic rings containing C, O, N, S, sulfo, sulfamoyl, alkoxysulfonyl, phosphono, hydroxyl, halogen, alkoxy, alkylthiol, acyloxy, aryl, alkenyl, aliphatic, acyl, carboxyl, amino, cyanoalkoxy, diazonium, carboxyalkylcarboxamiάo, alkenyl, thio, cyanoalkoxycarbonyl, carbamoylalkoxycarbonyl, alkoxy carbonylamino, cyanoalkylamino, alkoxycarbonyl- alkylamino, sulfoaklylamino, alkylsulfamoylaklyl- amino, oxido, hydroxy alkyl, carboxy alkylcarbonyl- oxy, cyanoalkyl, carbonyloxy, carboxyalkylthio , arylamino, heteroarylamino, alkoxycarbonyl, alkyl- carbonyloxy, carboxyalkoxy, cyanoalkoxy, alkoxy- carbonylalkoxy, carbamoylalkox , carbamoylalkyl carbonyloxy, sulfoalkoxy, nitro, alkoxyaryl, halogenaryl, amino aryl, alkylaminoaryl, tolyl, alkenylaryl, allylaryl, alkenyloxyaryl, allyloxyaryl, allyloxyaryl, cyanoaryl, carbamoylaryl, carboxyaryl, alkoxycarbonylaryl, alkylcarbonyoxyaryl, sulfoaryl, alkoxysulfoaryl, sulfamoylaryl, anά nitroaryl. EXPERIMENTAL SECTION I Synthesis Synthesis of MTL 7-3, anά MTL J-l Step A: Preparation of p-K,N-άimethylaminobenzoyl chloriάe ( In a rounά bottom flask fitteά with a reflux conάenser is placeά 4 g of p-άimethylaminobenzoic acid anά 8 ml of oxalylchloriάe. The evolution of gas starts immeάiately anά the spontaneous reaction is run at room temperature for 15 minutes. 8 ml of toluene is aάάeά anά anά the mixture is heateά to gentle reflux for one hour. The reaction mixture is then άistilleά to άryness unάer reάuceά pressure to proάuce a blue-green soliά which is washeά with ether anά άrieά on a watch glass. Step B: Preparation of p-dimethylaminobenzaniliάe A solution of 0.95 g of aniline in 10 ml of άry ether containing 2.2 g of K ^° was heated to reflux temperature. To the refluxing mixture 2 g of p-άimethylaminobenzoyl chloride was added as a powder slowly through the condenser port. The reaction was refluxed for 1.5 hours anά the ether distilled off. Cold water was adάeά to the resiάue anά the p-άimethylaminobenzaniliάe collecteά by filtration. Yielά 1.51 g orange-red powder. Anilide functionality confirmed by IR. Step C: Preparation of p-N,N άimethyl-p-N-ethyl-N-2-chloroethylbenzophenone, 1.5 g of dry, powdered p-dimethylbenzaniliάe, 2.4 g of N-ethyl-N-2-chloroethylaniline, anά 1.3 ml of phosphorus oxychloriάe were mixeά in a 25 ml 2-neckeά flask, fitteά with a thermometer immersed in the reation mixture anά a reflux condenser having a CaCl„ drying tube on top. The reaction was warmed slowly until an exothermic reaction occured. The temperature was maintained at less than 100 C by periodic immersion of the flask in ice water. The reaction was then maintained at 95 C for one hour to yield a dark green liquid. The reaction mixture was then hydrolyzeά in a 150 ml beaker with the addition of a solution of 1.36 ml of concentrated HC1 to 10.4 ml of distilled H 2 0, τhe beaker was covered with a watch glass and heated on a hot water bath for 1.5 hours to yield a green-yellow solution. 10:1 cold water was addeά to the hydrolyzed mixture to form a brilliant purple solution which was filtered. The filtered product was dissolveά in a minimum volume of ethanol, anά twice the volume of colά H_0 was aάάeά. The ketone was then extracteά in an equal volume of chloroform which was removeά by distillation to dryness under reduceά pressure. Brilliant purple soliά proάuct. Ketone confirmeά by IR anά NMR. Step D: Preparation of l-(4-N,N-άimethylaminophenyl)-l-(4-N-ethyl-N-2-chloroet hylphenyl) ethylene. Benzene One ml of a 3 molar etherial solution of magnesium bromide was evaporated almost to dryness unάer reάuceά pressure in a 50 ml three neckeά flask equippeά with a thermometer anά nitrogen sparger. The grey moist solution was suspended in 1.3 ml of dry benzene. The flask was then equipped for refluxing by the adάition of a conάenser fitteά with a CaCl„ άrying tube anά an aάdition funnel. 0.017 moles of the ketone dissolved in 4.4 ml of boiling benzene was then placed in an addition funnel and adάed dropwise to the warmeά methyl magnesium bromiάe-benzene slurry over a half hour perioά. The resulting solution was refluxeά for one hour. The completion of the reaction was evident by the color change of the solution from brilliant purple to blue. The reaction mixture was cooled to room temperature, and 0.785 ml of saturated NH.C1 was cautiously addeά. Aάάitional NH.C1 was aάded until two layers were apparent with the blue alcohol _ 3 product in the bottom H_0 layer. 1.7 x 10 g of p-toluenesulphonic acid was adάeά, anά the solution was boileά on a water bath with the aάάition of benzene until the evaporation of H_0 was complete anά only the benzene layer remaineά. The aciά containeά in the reaction mixture was then removeά by the aάάition of 0.73 x 10 -3 g of soάium bicarbonate. The solvent was reάuceά to dryness under reάuceά pressure to yield light blue crystals. Step E: Preparation of a perchlorate of 1,5-άi-(p-N-2-chloroethyl-N-ethylaminophenyl)-l,5-bis-( p-N,N-άimethylaniline)-l,3-pentaάiene. C1 Acetic Anhydride HCIO^ C10, -4 A mixture of 8 . 7 x 10 mo les of l- ( 4-N , N-άimethylaminophenyl ) -l- ( 4-N-2-chlo roethyl-N-et hylaminophe-nyl)ethylene, 0.13 ml of ethyl orthoformate, anά 0.39 ml of acetic anhyάriάe was treated with a solution of 0.035 ml of 72 percent perchloric acid and 0.35 ml of acetic aciά previouly cooleά to 0 C. The resulting mixture was alloweά to stanά at room temperature for 8 days, after which time it was treated with 0.22 ml of ether and kept an adάitional άay at room temperature. The conάensation proάuct was washeά with acetic aciά, ethanol, anά ether. The pale blue-green crystals were dissolved in a minimum volume of warm dry ethanol. The solution was centrifuged to pellet a white precipitate. The άark blue supernatant solution was removeά anά distilled to dryness under reduceά pressure. The blue crystals where placeά on watch glass and placed in the dark. The structure of the condensation compound was confirmed by IR and NMR. Step F: Preparation of 1,5-άi-(p-N-2-(N-(4-aminobutyl)-N-ethyl isolminol) -N-ethylaminophenyl)-l, 5-bis-(p-N,N-άimethyla niline)-l,3-pentaάiene. _5 5 mg (1.8 x 10 moles) of N-(4-aminobutyl)- N-ethylisoluminol was suspendeά in 0.1 ml of pyriάine _5 in a small test tube. 30 mg (3.6 x 10 moles) of the pentaάiene was άissolveά in 0.5 ml of pyriάine anά 0.25 ml of DMSO. This latter solution was aάάeά άropwise to the former while vigorously stirring at room temperature initially then with intermittant imersion in a water bath at 35 C. The isoluminol which was only slightly soluble in pyriάine went into solution as the reaction progresseά. The reaction mixture was stirreά anά intermittantly immerseά in the water bath at 35 C until the reaction was complete. This reaction anά all subsequent reactions were protecteά from άirect light. - Ill - Step G: Preparation of Luminide, MTL 7-3 (2, 6-di-(p-N-2-(N-(4-aminobutyl)-N-ethylisoluminol)-N-e thylamino- phenyl)-2, 6-bis-(p-N,N-dimethylanilino)-3, 5-hexaάinenit rile) . 5 mg of solid KCN and 1 ml of distilled H 2 0 were aάded to the blue-grey solution of 1,5-άi-(p-N-2-(N-(4-aminobutyl)-N-ethylisoluminol)-N-et hylaminophe-nyl)-l, 5-bis-(p-N,N-dimethylanilino)-l,3-pe ntadiene in pyriάine/DMSO solvent. The solution was acidified by addition of sulphuric aciά and the evolving HCN gas was removeά by evaporating the solvent to άryness under reduceά pressure. The pale green crystals were redissolveά in DMSO to yield a pale green liquiά. IR anά NMR confirmeά the structure. Step H: Preparation of Luminiάe MTL J-l (5-phosphonoformate-1,5-άi-(p-N-2-(N-(4-aminobutyl) -N-ethylisoluminol)-N-ethylaminophenyl)-l,5-bis- (p-N,N-άimethylaniline)-1,3-pentaάiene) . 1 MTL J-l was prepared by the equimolar adάition of disodium phosphonoformate dissolveά in H-O to a DMSO solution of 1,5-άi-(p-N-2-(N-(4-aminobutyl)-N-ethylisoluminol) -N-ethylaminophenyl)-l,5-bis(p-N,N-άimethylaniline)-1,3 -pentaάiene such that the final solvent was 4:3 DMSO/H_0. The reaction mixture was protecteά from light, anά the colorless reaction proάuct solution was packageά in light protecting vials and refrigerated at 4 C. Methoάs of synthesis of triphenylmethane άyes appear in Appenάix I. Methoάs of synthesis of polymethine άyes appear in Appenάix II. Methoάs of synthesis of azo anά άiazopolymethine άyes appear in Appenάix III anά IV, respectively. Methoάs of synthesis of quaternary ammonium salt poly methines appear in Appenάix V. Methoάs of synthesis of the intermeάiates, tetramethylortho carbonate anά substituteά ethylenes appear in Appenάix VI. Methoάs of synthesis of inάoline baseά άyes appear in Appenάix VII. Methoάs of synthesis of άyes with more than one chromophore appear in Appenάix VIII. Methoάs of forming a leucocyaniάe appear in Appenάix IX. Further Exemplary Material Example 1. The compound shown as formula 6 is prepared as follows: Phenolphthalein is converteά to the corresponάing aciά chloriάe by treatment with oxalyl chloriάe. The aciά chloriάe is reacteά with chloromethylami e to form the corresponάing amiάe which is in turn reacteά with a άioxetan such as compounά 4 to give aάάuct 5 where compounά 4 is prepareά from the appropriate starting άioxtene by a methoά άescribeά by Schaap. The aάάuct 5 is converteά to the final proάuct by treatment with Captopril. Example 2 . The compound shown as formula 10 is prepared as follows: Compounά 7 is acylateά with an acriάinium ester such as compounά 8 to give aάάuct 9 which is treateά with prostaglanάin E_ to give the final proάuct 10. Examp le 3 . The compound shown as formula 14 is prepared as follows: > - 127 - Compounά 11 is acylateά with a biacridinium derivative such as 12 to give adάuct 13 which is treateά with 5-(p-sulfamylphenylazo) salicylic aciά to give the final proάuct 14. Example 4. The compounά shown as proάuct 18 is prepareά as follows: ( 1 6 ) Compounά 15 is reacteά with the carboxylate 16 to form the ester 17 where 16 is formeά by linking an oxiάation reάuction agent such as a άerivative of 2, 6-άichloro phenolinάophenol with a άioxene carboxylate άerivative. The ester 17 is reacteά with p-glycolohyάroxamate to give the final proάuct. Example 5. The compounά shown as formula 22 is prepareά as follows: ( 1 9) Compounά 19 which is formeά using an appropriately substituteά aniline is reacteά with aάάuct 20 to give aάάuct 21 where aάάuct 20 is formeά by alkylation of the aromatic ring of an active oxalate άerivative with a molecule which can accept electrons via electron transport. Aάάuct 21 is treateά with Baclofen to form the proάuct 22. Example 6. The compounά shown as formula 26 is prepareά as follows: T Compound 23 is prepared with the appropriately substituted ethoxy groups which is then reacted with a phthalhydraziάe such as 24 to form aάάuct 25. The final proάuct 26 is formeά by treatment of aάάuct 25 with γ-aminobutyric acid. Example 7 . The compound shown as formula 30 is prepareά as follows: 138 Compound 27 is reacted with adάuct 28 which is formeά by akylation of an active oxalate by a methylene blue άerivative. The proάuct aάάuct 29 is treateά with aάenosine 3', 5'-cyclic monophosphate to yielά the final proάuct 30. Example 8. The compound shown as formula 34 is prepared as follows: (32 ) X α < T O T Compounά 31 is acylateά with an active oxalate such as 32 to yielά aάάuct 33. Aάάuct 33 is treateά with Riάavirin to yielά the final proάuct 34. Example 9. The compounά shown as formula 38 is prepareά as follows: T Compounά 35 is reacteά with an alkyl haliάe άerivativeά active oxalate such as 36 to give adduct 37 which is treated with phosphonoacetate to give the final product 38. Example 10. The compound shown as formula 42 is prepared as follows : (40 ) X O J Compounά 39 is prepareά using the proper chloromethyl substituteά benzene anά reacteά with a άioxene άerivative such as 40 to yielά aάάuct 41. Aάάuct 41 is treateά with U-7130 to give the final proάuct 42. Example 11. The compound shown as formula 47 is prepared as follows: ^r Compounά 43 is άehyάrateά anά treateά with an inάole ketone άerivative άioxene such as 44 to give intermediate adάuct 45 which is hydrolyzeά to the ketone aάάuct 46. Aάάuct 46 is treateά with N-(phosphonacetyl)-L-asparate to yielά the final product 47. Example 12. The compounά shown as formula 51 is prepareά as follows: ( 49 ) _J. n ___ ** J T Compounά 48 is prepareά from the proper chloromethyl naphthalene anά reacteά with a phthalhyάraziάe such as 49 to give aάάuct 50 which is reacteά with trans-4-aminocrotonic aciά to give the final proάuct 51. Example 13. The compounά shown as formula 56 is prepareά as follows: f Compounά 52 is reacteά with p-toluene sulfonyl chloriάe to give tosylate aάάuct 52 which is reacteά with an active oxamiάe that has an alcoholic function such as 54 to give ether aάάuct 55. The aάάuct 55 is reacteά with compactin to give the final proάuct 56. Example 14. The compounά shown as formula 62 is prepareά as follows: ( 58 ) (61) Compounά 57 is reacteά with Mg to form the Grignard reagent 58 which is reacted with a dioxene inάole άerivative with an alάehyάe or ketone functionality such as 59 to give the alcohol 60. Aάάuct 60 is reacteά with 4-amino-hex-5-enoic aciά, 61, to give the final proάuct 62. Example 15. The compounά shown as formula 67 is prepareά as follows: ( 63 ) > T x o III i 1 o = CJ Cft < ^ o 3; X ■ o = υ 1 1 o υ The compounά 63 is reacteά with an aciά haliάe such as 64 to give adduct 65. The acid halide 64 is prepareά from the corresponάing aciά by reaction with oxalyl chloriάe. The original acid is prepareά by reacting a phenazine possessing an alkyl haliάe anά a carboxylic acid function with an inάole άerivative that has a amino group. The aάduct amiάe 65 is reacted with but-3-ynoyl-CoA, 66, to give the final product 67. Example 16. The compound shown as formula 71 is prepared as follows: ( 68 ) T o The aldehyde compound 68 is reacteά with a phosphonium yliά of a ubiquinone nucleus linkeά to a inάole άioxene άerivative such as 69 to form aάάuct ethylene 70. (The yliά 69 is formeά by an acylation reaction of an inάole άerivative dioxene with a ubiquinone adduct followed by reaction with triphenylphosphine. ) The adduct 70 is reacted with DL-2-hyάrazino-α-methylάopa to form the final proάuct 71. Example 17 . The compounά shown as formula 76 is prepareά as follows : J The alkylchloriάe 72 is reacteά with alkyl amine Lophine άerivate 73 to yeilά aάάuct 74 which is reacted with disodium cromoglycate, 75, to form the final proάuct 76. Preparations anά Routes of Aάministration of Luminiάes Luminiάes can be aάministereά orally, intramuscularly or intraveneously. Meάicinal formulations which contain one or more Luminiάe compounάs as the active compounά can be prepareά by mixing the Luminiάe (s) with one or more pharmacologically acceptable excipients or άiluents, such as, for example, fillers, emulsifiers, lubricants, flavor correcting agents, άyestuffs or buffer substances, anά converting the mixture into a suitable galenic formulation form, such as, for example, tablets, άragees, capsules or a solution or suspension suitable for parenteral administration. Examples of excipients or diluents which may be mentioned are tragacanth, lactose, talc, agar - agar, polyglycols, ethanol and water. Suspensions or solution in water can preferably be used for parenteral administration. Also, Luminides can be prepared as sterile lyophilized powάer to which a sterile solvent such as water or άimethylsulfoxiάe is aάάeά. Luminiάes are also prepareά as a sterile lyophilizeά powάer containing άeoxycholate to effect a colloidal dispersion of insoluble Luminiάe. These preparations are aάministereά as injectables incluάing intramuscular anά intravenous aάministration. Topical Luminiάes can be prepareά as a cream, lotion, gel, anά ointment. It is also possible to aάminister the active compounάs as such without excipients or diluents, in a suitable form, for example in capsules. Luminiάes can be packageά employing the usual sorts of precautious which the pharmacist generally observes. For example, the preparations may be packageά in light protecting vials anά may be refrigerateά if necessary. EXEMPLARY LUMINIDE PHARMACEUTICALS Prostaglanάins possess potent renal, carάiac, hemoάynamic, anά other physiological effects; however, the free agents are 95% inactivateά άuring one passage through the pulmonary circulation anά are essentially eliminateά in 90 seconάs from intravascular injection. A luminiάe which is resistant to intravascular inactivation comprising a C functionality of prostaglanάin A, A_, B., E., E_, or an analogue which possesses a vasoάilatory effect on coronary arteries anά other human vascular beάs is an agent for the treatment of ischemic heart άisease anά is a antihypertensive agent with a long halflife. A luminiάe which is resistant to intravascular inactivation comprising a C functionality of postaglanάin E, F, A or an analogue which possesses a positive carάiac inotropic effect is an inotropic agent with a long halflife. A luminiάe which is resistant to intravascular inactivation comprising a C functionality of prostaglanάin A, E, or an analogue prostaglanάin which possesses natriuretic anά άiuretic activity is a άiuretic agent with a long halflife. A luminiάe which is resistant to intravascular inactivation comprising a C functionality of prostaglanάin A, G, E,, E_ or an analogue such as 15(S)-15-methyl p GE 2 methylester, 16,16-άimethyl PGE 2 , AY-22,093, AY-22,469, AY-22,443, or 15(R)-15-methyl GE 2 which inhibits gastric acid secretion is an agent for the treatment of peptic and duodenal ulcer disease with a long halflife. A luminide which is resistant to intravascular inactivation comprising a C functionality of prostaglandin D_, E. or an analogue which inhibits platelet aggregation is an antithromboembolic agent with a long halflife. A luminiάe which is resistant to intravascular inactivation comprising a C functionality of prostaglanάin E.. , E_ or an analogue which causes bronchial άilatation is an agent for the treatment of asthma and allergic and hypersentivity reactions with a long halflife. A luminide which is resistant to intravascular inactivation comprising a C functionality of prostaglandin F_ or an analogue which causes abortion by luteolysis is an agent for therapeutic abortion with a long halflife. A luminide which is resistant to intravascular inactivation comprising a C functionality of prostaglandin A„, E,, E_, or an analogue which inάuces erythropoiesis by stimulating the release of erythropoietin from the renal cortex is an agent for the treatment of anemia. A luminiάe which is resistant to intravascular inactivation comprising a C functionality of prostaglanάin E or an analogue which modulates T lymphocytes to decrease their ability to reject an allogenic graft is an agent to prolong allograft survival. A cellular permeant luminide comprising a C functionality of cellular impermeant 2' -isopropyl -4' -(trimethylammonium chloride) -5" -methylphenyl piperidine -1-carboxylate (Amo 1618) which inhibits the cyclization of trans-geranyl-geranyl-PP to copalyl-PP during Kaurene synthesis is a fungicidal agent. A cellular permeant luminiάe comprising a C functionality of cellular impermeant aάenosine cyclic 3', 5'-monophosphate or an analogue which inhibits the release anά formation of phlogistic meάiators such as histamine anά kinins is an agent for treating asthma anά hypersensitivity anά anaphylactic reactions. A cellular permeant luminiάe comprising a C functionality of cellular impermeant 4'-sulfamylphenyl - 2-azo -7-acetamiάo -1-hyάroxynaphthalene -3, 6-άisulfonate (Neoprontosil) , 4'-sulfamyl -2, 4-άiaminoazobenzene (Prontosil) , or 5-(p-sulfamylphenylazo) salicylic aciά (Lutazol) which possess potent carbonic aciά anhyάrase inhibition is a άiuretic agent. A cellular permeant luminiάe comprising a C functionality of a cellular impermeant analogue of S-aάenosyl homocysteine or sinefungin is an oncostatic agent. A cellular permeant luminiάe comprising a C functionality of the cellular impermeant phosphoglycolohyάroxamate which inhibits Class II alάolases present in bacterial anά fungi anά is noninhibitory of Class I alάolases present in animals is an antibacterial anά antifungal agent. A cellular permeant luminiάe comprising a C functionality of a cellular impermeant inosine analogue such as formycin B which inhibits nucleotiάe phosphorylase άuring nucleotiάe metabolism is an agent for άisorάers of purine metabolism such as gout, is an agent that alters the toxicity anά/or antitumor behavior of other analogue - containing nucleosiάes such as 6-thioguanosine or 6-mercaptopurine ribonueleosiάe, anά is an immunosuppressive agent by άisruption of purine metabolism. A cellular permeant luminiάe comprising a C functionality of cellular impermeant phosphonoformate (Foscarnet) which inhibits the HIV reverse transcriptase enzyme is an agent for the treatment of acquireά immunoάeficiency synάrome. The synthesis anά the results of treatment of C3H mice infecteά with Raucher Spleen Focus Forming Virus with MTL J-l, a cellular permeant luminiάe comprising a C functionality of phosphonoformate, is given in Experimental Secions 1 anά 3, respectively. A cellular anά blooά-brain barrier permeant luminiάe comprising a C functionality of cellular anά blooά brain-barrier impermeant γ-amino-butyric aciά (GABA) which is the major inhibitory neurotransmitter in the mannalian central nervous system or comprising a C functionality of a cellular anά blooά-brain barrier impermeant inhibitor of the GABA-άegrading enzyme, GABA: 2-oxoglutarate aminotransferase such as gabaculine, N-(5 '-phosphopyridoxyl) -4-aminobutyric aciά, ethanolamine -o-sulfate, γ-vinyl GABA, or γ-acetylenic GABA; or comprising a C functionality of a cellular anά blooά-brain barrier impermeant compounά which enhances GABA release such as Baclofen is an anti-convulsant, muscle relaxant, seάative, anά anxiolytic agent. A cellular permeant luminiάe comprising a C functionality of a cellular impermeant oligonucleotiάe which binάs to RNA or DNA anά blocks transcription or translation of HIV or P-glycoprotein gene proάucts is an agent for the treatment of AIDs anά chemotherapeutic άrug, resistance, respectively. A blooά-brain barrier permeant luminiάe comprising a C functionality of blooά-brain barrier impermeant adenosine which binds to brain purinergic receptors to suppress opiate withάrawal is an agent for the management of opiate withάrawal synάrome. A slowly releasing peripherally acting luminiάe comprising a C functionality of aάenosine which causes coronary vasoάilatation is a long acting agent for the . treatment of ischemic heart άisease. A cellular permeant luminide comprising a C functionality of cellular impermeant 3-hyάroxy -3-methylglutarate, 3-hyάroxybutyrate, 3-hyάroxy -3-methylpentanoate, 4-bromocrotonyl -CoA, but-3-ynoyl -CoA, pent -3-ynoyl -CoA, άec -3-ynoyl-CoA, ML-236A, ML-236B (compactin) , ML-236C, mevinolin, mevinolinic aciά, or a mevalonic aciά analogue which is an inhibitor of 3-hyάroxy -3-methylglutaryl -CoA reάuctase which catalyzes the rate-limiting anά irreversible step of cholesterol synthesis where inhibition at this step does not leaά to the accumulation of nonmetabolizable precursors is an anticholesterol agent. A cellular permeant luminiάe comprising a C functionality of cellular impermeant thioinosinate which suppresses T lymphocytes is an immunosuppressant agent. A cellular permeant luminάe comprising a C functionality of cellular impermeant Suramin, which is a powerful inhibitor of energy άriven calcium uptake by the sarcoplasmic reticulum anά is an intracellular inhibitor of Na -K ATPase where both activities increase intracellular calcium concentrations with a concomitant inotropic effect is a carάiac inotropic agent. A cellular permeant luminiάe comprising a C functionality of a cellular impermeant norepinephrine N-methyltransferase inhibitor such as 2,3-άichloro -α-methylbenzylamine, 2,3-άichlorobenzylamine, 2,3-άichlorobenzamiάine, or 3,4-dichlorophenyl- acetamiάine is a specific epinephrine action blocking agent. A cellular permeant luminiάe comprising a C functionality of cellular impermeant adenosine cyclic 3 ',5 '-monophosphate or a cAMP analogue which blocks the synthesis of fatty aciάs anά cholesterol in the liver is an antilipiάemic agent. A cellular permeant luminiάe comprising a C functionality of a cellular impermeant inhibitor of άihyάroxyphenylalanine άecarboxylase άuring the synthesis of epinephrine anά norepinephrine such as psitectorigenin, genistein, 3 ' ,4 ' , 5,7-tetrahyάroxy- 8-methylisoflavone, orbol, 8-hyάroxygenistein, 3 ' ,5,7-trihyάroxy-4 ' , 6-άimethylisoflavone, 3 ' ,5,7-tri- hydroxy-4 ' ,8-άimethoxyisoflavone, D,L-B-(5-hyάroxy-3- inάolyl)-α-hyάrazinopropionic aciά, D,L-α-hyάra- zino-α-methylάopa, D,L-B-(3-indolyl) -α-hydrazino- propionic aciά, a άerivative of phenylalanine such as N-methyl-3,4-άopa, α-acetamiάo-3,4-άimethyoxy- cinnamic aciά, DL-α-methyl-3,4-άopa, α-methyl- B-(3-hyάroxy-4- methoxyphenyl)alanine, α-methyl- 3, -άimethoxyphenylalanine, or ά-catechin; D,L-B-(3- inάolyl)-α-methyl-α- hydrazinopropionic acid (R)-3 [3,4-άihyάroxyphenyl]-1- fluoropropylamine, (S)-α-fluoromethylάopa, (S)-α-fluoromethyl- tyrosine, 5-(3,4-άihyάroxycinnamoyl) salicylic aciά, 3-hyάroxycinnamic aciά, caffeic aciά, 3-mercapto- cinnamic aciά, α-methyl-3-hyάroxycinnamic aciά, α-ethyl-3- hydroxycinnamic aciά, 3-hyάroxy-w- nitrostyrene, 3,4-άihyάroxyhyάrocinnamic aciά, 3-hyάroxybenzalacetone, 3-hyάroxychalone, 3-hyάroxy- benzal furanyl ketone, 3-hyάroxybenzal thiophenyl ketone, 3 ' ,4 '-dihydroxyflavone, 8-0-glucoseflavone, flavone, 3-hydroxyphenyl pyruvic aciά, 3,4-dihydroxy- phenylpyruvic acid phenylthiopyruvic acid, 4-hydroxy- phenylpyruvic aciά, άithiosalicyclic aciά, l-hyάroxy2- naphthoic aciά, 3-hyάroxy-7-sulfo-2-naphtholic aciά, 3,5-άihyάroxy-2-naphtholic aciά, 4-chlorocinnamic aciά, 2-chlorocinnamic aciά, 2,4-άichlorocinnamic aciά, 3-nitrocinnamic aciά, 3,5-άibromo-2-hyάroxycin- namic aciά, 2,4,6-triioάo -3-hyάroxycinnamic aciά, 2-hyάroxy-4'-cyanochalone, 4-(4-hyάroxycinnamoyl) benzylnitrile, 2-(4-hyάroxycinnamoyl) -1,4-άihyάroxy- benzene, quercetin-6'-sulfonic aciά, 5-(2-hyάroxy-3,5- άibromocinnamoyl) salicylic aciά or 5-(3-hyάroxycin- namoyl) salicylic aciά is an antihypertensive agent. A sperm permeant luminiάe comprising a C functionality of sperm impermeant inhibitors of acrosin, a proteolytic enzyme locateά in the acrosome of sperm, such as tosyl lysine chloromethyl ketone, N-α-tosyl-L-arginine chloromethyl ketone, or ethyl p-guaniάinobenzoate is a contraceptive agent. A cellular permeant luminiάe comprising a C functionality of cellular impermeant aάenosine cyclic 3 ',5'-monophosphate (cAMP) , N 6 ,02-άibutyry- laάenosine cyclic 3 ' ,5'-monophosphate or an analogue which proάuces an inotropic response is a carάiac inotropic agent. A cellular permeant luminiάe comprising a C functionality of a cellular impermeant aάenosine kinase enzyme inhibitor such as 6,6'-άithiobis (9-B-D-ribofuranosylpurine) is a chemotherapeutic agent anά an immunosuppressive agent. A mitochonάrial anά blooά-brain barrier permeant luminiάe comprising a C functionality of a mito¬ chonάrial anά blooά-brain barrier impermeant inhibitor of monoamine oxiάase such as phenylhyάrazine, phenyl- ethyliάenehyάrazine, isopropylhyάrazine, or iproniaziά is an antiάepressant. A cellular anά blooά-brain barrier permeant luminiάe comprising a C functionality of a cellular and blood-brain barrier impermeant inhibitor of catechol-o-methyltrasferase such as 3,5-diioάo- 4-hyάroxybenzoic aciά, S-3 '-άeoxyaάenosylL- homocysteine, pyrogallol, R04-4602, gallic aciά, 3,5-άihyάroxy-4-methylbenzoic acid, 1,3-dihyάroxy- 2-methoxybenzene, l-hyάroxy-2,3-άimethoxybenzene, 2-hyάroxy-l,3-άimethoxybenzene, 1,3-άihyάroxy- 4-methoxybenzene, catechol, 3,4-άihyάroxybenzoic aciά, caffeic aciά, 5, 6-άihyάroxyinάole, noradnamine, dopacetamiάe, H 22/54, quercetin, norάihyάroguaiaretic aciά, U-0521, arterenone, methylspinazarin, MK 486, άopa, papaveroline, isoprenaline, 7,8-άihyάroxy- chlorpromazine, 3-hyάroxy-4-pyriάone, tetrahyάroi- soquinoline pyridoxal 5 '-phosphate, iodoacetic aciά, 3-mercaptotyramine, dehydrodicaffeic acid dilactone, methylspinazorin, 3 ' ,5,7-trihyάroxy-4 ' ,6-άimeth- oxyisoflavone, 3 ' ,5,7-trihyάroxy- 4 ' ,8-άimeth- oxyisoflavone, 6,7-άihyάromethylspinazarin, S-aάenosylhomocysteine, S-tuberciάinylhomocysteine, 3 ' ,8-άihyάroxy-4 ' , 6,7-trimethoxyisoflavone,7-0-methylspi nochrome B, 6-(3-hyάroxybutyl)-7-0-methylspinachrome B, 3,5-άiioάosalicyclic aciά, or pyriάoxal-5'- phosphate is an antiάepressant agent which increases brain levels of monoamines anά is an agent to block the metabolism of L-άopa aάministereά for the treatment of Parkinsonism. A cellular permeant luminiάe comprising a C functionality of a cellular impermeant inhibitor of aάenosine άeaminase which blocks the metabolism of aάenosine such as coformycin, arabinosyl-6-thiopurine, 6-methylthioinosine, 6-thioinosine, 6-thioguanosine, N -methylaάenosine, N -methylaάenosine, 2-fluoroάeoxyaάenosine, 2-fluoroaάenosine, inosine, 2'-άeoxyinosine, άeoxycoformycin, 1,6-άihyάro- 6-hyάroxymethyl purine ribonucleosiάe, erythro-9- (2-hyάroxy-3-nonyl)aάenine, or 9-B-D-arabinofuranosyl- 6-hyάroxylaminopurine is a vasoάilatory agent, an immunosuppressive agent, a chemotherapeutic poten¬ tiating agent, anά an agent to enhance carάiac recovery following ischemia. The mechanism in the first case involves the accumulation of aάenosine which is a vasoάilatory agent; the mechanism in the seconά case involves άisruption of purine metabolism; the mechanism in the thirά case involves the άisruption of the άegraάation of purine analogue chemotherapeutic agents; the mechanism in the fourth case involves blocking the loss of catabolic proάucts of aάenosine triphosphate in the form of purine nucleotiάes anά oxypurines άuring ischemia. Aάάitional luminiάes effective in enhancing post ischemic carάiac recovery by the latter mechanism incluάe those with C moieties of inhibitors of aάenylate kinase, 5'-nucleotiάase, anά aάenosine translocase such as p 1,p5-άiaάenosine penta- phosphate, α,B-methylene aάenosine άiphosphate, anά nitrobenzyl-6-thioinosine, respectively. A blooά-brain barrier permeant luminiάe comprising a C functionality of a blooά-brain barrier impermeant inhibitor of γ-aminobutyric aciά uptake such as D,L-2,4-άiaminobutyric aciά, D,L-B-hyάroxy GABA, (-)-nipecotic aciά, trans-4-aminocrotonic aciά, cis-3-aminocyclopentane- 1-carboxylic aciά, trans-3- aminocyclopentane-1-carboxylic aciά, B-guaniάino- propionic aciά, homohypotaurine, 4-aminopentanoic aciά, homotaurine, B-alanine, imiάazoleacetic aciά, 6-aminohexanoic aciά, D,L-camitine, D,L-2,6-άiamino- pimelic aciά, D,L-2-fluoro GABA, guaniάino acetic aciά, 2-hyάrazinoproρionic aciά, taurine, D,L-orni- thine, or sulphanilamine potentiates the inhibitory action of GABA anά is a muscle relaxant, anticon- vulsant, seάative, and anxiolytic agent. A cellular permeant luminiάe comprising a C functionality of cellular impermeant inositol 1,4,5-triphosphate which is a major second messenger for stimulating a whole range of cellular processes such as contraction, secretion, and metabolism is an agent for activating these processes including secretion of neural transmitters to function as an agent for the treatment of mental disorάers or secretion of insulin to function as a hypoglycemic agent. A cellular permeant luminiάe comprising a C functionality of cellular impermeant guanosine 5" cyclic monophosphate or 8-bromo guanosine 5' cyclic monophosphate which relaxes smooth muscle is an antihypertensive anά bronchodilator agent. A cellular and blood-brain barrier permeant luminide comprising a C functionality of a cellular and blood-brain barrier impermeant inhibitor of the uptake system for glycine, the inhibitory synaptic transmitter of the spinal cord, such as hyάrazihoacetic aciά is an agent for spinal reflex inhibition. A cellular permeant luminiάe comprising a C functionality of a cellular impermeant isoquinoline- sulfonamiάe inhibitor of protein kinase C, cAMP-άepenάant protein kinase, or cGMP-άepenάent protein kinase such as N-(2-aminoethyl)- 5-isoquino- linesulfonamiάe is an agent which blocks the secretion, contraction, anά metabolic events regulateά by these mediators of external physiologic stimuli. A cellular permeant luminiάe comprising a C functionality of cellular impermeant Ribavirin which is active against HSV-1 anά 2, hepatitis, anά influenza viruses, or phosphonoacetic aciά which is a highly specific inhibitor of Herpes Simplex virus inάuceά polymerase anά is active against HSV-1 anά HSV-2, or aάenine arabinoside (ara-A), cytosine arabinosiάe (Ara-C) , ara-A 5'-monophosphate (ara-AMP), or hypoxanthine arabinosiάe (ara-Hx) which is active against HSV or phagicin which is active against vaccinia anά HSV, or 4-fluoroimiάazole, 4-fluoroimi- άazole-5-carboxylic aciά, 4-fluoroimiάazole- 5-carbox- amiάe, 5-fluoro-1-B-D-ribofurano- sylimiάazole-4- carboxamiάe, 5-amino-l-B-D-ribofuranosyl- imiάazole-4- carboxamiάe, poly (I) • poly (C) , sinefungin, ioάoάeoxyuriάine, 9-(2-hyάroxy-ethoxymethyl) guanine, gliotoxin, άistamycin A, netropsin, congociάine, corάycepin, 1-B-D-arabinofuranosylthymine, 5,6-άi- hyάroxy-5-azathymiάine, pyrazofurin, toyocamycin, or tunicamycin is an antiviral agent. A cellular permeant luminάe which comprises a C functionality of a cellular impermeant inhibitor of fungal chitin synthetase such as polyoxin D, nikko- mycin Z, or nikkomycin X; or which comprises a C functionality of an impermeant antifungal agent such as ezomycin A., A_, B 1 , B_, C,, C_, D., or D_ or platenociάin, septacidin, sinefungin, A9145A, A9145C, or thraustomycin is an antifungal agent. A blood-brain barrier permeant luminiάe comprising a c functionality of a blooά-brain barrier impermeant inhibitor of central nervous system carbonic anhyάrase such as methazolamiάe, or 4 2-benzoylιmmo-3-methyl-Δ -1,3,4-thiaάiazoline- 5-sulfonamiάe substituteά at the benzolyl group with 3,4,5-trimethoxy, 2,4,6-trimethoxy, 2,4,5-trimethoxy, 4-chloro, 4-bromo, 4-iodo, or hydrogen is an anticonvulsant agent. A cellular and blood-brain barrier permeant luminide comprising a C functionality of a cellular and blooά-brain barrier impermeant inhibitor of dopamine-B-hydroxylase during the synthesis of norepinephrine anά epinephrine such as fuscaric aciά, 5-(3 ' ,4 '-άibromobutyl)picolinic aciά, 5-(3'-bromo- butyl) picolinic aciά, 5-(3 ' ,4'-άichlorobutylpicolinic aciά, YP-279, benxyloxyamine, p-hyάroxybenzyloxyamine, U-21,179, U-7231, U-6324, U-0228, U-5227, U-10,631, U-10,157, U-1238, U-19,963, U-19,461, U-6628, U-20,757, U-19,440, U-15,957, U-7130, U-14,624, U-22,996, U-15,030, U-19,571, U-18,305, U-17,086, U-7726, άimethylάithiocarbamate, άiethylάithio- carbamate, ethylάithiocarbamate, 2-mercaptoethyl- guaniάine, thiophenol, 2-mercaptoethylamine, 3-mercaρ- topropylguaniάine, 3-mercap- topropyl-N-methyl- guaniάine, 2-mercaptoethanol, 2-mercaptoethyl- N-methylguanidine, 2-mercaρtoethyl-N,N'- dimethyl- guaniάine, 4,4, 6-trimethyl -3,4-άihyάropyrimiάine- 2-thiol, N-phenyl-N'-3-(4H-l,2,4-trizolyl)thiourea, methylspinazarin, 6,7-άimethylspinazarin, 7-0-methy- spinochrome B, 6-(3-hyάroxybutyl)-7-0-methylspina- chrome B, aquayamycin, chrothiomycin, frenoclicin, N-n-butyl-N'-3-(4H-l,2,4-trazolyl) thiourea, propyl- thiouracil, mimosine, mimosinamine, or mimosinic aciά is an antihypertensive agent. A cellular permeant luminiάe of a cellular impermeant inhibitor of histidine άecarboxylation άuring the synthesis of histamine such as 2-hyάroxy-5-carbomethoxybenzyloxyamine, 4-toluene- sulfonic aciά hydrazide, 3-hydroxy benzyloxyamine, hyάroxylamine, aminooxyacetic aciά, 4-bromo-3-hyάroxy- benzyloxyamine (NSD-1055), rhodanine substituted in the 3 position with p-chlorophenethyl, p-chlorobenzyl, p-methylthiobenzyl, p-methylbenzyl, p-fluorobenzyl, amino, 3,4-άichlorobenzyl, p-bromobenzyl, p-methoxy- benzyl, p-bromoanilino, p-iodoanilino, p-chloro- anilino, p-toluiάino, anilino, 2,5-άichloroanilino, άimethylamino, or p-rnethoxyphenyl; 2-n_ercaptobenzimidazole-l,3-άimethylol, 4-bromo-3- hyάroxy -benzoic aciά, 4-bromo-3-hyάroxybenzyl alcohol, 4-bromo-3-hyάroxy-hippuric aciά, (R,S)-α- fluoromethyl- histiάine, (S)-α-fluoromethylester, L-histidine ethyl ester, L-histiάinamiάe, D,L-3-amino- 4-(4-imiάazolyl)-2-butanone, 2-bromo-3-hyάroxy- benzyloxyamine, 5-bromo-3- hyάroxybenzyloxya ine, 4, 6-άibromo- 3-hyάroxybenzyloxyamine, aminooxypropionic aciά, benzyloxyamine, 4-bromo-3- benzenesulfonyloxybenzyloxyamine, 3' ,5,7-trihyάroxy- 4',6- άimethoxyisoflavone, lecanor'ic aciά, N-(2,4-άihyάroxybenzoyl)- 4-aminosalicylic aciά, or 3 * ,5,7-trihyάroxy-4' ,8- άimethoxyisoflavone is an agent for the treatment of allergy, hypersensitivity, gastic ulcer, anά inflamation. Luminiάes also comprise C functionalities of pharmaceutical molecules as appear in Physicians Desk Reference, Eάwarά R. Barnhart, 41th eά., 1987, Meάical Economics Company Inc., N.J.; USAN anά the Dictionary of Druσ Names. eά. by Mary C. Griffiths, The Uniteά States Pharmacopeάial Convention, (1986) ; anά The Pharmacological Basis of Therapeutics, eά. by A.G. Gilman, L. Goodman, A. Gilman, 7th eά., (1985), MacMillan Publishing Co., N.Y., N.Y. , (incorporateά by reference) where the pharmacokinetics anά/or the pharmacoάynamics of these agents are altereά via delivery to the site of action by way of a luminide agent such that the therapeutic effect or therapeutic ratio is enhanceά. Some examples follow which are not meant to be exhaustive. A luminide with high permeance to the blood-brain barrier comprising a C functionality of a centrally acting converting enzyme inhibitor such as captopril which possesses a lesser blood-barrier permeance is an agent with increased efficacy of the central nervous system antihypertensive effect of the centrally acting converting enzyme inhibition incluάing captopril. A luminiάe with an A moiety which reacts with free raάicals anά electron carriers in the cytosol of bacteria to effect release of the C moiety and which possesses greater permeance or B-lactamase resistance than its C moiety of a bacterial wall synthesis inhibitor such as a penicillin, cephalosporin, or cephamycin is a more efficacious and broaά spectrum antibacterial agent than the free C moiety. A luminiάe possessing more favorable pharmacokinetics or pharmacodynamics than its C moiety of an agent which blocks bacterial synthesis of tetrahydrofolate such as a sulfonamiάe (an analogue of p-aminobenzoic aciά) incluάing sulfanilamiάe, sulfaάiazine, sulfamethoxazole, sulfisoxazole, or sulfacetamiάe or an inhibitor of άihyάrofolate reάuctace incluάing pyrimethamine, cycloguanil, trimethoprin, isoaminopterin, 9-oxofolic aciά, or isofolic aciά is a more efficacious antibacterial than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than it C functionality of a bactericiάal agent such as naliάixic aciά or oxolinic aciά is a more efficacious antibacterial than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of an inhibitor of bacterial protein synthesis such as vancomycin, an aminogylcosiάe, erythromycin, tetracyclin, or chloramphenicol is a more efficacious antibacterial agent than the free C moiety. A luminiάe prossessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of an inhibitor of viral DNA polymerase such as vidarabine is a more efficacious antiviral agent than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety which is tuberculostatic or tuberculociάal such as isoniaziά or a inosalicyclic aciά is a more efficacious agent for the . treatment of tuberculosis than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmoάynamics than its C moiety of an anthelmintic agent such as oxamniquine, piperazine, metroniάazole, άiethylcarbamazine, paromomycin, niclosamiάe, bithionol, metrifonate, hycanthone, άichlorophen, or niclosamiάe is a more efficacious anthelmintic agent than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of an H^-blocking agent such as cimetiάine or ranitiάine is a more efficacious anti-ulser agent than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of an agent which blocks release of norepinephrine such as sotalol, guanethiάine, pinάolol, pronethalol, O 592, practolol, oxprenolol, or pronethalol is an antiarrhythmic, antihypertensive anά antipsychotic agent. A luminide possessing more favorable pharmaco¬ kinetics or pharmacodynamics than its C moiety of a xanthine oxidase inhibitor such as allopurinol, thioinosinate, 5,7-άihyάroxyρyrazolo [1,5-a] pyrimidine substituted at the 3 position with hyάrogen, nitro, bromo, chloro, phenyl, 3-pyridyl, p-bromophenyl, p-chlorophenyl, p-acetylanilino, p-tolulyl, -tolulyl, naphthyl, or 3,4-methyl- eneάioxyphenyl; 8-(m-bromoacetamidobenzyl- thio)hypoxanthine, 8-(m-bromoacetamidobenzyl- thio)hypoxanthine, guanine substituteά at the 9 position with phenyl, 4-chlorophenyl, 3-chlorophenyl, 3,4-dichlorophenyl, 4-methoxyphenyl, 3,4-άimeth- oxyphenyl, 4-άimethylaminophenyl, 4-aminophenyl, 3-aminophenyl, 3-trifluormethylphenyl, 4-benzamido, 4-carboxylρhenyl, 4-methylpheyl, 4-ethylphenyl, 3-methylphenyl, B-naphthyl, or 4-ethoxyphenyl; 4, 6-άihyάroxypyrazolo [3,4-d] pyrimidine, 4-trifluoro- methylimiάazoles substituteά at the 2 position with phenyl, p-chlorophenyl, p-methoxyphenyl, p-acetylani¬ lino, p-nitrophenyl, p-dimethylaminophenyl, p-cyano- phenyl, p-fluorophenyl, p-carboxyphenyl, m-chloro- phenyl, 3,4-άichlorophenyl, 4-pyriάyl, 3-pyriάyl, 2-quinolyl, 6-quinolyl, 4-quinolyl, 7-quinolyl, 2-pyrazinyl, or l-(2-pyriάyl-4-trifluoromethyl- 5-bromoimidazolyl; 5-(4-pyridyl)-l,2,4-triazoles substituted at the 5 position with 4-ρyridyl, 3-pyridyl, 2-pyridyl, phenyl, p-chlorophenyl, m-chlorophenyl, p-sulfonamidophenyl, 3,5-άichloro- phenyl, 3,5-άicarboxyphenyl, 6-quinolyl, 2-furyl, 4-pyriάazinyl, 2-thienyl, 2-pyrimiάinyl, 4-pyrimi- άinyl, or 4-pyrazinyl; άifunisal, 4(or 5)-(2-amino- ethylthio-azo)imidazole-5(or 4)-carboxamide, 4 (or 5)-diazoimidazole-5(or 4)-carboxamide , or S-[5(or 4)-carbamoyl-4(or 5)-imiάazolyl azo] cysteine is a more efficacious agent for the treatment of gout anά hyperuricemic conάitions than the free C moiety. A .luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety which inhibits DNA synthesis such as a bis-thiosemicar- bazone, 3,5-diisopropylsalicyl- hyάroxamic acid, 4-hyάroxybenzoylhyάroxamic aciά, 3-methylsalicyl- hyάroxamic aciά 2,5-άihydroxybenzoylhydroxamic aciά, or 2-hydroxy-3,4,5-trimethoxybenzoylhyάroxamic aciά; or which inhibits nucleotide synthesis such as N-(phosphoacetyl)-L-aspartate which inhibits asparatate transcarbamylase άuring pyrimiάine synthesis, or azaserine or 6-άiazo-5-oxo-L-norleucine which inhibits purine synthesis at the phosphori- bosyl-formyl-glycineamiάine synthetase step; or which is an antifolate such as methotrexate, 2,4-άiamino-5-benxyl-6-(4-phenylbutyl) pyrimiάine, 2,4-diamino- 5-phenyl-6-(4-phenylbutyl) pyrimiάine, 2,4-diamino-5-phenyl- 6-(3-anilinopropyl) pyrimiάine, 2-amino-4-hyάroxy-5-ρhenyl- 6-(3-p-aminobenzoyl- glutamic aciά propyl) pyrimiάine, N-[p-[[(2,4-άiamino-6-quinazolinyl)methyl]methylamino] benzoyl]-L-glutamic aciά, N-[p-[2,4-άiamino-5- methylquinazolinyl)methylamino]benzoyl] -L-aspartic acid, N-Cp-[[(2-amino-4-hyάroxy-6-quinazolinyl) methyl]methylamino] benzoyl]-L-glutamic a.ciά, 2,4-άiaminoquinazolines: CCNSC 105952, CCNSC 112846, CCNSC 121346, CCNSC 122761, CCNSC 122870, CCNSC 529859, CCNSC 529860, or CCNSC 529861; 8-aza GMP, 7-deaza-8-aza GMP, 2'-dGMP, B-D-arabinosyl GMP, pentopyranine A-G, B-ribofuranosyl-l,3-oxazine-2,4- άione, pyrazofurin, 6-(p-chloroacetylanilinomethyl)-5- (p-chlorophenyl)-2,4- άiaminiopyridine, 6-(p-chlora- cetylvinylanilinomethyl)-5- (p-chlorophenyl)-2,4- diaminopyridine, 6-(p-chloroacetyl- ethylanilino- methy1)-5-(p-chlorophenyl)-2,4-diamino pyriάine, 6-(p-chlorophenylbutylanilinomethyl)-5-(p-chlorophenyl)- 2,4- άiamino pyriάine, p-(2,6-diamino-l,2-dihyάro-2, 2-dimethyl- S-triazin-1-yl) phenylpropionyl sulfanilylfluoride or variants of the propionamiάe briάge of acrylamiάo, N-ethylsulfonamiάo, N-ethylcaboxamiάo, oxyacetamiάo, or oxythyloxy; or which inhibits purine or pyrimidine synthesis such as xylosyladenine, 6-azauriάine, 5-aminouriάine, 5-azaorotic aciά; or which inhibits nucleotiάe interconversion such as hadaciάin, 6-mercaptopurine, azathioprine, nitro-άUMP,psicofuranine, άecoyinine, 5-fluorouracil, 5-fluoroάeoxyuriάine, shaάowmycin; or which inhibits nucleotide utilization such as cytosine arabinoside, arabinosyladenine; or which becomes incorporateά into polynucleotides such as 8-azagua- nine, tuberciάine, toyocamycin, sangivamycin, formycin, 7-άeazainosine, 8-azainosine, or 7-thia-7, 9-άiάeazainosine; or which is a glyoxalase inhibitor such as Glyo-I, or Glyo-II, is a more efficacious antineoplastic agent than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of an agent which blocks synthesis of prostaglandin A„ which effects platelett aggregation such as salicylic acid, pyrogallol, 5,8,11,14-eicosatetraynoic acid, α-naphthol, guaiacol, propylgallate, nordihyάro- guiaretic aciά, N-0164, benzyάamine, 9,ll-azoprosta-5, 13-άienoic aciά, 2-isopropyl-3-nicotinylindole, is a more efficacious antithrombotic agent than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of an agent which blocks prostaglandin synthetase such as inάomethacin, sulinάac, tolmetin, mefenamic aciά, ibuprofen, naproxen, fenoprofen, fluribiprofen, ketoprofen, meclofenamic aciά, flufenamic aciά, niflumic aciά, benzyάamine, oxyphenbutazone, asprin, acetaminophen, salicylamide, O-carboxyάiphenylamine, tolectin, diclofenac, 2,7-άihydroxynaphthalene, 5-(4-chlorobenzoγl)- l-methylpyrrole-2-acetic aciά, 5-(4-methylbenzoyl)-l,4- dimethylpyrrole-2-acetic aciά, 5-(4-chlorobenzoyl)-l,4- dimethylpyrrole-2- acetic aciά, 5-(4-fluorobenzoyl)-l,4- dimethylpyrrole- 2-acetic aciά, 5-(4-chlorobenzoyl)-l,4- άimethylpyrrole-2-(2-propionic acid), 5,6-dehyάro- arachidonate, 11,12-dehydroarachidonate, or 5,8,11,14-eicosatetraynoate; or of an agent which blocks lipoxygenase or blocks leukotriene action such as B 755C, FPL 55712, or U-60,257 is a more efficacious nonsteroidal anti-inflammatory agent than the free C moiety. A luminide possessing more favorable pharmaco¬ kinetics or pharmacodynamics than its C moiety of an antiarrhythmic agent such as procainamide or quiniάine is a more efficacious antiar hythmic agent than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of an inhibitor of hepatic synthesis of Vitamin άepenάent clotting factors such as warfarin soάium, dicumarol, 4-hydroxycoumarin, phenprocoumon, or acenocoumarol is a more efficacious anticoagulant than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety which άirectly relaxes vascular smooth muscle such as hyάralazine, minoxiάil, or isoxsuprine is a more efficacious antihypertensive agent than the free C moiety. - 195 - - . :> ., ~ . A luminide possessing more favorable pharmaco¬ kinetics or pharmacodynamics than its C moiety of a Na + -K + -ATPase inhibitor such as digtoxigenin, digoxigenin, cymarol, periplogenin, or strophan- thiάiol, or ouabain glycosides, cardenolides, or basic esters, or ICI-63,632, ICI-63,605, ICI-62-655, ICI-62,838, ICI-69,654, ICI-58,622, ICI-61,374, ICI-57,267, ICI-61,424, ICI-61,411, ICI-65,199, ICI-70,898, ICI-70,899, ICI-70,900, ICI-70,901, ICI-62,966, ICI-65,210, ICI-63,116, ICI-62,936, ICI-65,551, ICI-63,978, ICI-62,276, ICI-63,056, ICI-67,135, ICI-67,167, ICI-67,134, ICI-67,875, ICI-67,880, or ICI-61,558 is a more efficacious inotropic agent than the free C moiety. A luminide possessing more favorable pharmaco¬ kinetics or pharmacodynamics than its C moiety which is a calcium channel blocker such as prenylamine, verapamil, fendiline, gallopamil, cinnarizine, tiapamil, diltiazem, bencyclan, or nifedipine; or an agent which stabalizes calcium binding to cellular calcium stores and thereby inhibits the release of this calcium by contractile stimuli such as 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate (TMB-8) is a more efficacious vasodilatory agent than its free moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacodynamics than its C moiety of a monoamine oxidase inhibitor such as tranylcypromine, phenylethylamine, trans-cinnamic acid, phenelzine, or isocarboxazid is a more efficacious antiάepressant agent than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of a benzoάiazepine compounά such as clorazepate is a more efficacious tranquillizer than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of an antiseizure agent such as valproic aciά is a more efficacious antiepileptic agent than the free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of an agent which causes repression of the synthesis of HMG-CoA reάuctase such as 20-α-hyάroxycholesterol, 22-ketocholesterol, 22-α-hyάroxycholesterol, 25-hyάroxycholesterol, 22-B-hyάroxycholesterol, 7-α-hyάroxycholestero1, 7-B-hyάroxycholestero1, 7-ketocholesterol, or kryptogenin; or of an agent which inhibits HMG-CoA reάuctase such as, lorelco; or of an agent which inhibits lipolysis such as 5-methyl- pyrazole -3-carboxylic aciά (U-19425) , nicotinic aciά, uriάine, inosine, 3,5-άimethylisoxazole (U-21221) , 3,5-άimethypyrazole, prostaglanάin E_, eritaάenine, or eritaάenine isoamyl ester; or of an agent which inhibits lipogenesis such as ascofuranone, (-)-hydroxycitrate, or tetrolyl-CoA; or of an agent which is hypocholesterolemic such as lentysine; or of an agent which lowers triglyceriάes such as lopid; or of an agent which is an inhibitor of acetyl-CoA carboxylase άuring lipogenesis such as 2-methyl -2-[p-(1,2,3,4-tetrahyάro-l-naphthyl)-phenoxy]-propionat e (SU13437) , 2-(p-chlorophenoxy)-2-methylpropionate, kynurenate, xanthurenate, kynurenine, 3-hyάroxy- anthranilate, or 2-methyl-2- [p-(p-chlorophenyl)- phenoxy] propionate; or of an agent which is an inhibitor of hepatic B-lipoprotein proάuction such as orotic aciά is a more efficacious hypolipiάemic agent than its free C moiety. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics than its C moiety of a vasoάilater such as WS-1228A, or WS-1228B; or of an anti-inflammatory agent such as amicomacin A is a more efficacious vasodilator or anti-inflammatory agent, respectively, than the free C moiety. A luminide with more favorable pharmacokinetics or pharmacodynamics than its C moiety which is a protease inhibitor such as leupeptin; or which is an inhibitor of pepsin such as a pepstatin, a pepstanone, or a hydroxypepstatin is a more efficacious agent for the treatment of muscular άystrophy or peptic ulcer άisease, respectively, than its free C moiety. A luminiάe with more favorable pharmacokinetics or pharmacoάynamics than its C moiety of an inhibitor of cell surface enzymes such as bestatin, amastatin, forphenicine, ebelactone, or forphenicin is a more efficacious immunomoάifier agent than its free C moiety. A luminiάe with more favorable pharmacokinetics or pharmacoάynamics such as enhanced permeability relative to its C moiety of a phosphodiesterase inhibitor such as theophyllineacetic aciά, theophyl- line, άyphylline, άisoάium cromoglycate, 6-n-butyl- 2,8-άicarboxy-4, 10-άioxo-l,4,7,10- tetrahyάro-1,7- phenanthrolin, 2-chloroaάenosine, άipyriάamole, EG 626, AY-17,605, AY-17,611, AY-22,252, AY-22,241, cis-hinokiresinol, oxy-cis-hinokiresinol, tetra- hyάro-cis- hinokiresinol, trans-hinokiresinol, άehyάroάicaffeic aciά, 2, 6,4 '-trihyάroxy-4- methoxybenzophenone, p-hyάroxyphenyl crotonic aciά, papaverine, 3-(5-tetrazolyl)-thioxanthone- 10,10-άioxiάe, 3-carboxythioxanthone-10,10-άioxiάe, W-7, HA-558, MY-5445, OPC-3689, OPC-13135, or OPC-13013, reticulol, PDE-I, or PDE-II is a more efficacious carάiac stimulant, άiuretic, vasoάilator, platelett aggregation inhibitor, anά an agent for the treatment of asthma anά allergic reaction than its free C moiety. Such a luminiάe comprising a C moiety of ICI 74,917 is also a more efficacious agent for the treatment of asthma anά allergic reactions. A luminiάe possessing more favorable pharmaco¬ kinetics or pharmacoάynamics such as enhanceά cellular or blooά-brain barrier permeability or resistance to inactivation by tissue άehalogenases anά transaminases than its C functionality of an inhibitor of tyrosine hyάroxylase, the enzyme catalyzing the rate-limiting reaction in the biosynthesis of norepinephrine, such as azaάopamine, isopropylazadopamine, dimethylaza- άopamine; triphenolic compounds such as n-propylgal- late; diphenolic benzoic aciά άerivatives such as 3,4-άihyάroxybenzoic aciά; phenylcarbonyl άerivatives such as 3,4-άihyάroxybenzalάehyάe, arterenone, or aάrenalone; H 22/54, 3-iodo-L-tyrosine, D,L-α- methyl-p-tyrosine, L-3-iodo-α-methyltyrosine, 3-bromo-α-methyltyrosine, gentistic acid, 3-chloro- α-methyltyrosine, phenylalanine derivatives, 3,5-άiioάo- L-tyrosine, 3,5-άibromo-L-tyrosine, 3-bromo-α-methyl-L- tyrosine, 3-fluro-α-methyl- L-tyrosine, catechol analogues, 3,4-άihyάroxyphenyl- ethylacetamiάe, 3,4-άihyάroxyphenyliso- proplyaceta- miάe, 3,4-άihyάroxyphenylbutylacetamiάe, 3,4-άi- hyάroxyphenylisobutylacetamiάe, D,L-c_-rnethylphenyl- alanine, D,L-3-ioάophenylalanine, D,L-4-ioάophenyl- alanine, D,L-α-methyl-3-ioάophenylalanine, D,L-α-methyl-3- bromophenylalanine, D,L-α-methyl- 3-chlorophenylaIanine, D,L-α-methyl-3-fluoro- phenylalanine, mimosine, mimosinamine, mimosinic aciά, 7-0-methylspinochrome B, 6-(3-hyάroxybutyl)-7-0- methylspinachrome B, aquayamycin, chrothiomycin, frenolicin, fuscaric aciά, pentylpicolinic aciά, dopstatin, methylspinazarin, 6,7-άihyάroxymethyl- spinazarin, 3-ethyl-α-methyltyrosine, 3-methyl- α-methyltyrosine, 3-isopropyl-α-methyltyrosine, 3-allyl-α-methyltyrosine, 3-[4-hydroxy-3- (2-methylallyl)-phenyl]-2-methylalanine, 3-[3-(2,3- epoxypropyl)-4-hyάroxyphenyl]-2-methylalanine, 3-isobutyl-α-methyltyrosine, 3-methylvinyl- α-methyltyrosine, 5-methyl-6,7-άiphenyl- tetrahydropterin, 3-[2,3-dihydro-2,2- άimethyl-5-benzofuranyl]-2-methylalanine, 3-[2,3-άihyάro-2,2-άimethyl-5-benzofuranyl]-2-methylalan ine, α-methylάopa, or ethyl-3-amino-4H-pyrrolo [3,4c] isoxazole carboxylate is a more efficacious antihypertensive agent than the free C moiety. In aάdition, luminides which provide controlled extracellular release of biologically active substances such as drugs and proteins including enzymes and hormones are herein discloseά as macromolecular luminiάes. Luminiάes, each comprising a C functionality of a άrug or protein such as insulin, erythropoietin, interleuken 2, interferon, growth hormone, atrial natriuretic factor, tissue plasminogen activator, an anti-inflammatory άrug, an antihypertensive άrug, an inotropic άrug, a contraceptive άrug, etc., are attached to a polymeric material to which an enzyme is immobilized to form a macromolecular luminiάe. The enzyme molecules react with molecules in the ambient extracellular environment at a rate in proportion to their concentration to proάuce peroxiάe or free raάicals which react with the A functionality molecules causing them to achieve a high energy electronic state which is followed by the release of the C molecules where the release of C is in proportion to the ambient concentration of the substrate of the enzyme. For example, a macromolecular luminide which provides a release of insulin in proportion to the ambient glucose concentration comprises luminiάe molecules, each comprising a C functionality of insulin, covalently bound to a biocompatible polymer to which the enzyme glucose oxidase is immobilized. The immobilized enzyme reacts with glucose at a rate proportional to the ambient glucose concentration to produce peroxide which reacts with the A functionality molecules of the attached luminide molecules to effect release of insulin. Because the insulin release is in proportion to the glucose concentration this macromolecular agent represents a very effective diabetic therapy. As an adάitional example, carάiac ischemia results in the proάuction anά release of άegraάation proάucts of purines such as xanthine. The enzyme xanthine oxiάase oxidizes xanthine and directly reduces oxygen to hydrogen peroxide. Furthermore, tissue plasminogen activator (TPA) is an effective agent for the treatment of myocardial infarction because this agent effects the lysis of fibrin clots in coronary arteries to establish reperfusion. Cardiac recovery is. enhanced by diminishing the delay between the occlusion event anά the aάministration of TPA. Thus, a macromolecular luminide comprising luminide molecules, each comprising a C functionality of TPA, bounά to a biocompatible polymer to which xanthine oxiάase is immobilizeά is an agent which releases TPA in proportion to the proάucts of carάiac ischemia. Thus, it is a highly effective agent to resolve myocarάial infarctions. In another emboάiment, luminiάe molecules, each comprising an A functionality which achieves a high energy electronic state via a reάuction reaction, are attacheά to a conάucting polymer to which an enzyme is immobilizeά. The immobilizeά enzyme oxiάizes > molecules in the ambient environment and transfers electrons to the conducting polymer which reduces the A functionality molecules directly or indirectly via the optional D functionality molecules to effect release of the C molecules. In the latter embodiment, the conducting polymer derivatizeά with an enzyme, can be replaceά with an electrocatalytic polymer which is reάuceά άirectly by molecules in the ambient environment and transfers the electrons to the luminide molecules to effect release of the C molecules. For example, polyvinylferrocene and poly-[N-(9,10-anthroquinone)- ethylenimine are conάuctive polymers anά electrocatalytically oxiάize glucose. Thus, a macromolecular luminide for the treatment of diabetes comprises a conducting polymer such as polyvinylferrocene to which glucose oxidase is optionally bound and to which luminide molecules are bound where the A functionality molecules of the polymer attacheά luminiάes achieve a high energy electronic state via a reάuction reaction. The polymer is reάuceά when glucose oxiάase accepts electrons from glucose anά transfers them to the polymer. Or, the electrocatalytic polymer is reάuceά άirectly by glucose. The reάuceά polymer reάuces the A functionality molecules άirectly or inάirectly via the optional D functionality molecules to effect release of insulin molecules in proportion to the ambient glucose concentration. Furthermore, macromolecular luminiάes can be άirecteά to a specific extracellular target site such as an anatomical or biological compartment or organ by further attaching monoclonal antiboάy molecules to the polymer of the macromolecular luminiάe which binά to a molecule at the desired target site. In aάάition to pharmaceutical agents, luminiάes also comprise pesticiάes including herbicides, fungicides, miticides, nematocides, fumigants, growth regulators, repellants, defoliants, rodenticides, molluscicides, algicides, desicants, antehelmintics, and bactericides. These luminides can be obtaineά by one skilleά in the art by combining the functionalities. A, B, anά optionally, D, of energy άonor, energy acceptor, anά electron transfer functionality, respectively, with a C moiety which possesses pesticidal activity. C moieties include those that appear in Chemical Week Pesticides Register. Robert P. Ovellette anά John A. King, 1977, McGraw-Hill Book Company (incorporateά by reference) anά analogues of these agents. Enhanceά pesticiάal effectiveness is acheiveά via improveά άelivery of these agents to their target receptors by way of luminiάe molecules which possess άesirable properties such as increaseά permeance to the cells of the organism relative the free C moieties. EXPERIMENTAL 2 Release Reaction MTL 7-3 was testeά for release of the nitrile group as free cyaniάe άuring the reaction of the isoluminol group with hyάrogen peroxiάe as follows: 1.2X10 -5 moles of 1, 5-άi-(p-N-2- (N-(4-aminobutyl) -N-ethylisoluminol) -N-ethylaminophenyl) -1,5-bis-(p,N,N-άimethylani1ine) -1,3-pentaάiene was reacteά with an excess of cyaniάe in a 4/4/1 DMSO/pyriάine/H 2 0 solvent. The solution was aciάifieά to pH one anά άistilleά unάer vacuum until gas no longer evolveά. The proάuct was split into six equal aliquots of approximately one milliliter volume. A volume of .1ml of 1M NaOH was aάάeά to all aliquots. A volume of .05ml of 3% hyάrogen peroxiάe was aάded to 3 of the aliquots. After five minutes cyaniάe was assayeά following the proceeάure of Gunther anά Blinn. This proceeάure involves the aάάition of acid to the sample which is heated to distill hydrocyanic acid which is captured in a basic solution to which a colorimetric reagent is adάed to develop a color which is compared to a stanάarά curve. The results are as follows: TEST ONE Sample Releaseά cyaniάe (ug) Blank 0 MTL 7-3 22.2 MTL 7-3/H 2 0 2 26.4 Sample Releaseά cyaniάe (ug) Blank 0 MTL 7-3 21.5 MTL 7-3/H 2 0 2 27.0 TEST THREE Sample Releaseά cyaniάe (ug. Blank 0 MTL 7-3 15.0 MTL 7-3/H 2 0 2 30.5 The release reaction test was repeateά as follows: 4.5X10 -6 moles of 1,5-άi-(p-N-2-(N-(4-aminobutyl) -N-ethylisoluminol) -N-ethylaminophenyl) -l,5-bis-(p-N,N- άimethylaniline) -1,3-pentaάiene was reacteά with excess cyaniάe in a 1:1 DMSO/H 2 0 solvent. The solution was aciάifieά to ph one anά was άistilleά for 90 minutes unάer reάuceά pressure. The volume of the solution was maάe 4 milliliters by aάάition of H_0. The solution was maάe basic by aάάition of IM NaOH anά was split into two equal volume aliquots. .05 milliliters of 3% H 2°2 was adt3 - e c- to one aliquot. Both aliquots stooά for 5 minutes, anά then cyaniάe was άetermineά as previously άescribeά. The results are as follows: TEST FOUR Sample Releaseά cyaniάe (ug. Blank 0 MTL 7-3 73.4 MTL 7-3/H 2 0 2 109.1 The results inάicate that cyaniάe was releaseά as a result of a reaction of hyάrogen peroxiάe with the luminiάe compounά. The release of lesser amounts of cyaniάe άuring the control experiment is consistent with the thermochromic properties of the luminiάe compound at elevated temperatures as the samples were heated άuring the cyaniάe άetermination proceeάure. EXPERIMENTAL 3 Efficacy of Treatment of C3H Mice Infecteά with Raucher Spleen Focus Forming Virus with Luminide MTL J-l. The effectiveness of MTL J-l was testeά in C3H mice against the virus RSFFV (Raucher Spleen Focus Forming Virus) which is a retrovirus anά is a valiά animal moάel for HIV infection by application to the above iάentifieά mice accorάing to the following proceάure: Three groups of two month olά C3H mice, each comprising four animals were proviάed as one control and two test groups; wherein, the three groups (I-III) were subjected to an infectious άose of RSFFV on άay one. The first group (I) serveά as control anά receiveά no treatment. Group II anά III were treateά with lOuM total boάy weight concentration of the άrug Foscarnet anά the test compounά MTL J-l, respectively which was aάministereά each άay for άays 5 through 9. The animals were sacrificeά on άay 14, where upon the spleens where removeά anά weigheά. The results are surnmarizeά in the following table: TABLE 1 I II III Enάing Weight 21.1 21.2 22.5 (grams) Weight change 1.675 0.15 2.25 (grams) Spleen weight .083 .079 .068 Normalizeά (grams) The tests were reάone with a seconά control group (IA) having no infection of RSFFV anά receiving no treatment with any άrug, wherein groups I anά IA comprise four mice each, anά groups II anά III comprise five mice each, proviάing the results summarizeά below: TABLE IA II III Enάing Weight 18.5 18.6 19.6 19.2 (grams) Weight change +1.0 +1.8 +1.6 +1.5 (grams) Spleen weight 0 . 046 0 . 060 0 . 061 0 . 049 Normalizeά (grams) These results inάicate that MTL J-l was nontoxic as άemonstrateά by an absence of weight loss anά that MTL J-l was highly effective as demonstrated by the absence of splenomegaly in the animals administered this compound. The biologically active substances not specifically mentioned are incluάeά in, anά functionally applicable as a άrug in the compounά of the present invention. Also, the references referreά to herein or fileά herewith are hereby incorporateά by reference. Moάifications anά substitutions maάe by one of skilleά in the art are consiάereά to be within the scope of the present invention, which is not to be limiteά except by the claims. APPENDIX I Triphenyl Methanes Triphenyl methane dyes have been known and used for many years. Consequently many general-type syntheses have been worked out and published. The following four synthesis methods have been used almost exclusively for the 15 triphenyl methane dyes synthesized. Method A. Michler's Ketone Methoά To equal molar quantities of a p-amino benzophenone or άi-(p-amino) benzophenone (Michler's type ketones) anά aromatic amines, such as anilines anά naphthyl amines, sufficient toluene-phosphorous oxychloriάe solution is added (3-5) to dissolve the reactants at 50°C. The temperature is raised to 80°C anά the solution is stirreά for approximately 45 minutes or until the mass becomes very viscous. The sample is cooleά anά 10 ml of water aάάeά for each ml of phosphorous oxychloriάe useά, anά heateά to boiling. The solution is cooleά anά treateά with 6N soάium hyάroxiάe solution until the pH is 8 or more. The sample is steam-άistilleά to removeά the last trace of any toluene or steam volatile unreacteά amine. It is cooleά anά the aqueous phase poureά off. The organic phase is άissolveά in hot methanol-acetic aciά (1:1) solution. The soάium salt of the anion for the άye form άesireά is then aάάeά. The sample is cooleά anά ether aάάeά slowly, while stirring to effect crystallization of άye. This methoά varies slightly from the known publisheά methoάs, but has been founά to have several aάvantages for laboratory preparation of άyes of the types: / >N where any one of the phenyl groups may be replaceά by a naphthyl group. Method B. Michler's Hydrol Method Part 1. Triphenylmethane type compounds may be produceά by the conάensation of a άiphenyl substituteά seconάary alcohol anά an aromatic ring. The seconάary alcohol is of a type calleά Michler's hydrol of the general type formula: which is produceά by the controlleά reάuction of the corresponάing ketone with soάium amalgam in alcohol as a solvent. The hyάrol is separateά from an alcohol-water mixture, άrieά, anά storeά in a vacuum άessicator. The hyάrol is then conάenseά with the άesireά substituteά benzene ring of the general-type formula: in concentrateά sul Q furic aciά : anά at a temperature below 60°C for several hours. The reaction mixture is άiluteά with water anά the acid neutralized until the condensation product is precipitated out. The product has the general-type formula: Part 2. The condensation product is then oxiάizeά with leaά peroxiάe in an aciάic-aqueous meάia to the general-type formula: Any excess lead peroxide is neutralized with sodium carbonate. The lead is precipitated with sodium sulfate anά filtereά off. The aciά is neutralized to a pH of 7 and the dye salted out as the chloriάe or as the zinc chloriάe άouble salt. This methoά was founά to be useful in preparing triphenyl methane άyes where one of the phenyl groups is to have substituents other than an amino group. APPENDIX II Methoά C. Aniline - Benzalάehyάe Methoά Unάer reflux, a two-mole quantity of an aniline anά one mole of a benzalάehyάe is heateά with zinc chloriάe as a catalyst to proάuce the true leuco form of the άesireά άye. A stoichiometric quantity of leaά άioxiάe paste anά hyάrochloric aciά is aάάeά to a weigheά quantity of the leuco άye. This is stirreά for 30 minutes anά then filtereά. Soάium sulfate is aάάeά to precipitate any soluble leaά salts, which is then filtereά anά the filtrate neutralizeά. A neutral salt is aάάeά to salt out the άye. (The salt chosen for salting out will άepenά on the anion form of the άye άesireά. ) Methoά D. Al yl Haliάe Methoά Dyes of the type may be reacted with alkyl iodides in an alkaline methanol solution to replace the hydrogen on each amino group with the alkyl group of the alkyl iodiάe to yielά άyes of the type: of the 15 triphenyl methan άyes synthesizeά, 6 were founά to be phototropic and were previously tabulated under 3.2.6.1. For the other nine dyes, no phototropic systems have yet been developeά. Poly ethines Polymethines (refs. 13, 18, 19) may be classifieά generally by the άegree of symmetry airounά the conjugateά carbon chain. If we represent the polymethines by the general formula: we may further classify the άyes on the basis of the iάentify of the various R groups. It is prerequisite to this family that at least two of the R groups be capable of extenάing the conjugation of the chain by accepting a positive charge, being such a group. Where R, anά R. meet the prerequisite of the family anά either R„ or , or both are hyάrogen, the άyes may be prepareά by methoάs I anά II of the four general methoάs given in the succeeάing pages. Where R. is hyάrogen anά R., R 2 anά R_ are other than hyάrogen anά at least two of them meet the prerequisite of the family, the άyes may be prepareά by methoάs I or IV. Where none of the R's are hyάrogens, the άyes may be prepareά by methoάs II or III; the choice of methoά will άepenά on the value of n anά the άegree of symmetry άesireά. When the value of n is to exceeά 1, methoά III cannot be useά. Methoά III has the aάvantage of giving any choice of symmetry from totally unsymmetrical to totally symmetrical, but the value of n is limiteά to 1. Methoά I. Reaction of a p-aminophenyl alkene anά a p-aminophyenl alkene alάehyάe Equimolar quantities of a p-aminophenyl alkene of the class (where RcL can equal H, aryl, alkyl, or arylamine groups) anά p-aminophenyl alkene alάehyάe of the class WHERE N = 0_ 1 (where n=0,l) are alloweά to react in a nonaqueous solvent with an aciά catalyst such as acetic aciά, or acetic anhyάriάe, anά the aciά of the άesireά άye form. The reaction mixture is allowed to stand for 5 days at room temperature. This is poured into water and neutralized until the dye precipitates. The precipitate is filtered off, drieά, anά recrystallizeά from anhyάrous alcohol. This will produce a dye of the general-type formula as depicted below: Methoά II. Reaction of p-Aminophenyl alkene anά an Orthoester Methoά Ila. (for compounάs having 5 or more methine carbon atoms) Two molar proportions of a p-aminophenyl alkene of the class (where R can equal H, aryl, alkyl, or arylamine group) with one molά of an orthoester of the class y OR CH [ = CH-CH I \ n WHERE N = 0.1 .2, OR 3 OR OR (where m=0, 1, 2, or 3) are alloweά to react in a nonaqueous solvent, containing an aciά catalyst such as acetic anhyάriάe anά the aciά to form the άesireά carbonium compounά. The reaction mixture is alloweά to stanά at room temperature for several hours. Ether is aάάeά to precipitate the άye. The precipitate is filtereά anά washeά with ether or an ether-polar solvent mixture. The precipitate is άrieά in vacuum. This will proάuce a compounά of the general-type formula as pictureά below: (where n=0, 1, 2, 3, or 4). Methoά lib. By substituting tetramethyl ortho carbonate for the orthoester of methoά Ila anά by increasing the p-aminophenyl alkene to a molar proportion of three, a new type of compounά was prepareά, having the general structure: A nitrogen άeter ination on using a Coleman nitrogen analyzer founά 8.58 percent nitrogen (theoretical 8.61). Methoά III. Reaction of a Ketone anά a l-(p-Aminophenyl. -1-(R. Alkene A ketone of the general-type formula is refluxeά with a substituteά alkene, of the general-type formula where R is something other than hyάrogen with phosphorous oxychloriάe as the solvent catalyst. At the enά of the reflux, the reaction mixture is cooleά anά poureά into water anά treateά with a salt of the aciά to yielά the άesireά anion form of the άye. The aqueous mixture is neutralizeά with soliά soάium acetate until the dye precipitates. This method yields a άye of the general-type formula where R anά R, may be equal or άifferent 22 - - - Methoά IV. Reaction of a Ketone anά a p-Aminophenyl Alkene A ketone of the general-type formula is refluxeά for 5 hours with a substituteά alkene of the general-type formula with phosphorous oxychloriάe as a solvent catalyst. At the enά of the 5-hour reflux time, the reaction mixture is cooleά anά poureά into water anά treateά with a salt of the aciά to yielά the άesireά anion form of the άye. The aqueous mixture is neutralizeά with soliά soάium acetate until άye precipitates. This methoά yielάs a άye of the general-type formula: where R anά R, may be equal or άifferent, Organic Synthesis Proceάures Methoά No. 1: Polymethine dyes Example: Preparation of dye PP 2109 Step A: Preparation of p-Fluorobenzaniliάe A solution of aniline, 23.7 g (0.255 mole) in 250 ml of άry ether containing 55.3 g of potassium carbonate was heateά to reflux temperature. To the refluxing mixture, 50 g (0.32 mole) of p-fluoro- benzoyl chloride was added over a perioά of one hour. The reaction mixture was refluxeά for four hours anά the ether άistilleά off. Colά water was added to the residue and the p-fluorobenzaniliάe collecteά by filtration. Yielά: 64 g, metling point 196°C, white crystalline powάer. Step B: Preparation of p-N,N-Di-n-ρropylamin-ρ-fluorobenzophenone 64 g (0.3 mole) of άry, powάereά p-fluorobenzaniliάe, 100 g (0.6 mole) of N,N-άi-n-propylaniline, anά 55 ml of phosphorous oxychloriάe were mixeά in a 500 ml three-πeckeά flask fitteά with a stopper, a thermometer anά a reflux conάenser having a CaCl_ άrying tube on top. The reaction mixture was warmed gently until the temperature reached 100°-112°C, at which point an exothermic reaction occurreά anά the temperature rose to 160°C. As soon as the exothermic reaction was noteά, the mixture was immeάiately cooled by swirling the flask in ice water. The cooling was continueά until the temperature άroppeά to 100°-105°C. This temperature range was helά for three hours . The reaction mixture was then hyάrolyzeά in a three liter beaker by the aάάition of 58 ml concentrateά hyάrochloric aciά in 445 ml water. The reaction mixture was alloweά to stanά for eight to twelve hours to complete the hyάrolysis. An aάάitional 4100 ml of water was then aάάeά to precipitate the ketone formeά. This was filtereά, washeά thoroughly with colά water, reslurrieά anά refiltereά. Yielά: 45 g, light green sanάy crystals, melting point 85°-87°C. Step C: Preparation of l-(4-N,N-Di-n-propylamino-ρhenyl)-l-(4-fluorophenyl) ethylene - 223 - " - > ..< ~ - Sixty ml of a 3 molar etherial solution of methyl magnesium bromide was evaporated almost to dryness under reduced pressure in a 500 ml three-necked flask equipped with thermometer and nitrogen sparger. The grey moist residue was suspendeά in 75 ml of άry benzene. The flask was then equippeά for refluxing by the aάdition of a condenser fitted with a CaCl- drying tube and an adάition funnel. A 0.1 mole portion of the ketone dissolved in 250 ml of boiling benzene was then placed in the adάition funnel anά aάάeά άropwise to the warmed methyl magnesium bromide-benzene slurry over a half-hour period. The resulting redάish solution was refluxed for three hours. The termination of the reaction was indicateά by the faάing of the initial reάάish color to a pale yellow. The reaction mixture was then cooleά to room temperature anά cautiously treateά with 45 ml of saturateά ammonium chloriάe solution. This mixture was filtered and the filtrate boiled with 0.1 g of p-toluenesulphonic acid until the evolution of water was completeά. The aciά containeά in the reaction mixture was then removeά by the aάάition of 0.5 g of soάium bicarbonate. The volume was reάuceά to one half by evaporation unάer reάuceά pressure. Five hunάreά ml of άry ethanol was addeά to the remaining solution, which was then alloweά to cool with the subsequent precipitation of the ethylene compounά. The precipitate was filtereά, washeά with 50 ml ice colά ethanol, anά the crystals άrieά in a vacuum oven. Yield: 86 percent of theory: melting point 101°-102°C. Step D: Preparation of a perchlorate of l,5-άi-(ρ-fluorophenyl)-l,5-bis-(p-N,N-άi-n-propyl- anilino)-1,3-pentadiene Acetic HCIO, Anhydride A mixture of 23.6 g (0.08 mole) of l(4-N,N-άi-n- propylaminophenyl)-l-(4-fluorophenyl)ethylene, 12 ml of ethyl orthoformate anά 50 ml of acetic anhyάriάe was treateά with an ice-colά solution of 4 ml of 72 percent perchloric aciά άissolveά in 50 ml of acetic anhyάriάe. The resulting άark reά solution was heateά in a water bath at 85°C for one hour, after which another 12 ml of ethyl orthoformate was addeά. The mixture was than alloweά to stanά at room temperature for 18 hours to precipitate the conάensation proάuct. The precipitate was collecteά anά washeά with acetic aciά, ethanol anά ether. Yielά: 68 percent baseά on perchloric aciά, golάen brown crystals melting with άecomposition at 277°C. Methoά No. 2: Polymethine άyes Example: Preparation of άye PP 2110 Step A: Preparation of 3-Amino-4-methoxy- '-N,N-Di-methylaminobenzophenone 90-95 # C -C. I! HH. CH3O N(CH- ) . 2 Fifty grams (0.2 mole) of 3-amino-4-methoxy- benzanilide, 70 g (0.58 mole) N,N-dimethylaniline anά 36 g P0C1- were heateά on a water bath at 90°C to 95°C for 4 to 6 hours. The proάuct was then cautiously poureά into a solution of 23 ml of concentrated hydrochloric acid in 250 ml water. The resulting solution was warmeά at 80°C until the initial reάάish color άisappeareά, inάicating that the aniline was completely hyάrolyzeά. A liter of water was aάάeά to precipitate the ketone, which was filtereά, washed with colά water, anά recrystallizeά from a 2:1 aqueous alcohol solution. Yielά: 38 g of slightly yellowish crystals, metling point 82°C. Step B: Preparation of l(4-N,N-Dimethylamino- phenyl)-l-(3-amino-4-methoxyphenyl)ethylene + CH- j MgBr Fifty ml of a 3 M ethereal solution of methyl magnesium bromiάe was evaporateά almost to άryness unάer reάuceά pressure. Dry nitrogen was aάmitteά to the reaction flask anά the gray resiάue was suspenάeά in 75 ml of άry benzene. The slurry was warmeά, then 26.6 g (0.1 mole) of the ketone compounά άissolveά in 250 ml boiling benzene was added over a 15-minute period. The resulting solution was refluxed until the pale yellow color fadeά to colorless (45 minutes) . The mixture was cooleά anά treateά with 50 ml of a saturateά NH 4.C1 solution. The colorless solution was filtereά through a folάeά filter paper without applying vacuum anά in the absence of strong light. The filtrate was boileά with 0.1 g p-teluenesulfonic aciά until the evolution of water was complete. The cooleά solution was neutralizeά by the addition of 0.2 g dry NaHCO- anά then reάuceά to 1/4 volume by evaporating the solvent unάer reάuceά pressure. The remaining solution was άiluteά with 250 ml of άry ethanol anά the ethylene proάuct alloweά to precipitate over 12 hours. Yielά: 34 percent of theory, yellow hygroscopic flakes, melting point 118°C. Step C: Condensation Reaction Leading to Dye (A perchlorate of 1,5-di-(3-amino-4-methoxyphenyl)- 1,5-bis-(p-N, -άimethylaniline)-1,3-pentaάiene. A mixture of 26.9 g (0.1 mole) of l(4-N,N-άi- methylaminophenyl)-l-(3-amino-4-methoxyphenyl)ethylene, 15 ml of ethyl orthoformate anά 45 ml acetic anhyάriάe was treateά with a solution of 4 ml of 72 percent perchloric aciά anά 40 ml acetic aciά previously cooled to 0°C. The resulting mixture was allowed to stand at room temperature for 5 άays, after which it was treateά with 25 ml of ether anά kept an aάάitional άay at room temperature. The precipitate formeά was filtereά anά washeά with acetic aciά, ethanol, anά ether, anά άrieά in a vacuum άessicator. Product: sandy crystals, dark brown, melting point 209°-210°C. Note: The reaction should be run at room temperature. Condensation at elevated temperatures yields a black, insoluble polymerization product. APPENDIX III Azo Polymethines Dyes of the general structural type are prepared by conάensation of p-aminophenyl alkene alάehyάes or ketones with auramine-type hyάrochloriάes . One such άye was prepareά : 1,1,5-tris-4( , -άimenthyamino) henyl-2-azo, pentene carbonium chloriάe which showeά only very slight yellow phototropy. - > • - ' "~ " - 229 - APPENDIX IV Diazo Polymethines A new type of dye, believed to have the general structures, was prepared by nitrosation of auramine-type structures with nitrous aciά to yielά This is then reacteά with p-aminophenyl alkenes to yield structures of Type A. Confirmation of structure is incomplete, but significant to this work is that the above series of reactons yield phototropic materials. The position of the -N-N- group in the carbon chain may be changed to occupy the 1 and 2 positions, as well as the above shown 2 and 3 positions, by using a secondary amine in place of B in the above series of reactions. With nitrogen atoms in the 1 anά 2 positions, the 1 position nitrogen becomes a quaternary ammonium atom in one of the resonance states of the molecule. One άye of each of these types was prepareά. Both were founά to phototropic. They are: 1,1,5,5-tetrakis-[4-(N, -άimethylamino)phenyl]-2,3- άiazo pentene carbonium (Code PP2031) 1,l-bux-[4-(N,N-dimethylamino)phenyl-3,4-bis-(phenyl)] 3,4-άiazo butene carbonium (Coάe PP 2030) APPENDIX V Quaternary Ammonium Salt Polymethines Three dyes of the type were prepared and testeά for phototropy, N-(p-dimethylamino cinnamylidine)-N,N-diphenyl ammonium proved to be phototropic but broke down rapidly under ultraviolet light N-(p-άimethylamino cinnamyliάine)-N,N-άiethanol ammonium, anά N-(p-άimethyl amino cinnamyliάine) N,N-άi-4(N,N-άimethylamino)phenyl ammonium were not phototropic. The άyes where prepareά by the conάensation of άimethylamino cinnamic alάehyάe with the hyάro- chloriάe of seconάary amines in warm, anhyάrous alcohol accorάing to the methoά of Brooker. APPENDIX VI Intermeάiates Although most types of άye intermeάiates are available, specific compounάs necessary to this work were not available on the commercial market. It was necessary to synthesize 13 such intermediates. The syntehsis or type synthesis of these intermediates are for the most part given in standarά works on synthesis άyes anά άye intermeάiates. The synthesis of tetramethyl orthocarbonate and ethylenes of the type are reported herein. Synthesis of Tetramethyl Ortho Carbonates To 500 grams of cold dry methanol under reflux, 80 grams of metallic sodium in large pieces are adάeά. (The alcohol solution has to be cooleά externally with ice water to prevent loss of methanol through the reflux conάenser.) Before all of the soάium has άissolveά, 100 grams of chloropicrin that has been άiluteά with 200 ml of methanol is slowly άroppeά in. The solution is refluxeά for one hour. The methanol is άistilleά off until the resiάue seems almost dry. This is then dissolved in 600 cc of water, and the aqueous solution is extracted with three 200-ml portions of ether. The composited ether extracts are drieά over calcium chloriάe. The ether is fractionateά from the άrieά solution anά a little soάium methoxiάe in methanol is aάάeά to the resiάue to react with any unreacheά chloropicrin. This is allowewd to stand overnight. The solution is fractionateά, collecting one fraction between 110°-115°C- Synthesis of Type Ethyleπes Methyl magnesium bromiάe in ethyl ether is placeά into a rounά bottom flask equppeά with a conάenser anά an aάάition funnel. The ther is άistilleά off, anά the methyl magnesium bromiάe then taken up with anhyάrous benzene. A ketone is άissolveά in anhyάrous benzene anά aάάeά άropwise to the Grignarά reagent with continuous heating. After the aάάition is completeά, the mixture is refluxeά for three more hours. After cooling, sufficient ammonium chloriάe solution (saturateά aqueous solution) is very carefully aάάeά in orάer to άissolve any free magnesium. The Grignarά complex is άecomposeά with hyάrochloric aciά. After άecomposition of the complex is complete, the solution is alloweά to come to room temperature. After making sure the solution is alkaline to phenolphthalein, the benzene solution is άecanteά off of the soliάs. The soliάs are washeά with two 50-ml positions of ether anά the washings combineά with the benzene solution. The ether-benzene solution is άrieά over anhyάrous soάium sulfate. The ether anά benzene are then άistilleά off leaving a resiάue. This resiάue is vacuum-άistilleά at 2-5 mm of Hg. APPENDIX VII Methoά No. 3: Inάoline base άyes Example: Preparation of άye PP 1210 Step A: Synthesis of p-[N-(2-chloroethyl)-N-ethyl] aminobenzalάehyάe 1 At 50°C 82.5 parts by weight of N-(2-hyάroxyehtyl)-N-ethylaniline were aάάeά άropwise to 90 parts by weight of phosphorous oxychloriάe. The solution was then heateά at 90°C for 6 hours. After colling to 0°C, a mixture of 150 parts by weight of N-methylformaniliάe, 170 parts by weight of phosphorus oxychloriάe, anά 120 parts by weight of benzene was aάάeά to the above solution. The mixture was heateά for a few hours at 30-35°C. After neutralization with an aqueous solution of soάium hyάroxiάe, the benzene solution of the alάehyάe proάuct was separateά. After evaporating the benzene, p-N-chloroethyl-N-ethylamino benzalάhyάe remaineά as a slightly yellow oil which harάeneά on stanάing anά coulά be recrystallizeά from ethanol. The recrystallizeά alάehyάe haά a white flaky appearance anά a melting point of 283°C. Step B: Synthesis of άye PP 2120, Chloriάe of 2,3,3-trimethyl-2-[p-(N-2-chloroethyl-N-ethyl)amino-β-s tyryl] inάoline. p-(N-Chloroethyl-N-ethyl)amino benzalάehyάe (12.5 parts by weight) was refluxeά for 6 hours at 100°C with 8.5 parts by weight of l,3,3-trimethyl-2-methylene-inάoline in 60 parts by weight of glacial acetic acid. The mixture was then poured into water and the condensation proάuct was salteά out with soάium chloride. The crude dyestuff was obtaineά as a άark bronze resinous liquiά which harάeneά upon standing and could be crushed into shiny bronze particles. The pure dye was obtained by recrystallization from hot water, m.p. 167-168°C. APPENDIX VIII Methoά No. 4: Dyes with more than one chromophore Example: Preparation of dye PP 2131 Step A: Synthesis of phenetolazobenzaldehyάsulphonic aciά One hunάreά grams of Chrysophenin G concentrate, which was equivalent to about 92 grams of the pure compounά, was άissolveά in 6 liters of boiling water. The solution was cooleά to 0-5°C by the aάdition of ice and then saturateά with soάium chloriάe. A 3 percent solution of potassium permanganate was slowly adάeά with vigorous agitation until a pale pink color persisteά. (The quantity of permanganate requireά was 29 grams.) The precipitate which formeά άuring the reaction was alloweά to settle anά was collecteά by siphoning off the supernatant liquor. The proάuct was isolated by boiling the precipitate two or three times with one liter of water, filtering off the manganese dioxiάe and adding potassium chloride to the hot water solution until precipitation was complete. An adάitional small quantity of alάehyάe was isolateά by salting it out of the supernatant liquor with potassium chloriάe. The proάuct precipitateά from water in orange-coloreά microscopic neeάles. Step B: Synthesis of Dye PP 2131, perchlorate of 1, l-bis-(ρ-N,N-άimethylamino)phenyl-3-[2-sulfonato-4-(p -ethoxyphenylazoO] phenyl propene. Phenetoleazobenzalάehyάe sulphonic aciά (1.86 parts by weight) was refluxeά for 6 hours at 100°C with 1.33 parts by weight of 1, l-bis-(4-N,N-άimethylarnino)phenyl ethylene is 25 parts by weight of glacial acetic aciά. The conάensation proάuct was then poureά into water anά salteά out. The άyestuff was obtaineά as a thick άark green liquiά which harάeneά upon stanάing to a crushable soliά, melting point 78-92°C. An attempt to recrystallize the άye using a variety of solvents was unsuccessful. APPENDIX IX Example 1 - Xylene Blue VS cyaniάe To a solution of 25 g. of commercial Xylene Blue VS, Colour Inάex No. 672, in 150 ml. of water is aάάeά 4.5 g. of 95% soάium cyaniάe anά the mixture is heateά in a pressure bottle for 1 hour. Suitable precautions shoulά be taken to avoiά cuts by glass wet with soάium cyaniάe solution in the event of the explosion of the bottle. The solution is then cooleά, alloweά to stanά for 1 άay at 25°C. anά filtereά from the precipitateά Xylene Blue VS cyaniάe άisoάium salt having the formula The άisoάium salt is reaάily soluble in water to yielά a colorless solution that slowly becomes blue on exposure to raάiation of wave length 2537 A. The color change is much slower than with a solution of a representative basic άye cyaniάe, such as malachite green syaniάe in alcohol, anά thus is useful in the actinometry of more intense raάiation. The free aciά form of Xylene Blue VS cyaniάe, having the formula may be prepareά by treatment of a solution of 11 g. of the άisoάium salt in 100 ml. of water with 11.2 ml. of concentrateά hyάrochloric aciά. After the mixture has stooά at room temperature for 2 άays, the colorless precipitateά from aciά is collecteά on a filter, washeά with water, anά air άrieά. It is sparingly soluble in water. A άilute, colorless, aqueous solution of the free aciά color blue on ultra-violet irraάiation at a speeά intermeάiate between that of the solutions of the soάium salt anά of alcoholic solutions of malachite green cyaniάe. The barium salt of Xylene Blue VS cyanide having the formula 2 may be prepared by neutralization of a hot 1/2 of 1% aqueous solution of the free acid to pH 3.4 with N/10 barium hyάroxiάe solution. The neutralizeά solution is cooleά to room temperature, alloweά to stanά for 3 άays, anά filtereά from the colorless, crystalline barium salt. The barium salt is less soluble in water than the free aciά, but quite sufficiently soluble to give photosensitive solutions that behave on exposure to ultra-violet like solutions of the soάium salt. References 1. Schuster, G.B., Schmidt, S.B., Bioluminescense and Chemiluminescence, edited by Marlene A. Deluca and William D. McElroy, (1981), pp. 23-29. 2. Berger, A.W. , et al., Photochemistry and Photobiology, Vol. 4, (1965), pp. 1123-1127. 3. Philbrook, G.E., et al., Photochemistry and Photobiology, Vol. 4, (1965), pp. 1175-83. 4. White, E.H., et al., Photochemistry and Photobiology, Vol. 4, (1965), pp. 1129-55. 5. Philbrook, G.E., et al., Photochemistry and Photobiology, Vol. 4, (1965), pp. 869-76. 6. Rauhut, M.M. , et al., Photochemistry and Photobiology, Vol. 4, (1965), pp. 1097-1110. 7. McCapra, F., et al., Photochemistry and Photobiology, Vol. 4, (1965), pp. 1111-1121. 8. McCapra, F., et al., Chemical Communications, No. 15, (1966), pp.522-23. 9. Gorsuch, J.D., "Studies of the Chemiluminescence of Luminol," M.I.T. Ph.D. Thesis, 1969. 10. Legg, K.D., "The Chemiluminescence of Lucigenin," M.I.T. Ph.D. Thesis, 1969. 11. Lytle, F.E., "Chemiluminescence and Photoluminescence of Ruthenium Chelates," M.I.T. Ph.D. Thesis, 1968. 12. Allen, R.C., Chemical and Biological Generation of the Excited State, editeά by Adam Waldeman, 1982, pp. 309-45. 13. Bowen, E.J., "Chemiluminescence in Solutions," in Luminescence in Chemistry. Editeά by E.J. Bowen, D. Van Nostrand Co. Ltd, Lonάon, (1968) pp. 183-190. 14. Tuemmler, W.B., anά Wiάi, B.S., J Amer Chem Soc, Vol. 80, (1958), pp. 3772-75. 15. Mac Nair, R.N., Photochemistry anά Photobiology, Vol. 6, (1967), pp. 779-97. 16. Chalkley, L., U.S. Patent No. 2,885,303, (1958). 17. Chalkley, L., U.S. Patent No. 2,936,235, (1957). 18. Chalkley, L., U.S. Patent No. 2,829,148, (1958). 19. Chalkley, L., U.S. Patent No. 2,839,542, (1958). 20. Chalkley, L., U.S. Patent No. 2,839,543, (1958). 21. Brown, Glenn, Photochromism, pp. 294-375. 22. Wilkinson, F. , "Intramolecular Electronic Energy Transfer Between Organic Molecules," in Luminescence in Chemistry, Edited by E. J. Bowen, D. Van Nostranά Co. LTD., London, (1968), pp. 154-182. 23. Lippman, R.D., Bioluminescence and Chemiluminescence, Editeά by Marlene A. Deluca and William D. McElroy, (1982), pp. 373-81. 24. Dreyer, J.F., "Self-Attenuating Ophthalmic Filter," Rept. WADD-TR-60-632 Feb., 1961. AD 322820. 25. Dreyer, J.F., Harries, R.W., MacNair, R.N., Feldman, D., "Investigation of Materials and Systems for Protection Against Flash Blindness Effects of Nuclear Detonations," Rept. 68-38-CM, AD 688692. 26. Polacoat, Inc., "Development of a Means to Provide Protection for Eyes Against the Dazzle Effects of Nuclear Detonations," Quart. Rept. No. 5 on Contract DA-19-129 qm-1534, April 1961, AD 446865; also AD 447113 and 298225. 27. Van Dyke, K. , Bioluminescence and Chemiluminescence, Vol. 1, CRC Press, Inc., 198.5, pp. 1-42. 28. Zaklike, K.A. , et. al., Photochemistry and Photobiology, Vol. 30, (1979), pp. 35-44. 29. Schaap, A.P., Burns, P.A., and Zaklika, K.A. , J. Am. Chem. Soc, 99 (1977), pp. 1270-1272. 30. D'lorio, A., Mavrides, C, Canaάian Journal of Biochemistry anά Physiology, (1963), Vol. 41, pp. 1779-1784. 31. Vrang, L., Oberg, B., Antimicrobial Agents anά Chemotherapy, (1986), 29, pp. 867-872. 32. Schnebli, H.P., et. al.. Journal of Biological Chemistry, (196-7), Vol. 242, pp. 1997-2004. 33. Roberts, E., Biochemical Pharmacology, (1974), Vol. 23, pp. 2637-2649. 34. Ranάo, R. , Bangerter, F. W. , Journal of the American ' Chemical Society, (1976), Vol. 98, pp. 6762-6764. 35. Tunnicliff, G., et. al., Experientia, (1977), Vol. 33, pp. 20-22. 36. Kobayashi, K. , et. al., Febs Letters, (1977), Vol. 76, pp. 207-210. 37. Meάicinal Chemistry A Biochemical Approach, Thomas Nograάy, (1985) Oxforά University Press, N.Y. , N.Y. , pp. 193-203. 38. Jung, J.M. , Metcalf, B.W., Biochemical anά Biophysical Research Communications, (1975), 67, pp. 301-306. 39. Ranάo, R. , Bangester, F.W., Biochemical anά Biophysical Research Communications, (1977), Vol. 76, pp. 1276-1281. 40. Buu, N.T., Van Gelάer, N.M. Br. J. Pharmac, (1974), 52, pp. 401-406. 41. Enzyme Inhibitors, editeά by Urs Broάbeck, (1980) pp. 85-95. 42. Enzyme Inhibitors, eά. by Urs Broάbeck, (1980), pp. 61-74. 43. Drug Action anά Design: Mechanism Baseά Enzyme Inhibitors. ed. by Kalman, , (1979), pp. 13-27. 44. Fuller, R.W. , Nagarajan, R. , Biochemical Pharmacology, (1978) pp. 1981-1983. 45. Barchardt, R.T., Wu, Y.S., Journal of Medicinal Chemistry, (1975), 18, pp. 300-303. 46. Enzyme Inhibitors, ed. by Urs Brodbeck, (1980), pp. 223-244. 47. Receptor Binάing in Drug Research, eά. by Robert A. O'Brien, pp. 235-259. 48. Kanάutsch, A.A., Chen, H.W., Journal of Biological Chemistry, (1973), 248, pp. 8408-8417. 49. Fimognari, G.M., Roάwell, V.W. , Biochemistry, (1965) 4, pp. 2086-2090. 50. Bloxham, D.P., Biochem J., (1975), 147, pp. 531-539. 51. 3-Hvάroxy-3-Methylqlutaryl Coenzyme A Reάuctase. ed., by John R. Sabine, CRC Series in Enzyme Biology, CRC Press, Inc. Boca Raton, Florida. 52. Design of Active-Site-Directeά Irreversible Enzyme Inhibitors, B.R. Baker, (1975), p. 9. 53. Inhibitors of DNA anά RNA Polvmerases, International Encyclopedia of Pharmacology and Therapeutics, Section 103, edited by Prem S. Sarin and Robert C. Gallo, Pergamon Press, N.Y., N.Y. 54. Mao, J.C., Robishaw, E.E., Biochemistry, (1975), 4, pp. 5475-5479. 55. Layton, D., Azzi, A., Biochemical anά Biophysical Research Communications, (1974) 59, pp. 322-325. 56. Saari, W.S., et. al., J. Am. Chem. Soc, (1967), 10, pp. 1008-1014. 57. Bergstranά, H. , et. al., Molecular Pharmacology, (1977), 13, pp. 38-43. 58. Fuller, R.W. , et. al.. Journal of Meάicinal Chemistry, (1975), 18, p. 304. 59. Bricker, L.A. , Levey, G.S., Journal of Biological Chemistry, (1972), 247, pp. 4914-4915. 60. Khwaja, T.A. , et. al., Biochemistry, (1975), 14, pp. 4238-4244. 61. Bertelli, A., et. al., Experientia, (1976), 32, p. 361-362. - 25! - 62. Medicinal Chemistry A Biochemical Approach, Thomas Nogrady, (1985) Oxford University Press, N.Y., N.Y., pp. 274-285. 63. Prostaglanάin Synthetase Inhibitors: New Clinical Applications , (1980) Alan R. Liss Inc., N.Y., N.Y., pp. 231-256. 64. The Pharmacological Basis of Therapeutics, eά. by A.G. Gilman, L. Gilman, 6th eά., (1980) MacMillan Publishing Co., N.Y., N.Y., pp 668-681. 65. Way, L., Durbin, R.P., Nature, (1969), 221, pp. 874-875. 66. Kattlove, H.E., Biochimica et. Biophysica Acta, (1974), 372, pp. 135-140. 67. Meάicinal Chemistry A Biochemical Approach. Thomas Nograάy, (1985), Oxforά University Press, N.Y. , N.Y. , pp 358-361. 68. Porter C.C., Watson, L.S., J. Am. Chem. Soc, (1967), 10, pp. 852-855. 69. Sourkes, T.L., Arch. Biochem. Biophys . , (1954), 51, pp. 444-456. 70. Hartman, W.J., et. al., J. Biol. Chem., (1955), 216, pp. 507-529. 71. Collins, K.D., Stark, G.R., Journal of Biol. Chem. (1971), 246, pp. 6599-6605. 72. Lienharά, G.E., Science, (1973), 180, pp. 149-154. 73. Fall, R.R., West CA. , Journal of Biol. Chem., (1971), 246, pp. 6913-6928. 74. Coleman, J.E., Journal of Biol, Chem., (1968), 243, pp. 4574-4587. 75. Agarwal, R.P., et. al., Biochemical Pharmacology, (1975), 24, pp. 693-701. 76. Agarwal, R.P., et. al., Biochemical Pharmacology, (1977) 26, pp. 359-367.. 77. Sheen, M.R. , et. al., Mol. Pharmacol., (1968), 4, pp. 293-299. 78. Analysis of Insecticiάes anά Acariciάes, Gunther anά Blinn, (1955), Interscience, N.Y. , N.Y. , pp. 401-404. 79. The Pharmacological Basis of Therapeutics, eά. , by A.G. Gilman, L. Gooάman, A. Gilman, 6th eά. , (1980), MacMillan Publishing Co., N.Y. , N. Y. 80. Berriάge, M.J., Ann. Rev. Biochem. , (1987), 56, pp. 159-93. 81. Calcium Antagonists anά Carάiovascular Disease, eάiteά by L. H. Opie, (1984), Raven Press, N. Y. , pp. 165-173. 82. Johnston, G.A.R., Iversen, L.L., Journal of Neurochemistry, (1971), 18, pp. 1951-1961. 83. Chiou, C. Y. , Malagodi, M. H. , Br. J. Pharmac, (1975), 53, 279-285. 84. Inagaki, M. , et. al., J of Biol. Chem., (1985), 260, pp. 2922-2925. 85. Inagaki, M. , et. al., Biochemistry, (1984), 23, 5036. 86. Weinstock, M. , Life Sciences, (1976), 19, pp. 1453-1466. 87. Hare, L.E. et. al., Journal of Meάicinal Chemistry, (1974), 17, pp. 1-5. 88. Levitt, M. , et . al., Biochemical Pharmacology, (1972), Vol. 16, pp. 1313-1321. 89. Nagatsu, T., et . al., Biochemical Pharmacology, (1972), Vol. 21, pp. 1945-1953. 90. Taylor, R.J., et. al., Biochemical Pharmacology, (1968), 17, pp. 1779-1788. 91. Nagatsu, T., et. al., J. Biol. Chem., (1964), 239, pp. 2910-2917. 92. Taylor, R.J., Ellenbogen, L., Life Sciences, (1967) 6, pp. 1463-1466. 93. Unάenfrienά, S., et. al., Biochemical Pharmacology, (1965), 14, pp. 837-845. 94. Weinholά, P.A., Rethy, V.B., Biochemical Pharmacology, (1969), 18, pp. 677-680. 95. Uretsky, N.J., et. al.. The Journal of Pharm. anά Exp. Therp., (1975), 193, pp. 73-87. 96. El Masry, M.H. , et. al., Journal of Meάical Chemistry., (1975), 18, pp. 16-20. 97. Counsell, R.E., et. al., Journal of Meάical Chemistry, (1970), 13, pp. 1040-1042. 98. Robert, A., et. al., Life Sciences, (1974), 14, pp. 533-538. 99. Kollonitsch, J., et. al., Nature, (1978), 274, 906-908. 100. Polakoski, K.L., McRorie, R.A. , Journal of Biol. Chemistry, (1973), 248, pp. 8183-8188. 101. Way, L. Durbin, R.P., Nature, (1969), 221, pp. 874-875. 102. Lippmann, W. , Seethaler, K. , Experientia, (1973), 29, pp. 993-995. 103. Lippmann, W. , Experientia, (1973), 29, pp. 990-991. 104. Chen, F.W.K., et. al., Prostaglanάins, (1977), 13, pp. 115-125. 105. Hiάaka, H. , Nautre, (1971), 231, pp. 54-55. 106. Hiάaka, H. , et. al., Mol. Pharm., (1973), 9, pp. 172-177. 107. Van Der Schoot, J.B., et . al., Journal of Pharm. Exp. Therp., (1963), 141, pp. 74-78. 108. Hidaka, H., et. al., Journal of Pharm. Exp. Therp., (1974), 191, pp. 384-392. 109. Johnson, G.A., et. al., Journal of Pharm. Exp. Therp., (1969), 168, pp. 229-234. 110. Nagastu, T. , et. al., Experientia, (1972), 28, pp. 779-780. 111. Lippmann, W. , Lloyά, K. , Biochemical Pharmacology, (1969), 18, pp. 2507-2516. 112. Diliberto, E.J., et. al., Biochemical Pharmacology, (1973), 22, pp. 2961-2972. 113. Porter, C . C . , Torchiana, M.L., Biochemical Pharmacology, (1971), 20, pp. 183-191. 114. Oyama, H., et . al., Biochemical Pharmacology, (1976), 25, pp. 277-280. 115. Catignani, G.L., Neal, R.A., Life Sciences, (1975), 16, 1915-1922. 116. Hashiguchi, H., Takahashi, H., Mol. Pharm., (1977), 13, pp. 362-367. 117. Symes, A., Sourkes , T.L., Biochemical Pharmacology, (1974), 23, pp. 2045-2056. 118. Tipton, K.F., Biochem. J. , (1972), 128, pp. 913-919. 119. McEwen, CM., et. al. , Biochemistry, (1969), 8, pp. 3963-3972. 120. Balάessarini, R.J., Greiner, E., Biochemical Pharmacology, (1973), 22, pp. 249-256. 121. Gulάberg, H.C, Marsden, CA. , Pharmacological Reviews, (1975), 27, pp. 135-206. 122. Olsen, R.W. , et. al., Mol. Pharm., (1975), 11, pp. 558-565. 123. Johnson, G.A., et. al., Journal of Neurochemistry, (1976), 26, pp. 1029-1032. 124. Johnson, G.A. , Iversen, L.L., Journal of Neurochemistry, (1971), 18, pp. 1939-1950. 125. Simon, J.R. , Martin, D.L., Archives of Biochemistry and Biophysics, (1973), 157, pp. 348-355. 126. Springer, R.H., et. al., Journal of Med. Chem., (1967), 19, pp. 291-296. 127. Baker, B.R., Kozma, J. , Journal of Med. Chemistry, (1967), 10, pp. 682-685. 128. Baker, B.R., Wood, W.F., Journal of Med. Chemistry, (1967), 10, pp. 1101-1105. 129. Spector, T., Johns, D.G., Journal of Biol. Chemistry, (1970), 245, pp. 5079-5085. - > - " " - 257 - 130. Baldwin, J.J., et. al., Journal of Meά. Chemistry, (1975), 18, pp. 895-900. 131. Duggan, D.E., et. al., Journal of Meά. Chemistry, (1975), 18, pp. 900-905. 132. Ferraccioli, G., et. al., J. Rheumatol, (1984), 11, pp. 330-332. 133. Iwata, H., et . al.. Biochemical Pharm., (1969), 18, pp. 955-957. 134. Iwata, H., et . al.. Biochemical Pharm., (1973), 22, pp. 1845-1854. 135. Huszti, Z., Sourkes, T.L., Journal of Pharm. Exp. Therp., (1975), 192, pp. 432-440. 136. Leinweber, F.J., Braun, G.A., Mol. Pharm., (1970), 6, pp. 146-155. 137. Lorenz, W. , Werle, E., Bioch. Pharm., (1969), 17, pp. 539-549. 138. Ellenborgen, L., et. al., Biochem. Pharm., (1973), 22, pp. 939-947. 139. Ellenborgen, L., et. al., Biochem. Pharm., (1969), 18, pp. 683-685. 140. Alston, T.A., Abeles, R.H., Biochemistry, (1987), 26, pp. 4082-4085. 141. Ellenbogen, L., et. al., Biochem. Pharm., (1969), 18, pp. 683-685. 142. Lukes, J.J., Neiforth, K.A. , Journal of Meά. Chemistry, (1975), 18, pp. 351-354. 143. Collins, D., Journal of Biol, Chemistry, (1974), 249, pp. 136-142. 144. Kanάutsch, A.A. , Chen, H.W. , Journal of Biol. Chemistry, (1974), 249, pp. 6057-6061. 145. Kanάutsch, A. . , Chen, H.W. , Journal of Biol. Chemistry, (1973), 248, pp. 8408-8417. 146. Kupiecki, F.P., Marshall, N.B., Journal of Pharm. Exp.. Therp., (1968), 160, pp. 166-170. 147. Kypson, J. , Hait, C, Journal of Pharm. Exp. Therp., (1976), 199, pp. 565-574. 148. Pereira, J.N., Hollanά, G.F., Journal. Pharm. Exp. Therp., (1967), 157, pp. 381-387. 149. Dulin, W.E., et. al., Proceeάings of the Society for Experimental Biology anά Meάicine, (1965), 118, pp. 499-501. 150. Dulin, W.E., Gerritsen, G.C, Proceedings of the Society for Experimental Biology and Meάicine, (1966), 121, pp. 777-779. 151. Walάvogel, E.R.F., et. al., Mol. Pharm., (1967), 3, pp. 429-441. 152. Lowenstein, J.M., Journal of Biol. Chemistry, (1971), 246, pp. 629-632. 153. Maragoudakis, M.E., Journal of Biol. Chemistry, (1971), 246, pp. 4046-4052. 154. Maragoudakis, M.E., Hankin, H., Journal of Biol. Chemistry, (1971), 246, pp. 348-358. 155. Hashimoto, T., et. al., Eur, J., Biochem., (1971), 24, pp. 128-139. 156. Maragoudakis, M.E., Biochemistry, (1970), 9, pp. 413-417. 157. Braάy, R.O., Biochem. Biophys. Acta, (1963), 70, pp. 467-468. 158. Rokujo, T., et. al., Life Sciences, (1970), 9, pp. 379-385. 159. Dalton, C, et. al., Prostaglanάins, (1974), 7, pp. 319-327. 160. Winάmueller, H.G., Levy, R.I., Journal of Biol. Chemistry, (1967), 9, pp. 2246-2254. 161. Roheim, P.S., et. al., Biochem. Biophys. Research. Comm. , (1965), 20, pp. 416-421. 162. Smith, D.A., e . al., Geriatics, (1987), 42, pp. 55-62. > - 260 - 163. Falcon, M.G., Jones, B.R., Journal of Gen. Virol., (1977), 36, pp. 199-202. 164. Meek, E.S., Takahashi, M. , Nature, (1968), 220, p. 882. 165. De Clercq, E., Luczak, M. , Life Sciences, (1975), 17, pp. 187-194. 166. Becker, Y. , Pharmac Ther., (1980), 10, pp. 119-159. 167. Asano, T. , Ochiai, Y., Mol. Pharm., (1977), 13, pp. 400-406. 168. Iwai, H., Journal of Biochem., (1974), 76, pp. 419-429. 169. Lippmann, W. , Experientia, (1974), 30, pp. 237-239. 170. Nikaiάo, T., et. al., Planta Meάica, (1981), 43, pp. 18-23. 171. Vigάahl, R.L., et. al., Biochem. Biophys. Research Comm., (1971), 42, pp. 1088-1094. 172. Tateson, J.E., Trist, D.G., Life Sciences, (1976), 18, pp. 153-162. 173. Evans, D.P., Thomson, D.S., Br. J. Pharmac, (1975), 53, pp. 409-418. 174. Simmonάs, H.A., et. al.. Lancet, (1978), Jan. 14, pp. 60-63. 175 . Trotta , P . P . , et . al . , Mol . Pharm. , ( 1978 ) , 14 , pp . 199-209 . 176. Deibel, M.R. , et. al., Biochemical Medicine, (1981), 25, pp. 288-297. 177. Humphrey, S.M., e . al., Journal of Surgical Research, (1987), 43, pp. 187-195. 178. Beard, N.A., et. al., Br. J. Pharmac, (1975), 54, pp. 65-74. 179. Chignard, M. , Vargafting, B.B., Prostaglanάins, (1977), 14, pp. 222-240. 180. Panganamala, R.V. , et. al., Prostaglanάins, (1977), 14, pp. 261-271. 181. Kulkarni, P.S., Eakins, K.E., Prostaglanάins, (1976), 12, pp. 465-469. 182. Downing, D.T., et. al., Biochem., Biophys. Research Comm., (1970), 40, pp. 218-223. 183. Gorman, R.R., et. al., Biochem. Biophys. Research Comm., (1977), 79, pp. 305-313. 184. Cushman, D.W., Cheung, H.S., Biochem. Biophys. Acta, (1976), 424, pp. 449-459. 185. Taylor, R.J., Salata, J.J., Biochemical Pharmacology, (1976), 25, pp. 2479-2484. 186. Ku, E.C, et. al., Biochemical Pharmacology, (1975), 24, pp. 641-643. 187. Burghuber, O.C, et. al., Am. Rev. Respir. Dis., (1985), 131, pp. 778-785. 188. Michelot, R.J., et. al., Mol. Pharm., (1977), 13, pp. 368-373. 189. Kessel, D., McElhinney, R.S., Biochemical Pharmacology, (1975), 24, pp. 133-137. 190. Gale, G.R., et. al., J. Meά. Chem., (1970), 13, pp. 571-574. 191. The Molecular Basis of Antibiotic Action, eά. by E.F. Gale, (1981), pp. 258-401. 192. Hillcoat, B.L., et. al., J. Biol. Chem., (1967), 242, pp. 4777-4781. 193. Carlin, S., et. al., Mol. Pharm., (1974), 10, pp. 194-203. 194. Johns, D.G., et. al., Biochemical Pharmacology, (1970), 19, pp. 1528-1533. 195. Baker, B.R., et. al., J. Meά. Chem., (1967), 10, pp. 1134-1138. 196. Baker, B.R., Lourens, G.J., J. Meά. Chem., (1968), 11, pp. 666-672. " - > : '" " " - 263 - 197. Nair, M.G., et . al., J. Med. Chem., (1974), 17, pp. 1268-1272. 198. Ferone, R. , J. Biol. Chem., (1970), 245, pp. 850-854. 199. LaFon, S.W., et. al., J. Biol. Chem., (1985), 260, pp. 9660-9665. 200. Spector, T., Miller, R.L., Biochemica et . Biophysica Acta, (1976), 445, pp. 509-517. 201. Advances in Enzvmology, ed. by Alton Meister, (1987) pp. 59-101. 202. Umezawa, H., Ann. Rev. Microbiol., (1982), 36, pp. 75-99. 203. Walsh, C.T., Ann. Rev. Biochem., (1984), 53, pp. 493-535. 204. De ain, A., Biochem. Soc. Symp., (1983), 48, pp. 117-132. 205. Suhadolnik, R.J., Progress in Nucleic Aciά Research anά Moleulor Biology, (1979), 22, pp. 193-291. 206. Free, CA. , et . al., Biochem. Pharm., (1971), 20, pp. 1421-1428. 207. Enzymes , Dixon, M. anά Webb., E.C, Acaάemic Press Inc., N.Y. , N.Y., (1964), p. 407. 208. Konάo, T., et. al., Diabetes Care, (1982), vol. 5, Number 3, pp. 218-221. 209. Higgins, I.J., Hill, H.A.O., Plotkin, E.V. , Eur. Pat. Appl. EP78,636. 210. Miller, L.L., J. Electroanal. Chem., (1981), 117, pp. 267-281. 211. Mills, R.L., U.S. Patent Appl. 784,243. 212. Gros, P., et. al., Cell, (1986), 47, pp. 371-380. 213. Sanchez-Pescaάor, R. , et. al., Science, (1985), 277, pp. 484-492. 214. The Enzymes, eά. by Paul D. Boyer, (1975), 3rά eάition, Vol. XII, Part B, Academic Press, N.Y. , N.Y. 215. De Clercq, E., and Balzarini, J., Antiviral Research, Suppl. I, (1985), pp. 89-94.

Claims: C L A I M S What is clai eά is: 1. A chemical compounά having the formula A-B-C, where A is an energy donor functionality activatable by an intracellular compartment environment and capable of transferring energy from its own excited state to the B functionality; B is an energy acceptor functionality which receives energy from A to achieve an excited state; anά C is a drug moiety covalently bondeά to B, wherein the relaxation of the exciteά state of B causes heterolytic cleavage to the covalent bonά of C, releasing C to the intracellular compartment. 2. The chemical compounά of claim 1, further incluάing D, an energy transfer functionality covalently bonάeά to A, having a compounά formula D-A-B-C 3. The chemical compounά of claim 1, further incluάing D, an energy transfer functionality, covalently bonάeά to A anά B, having a compounά formula A-D-B-C 4. The chemical compounά of claim 1, further incluάing, D, an energy transfer functionality, covalently bonάeά to B, having a compounά formula A-B-C. I D 5. The chemical compound of claim 1, wherein A comprises a molecule selected from the group comprising thermal, nuclear, chemical vibrational, anά chemical electronic energy άonor functionalities. 6. The chemical compounά of claim 5, wherein A comprises a chemiluminescent molecule. 7. The chemical compounά of claim 6, wherein saiά chemiluminescent compounά comprises a compounά selecteά from table 1. 8. The chemical compounά of claim 1, wherein B comprises a chromophore. 9. The chemical compounά of claim 8, wherein saiά chromophore comprises a molecule selecteά from table 2. 10. The compounά of claim 1, wherein C effects a therapeutic functional change anά comprises a molecule which bonάs to a receptor incluάing functional macromolecular components incluάing enzymes, proteins, nucleic aciάs anά ions or which is incorporateά into cellular components. 11. The chemical compounά of claim 10, wherein C comprises άrugs selecteά from table 3 anά the exemplary luminiάe pharmaceuticals section. 12. The chemical compounά of claim 2, wherein D is a molecule comprising a member of a reάox pair. 13. The chemical compounά of claim 12, wherein D is a molecule selecteά from table 4. 14. The chemical compound of claim 1, wherein the excited state of the high energy functionality includes electrons deriveά from the electron carriers of the organism to which the compounά was aάministereά. 15. The chemical compounά of claim 2, wherein the άrug is άelivered to the desired site according to one of the permeability of said hybrid molecule to the desireά cellular, the biological compartment anά the resistance of saiά hybriά molecule to άegraάation or elimination. 16. A pharmacentical composition comprising an effective άosage of the compounά of claim 1, in combination with an acceptable form of pharmacentical carrier for the therapatic treatment at least one of infectious άisease, autoimmune άisease, cancer, hyperlipiάemia, elevateά cholesterol levels, epilepsy, transplant rejection, throboembolic άisease, asthma, allergies, hypersensitivity reactions, άisorάers of nucleotide metabolism, anemia, heart failure, hypertension, depression, ulcer disease, edema, ischemic heart disease, opiate withdrawal, muscular dystrophy, pregnancy prevention, hypercoagulability, arrhythmia, arthritis, therapeutic abortion, gout, and hyperuricemia. 17. The pharmaceutical composition of claim 16, comprising an effective amount of the compound of claim 1 selecteά to effect a therapeutic functional change. 18. The pharmaceutical composition of claim 16, wherein saiά pharmaceutical carrier comprises at least one of tragacanth, talc, agar-agar, lactose, polyglycols, ethanol anά water. 19. The pharmaceutical composition of claim 16, having the form of a tablet liquid, gel, cream, ointment or lotion. 20. A methoά of treatment, comprising the step: Administering an effective amount of the compound of claim 11. 21. The method of treatment of claim 20, wherein the step of administering comprises one of topical application, injection and oral administration. 22. The method of treatment of claim 20, further comprising the step of repeated application of an effective amount of the compound of claim 11. 23. A methoά for releasing in active form anά for transporting an effector of a therapeutic functional change into at least one of an intracellular anά a biological compartment to the vicinity of its site of action comprising the steps of: selecting A as an energy άonor functionality; selecting B as an energy acceptor functionality; selecting C as the functional moάifier; preparing a pharmaceutical chemical having the general structure A-B-C; aάministering the pharmaceutical chemical to the organism having saiά response to saiά moάifier when άelivered in active form within saiά intracellular or biological compartment; activating A from the metabolic process wherein an energy transfer from A to B is proάuceά; releasing C from B in response to the energy transfer from A to B; ^ effecting a therapeutic functional change by the i action of releaseά C 24. A methoά of effecting a therapeutic functional change, comprising the steps of: preparing a metabolically active compounά of claim 1; aάministering the metabolically activateά compounά to an environment incluάing saiά intracellular environment; activating saiά metabolically activateά compounά by the metabolic activity of saiά cellular target; anά combining a portion of saiά metabolically activateά corapounά with saiά moάifiable target to effect a therapeutic functional change. 25. A system for effecting a therapeutic functional change comprising: a hybrid molecule including a drug molecule and a reversible bond to another molecule; and means for breaking said reversible bond, releasing said drug molecule to effect a therapeutic functional change. 26. The system of claim 25, wherein saiά reversible bonά releases saiά άrug molecule upon an energy j transfer; anά said means for reversing said reversible bond is saiά energy transfer. 27. The system of claim 25, wherein saiά hybriά molecule incluάes a photochromic element, anά saiά means for reversing saiά reversible bonά comprises a chemiluminescent compounά. 28. The system of claim 27, wherein saiά hybriά molecule comprises a luminiάe, wherein saiά luminiάe permeates specific άesireά biological or cellular compartment anά is resistant to inactivation or elimination. 29. A methoά of effecting a therapeutic functional change of an organism comprising the steps of: proviάing a first molecule; reversibly bonάing a seconά, άrug molecule thereto to form a hybriά molecule; placing the hybrid molecule intracellularly; breaking saiά reversible bonά causing saiά άrug molecule to be releaseά; effecting a functional therapeutic change to saiά organism by action of saiά releaseά άrug molecules. 30. A luminiάe class chemical compounά comprising: an energy source proviάing a source of quantum mechanical energy transfer from localizeά metabolic activity; an energy acceptor receiving saiά quantum mechanical energy transfer; anά a άrug reversibly bonάeά to saiά energy acceptor, wherein, saiά energy transfer is activateά upon the metabolic proάuction of peroxiάes anά oxygen free raάicals by cellular metabolism, said drug, having been released from said energy acceptor, bonds to a site of action, and the bonding of said drug to saiά site effects a j , therapeutic functional change. 31. The chemical compounά of claim 30, further comprising: receptor meάiated mechanisms for providing therapeutic functional change including; at least one of reversible and irreversible competitive agonism; antagonism including at least one of a suicide substrate, a transition state analogue mechanism, a noncompetitive or uncompetitive agonism, an antagonism; and a nonreceptor mediated mechanism including a counterfeit incorporation mechanism. 32. The chemical compound of claim 30, wherein: saiά energy acceptor is responsive to a selecteά molecule in the ambient extracellular environment, anά saiά drug released in relation to said selected molecule causing a moderation of said selected molecule. 33. The chemical compound of claim 31, wherein: said selected molecule comprising glucose, anά saiά άrug releaseά comprises insulin. 34. The chemical compounά of claim 31, wherein: saiά selecteά molecule comprises άegreάation proάucts of parines, anά saiά άrug releaseά comprises tissue plasminogen activator (TPA) . 35. The chemical compounά of claim 1, further comprising: a polymer; anά immobilizeά enzyme molecules. 36. The chemical compounά of claim 35, wherein: saiά polymer of claim 32 is conducting. 37. The chemical compound of claim 35, wherein: said polymer is biocompatible. 38. The chemical compound of claim 35, wherein: enzyme of claim 32 comprises at least one of glucose oxidase xanthine oxidase. 39. The chemical compound of claims 32 which further incluάing a monoclonal antiboάy molecule. 40. The chemical compounά of claim 1, further comprising an electrocalalytic polymer.

Inventors: MILLS RANDELL L, MILLS, RANDELL, L.
Applicants: MILLS RANDELL L, MILLS, RANDELL, L.
Application year: 1989
Main classification: C12Q1
IPC codes: A61K9, A61K38, A61K41, A61K45, A61K47