bluuebunny/crossref_metadata_2025 huggingface dataset:
Considerations in Platinum and Gold Drug Design and the Synthesis of Chloro(2,3‐Diphenyl‐1,3,4‐Thiadiazolium‐5‐Thiolato‐Sexo)Gold(I): The First Gold Meso‐Ionic Complex of Its Kind
Authors: Howe B. P.
Published: March 2007

It is evident that the chemistry of platinum is in a more advanced state than that of gold, mainly due to the success of the former in several anti‐cancer drugs. With a view to finding possible, new candidates with chemotherapeutic potential, the use of sulphur‐donor ligands bonded to platinum and gold is discussed herein in an attempt to promote the need to investigate similar ligands. Chloro(2,3‐diphenyl‐1,3,4‐thiadiazolium‐5‐thiolato‐Sexo)gold(I) has been synthesised using a standard reaction, whereby Au(III) is initially reduced to Au(I) then reacted with the ligand, 2,3‐diphenyl‐1,3,4‐thiadiazolium‐5‐thiolate.hydrochloride, isolated and finally characterised by elemental analyses and infrared spectroscopy. The compound is the first example of gold attached to a meso‐ionic compound. It has also been tested for anti‐bacterial and anti‐fungal activity and shown to possess moderate activity against Gram‐positive bacteria, although is inactive against, Gram‐negative bacteria and fungi.
Naturally Occurring Hydroxy Napthoquinones and Their Iron Complexes as Modulators of Radiation Induced Lipid Peroxidation in Synaptosomes
Authors: Kumbhar A. S. , Padhye S. B. , Jitender  , Kale R. K.
Published: March 2007

The modulation of radiation induced lipid peroxidation in synaptosomes by iron (II) and iron (III) complexes of two naturally occurring and therapeutically relevant naphthoquinones viz.
5,hydroxy‐1,4 naphthoquinone; juglone and 2,hydroxy‐1,4 naphthoquinone; lawsone, have been studied. At lower concentrations the complexes enhance lipid peroxidation predominantly through
redox cycling as observed for Fe(II)‐ juglonate while at higher concentrations the complexes tend to
limit lipid peroxidation through fast recombinations.
Synthesis, Characterization and Role of Anions (Nitrate, Sulphate, Oxalate and Acetate) \in the Biological Activity of Hydrazine Derived Compounds and Their Metal Chelates
Authors: Chohan Zahid H. , Sherazi S. K. A.
Published: March 2007

Hydrazine derived compounds and its Co(II), Cu(II) and Ni(II) chelates having the same metal ion but different anions (e.g., nitrate, sulphate, oxalate and acetate) have been synthesised and
characterised by their physical, spectral and analytical data. In order to evaluate the participating role of anions in the antibacterial activity, these synthesised ligands and its metal chelates have been
screened against bacterial species such as Staphylococcus aureous, pseudomonas aeruginosa, Klebsiella pneumonae and Proteus vulgarus, and the results are reported.
Rh2(CF3CONH) 4: The First Biological Assays of a Rhodium (II) Amidate
Authors: Espósito Breno Pannia , Zyngier Szulim Ber , de Souza Aparecido Ribeiro , Najjar Renato
Published: March 2007

The rhodium (II) complexes Rh2(tfa) 4.2(tfac) and Rh2(tfacam) 4 (tfacam = CF3CONH-,tfa = CF3COO-,tfac = CF3CONH2) were synthesized and characterized by microanalysis and electronic and vibrational spectroscopies. Rh2(tfacam) 4 was tested both in vitro (U937 and K562 human leukemia cells and Ehrlich ascitic tumor cells) and in vivo for cytostatic activity and lethal dose determination, respectively. This is the first rhodium tetra‐amidate to have its biological activity evaluated. The LD50 value for Rh2(tfacam) 4 is of the same order as that of cisplatin, and it was verified that the rhodium complex usually needs lower doses than cisplatin to promote the same inhibitory effects.
Interaction of Pd(II) and Pt(II) Amino Acid Complexes With Dinucleotides
Authors: Vicens Margarita , Caubet Amparo , Moreno Virtudes
Published: March 2007

The interaction of the dinucleotides d(ApG) and d(ApA) with [Pd(aa)Cl2], where aa = L‐ or D‐histidine or the methyl ester of L‐histidine, and with [Pt(Met)Cl2], where Met = L‐methionine was studied by  1H
and  13C NMR and CD measurements. In the case of the L‐histidine and L‐histidineOMe, the reaction with d(ApG) appeared to give the bifunctional adducts Pd(L‐Histidine)N1(1)N7(2) and Pd(L‐HisOMe)N1(1)N7(2), but the behavior with D‐histidine suggested the formation of the monofunctional adduct Pd(D‐His)N7(2). The reaction of L‐histidine with d(ApA) seemed to form the bimetallic adduct (L‐His)PdN7(1)N7(2)Pd(L‐His). The Pt(II)‐L‐methionine complex in both reactions with d(ApG) and d(ApA) seemed to yield mainly adducts Pt(L‐Met)N7(1)N7(2) but the existence of adducts Pt(L‐Met)N1(1)N7(2) cannot be ruled out.
Ternary Complexes of cis‐ (cis‐DDP) With Guanosine (guo), Cytidine (cyd) and the Aminoacids Glycine (gly), L‐Alanine (ala), L‐2‐Aminobutyric Acid (2‐aba), L‐Norvaline (nval) and L‐Norleucine (nleu)
Authors: Katsarou Erasmia , Charalambopoulos Costas , Hadjiliadis Nick
Published: March 2007

The ternary complexes of formulae cis‐[Pt(nucl)(amac)]NO3, where nucl = guo and cyd (guanosine and cytidine) and amac = the deprotonated aminoacids glycine (gly), L‐alanine (ala), L‐2‐aminobutyric acid (2‐aba), L‐norvaline (nval) and L‐norleucine (nleu), were prepared from the reactions of the binary chelated ones cis‐[Pt(amac)]NO3 with the nucleosides.

They were characterized by  1H,  13C and  195Pt NMR and IR spectra, together with elemental analysis and conductivity measurements. The aminoacids coordinate with Pt(II) in the ternary complexes with their terminal ‐NH2 groups, guo through N7 and cyd through N3. Ligand‐ligand hydrophobic interactions were also observed in the ternary complexes and were stronger with longer aliphatic chains of the aminoacids. The  3E sugar conformation increased by 5‐7% in the ternary systems, as compared to the free nucleosides, while the percentage of the gg conformation remained almost constant and the one of the anti conformation of the sugar increased also slightly.
Finally, the h conformer around the Cα‐Cβ bonds of the aminoacids reached a maximum in the binary systems and decreased again considerably in the ternary ones.
Spectral, Magnetic and Biological Studie on Some Bivalent 3d Metal Complexes of Hydrazine Derived Schiff‐Base Ligands
Authors: Chohan Zahid H. , Sherazi Syed K. A.
Published: March 2007

Metal(II) complexes of hydrazine derived Schiff‐base ligands of the type M(L) 2Cl2 where M = Co, Cu, Ni and Zn and L = L1 and L2 have been prepared and characterised by molar conductance, magnetic moment, elemental analysis and electronic, IR, H‐NMR and  13C spectral data.The different modes of chelation of the ligands and their comparative biological properties against different bacterial species are reported.
X‐Ray Structure and In Vitro Anti‐Tumoural Activity of the Dimeric Bis[(2‐Phenyl‐1,2‐Dicarba‐Closo‐Dodecaborane‐1‐Carboxylato)‐Di‐n‐Butyltin] Oxide
Authors: Tiekink Edward R. T. , Gielen Marcel , Bouhdid Abdeslam , Willem Rudolph , Bregadze Vladimir I. , Ermanson Lidia V. , Glazun Sergey A.
Published: March 2007

X‐ray diffraction studies reveal the structure of , 1, to conform to the common motif found for compounds. The dimer features a central Bu4Sn2O2 unit (two‐fold symmetry) with the two Bu2Sn groups being linked via bridging oxygen atoms, each of which also carries an exocyclic Bu2Sn moiety. The two pairs of exo‐ and endo‐cyclic tin atoms are each linked via an almost symmetrically bridging carboxylate ligand and the two remaining ligands coordinate an exocyclic tin atom only, in the monodentate mode. The in vitro anti‐tumour activity of 1, determined against a variety of cell lines, is compared with those of the corresponding 2‐methylcarboranylacetate, derivative 2, and with clinically used compounds.
Antitumour Activity of a pt(III) Derivative of 2‐Mercaptopyrimidine
Authors: Cervantes G. , Prieto M. J. , Moreno V.
Published: March 2007

The complex [Pt2Cl2(Spym)4], where Spym = 2‐mercaptopyrimidine, was synthesized and
analyzed spectroscopically. The presence in the  195Pt NMR spectrum, of only one signal for the Pt(III) indicates the symmetrical arrangement of the ligands and the identical setting of N, S and Cl atoms, PtS2ClN2, for the two Pt atoms being different to other compounds described in the
literature. The interaction of this complex with DNA was studied by several techniques, including circular dichroism, melting temperature determination, electron microscopy (EM) and atomic force
microscopy (TMAFM). Preliminary results show a high activity against HL‐60 and HeLa tumour lines for the Pt‐2‐mercaptopyrimidine complex in comparison with cisplatin activity. Higher values for IC50 were obtained, while the values of LD50 were lower than those for cisplatin.
Determination of Biotransformation Products of Platinum Drugs in Rat and Human Urine
Authors: Tang Xia , Hayes, Jerry W. , Schroder Louis , Cacini William , Dorsey John , Elder R. C. , Tepperman Katherine
Published: March 2007

Cisplatin is an extremely effective cancer chemotherapeutic agent, but its use is often accompanied by toxicity. Second generation drugs such as carboplatin are becoming more widely used because of reduced toxicity. Since biotransformation products have been implicated in the toxic responses, we have begun to investigate the reactions of cisplatin and carboplatin with potential biological ligands. Reaction products were characterized using HPLC with inductively
coupled plasma ‐ mass spectrometry (HPLC‐ICP‐MS),  1H and  13C NMR and fast atom bombardment ‐ mass spectrometry (FAB‐MS). Three Pt‐creatinine complexes, cis‐, cis‐ and cis‐, were synthesized and the platinum was shown to coordinate to the ring nitrogen, N(3). Human urine samples from patients on cisplatin chemotherapy were shown to contain cisplatin, its hydrolysis product and biotransformation products containing Pt‐creatinine, Pt‐urea and Pt‐uric acid complexes. Urine from carboplatin patients shows fewer biotransformation products. Studies with control and diabetic (protected against cisplatin toxicity) rats showed systematic differences in the biotransformation products formed on administration of cisplatin.
The Synthesis and Antitumor Activity of the Sodium Salt and Copper(II) Complex of N‐[(Trimethylamineboryl)‐Carbonyl]‐L‐PhenylalanineMethyl Ester
Authors: Miller M. C. , Sood A. , Spielvogel B. F. , Hall I. H.
Published: March 2007

Sodium N‐[(trimethylamineboryl)‐carbonyl]‐L‐phenylalanine 2 and {N‐[(trimethylamineboryl)‐carbonyl]‐L‐phenylalanyl‐
carbxylato}‐bis‐{N‐[(trimethylaminebryl)‐carbonyl]‐L‐phenylalanine} dicopper (II) 3 were
successfully synthesized. The agents blocked L1210 leukemic cell DNA and RNA syntheses by inhibiting
multiple enzyme activities for nucleic acid synthesis, e.g. PRPP amido transferase, IMP dehydrogenase, DNA
polymerase α, thymidine kinase, and TMP kinase. The copper (II) complex 3 demonstrated improved ability
to inhibit L1210 partially purified DNA topoisomerase II compared to the parent compound while the sodium
salt was inactive at 100 μM.
Carbonic Anhydrase Inhibitors. Part 551 Metal Complexes of 1,3,4‐Thiadiazole‐2‐Sulfonamide Derivatives: In Vitro InhibitionStudies With Carbonic Anhydrase Isozymes I, II and IV
Authors: Supuran Claudiu T. , Scozzafava Andrea , Briganti Fabrizio , Ilies Marc A. , Jitianu Andrei
Published: March 2007

Coordination compounds of 5‐chloroacetamido‐1,3,4‐thiadiazole‐2‐sulfonamide (Hcaz)
with V(IV), Cr(lll), Fe(ll), Co(ll), Ni(ll) and Cu(ll) have been prepared and characterized by standard
procedures (spectroscopic, magnetic, EPR, thermogravimetric and conductimetric
measurements). Some of these compounds showed very good in vitro inhibitory properties against
three physiologically relevant carbonic anhydrase (CA)isozymes, i.e., CA I, II, and IV. The
differences between these isozymes in susceptibility to inhibition by these metal complexes is
discussed in relationship to the characteristic features of their active sites, and is rationalized in
terms useful for developing isozyme‐specific CA inhibitors.
Potential Application of Copper Aspirinate in Preventing andTreating Thromboembolic Diseases
Authors: Liu Weiping , Xiong Huizhou , Yang Yikun , Li Ling , Shen Zhiqiang , Chen Zhihe
Published: March 2007

The efficacy of copper aspirinate against thrombotic diseases has been tested
in animal models. The results show that copper aspirinate, following ig pretreatment
for 7 days at 0.012mmol/kg markedly prolonged the bleeding time and inhibited the
mortality induced by arachidonic acid (AA) in mice. On cereral ischemia model
pretreatment with 0.018mmol/kg copper aspirinate ig significantly increased
survival of animals and the density of intact hippocampal CA1 cells and decreased
brain calcium concentration. Its anticerebral ischemia activity was superior to or
equal to nimodipine. It is, therefore, suggested that copper aspirinate is very promising
in becoming an antithrombotic drug in preventing and treating thrombotic diseases.
The Development of Novel Organotin Anti‐Tumor Drugs: Structure and Activity
Authors: de Vos Dick , Willem Rudolph , Gielen Marcel , van Wingerden Kyra E. , Nooter Kees
Published: March 2007

An overview of the development of anti‐tumor organotin derivatives in selected classes of
compounds is presented and discussed. High to very high in vitro activity has been found,
sometimes equaling that of doxorubicin. Solubility in water is an important issue, dominating
the in vivo testing of compounds with promising in vitro properties.
The cytotoxicity of the compounds was increased by the presence of a bulky group, an active substituent or one or
more polar substituents. Polar substituents may also improve the water solubility. Although
organotin derivatives constitute a separate class of compounds, the comparison with cisplatin
is inevitable. Among the observed toxicities, neurotoxicity, known from platinum cytostatics,
and gastrointestinal toxicity, typical for many oncology drugs, have been detected. Further
research to develop novel, useful organotin anti‐tumor compounds should be carried out.
Synthesis, Characterization and In Vitro Antitumour Activity ofDi‐n‐Butyl, Tri‐n‐Butyl and Triphenyltin 3,6‐Dioxaheptanoates and3,6,9‐Trioxadecanoates
Authors: Kemmer Martine , Gielen Marcel , Biesemans Monique , de Vos Dick , Willem Rudolph
Published: March 2007

A series of di‐ and triorganotin 3,6‐dioxaheptanoates and 3,6,9‐trioxadecanoates were synthesized and
characterized by  1H,  13C and  117Sn NMR, electrospray mass and  119mSn Mössbauer spectroscopy, as well as
elemental analysis. Their in vitro antitumour activity against seven tumoural cell lines of human origin, two
breast cancers (MCF‐7, EVSA‐T), a colon carcinoma (WiDr), an ovarian cancer (IGROV), a melanoma (M 19
MEL), a renal cancer (A 498) and a non small cell lung cancer (H 226), is reported. They are characterized by
similar inhibition doses ID50 as the analogous di‐ and triorganotin derivatives of 4‐carboxybenzo‐15‐crown‐5
and ‐18‐crown‐6 and in some cases by much lower ID50 values than clinically used reference compounds such
as doxorubicine and methotrexate.
DNA Binding of Some Chiral Metallointercalators Derived From9,10‐Phenanthrenediamine
Authors: Murphy-Poulton Susan F. , Vagg Robert S. , Vickery Kymberley A. , Williams Peter A.
Published: March 2007

A study of the interaction with calf thymus DNA is described of a novel set of chiral ternary complex cations of general form (where N4-tet is the chiral linear tetradentate
R*R*‐picchxn or R*R*‐picchxnMe2). Individual equilibrium binding constants (KB) have been
determined from spectroscopic titrations employing the hypochromism induced in the visible
absorbance of the cations on interaction with the nucleic acid. These demonstrate both stereo‐ and
enantioselectivity in the binding interactions. These KB data, together with induced circular
dichroism and DNA thermal denaturation results, are all indicative of selective intercalation of the
bidentate components of the cations into the nucleobase stack of the duplex. Supportive
evidence for a secondary binding mode for the picchxn complexes is provided by the different
mutagenicity profiles obtained for related cations.
Synthesis and Antifungal Activity of Some Organotin(IV) Carboxylates
Authors: Bonire Josiah J. , Ayoko G. Adefikayo , Olurinola Philip F. , Ehinmidu Joseph O. , Jalil Neelam S. N. , Omachi Andrew A.
Published: March 2007

Six diorganotin(IV) carboxylates prepared by reacting diorganotin(IV) dichlorides with the
respective silver carboxylate have been tested for antifungal activity against Aspergillus. niger, Aspergilluus flavus and Pencillium. citrinum in Sabourand dextrose broth. The compounds
generally exhibit greater fungitoxicity than the diorganotin(IV) dichlorides and the carboxylic acids
from which they were synthesized. In keeping with the generally accepted notion that the
organotin moiety plays an important role in deciding the antifungal activity of an organotin
compound, the diphenyltin(IV) compounds were more active than their di‐n‐butyltin(IV) analogues.
However, the order of increasing fungitoxicity of the compounds parallels that of the uncomplexed
carboxylic acids. The implications of the results are discussed.
Anti‐Arthritic Activity in Rats of Some Phosphinegold(I) Thionucleobases and Related Thiolates
Authors: Whitehouse Michael W. , Cookson Peter D. , Siasios George , Tiekink Edward R. T.
Published: March 2007

A number of phosphinegold(I) thiolates where, generally, the thiolate is derived from a
thionucleobase, have been screened for anti‐arthritic activity in Dark Agouti rats, a gold
sensitive model for arthritis. Potency and toxicity data showed that, generally, the Ph3P derivatives and species based on thiopurines were the most effective and that with other
complexes enhanced activity was accompanied by greater toxicity.
Six‐ and Seven‐Membered 1‐Oxa‐4‐Aza‐2‐Silacyclanes as PossibleCorrectors of Adaptational Mechanisms
Authors: Kurochka Andrey V. , Agafonova Ol′ga V. , Losev Aleksandr S. , Mamaeva Elizaveta A. , Bylikin Sergey Yu. , Negrebetsky Vadim V. , Kramarova Evgeniya P. , Shipov Aleksandr G. , Baukov Yuri I.
Published: March 2007

The biological activity of eight 1‐oxa‐4‐aza‐2‐silacyclanes with the OSiCH2N fragment
including 6‐membered 2‐sila‐5‐morpholinones (1–3) and 4‐acyl‐2‐silamorpholines (4–6)and
previously unknown 7‐membered derivatives of salicylic acid (7, 8) was studied. Compounds 1 and 3–6 show the certain antihypoxic action. Compounds 2 (40 mg/kg), 4 (20 mg/kg), 6 (40 mg/kg), 7 (20 mg/kg) and 8 (40 mg/kg) reduce the physical serviceability of intact animals.
Compound 1 (20 mg/kg) influences the physical serviceability in a moderate‐positive way on
the background of chlorophos‐poisoning. Compounds 5–8 displayed protective properties
against chlorophos‐poisoning at the LD50 dose and compounds 2, 4, 5, 7 at the LD100 dose.
Influence of compounds 1 and 2 on the emotional‐research behavior of mice was studied.
Studies on Some Biologically Cobalt(II), Copper(II) and Zinc(II)Complexes With ONO, NNO and SNO Donor Pyrazinoylhydrazine‐DerivedLigands
Authors: Chohan Zahid H. , Praveen Marapaka , Sherazi Syed K. A.
Published: March 2007

Biologically active complexes of Co(II), Ni(II), Cu(II) and Zn(II) with novel ONO, NNO and
SNO donor pyrazinoylhydrazine‐derived compounds have been prepared and characterized on the basis of
analytical data and various physicochemical studies. Distorted octahedral structures for all the complexes
have been proposed. The synthesized ligands and their complexes have been screened for their antibacterial
activity against bacterial species Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonae. The activity data show the metal complexes to be more active than the parent free
ligands against one or more bacterial species.
Synthesis, Characterization and Antitumour Activities of Di‐n‐Butyl‐ and Dimethyltin D‐(+)‐Camphorates
Authors: Gielen Marcel , Dalil Hassan , Mahieu Bernard , de Vos Dick , Biesemans Monique , Willem Rudolph
Published: March 2007

The synthesis and characterization di‐n‐butyl‐ and dimethyltin D‐(+)‐camphorates, respectively
compounds 1 and 2, are reported. Compound 1 displays antitumoural activity in vitro, and is more
active than cisplatin, 5‐fluorouracil and etoposide against seven tumoural cell lines of human origin,
but less active than methotrexate and doxorubucin.
Distribution of Copper in Rats Submitted to Treatment With Copper Aspirinate
Authors: Liu Weiping , Yang Yikun , Xiong Huizhou , Lu Ying , Yang Rong
Published: March 2007

The distribution of copper in Sprague – Dawley rats following a three month oral
administration of 0,10 or 50mg/kg copper aspirinate has been investigated. Metal
content was determined by ICP – AES in blood, brain, kidney, liver, lung, spleen, and
dejection. The results show that treatment with copper aspirinate did not cause
accumulation of copper in rats and excess ingested copper was excreted through
feces.
Ternary Copper(II) Complexes With Indomethacin, a PotentNon‐Steroidal Antiinflammatory Drug. Crystal Structure of Bis(Dimethylformamide)‐Tetrakis[1‐(4‐Chlorobenzoyl)‐5‐Methoxy‐2‐Methyl‐1‐H‐Indole‐3‐Acetato]Dicopper(II).Antiinflammatory Properties andPrevention of Gastrointestinal Side Effects by Nanocapsules
Authors: Guessous Fadila , Daran Jean-Claude , Viossat Bernard , Morgant Georges , Labouze Xavier , Leroy Anne Laure , Roch-Arveiller Monique , Dung Nguyen-Huy
Published: March 2007

Two ternary copper(ll) complexes of indomethacin [1‐(4‐chlorobenzoyl)‐5‐methoxy‐2‐
methyl‐1‐H‐indole‐3‐acetic acid] called hereafter lndo, were prepared and characterized by single
crystal X‐ray diffraction. The first complex Cu2(Indo) 4(DMF) 2 I crystallizes in space group P‐1 (a =
10.829(2), b = 13.379(2), c = 16.491(3) Å; α = 105.58(2), β = 101.06(2), γ = 106.96(2)°; V= 2104.6(6) Å3, Z= 1). The title molecule is a centrosymmetric binuclear complex, with Cu atoms
bridged by the carboxylate moieties of four indomethacinate ligands. The four nearest O atoms
around each Cu atom form a square planar arrangement with the square pyramidal coordination
completed by the O atom of N,N′‐dimethylformamide. Daily administration for seven days of 1 mg/kg
of indomethacin, I and I encapsulated into liposomes induces a weak inflammation of rat gastrointestinal
tract. I was less inflammatory than indomethacin but the better protection was brought by
encapsulation of the compound. This might be of interest in sustained therapies of chronic
inflammatory diseases.
Synthesis, Characterization and AntitumourActivity of Metal Complexes of 5‐Carboxy‐2‐Thiouracil
Authors: Singh Udai P. , Singh Sudha , Singh Sukh Mahendra
Published: March 2007

Metal complexes of 5‐carboxy‐2‐thiouracil with Mn(ll), Co(ll), Ni(ll), Cu(ll), Zn(ll) and Cd(ll) ions were synthesized,
characterized, and subjected to a screening system for evaluation of antitumour activity against Sarcoma‐180
(S‐180) tumour cells. The complexes were characterized by elemental analysis, infrared, electronic spectra, room
temperature magnetic measurements and powder X‐ray diffraction. The antitumour activity results indicate that
some complexes have antitumour activity both in vivo and in vitro against S‐180 tumour cells.
Interaction of Some Non‐Platinum Metal Anticancer Complexes WithNucleotides and DNA and The Two‐Pole Complementary Principle (TPCP)Arising Therefrom
Authors: Yang Pin , Guo Maolin
Published: March 2007

The binding modes of some non‐platinum metal anticancer complexes, Cp2TiCl2, Cp2ZrCl2,
, , (phen) (phen=Phenanthroline) and cis‐RuIICl2(DMSO) 3
(DMSO) (cis‐RDT) with nucleotides and DNA in aqueous solution at physiological pH values
were investigated by various modern techniques. 5′‐dGMP with Cp2TiCl2 or cis‐RDT forms
chelate complexes in which both N7 and phosphate of dGMP bind to the metal center.
Whereas Cp2ZrCl2 and all the diorganotin compounds can bind dGMP only via the phosphate
group. The investigations of the interactions between Cp2TiCl2 or and DNA indicate
that there are two types of binding sites on DNA for Cp2TiCl2, i.e., the base nitrogen rings and
the phosphate group, while can bind to DNA only via the phosphate group. At last,
by carefully comparing and analysing the binding modes‐activity relationships of the above
anticancer complexes and other non‐platinum and platinum anticancer complexes, a hypothesis
named “Two‐Pole Complementary Principle” was put forward.
Synthesis and Characterization of Coordinatively Unsaturated Copper(II) Complexes of 1,3‐Bis(2′‐Pyridyl)‐1,2‐Diaza‐2‐Butene and TheirAntityrosinase Activity
Authors: Bendre Ratnamala , Murugkar Anupa , Padhye Subhash , Kulkarni Pallavi , Karve Meena
Published: March 2007

The coordinatively unsaturated copper (II) complexes of 1,3‐bis(2′‐pyridyl)‐1,2‐diaza‐2‐
butene with different ancillary anions were synthesized which can bind to copper centers of
tyrosinase enzyme. The compounds were found to exhibit inhibitory activities against
mushroom tyrosinase and the nature and extent of inhibition is modulated according to the
type of ancillary anions.
Anti‐Inflammatory Activity of (Polyphenolic)‐Sulfonates and TheirSodium Salts in Rodents
Authors: Hall Iris H. , Murphy Margaret E. , Elkins Amy L.
Published: March 2007

A series of polyphenolic‐sulfonated compounds were observed to have potent anti‐inflammatory activity
and were protective against induced endotoxic shock in mice at 8 and 16 mg/kg, I.P. These agents proved
to be potent elastase inhibitors in human leukocytes and J774‐AI and IC‐21 mouse macrophages as well as
prostaglandin cyclo‐oxygenase inhibitors in J774‐AI macrophages. The compounds from 5 to 50 μM
inhibited TNFα release from IC‐21 macrophages and IL‐1 release from mouse P388D1 macrophages
induced by LPS. The binding of these cytokines to high affinity receptors on target cells, e.g. L929
fibroblasts and IL‐2 in HuT78 T lymphoma cells, were also suppressed by the agents. These compounds
blocked the adhesion of leukocytes and macrophages to the plasma membranes of L929 fibroblasts.
Functionalized Derivatives of Benzo‐Crown Ethers. Part 4.Antifungal Macrocyclic Supramolecular Complexes of Transition MetalIons Acting as Lanosterol‐14‐α‐Demethylase Ihibitors
Authors: Barboiu Mihai , Supuran Claudiu T. , Scozzafava Andrea , Guran Cornelia , Diaconescu Paula , Bojin Mihaela , Iluc Vlad , Cot Louis
Published: March 2007

Poly‐ and mononuclear metal complexes of 2,3,11,12‐bis[4‐(10‐aminodecylcarbonyl)]benzo‐18‐
crown‐6 (L) and Cu(II); Ni(II); Co(II) and Cr(III) have been synthesized and characterized by standard
physico‐chemical procedures. In the newly prepared complexes the crown moiety oxygen atoms of the
macrocyclic host did not generally interact with metal ions, whereas the two amino groups of the ligand always did. Several of the newly synthesized compounds act as effective antifungal agents against
Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 0.3 − 0.5 μg/mL
. The mechanism of antifungal action of these
coordination compounds is probably connected to an inhibition of lanosterol‐14‐α
‐demethylase, a metallo‐enzyme playing a key role in sterol biosynthesis in fungi, bacteria and eukariotes.
Down‐Regulation of Porcine Heart Diaphorase Reactivity byTrimanganese Hexakis(3,5‐Diisopropylsalicylate),Mn3(3,5‐DIPS) 6 , andDown‐Regulation of Nitric Oxide Synthase Reactivity by Mn3(3,5‐DIPS) 6 and Cu(II) 2(3,5‐DIPS) 4
Authors: Booth Billynda L. , Pitters Eva , Mayer Bernd , Sorenson John R. J.
Published: March 2007

Purposes of this work were to examine the plausible down‐regulation of porcine heart diaphorase (PHD) enzyme reactivity and nitric oxide synthase (NOS) enzyme reactivity by trimanganese hexakis(3,5‐diisopropylsalicylate), [Mn3(3,5‐DIPS) 6]
as well as dicopper tetrakis(3,5‐ diisopropylsalicylate, [Cu(II)2(3,5‐DIPS)4]
as a mechanistic accounting for their pharmacological activities.

Porcine heart disease was found to oxidize 114 μM
reduced nicotinamide‐adenine‐ dinucleotide‐3′‐phosphate (NADPH) with a corresponding reduction of an equivalent concentration of 2,6‐dichlorophenolindophenol (DCPIP). As reported for Cu(II)2(3,5‐DIPS)4, addition of Mn3(3,5‐DIPS) 6
to this reaction mixture decreased the reduction of DCPIP without significantly affecting the oxidation of NADPH. The concentration of Mn3(3,5‐DIPS) 6
that produced a 50% decrease in DCPIP reduction (IC50)
was found to be 5 μM
. Mechanistically, this inhibition of DCPIP reduction with ongoing NADPH oxidation by PHD was found to be due to the ability of Mn3(3,5‐DIPS) 6
to serve as a catalytic electron acceptor for reduced PHD as had been reported for Cu(II)2(3,5‐DIPS)4. This catalytic decrease in reduction of DCPIP by Mn3(3,5‐DIPS) 6
was enhanced by the presence of a large concentration of DCPIP and decreased by the presence of a large concentration of NADPH, consistent with what had been observed for the activity of Cu(II)2(3,5‐DIPS)4

Oxidation of NADPH by PHD in the presence of Mn3(3,5‐DIPS) 6
and the absence of DCPIP was linearly related to the concentration of added Mn3(3,5‐DIPS) 6
through the concentration range of 2.4 μM
to 38 μM
with a 50% recovery of NADPH oxidation by PHD at a concentration of 6 μM Mn3(3,5‐DIPS)6

Conversion of [3H] L‐Arginine to [3H] L‐Citrulline by purified rat brain nitric oxide synthase (NOS) was decreased in a concentrated related fashion with the addition of Mn3(3,5‐DIPS) 6
as well as Cu(II)2(3,5‐DIPS)4
which is an extention of results reported earlier for Cu(II)2(3,5‐DIPS)4. The concentration of these two compounds required to produce a 50% decrease in L‐Citrulline synthesis by NOS, which may be due to down‐regulation of NOS, were 0.1 mM and 8μM
respectively, consistent with the relative potencies of these two complexes in preventing the reduction of Cytochrome c by NOS.

It is concluded that Mn3(3,5‐DIPS) 6, as has been reported for Cu(II)2 (3,5‐DIPS)4
, serves as an electron acceptor in down‐regulating PHD and both of these complexes down‐regulate rat brain NOS reactivity. A decrease in NO synthesis in animal models of seizure and radiation injury may account for the anticonvulsant, radioprotectant, and radiorecovery activities of Mn3(3,5‐DIPS) 6
and Cu(II)2(3,5‐DIPS)4
.
Radioprotectant Activity of Dicopper(II) Tetrakis(3,5‐Diisopropylsalicylate) and Manganese(II) bis(3,5‐Diisopropylsalicylate) Alone and in Combination
Authors: Kuykendall, John A. , Ebert, Robert H. , El-Sayed lbrahim H. , Roberson Paula K. , Pham-Tran Van Anh , Booth Billynda L. , Brooks Tiffany , Willingham William M. , Sorenson John R. J.
Published: March 2007

Dicopper(ll) tetrakis(3,5‐diisopropylsalicylate), (Cu(II)2(3,5‐DIPS)4, manganese(II) bis(3,5‐diisopropylsalicylate), Mn(II)(3,5‐DIPS) 2
or combinations of them were used to treat gamma‐irradIated mice in examining the possibility that combination treatments might be more effective in increasing survival than treatment with either complex alone. Doses of 0, 10, 20, or 40 μmol
of each complex per kilogram of body mass were administered subcutaneously in a factorial design before 9 Gy gamna irradiation, an LD90
dose of irradiation. Doses of 0, 10, 20, or 40 μmol Cu(II) 2  (3, 5‐DIPS) 4
per kg of body mass produced 12, 28, 28, or 36 % survival, respectively, while doses of 0, 10, 20, or 40
μmol Mn(II)  (3, 5‐DIPS) 2
per kg of body mass prduced 12, 36, 20, or 24 % survival, respectively. However, the combination of 20
μmol  Cu(II) 2(3, 5‐DIPS) 4
and 10 μmol Mn(II)(3, 5 − DIPS) 2
produced the greatest survival, 48 %, which was 300 % greater than vehicle‐treated mice (P=0.01). It is concluded that specific combination treatments can be used to maximize survival of lethally irradiated mice.
Radioprotectant Activity of 5‐Diethylsulfonamoylsalicylatocopper(II) in Gamma Irradiated Mice
Authors: Kuykendall, John A. , Simmons, Hugh , Irving Henry J. , Wear Mark A. , Sorenson Paul G. , Tipton Linda G. , Maddox Kenchasha M. , Williams Elsie L. , Pham-Tran Van Anh , Credit Chassie , Chowdhury Israt L. , Khan Shaheen , Tipton J. Brooks , Willingham William M. , Sorenson John R. J.
Published: March 2007

Survival and changes in mean body mass of whole‐body irradiated mice were determined to examine the
radioprotectant activity of 5‐diethylsulfonamoylsalicylatocopper(II) [Cu(II) (5‐DESS)]. One of four groups of 25
female C57BL/6 mice were treated subcutaneously (sc)with 0, 10, 20, 40, 60, 80, 100, or 120 μmol
Cu(II)(5‐
DESS)/kg of body mass 3 hours before exposure to 8.0 Gy, gamma irradiation. In this paradigm, doses of Cu(II)(5‐
DESS) increased survival up to 92% above vehicle‐treated control mice (P = 0.008)
. Mean body mass
determinations revealed that mice treated with 80 to 120 μmol
Cu(II)(5‐DESS)/kg of body mass exhibited a smaller
decrease in body mass than other complex‐treated groups. These results support the hypothesis that Cu(II)(5‐DESS)
is an effective radioprotectant.
Effect of Acute and Chronic Oral Zinc Administration inHyperprolactinemic Patients
Authors: Madureira Guiomar , Bloise Walter , Mendonca Berenice Bilharinho , Brandão-Neto José
Published: March 2007

The inverse relationship between zinc (Zn++)
and prolactin (PRL) was detected in in vitro studies,
whereas in vivo results are contradictory. In order to evaluate this controversial subject we
studied patients with hyperprolactinemia. Basal serum Zn++
levels and serum PRL response to
acute and chronic oral Zn++ administration were evaluated in seven patients with prolactinomas
and one with idiopathic hyperprolactinemia. Serum PRL levels did not change after acute oral
Zn++ administration (37.5 mg), although Zn++
levels increased from 1.11 ± 0.15
to 2.44 ± 0.39 μg/mL(P<0.05)
. Zn++ administration (47.7 mg daily) during 60 days increased serum Zn++ levels
from 1.11 ± 0.15 to 1.59 ± 0.58 μg/mL (p < 0.05) but caused no change in serum PRL levels. The
TRH tolerance test (200 μg
) was performed before and after 60 days of Zn++
administration, and
PRL response to TRH was unchangeable and similar in both tests. We concluded that acute or
chronic Zn++
administration does not inhibit PRL secretion in basal condition or by TRH effect in
hyperprolactinemic patients.
Synthesis, Characterization and Antimicrobial Activity of d8-10 MetalComplexes of some 2‐Substituted‐1H‐Benzimidazoles
Authors: Ülküseven Bahri , Tavman Aydin , Ötük Gülten
Published: March 2007

The metal complexes of nine 2‐substituted‐1H‐benzimidazoles (I-IX) with Ni(II), Pd(II), Cu(II),
Ag(I), Zn(II) salts were synthesized. The compounds were characterized by melting point, analytical data, IR
spectroscopy and magnetic susceptibility. The antimicrobial activity of the compounds was determined by
the disk diffusion method in Mueller‐Hinton Agar on Staphylococcus aureusATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis, Candida albicans ATCC 10231. Cu(II)and Ag(I)complexes of II, III and IV showed considerable activity against S. aureus, S. epidermidis, Ps. aeruginosa, S. typhi, Sh. flexneri and C. albicans microorganisms, the ligands themselves
having no effect.
Hormone Anchored Metal Complexes. 1. Synthesis, Structure,Spectroscopy and In Vitro Antitumor Activity of TestosteroneAcetate Thiosemicarbazone and its Metal Complexes
Authors: Murugkar Anupa , Unnikrishnan Bindu , Padhye Subhash , Bhonde Ramesh , Teat Simon , Triantafillou Evangelia , Sinn Ekkehard
Published: March 2007

Testosterone acetate thiosemicarbazone (TATSC, 17‐β‐hydroxyandrost‐4‐one acetate thiosemicarbazone)
was synthesized and characterized by single crystal X‐ray structure determination. The copper and platinum
complexes of this steroid derivative were synthesized and characterized by spectroscopy and electrochemiatry.
The in vitro activity of these compounds against human breast cancer cell line MCF‐7 was tested. The
highest activity was found for the [Pt(TATSC)Cl2]
followed by [Cu(TATSC)Cl2]
and the ligand in
compariosn with cisplatin.
Structures of Gold(I) and Silver(I) Thiolate Complexes ofMedicinal Interest: A Review and Recent Results
Authors: Howard-Lock Helen E.
Published: March 2007

We review the crystal structures, electrospray ionization mass spectra (ESI‐MS) data and chiral
HPLC data for the racemic and optically pure mononuclear AuL2 complexes, and for racemic [AuLI]n and
optically pure [AgLII]n polymers (LI = thiomalate, LII = D‐penicillamine). We postulate an equilibrium between polymeric, mononuclear and free ligand species for [AuLII]n (gold sodium thiomalate or GST). The ESI‐MS
results clearly show a tetrameric principal species in the 1:1 gold polymers, [AuLI]n. For the 1:1 silver: D‐penicillamine complex, [AgLII]n, a non‐molecular crystal of double helical structure, the ESI‐MS results show
multi‐ligand‐silver species, including tetramers, pentamers and hexamers. Other, relevant gold, silver and
copper complexes are compared.
Different Coordination Modes of a Tripod Phosphine in Gold(I) andSilver(I) Complexes
Authors: Sevillano P. , García M. E. , Habtemariam A. , Parsons S. , Sadler P. J.
Published: March 2007

The following gold(I) and silver(I) complexes of the tritertiary phosphine 1,1,1‐
tris(diphenylphosphinomethyl)ethane, tripod , have been synthesised: Au3(tripod)X3
[X = Cl(1), Br(2), I(3)];
[Au3  (tripod)2Cl2  ]Cl
(4); Au(tripod)X [X = Br(5), I(6)];
(7), Ag(tripod)NO3
(8). They were
characterized by X‐ray diffraction (complexes 2, 3 and 4),  31P
NMR spectroscopy, electrospray and FAB mass
spectrometry and infrared spectroscopy. Complexes 2 and 3 show a linear coordination geometry for Au(I),
with relatively short Au‐P bond distances. Complex 3 has a Au•••Au
intramolecular distance of 3.326
,
while complex 2 had a short Au•••Au intermolecular interaction of 3.048
. Complexes 4-6 were found by
 31P
NMR spectroscopy studies to contain a mixture of species in solution, one of which crystallised as
[Au3(tripod|)2Cl2]Cl which was shown by X‐ray diffraction to contain both tetrahedral and linear Au(I), the
first example of a Au(I) complex containing such a mixture of geometries. The reaction of [Au3(tripod)Cl3] (1)
with tripod led successfully to the formation of and
. The silver(I)
complexes, 7 and 8 appear to contain linear and tetrahedral Ag(I), respectively.
Silver and Gold NMR
Authors: Zangger Klaus , Armitage lan M.
Published: March 2007

Silver and gold, together with copper, form the transition metal group IB elements in the periodic table and possess very different nuclear magnetic resonance (NMR) spectroscopic properties. While there is only one gold isotope ( 197Au)
, which has a spin of 3/2 and therefore a quadrupole moment, silver occurs in two isotopic forms ( 107Ag
and  109Ag
), both of which have a spin and
similar NMR spectroscopic properties. The unfavorable properties of gold have prevented its NMR
spectroscopic investigation thus far. On the other hand, there are several reports of silver NMR. However, the low sensitivity of silver, combined with its long relaxation times have rendered the
direct detection of silver possible only with concentrations greater than a few tenth molar. Reviewed here are the general limitations of silver NMR and some techniques to partially overcome these
limitations, as well as a summary of currently available chemical shift and scalar coupling data on  109Ag
.
Synthesis and Analgesic Activity of η6‐(Anisole)‐ Triscarbonyl‐Chromium(0)
Authors: Andrade e Silva Márcio Luís , Neto Alberto Federman , Miller Joseph
Published: March 2007

The general method for synthesis the η6‐(arene)‐triscarbonyl‐chromium(0) complexes was modified and applied for preparation of η6‐(anisole)‐triscarbonyl‐chromium(0) and the study of its analgesic activity was undertaken. A significant analgesic activity was observed after intraperitoneal injection, in Wistar rats. Two doses (30 and 50 mg/Kg of the body weight) of η6‐(anisole)‐ triscarbonyl‐chromium(0) were injected and the analgesic activity was evaluated by the Hot Plate Test method. They showed a significant analgesic effect in comparison with the control group and the group treated with dipyrone standard, but not so high when compared with the group treated with morphine standard. Overall, it was observed that the η6‐(anisole)‐ triscarbonyl‐chromium(0) was easily obtained by the modified synthetic method and was effective in increasing the pain threshold.
Electronic Structure of Dinuclear Gold(I) Complexes
Authors: Foley Janet B. , Gay Stanley E. , Turmel Christopher , Wei Gang , Jiang Tong , Narayanaswamy Ratnavathany , Foxman Bruce M. , Vela Michael J. , Bruce Alice E. , Bruce Mitchell R. M.
Published: March 2007

Cyclic voltammetry (CV) experiments on LL
complexes [LL = diphenylphosphinomethane
(dppm), diphenylphosphinopentane (dpppn); R* = p‐SC6H4CH3] show anodic sweeps that broaden by
about 25 mV on going from the longer (dpppn) to the shorter (dppm) bidentate phosphine ligand.
Changing concentrations had no effect on the shape of the waveform. The result suggests a weak
intramolecular metal‐metal interaction in dppm
that correlates well with rate acceleration
occurring in the reaction of dppm
with organic disulfides. Quantum yields for cis‐dppee(AuX) 2

[dppee = 1,2‐bis(diphenylphosphino)ethylene; X = Cl, Br, I] complexes,  Φ(disappearance), are significantly
higher in complexes with a softer X ligand, a trend that correlates well with aurophilicity. This result also
suggests that electronic perturbation caused by Au(I)‐Au(I) interactions is important in explaining the
reactivity of some dinuclear gold(I) complexes. The crystal structure for cis‐dppee(Aul) 2
shows short
intramolecular Au(I)‐Au(I) interactions of 2.9526 (6) , while the structure of trans‐dppee(AuI)2
, shows intermolecular Au(I)‐Au(I) interactions of 3.2292 (9) . The substitution of .As for P results in a ligand, cis‐diphenylarsinoethylene
(cis‐dpaee), that is photochemically active, in contrast to the cis‐dppee ligand.
The complexes, cis‐dpaee(AuX) 2, are also photochemically active but with lower quantum yields than the
cis‐dppee(AuX) 2
complexes.
[AU(DIEN)Cl]Cl2: Exchange Phenomena Observed by  1H and  13C NMR Spectroscopy
Authors: Best Sabine L. , Guo Zijian , Djuran Milos I. , Sadler Peter J.
Published: March 2007

The solution behaviour of the square‐planar gold(III) complex [Au(dien)Cl]Cl2
(dien = 1,5‐ diamino‐3‐azapentane) was investigated by  1H
and  13C
NMR spectroscopy. We have found that  1H NMR spectra of [Au(dien)Cl]Cl2
are characterised by exchange behaviour over the whole pH range, and some exchange effects are also seen in  13C
NMR spectra of the deprotonated hydroxo derivative of the complex in alkaline solution. An exchange rate of > 378 s-1
was determined from  1H
NMR spectra at pH∗2
(coalescence temperature 40 °C
). In slightly acidic solutions of the complex,  1H
chemical shifts are in accordance with the known deprotonation of the central amine group of the complexed diethylenetriamine ligand. In  13C
NMR spectra, two separate sets of resonances are observed for the chloro and the hydroxo complex of gold(III) diethylenetriamine. The hydroxo complex [Au(dien‐H)OH] +
shows exchange effects in  13C
NMR spectra. Variable temperature studies show the carbon atoms next to the central secondary amine to be inequivalent and each present in two different environments that are in intermediate to fast exchange on the NMR time‐scale.
A Screening Strategy for Metal Antitumor Agents as Exemplified byGold(III) Complexes
Authors: Fricker Simon P.
Published: March 2007

The use of a screening strategy based on human tumor cell lines, which are also tumorigenic in immune‐deprived mice, is described. Activity against the human tumor cells in vitro and in vivo, is complemented with studies on the mechanism of action. This aporoach is demonstrated using 2‐[(dimethylamino)‐methyl]phenyl (damp) gold(III) compounds of the type [Au X2(damp)], where X = chloride, thiocyanate, acetate, or the bidentate ligands oxalate and malonate. All compounds were shown to be selectively active against a human bladder tumor cell line (HT1376) in vitro, and active in an in vitro panel of ovarian tumor cell lines. The acetato complex was shown to be active in experimental animal models of both the HT1376 bladder tumor, and the CH1 ovarian tumor. Although the [AuX2(damp)] compounds share structural features in common with cisplatin, and exhibit interesting in vivo activity against human tumor cells, the data indicate that they have a very different biochemical mechanism from platinum‐based drugs and represent a potentially new class of metal‐based antitumor agents.
Resistance to Ag(I) Cations in Bacteria: Environments, Genes andProteins
Authors: Silver Simon , Gupta Amit , Matsui Kazuaki , Lo Jeng-Fan
Published: March 2007

Bacterial resistance to Ag(I) has been reported periodically with isolates from many environments
where toxic levels of silver might be expected to occur, but initial reports were limited to the
occurrence of resistant bacteria. The availability of silver‐resistance conferring DNA sequences now
allow genetic and mechanistic studies that had basically been missing. The genes determining Ag(I)
resistance were sequenced from a plasmid found in a burn ward isolate. The 14.2 kb determinant
contains seven recognized genes, arranged in three mRNA transcriptional units. The silE gene
determines an extracellular (periplasmic space) metal‐binding protein of 123 amino acids, including
ten histidine residues implicated in Ag(I) binding. SilE is homologous to PcoE, of copper resistance.
The next two genes, silR and silS, determine a two protein, histidine‐kinase membrane sensor and aspartyl phosphate transcriptional responder, similar to other two component systems such as CzcR and CzcS (for cadmium, zinc and cobalt resistance) and PcoR and PcoS (for copper resistance).
The remaining four genes, silCBAP, are co‐transcribed and appear to determine Ag+
efflux, with
SilCBA homologous to CzcCBA, a three component cation/proton antiporter, and SilP a novel P‐type
ATPase with a amino‐terminal histidine‐rich cation‐specificity region. The effects of increasing
Ag+
concentrations and growth medium halides (Cl-, Br- and I-)
have been characterized, with lower
Cl−
concentrations facilitating resistance and higher concentrations toxicity. The properties of this
unique Ag(I)‐binding SilE protein are being characterized. Sequences similar to the silver‐resistance
DNA are being characterized by Southern blot DNA/DNA hybridization, PCR in vitro DNA
synthesis and DNA sequencing. More than 25 additional closely related sequences have been
identified in bacteria from diverse sources. Initial DNA sequencing results shows approximately 5‐20% differences in DNA sequences.
Tc‐Glutathione Complex (Tc ‐GSH): Labelling, ChemicalCharacterization and Biodistribution in Rats
Authors: Baba K. , Moretti J. L. , Weinmann P. , Senekowitsch-Schmidtke R. , Ercan M. T.
Published: March 2007

The chemical structure of  99mTc
‐GSH has been estabilished using the  99Tc
isotope.
Labeling of glutathione with technetium in the presence of stanous chloride gave a high yield
result. In a comparative study between  99Tc
and  99mTc
glutathione, the Tc‐GSH complex obtained
was purified and characterized by uv, visible spectroscopy, HPLC, Biogel chromatography, mass
and NMR spectroscopy. Stoichiometric analysis showed a 2: 1 molar ratio of GSH/Tc for the
reaction. The molecular mass assessed by mass spectroscopy was 727 Da corresponding to an
oxo(bis) glutathione technetate. NMR studies demonstrated that each glutathione molecule was
coordinated to technetium via cysteinyl sulfur and nitrogen atoms. The biodistribution of the
complex was studied in normal rats. Blood clearance was rapid during the first hour involving a
biexponential curve ( t1/2
(1): 50 min, t1/2
(2): 400 min ). No radioactive accumulation was found in
any specific organ except kidney and bladder. All the activity excreted was found unchanged in
urine. In conclusion, Tc‐GSH displayed an anionic dimer form as GSH‐Tc‐GSH. We assume that the
complex is a tetradentate (2N,2S) complex containing a pentavalent technetium coordinated by two
thiol and nitrogen atoms of both GSH ligands, and an apical oxo group.