bluuebunny/crossref_metadata_2025 huggingface dataset:
An unexpected transformation of benzyl carbamates into α‐azidobenzeneacetamides
Authors: Strässler Christoph , Heimgartner Heinz
Published: December 2004

Successive treatment of benzyl carbamates 5 (Z‐protected secondary amines) with lithium diisopropylamide (LDA), diphenyl phosphorochloridate (DPPC1), and NaN3 yielded the corresponding ã‐azidobenzeneacetamides 6 in 45–50% yield (Schemes 2 and 3). In the case of Z‐protected diisopropylamine 5b, the phosphate 7 was isolated as a minor product. A reaction mechanism for this unexpected transformation is proposed in Scheme 4, the key step being the ring closure of a benzylic anion to give an oxirane intermediate B. In cursory experiments, it was demonstrated that ã‐azidobenzeneacetamides 6 can be used as 2‐phenylglycine synthons in the formation of dipeptides by using a phosphine‐mediated coupling (Scheme 5).
Synthesis and Evaluation of α‐Methylidene‐γ‐butyrolactone bearing flavone and xanthone moieties
Authors: Tzeng Cherngy‐Chyi , Zhao Yue‐Ling , Chen Yeh‐Long , Liou Shorong‐Shii , Wang Tai‐Chi , Chang Ya‐Ling , Teng Che‐Ming
Published: December 2004

In a search for inhibitors of platelet aggregation, a number of α‐methylidene‐γ‐butyrolactones 5 and 6 bearing flavone or xanthone moieties, respectively, were synthesized and evaluated for their antiplatelet activity against thrombin(Thr)‐, arachidonic‐acid(AA)‐, collagen(Col)−, and platelet‐activating‐factor(PAF)‐induced aggregation in washed rabbit platelets. These compounds were synthesized from 7‐hydroxyflavone (1) or 3‐hydroxyxanthone (2) via O‐alkylation (→ 3 and 4, resp.) and Reformatsky‐type condensation (Scheme). Most of the flavone‐containing α‐methylidene‐γ‐butyrolactones 5a–d showed potent antiplatelet effects on AA‐ and Col‐induced aggregation, while xanthone derivatives 6c–e were found to have the same pharmacological profile than aspirin in which only AA‐induced aggregation was inhibited (Table 1). However, 6c–e were approximately three to ten times more potent than aspirin (Table 2). For the vasorelaxing effects, 5a was the only compound which exhibited significant inhibitory activity on the high‐K+ medium, Ca2+‐induced vasoconstriction (Table3). Both 5a and 6a, with an aliphatic Me substituent at C(γ) of the lactone, were active against norepinephrine‐induced phasic and tonic constrictions while their γ‐aryl‐substituted counterparts 5b–f and 6b–f were inactive.
New Cyclophanes as Initiator Cores for the Construction of Dendritic Receptors: Host‐guest complexation in aqueous solutions and structures of solid‐state inclusion compounds
Authors: Wallimann Peter , Mattei Sebastiano , Seiler Paul , Diederich François
Published: December 2004

Cyclophanes 3 and 4 were prepared as initiator cores for the construction of dendrophanes (dendritic cydophanes) 1 and 2, respectively, which mimic recognition sites buried in globular proteins. The tetra‐oxy[6.1.6.1]paracyclophane 3 was prepared by a short three‐step route (Scheme 1) and possesses a cavity binding site shaped by two diphenylmethane units suitable for the inclusion of flat aromatic substrates such as benzene and naphthalene derivatives as was shown by 1H‐NMR binding titrations in basic D2O phosphate buffer (Table 1). The larger cyclophane 4, shaped by two wider naphthyl(phenyl)methane spacers, was prepared in a longer, ten‐step synthesis (Scheme 2) which included as a key intermediate the tetrabromocyclophane 5. 1H‐NMR Binding studies in basic borate buffer in D2O/CD3OD demonstrated that 4 is an efficient steroid receptor. In a series of steroids (Table 1), complexation strength decreased with increasing substrate polarity and increasing number of polar substituents; in addition, electrostatic repulsion between carboxylate residues of host and guest also affected the binding affinity strongly. The conformationally flexible tetrabromocyclophane 5 displayed a pronounced tendency to form solid‐state inclusion compounds of defined stoichiometry, which were analyzed by X‐ray crystallography (Fig. 2). 1,2‐Dichloroethane formed a cavity inclusion complex 5a with 1:1 stoichiometry, while in the 1:3 inclusion compound 5b with benzene, one guest is fully buried in the macrocyclic cavity and two others are positioned in channels between the Cyclophanes in the crystal lattice. In the 1:2 inclusion compound 5c, two toluene molecules penetrate with their aromatic rings the macrocyclic cavity from opposite sides in an antiparallel fashion. On the other hand, p‐xylene (= 1,4‐dimethylbenzene) in the 1:1 compound 5d is sandwiched between the cyclophane molecules with its two Me groups penetrating the cavities of the two macrocycles. In the 1:2 inclusion compound 5e with tetralin (= 1,2,3,4‐tetrahydronaphthalene), both host and guest are statically disordered. The shape of the macrocycle in 5a–e depends strongly on the nature of the guest (Fig. 4). Characteristic for these compounds is the pronounced tendency of 5 to undergo regular stacking and to form channels for guest inclusion; these channels can infinitely extend across the macrocyclic cavities (Fig. 6) or in the crystal lattice between neighboring cyclophane stacks (Fig. 5). Also, the crystal lattice of 5c displays a remarkable zig‐zag pattern of short Br…︁O contacts between neighboring macrocycles (Fig. 7).
New Anellation Methods for the Synthesis of 8H‐Heptaleno[1,10‐bc]furans,‐pyrroles, and ‐thiophenes
Authors: Hörndler Cornelia , Hansen Hans‐Jürgen
Published: December 2004

Heptaleno[1,2‐c]furan‐6‐carbaldehydes such as 8 or their thiocarbaldehyde or iminomethyl derivatives easily undergo thermal cyclization, followed by a [1,5]‐H shift, to give the corresponding heptalenodifurans, thienoheptalenofurans, as well as furoheptalenopyrroles (cf. Schemes 2 and 3). Generation of the 6‐acetyl derivative of 8 from the corresponding secondary alcohol 15 with 1‐hydroxy‐1,2‐benziodoxol‐3(1H)‐one 1‐oxide (IBX) at 0° (cf. Scheme 4) leads directly to the formation of the cyclization product 16 which, upon standing at room temperature, undergoes the [1,5]‐sigmatropic H‐shift to the final difuran 17. 1‐Formylheptalene‐4,5‐dicarboxylates such as 9 can also be cyclized thermally, followed by the [1,5]‐H shift, to the corresponding 8H‐heptaleno[1,10‐bc]furan‐5,6‐dicarboxylate 11. On thiation with Lawesson′s reagent, 9 yields directly the corresponding heptalenothiophene 13 (cf. Scheme 3).
Distamycin‐NA: A DNA Analog with an Aromatic Heterocyclic Polyamide Backbone. Part 1. Synthesis and structural analysis of monomers and dimers containing the nucleobase uracil
Authors: Sauter Guido , Stulz Eugen , Leumann Christian
Published: December 2004

The synthesis of the monomeric building block 13 and its constitutional isomer 12 of a new type of DNA analog, distamycin‐NA, is presented (Schemes 1 and 2). This building block consists of a uracil base attached to a thiophene core unit via a biaryl‐like axis. Next to the biaryl‐like axis on the thiophene chromophore, a carboxy and an amino substituent are located allowing for oligomerization via peptide coupling. The proof of constitution and the conformational preferences about the biaryl‐like axis were established by means of X‐ray analyses of the corresponding nitro derivatives 10 and 11. Thus, the uracil bases are propeller‐twisted relative to the thiophene core, and bidentate H‐bonds occur between two uracil bases in the crystals. The two amino‐acid building blocks 12 and 13 were coupled to give the dimers 15 and 16 using dicyclohexylcarbodiimide (DCC) in THF/LiCl and DMF, respectively. While the dimer 15 showed no atropisomerism on the NMR time scale at room temperature, its isomer 16 occurred as distinct diastereoisomers due to the hindered rotation around its biaryl‐like axis. Variable‐temperature 1H‐NMR experiments allowed to determine a rotational barrier of 19 ± 1 kcal/mol in 16. The experimental data were complemented by AM1 calculations.
[2+3] Cycloadditions of Azomethine Ylides with 1,3‐Thiazole‐5(4H)‐thiones
Authors: Mlostoń Grzegorz , Linden Anthony , Heimgartner Heinz
Published: December 2004

Thermal reactions of 1,2,3‐trisubstituted aziridines 1 with 1,3‐thiazole‐5(4H)‐thiones 6 in toluene yielded, in general, a mixture of two diastereoisomeric spirocyclic [2+3] cycloadducts. The formation of these products can be explained by a stereoselective electrocyclic ring opening of 1 to give an azomethine ylide 2 as the reactive intermediate, which is trapped immediately by 6 via a stereoselective 1,3‐dipolar cycloaddition. Only in the case of trans‐dimethyl 1‐(4‐methoxyphenyl)aziridine‐2,3‐dicarboxylate (trans‐1a), four diastereoisomeric cycloadducts were formed (Scheme 4). This result is rationalized by an isomerization of the intermediate azomethine ylide cis‐2a to trans ‐2a.
An Advantageous Synthesis of 1D‐ and 1L‐1,2,3,5/4‐Cyclohexanepentol
Authors: Biamonte Marco A. , Vasella Andrea
Published: December 2004

The title compounds D‐10 and L‐10 were prepared from 1 in eight steps and in a combined overall yield of 41–49%.
Synthesis of Bridgehead‐Functionalized Bicyclo[3.2.1]octanes via intramolecular titanium‐ and tributylstannane‐induced pinacol coupling
Authors: Egger Anita , Hunziker Jürg , Leumann Christian , Rihs Grethy
Published: December 2004

The synthesis of the enantiomerically pure, bridgehead‐functionalized bicyclo[3.2.1]octanes 11 and 16, containing a conformationally fixed trihydroxypropyl (aminodihydroxypropyl) unit, as well as the X‐ray structure of 11 are described. These compounds are of interest as sugar surrogates in the preparation of DNA analogs. Compounds 11 and 16 became available in 10 and 12 steps, respectively, and in an overall yield of 11 and 4% from D‐arabinose via a highly stereoselective pinacol coupling as the key step.
Prenylated Flavanones from Monotes engleri: On‐line Structure Elucidation by LC/UV/NMR
Authors: Garo Eliane , Wolfender Jean‐Luc , Hostettmann Kurt , Hiller Wolf , Antus SÁNdor , Mavi Steven
Published: December 2004

The CH2Cl2 extract of Monotes engleri Gilg. (Dipterocarpaceae) showed antifungal activity against the yeast Candida albicans in our bioautographic TLC assays. After a first fractionation of the crude extract, the bioactivity was located in one of the fractions. To perform an efficient targeted isolation of the active compounds, LC/UV/MS and LC/UV/NMR analyses of the crude extract and the active fraction were performed. LC/UV/, LC/MS, and LC/NMR data (1D and 2D) allowed the identification of 1 as (2S)‐2,3‐dihydro‐5,7‐dihydroxy–{3‐hydroxy‐4‐[(3‐methylbut‐2‐enyl) oxy]phenyl}‐4H‐1‐benzopyran‐4‐one, a new prenylated flavanone, named monoteson A. Subsequent isolation of 1 has permitted the determination of its absolute configuration on the basis of CD measurements. Theree other prenylated flavanoes 2–4 were isolated from the same extract. Compound 3 was identified as 2‐ (3, 5‐dihydroxyphenyl) ‐2,3‐dihydro‐5, 7‐dihydroxy‐6, 8‐bis (3‐methylbut‐2‐enyl)‐4 H‐1‐benzopyran‐4‐one, another new natural product, named monotesone B. The structures of 2 and 4 were established as selinone and lonchocarpol A, respectively. The antifungal activity against Candida albicans was determined for all compounds.
Synthesis of Oligonucleotides Containing 2′‐Deoxyisoguanosine and 2′‐Deoxy‐5‐methylisocytidine Using Phosphoramidite Chemistry
Authors: Jurczyk Simona C. , Kodra Janos T. , Rozzell J. David , Benner Steven A. , Battersby Thomas R.
Published: December 2004

The synthesis of oligonucleotides containing 2′‐deoxy‐5‐methylisocytidine and 2′‐deoxyisoguanosine using phosphoramidite chemistry in solid‐phase oligonucleotide synthesis is described. Supporting previous observations, the N,N‐diisobutylformamidine moiety was found to be a far superior protecting group than N‐benzoyl for 2′‐deoxy‐5‐methylisocytidine. 2′‐Deoxy‐N2‐[(diisobutylamino)methylidene]‐5′‐(4,4′‐dimethoxytityl)‐5‐methylisocytidine 3′‐(2‐cyanoethyl diisopropylphosphoramidite) (1c) incorporated multiple consecutive residues during a standard automated synthesis protocol with a coupling efficiency > 99% according to dimethoxytrityl release. Extending coupling times of the standard protocol to ≥ 600s using 2′‐deoxy‐N6‐[(diisobutylamino)methylidene]‐5′‐O‐(dimethoxytrityl)‐O2‐(diphenylcarbamoyl)isoguanosine, 3′‐(2‐cyanoethyl diisopropylphosphoramidite) (7e) led to successful incorporation of multiple consecutive 2′‐deoxyisoguanosine bases with a coupling efficiency > 97% according to dimethoxytrityl release.
Antitumor Agents. Part 184. Syntheses and antitubulin activity of compounds derived from reaction of thiocolchicone with amines: Lactams, alcohols, and ester analogs of allothiocolchicinoids
Authors: Shi Qian , Chen Ke , Brossi Arnold , Verdier‐Pinard Pascal , Hamel Ernest , McPhail Andrew T. , Lee Kuo‐Hsiung
Published: December 2004

7‐O‐Substituted analogs of deaminodeoxycolchinol thiomethyl ether were synthesized and evaluated for their inhibitory effects on tubulin polymerization in vitro. Ketone 9, a key compound in this study, was derived from thiocolchicone 6 by reaction with aniline. Reaction of compound 6 with MeNH2 or BuNH2 gave tetracyclic lactams 7 and 8, respectively. Optically active alcohols 11a and 11b were obtained from racemic 11 by chemical resolution including a separation of the comphanate diastereoisomers 12a and 12b, followed by basic hydrolysis. The (aR,7R)‐configuration of 12b was verified by X‐ray crystallographic analysis. Almost all racemic and optically active 7‐O‐acyl or 7‐O‐aroyl compounds had strong inhibitory effects on the tubulin polymerization reaction, with IC50 values from 1.7 to 5.1 μM. A few agents, such as the lactams 7 and 8, the camphanates 12a and 12b, the cyclohexanecarboxylates 19a and 19b, and, most notably, the (7S)‐benzoate 15a, had negligible effects on polymerization, yielding IC50 values greater than 40μM. Ketone 9 showed strong inhibition of tubulin polymerization comparable to that of thiocolchicone (6). Optically active alcohol 11a and acyl esters 13a and 14a with a (7S)‐configuration were more active than the (7R)‐esters 13b and 14b. However, the esters 15a–17a with a (7S)‐configuration were less active than the (7R)‐isomers 15b–17b, in which the (7R)‐benzoate 15b was at least 15‐fold more inhibitory than the (7S)‐isomer 15a. For the most part, the agents causing strongest inhibition of polymerization also caused the greatest inhibition of [3H]colchicine binding. NMR and optical rotatory data indicate that, in polar solvents, the equilibrium in esters with a 7‐O‐aroyl substituent, i.e., 15a,b, 16a,b, and 17a,b, is reversed from (aS) to (aR) or from (aR) to (aS), as compared to nonpolar solvents.
Synthesis of 1‐(1H‐Imidazol‐2‐yl)ethane‐1,2‐diol Derivatives: A novel class of protein kinase C inhibitors
Authors: Röhrle Andreas N. , Schmidhammer Helmut
Published: December 2004

Compounds 6–13 were prepared starting from 1‐(triphenlymethyl)‐protected 1H‐imidazoles 14 and 15 in several steps. Lithiation with BuLi in THF followed by reaction with (triphenylmethoxy)acetaldehyde (16) afforded 17 and 18, respectively. O‐Methylation of 17 and 18 gave diethers 19 and 20, respectively. The N‐ and O‐trityl protecting groups of 17–20 were cleaved by acid treatment to give deprotected compounds 21–24. Acylation with equimolar amounts (for mono‐ or di‐O‐acylation) of the corresponding acyl chlorides yielded 1H‐imidazoles 6–13. Compounds 7, 8, 10, and 11 exhibited moderate protein kinase C inhibition.
Synthesis of Vitamin‐B12 Derivatives with Peripheral Tris(oxyethylene) Chains
Authors: Pfammatter Michael J. , Darbre Tamis , Keese Reinhart
Published: December 2004

The new derivatives 7a–c, of vitamin B12, with a peripheral tris(oxyethylene) chain linked to the corrin ring by an amide or ester group, are prepared, and their ligand‐exchange reactions are investigated. Upon reduction of the aqua‐cyano complexes 8a–c with NaBH4, cleavage of the ‘outer’ ester and amide group is observed.
Synthesis of Vitamin‐B12 Derivatives with an Electropolymerizable Side Chain
Authors: Otten Thomas , Darbre Tamis , Cosnier Serge , Abrantes Luisa , Correia Jorge , Keese Reinhart
Published: December 2004

Three new derivatives of vitamin B12 with a pyrrole head group attached to the corrin ring have been prepared. Ligand‐exchange reactions and reduction provided reactive CoIII and CoII complexes. Their electro‐chemical properties and their potential for fixation at the surface of electrodes by electropolymerization were studied.
Glycosylidene Carbenes. Part 27. Glucosidation of titanium dioxide with 1‐aziglucoses: Preparation and characterization of modified titanium‐dioxide surfaces
Authors: Weber Martin , Vasella Andrea , Textor Marcus , Spencer Nicholas D.
Published: December 2004

Titanium‐dioxide surfaces have been glycosylated with the benzyl‐, 4‐fluorobenzyl‐, and acetyl‐protected diazirines 1–3. The modified TiO2 surfaces were characterized by contact‐angle measurement, X‐ray photoelectron spectroscopy (XPES), and time‐of‐flight secondary‐ion mass spectrometry (ToF‐SIMS). The main by‐products of the glucosidation (mostly azines and trehaloses) were identified. Their physisorption slightly reduces the efficiency of the glucosidation by 1 mM solution of 1 or 2 in CH2Cl2, but this influence is neutralized by repeating the glucosidation, or by using a 100 mM solution of the diazirines. The immobilized, acetylated glucosyl moieties were deacetylated in situ. Calculations based on the XPES peaks of Ti 2p and F 1s for the TiO2 surface modified with 2 indicated 1.5 ± 0.9 immobilized glucosyl moieties per nm2.
A Novel NO2/OH Exchange in α‐Nitro Ketones: A mechanistic investigation
Authors: Yurdakul Ayçil , Gurtner Christian , Jung Elena‐Silvia , Lorenzi‐Riatsch Annalaura , Linden Anthony , Guggisberg Armin , Bienz Stefan , Hesse Manfred
Published: December 2004

The reaction of α‐nitro ketones to the corresponding α‐hydroxy ketones under basic aqueous conditions, a novel transformation, was studied. The investigation revealed that the reaction is only possible with α‐nitro ketones that are CH‐acidic in the α′‐position and readily deprotonated under the reaction conditions. The NO2/OH exchange was established to proceed with retention of configuration at the stereogenic center, and labeling experiments have shown that the OH O‐atom originates, to a great extent, from the solvent. In particular, the stereochemical course of the reaction and the incorporation of external nucleophiles led us to propose a mechanism that involves neighboring‐group participation. The product formation is explained by a double SN2 reaction, which proceeds via a Favorskii‐like cyclopropanone intermediate.
Instrumentation for preparation and placement of subcutaneous implants
Authors: Kallus T. , Eklund G.
Published: December 2004

An instrument has been designed for the preparation and placement of subcutaneous implants in small laboratory animals. The usefulness and applications of the instrument have been assessed, based on experiences from 260 implants inserted subcutaneously on guinea pigs with the aid of the described instrument.
Mechanical properties of hydrophilic copolymers of 2‐hydroxyethyl methacrylate with ethyl acrylate,n‐butyl acrylate, and dodecyl methacrylate
Authors: Kolařík Jan , Migliaresi Claudio
Published: December 2004

Copolymers were prepared of 2‐hydroxyethyl methacrylate, which is strongly hydrophilic, with hydrophobic comonomers having a low glass transition temperature, i.e., ethyl acrylate, n‐butyl acrylate, and dodecyl methacrylate. The glass transition temperature, Tα (1 Hz), of polymers in the dry state (xerogels) was determined by means of dynamic mechanical measurements. The dependence of Tα on composition in all the three series of copolymers was described in terms of a one‐parameter equation. The equilibrium swelling of copolymers in water decreases more steeply than the weight fraction of 2‐hydroxyethyl methacrylate. When swollen in water to equilibrium, all copolymers with ethyl acrylate or n‐butyl acrylate are in the rubber‐like state; their tensile modulus E assumes values in the range 0.17–0.50 MPa. While poly(2‐hydroxyethyl methacrylate) has the modulus E = 0.39 MPa, the tensile strength σu = 0.32 MPa, and the strain‐at‐break ϵu = 1.81, for the weight fraction of the comonomer in the range 0.36 ⩽ w2 ≤ 0.56 it is possible to achieve σu and ≤ u lying in the respective ranges 0.7–0.9 MPa and 5–7. Copolymers with the dodecyl methacrylate content w2 < 0.2 or w2 > 0.8 are rubberlike, and at 0.30 ≤ w2 ≤ 0.62 they become leathery; the latter have the modulus E and strength σu within the ranges 12–32 and 3–4 MPa, respectively. The stress–strain curves of these copolymers evidence yielding and orientation hardening which have been tentatively explained by the nonhomogeneous composition and structure of the copolymers.
Preparation and strength of poly(ethylene terephthalate) fiber bundles for model synthetic tendons
Authors: Kolařík Jan , Vaníček Jiří , Migliaresi Claudio
Published: December 2004

Poly(ethylene terephthalate) fibers suited for model synthetic tendons were prepared on a pilot‐plant scale by additional drawing (postdrawing) of commercial textile fibers texturized by false twist. The modified fibers have a tensile modulus of 7–9 GPa, a one‐minute creep modulus of 5–6 GPa, tensile strength 0.55–0.63 GPa, and strain at break of 16–19%. It is essential for their application in synthetic tendons that plastic deformation was reduced to about 0.5%, which could be completely eliminated by subsequent mechanical conditioning of fibers. Since the strength of model tendons consisting of 20 vol % of fibers and of a hydrogel matrix is primarily determined by the strength of the fibers, some aspects of the theory of strength of fiber bundles are briefly recapitulated. The prediction is compared with earlier experimental results obtained for the synthetic tendons. Such an approach, taking into account the fiberstrength distribution in the bundle, predicts a strength of model tendons lower by 20–40% than does the rule of mixtures.
Ultrathin coating of plasma polymer of methane applied on the surface of silicone contact lenses
Authors: Ho Chung‐Peng , Yasuda H.
Published: December 2004

Silicone rubber has great advantages as a contact lens material because of its very high oxygen permeability, softness, and excellent mechanical strength and durability. Practical application is hampered by inherent characteristics of elastomers, i.e., high tackiness and highly hydrophobic surface properties. By applying a thin layer, e.g., 5 nm, of plasma polymer of methane, it was found that all these disadvantages can be eliminated without sacrificing high oxygen permeation rate, e.g., less than 15% reduction. Optimization of operational parameters to achieve this task has been investigated. It was also found that under optimum conditions the coating withstood severe and repeated flexing of the contact lens.
The effect of γ‐irradiation on collagen molecules, isolated α‐chains, and crosslinked native fibers
Authors: Cheung David T. , Perelman Natalya , Tong Deborah , Nimni Marcel E.
Published: December 2004

This study shows how collagen molecules are readily damaged by γ‐radiation at dosages commonly used for sterilizing biomedical products. At 1 Mrad, while the reported effectiveness of the radiation at such a low dosage to completely sterilize a material is questionable, less damage was caused to the collagen peptide backbone. Above such dosage, however, significant damage was clearly demonstrated with collagen alone and collagen in a chemically crosslinked tissue matrix. The enzyme digestion study showed that the material exposed to a very high dosage of radiation resisted degradation by pronase. However, molecular weight analysis showed a significant number of peptide bonds being cleaved by the radiation which could cause considerable changes in the long‐term characteristics of the material. Therefore, tissues exposed to high dosages of γ‐radiation should be tested for long term functional changees. We want to caution against the usag of the enzyme degradation assay as a universal test for all bioprosthetic derived from biological tissues.
Mechanism and strength of bonding between two bioactive ceramics in vivo
Authors: Fujita Yoshitsugu , Yamamuro Takao , Nakamura Takashi , Kitsugi Toshiaki , Kotani Seiya , Ohtsuki Chikara , Kokubo Tadashi
Published: December 2004

A study was conducted to examine the mechanism and strength of bonding between two bioactive ceramic plates in vivo. Rectangular plates (15 mm × 10 mm × 2 mm) of Bioglass®, apatitewollastonite‐containing glass ceramic (designated A‐W · GC), and two types of hydroxyapatite sintered a t 900° and 1200° (designated HA900 and HA1200) were prepared. Two plates of the same materials tied together with silk thread were implanted subcutaneously into rats. The force required to detach the mutually bonded bioactive ceramic plates was measured 4, 8,12, and 24 weeks after implantation. The interface between the two bonded plates was examined by SEMEPMA and thin‐film x‐ray diffraction analysis. At 24 weeks after implantation, 1991 the mutual bonding of Bioglassm and A‐W · GC was stronger than that of the two HA types. SEM‐EPMA and thin‐film x‐ray diffraction analysis of the bonded area of Bioglassm and A‐W · GC plates showed bonding zones with a patiteinthe margins, and a bonding zone with calcite in the center. The greater strength of bonding of Bioglassm and A‐W · GC plates compared with the two types of HA plate 24 weeks after implantation is explained by the wider bonding zone provided by the calcite layer formed in the center of the plates, which is considered to have been perfused with P04‐poor body fluids resulting from PO4 consumption for apatite formation in the margins. © 1992 John Wiley & Sons, Inc.
Polypropylene small‐diameter vascular grafts
Authors: Greisler Howard P. , Tattersall Charles W. , Henderson Scott C. , Cabusao Emma A. , Garfield Jacqueline D. , Kim Dae Un
Published: December 2004

Polypropylene's physical properties (e.g., high tensile strength) and relatively inert behavior suggest that fabrication into an arterial substitute may result in an efficacious prosthesis. Grafts were woven from polypropylene yarn into conduits 4 mm I.D. × 50 mm in length. Control grafts were Dacron and ePTFE. Baseline platelet aggregometry on all dogs was performed with 10−5M ADP. Aspirin and dipyridamole were given for three days preoperatively and maintained for 2 weeks after surgery. Fifty‐four grafts were placed into the aortoiliac position, two different graft materials per dog. The grafts were explanted at intervals of 2 weeks through 16 months; photographed for thrombusfree surface area determinations; and preserved for light, scanning, and transmission electron microscopy. Late (4–16 month) patency was 81% (13/16) for polypropylene, 69% (9/13) for Dacron, and 20% (1/5) for ePTFE. These data include one year patencies of 11/12 (92%) for polypropylene and 7/10 (70%) for Dacron. Late patency for polypropylene grafts was better than for PTFE (p < 0.05). Platelet aggregation status did not predict graft patency. Light microscopy of 2‐week polypropylene explants showed inner capsules composed of myofibroblasts and macrophages, with patchy areas of endothelial cells lining the lumen. By 1 month, a confluent endothelialized surface was seen in all polypropylene explants. Progressive thickening of inner capsules with myofibroblasts and collagen continued through 4 months, reaching a mean thickness of 142 ± 50 μm compared to 150 ± 30 μm for Dacron. These findings suggest potential clinical efficacy for polypropylene as an arterial substitute. © 1992 John Wiley & Sons, Inc.
Porous polyurethane vascular prostheses with variable compliances
Authors: Liu Shu Qin , Kodama Makoto
Published: December 2004

A new technique for the preparation of porous vascular prostheses was investigated. Polyurethane solution (5 to 15 wt%) was injected into a mold. After freezing at low temperature (0°C–196°C), solvents were dissolved out with water at 0°C to form porous tubes. The average pore size (several microns to 70 μm), pore occupation (10% to 51%), and compliance (3% to 35%) were easily changed by changing polyurethane concentration, freezing temperature, and freezing methods. Compliances could be decreased gradually by heat treatment. This technique can give a proper pore size (30‐60 μm) for tissue ingrowth, and a suitable compliance for matching with arteries and veins. This method might give a desired compliant graft for artificial implantation with the presently valid medical polymers. © 1992 John Wiley & Sons, Inc.
Biocompatibility and tissue regenerating capacity of crosslinked dermal sheep collagen
Authors: van Wachem P. B. , van Luyn M. J. A. , Damink L. H. H. Olde , Dijkstra P. J. , Feijen J. , Nieuwenhuis P.
Published: December 2004

The biocompatibility and tissue regenerating capacity of four crosslinked dermal sheep collagens (DSC) was studied. In vitro, the four DSC versions were found to be noncytotoxic or very low in cytoxicity. After subcutaneous implantation in rats, hexamethylenediisocyanatecrcrosslinked DSC (HDSC) seldom induced an increased infiltration of neutrophils or macrophages, as compared with normal wound healing; whereas new formation of collagen was observed. DSC crosslinked with glutaraldehyde (GDSC) followed by reaction with NaBH4 shortly after implantation showed an increased infiltration of neutrophils with a deviant morphology. Furthermore, a high incidence of calcification was observed, which may explain the minor ingrowth of giant cells and fibroblasts, and the poor formation of new rat collagen. Acyl azide‐crosslinked DSC (AaDSC) first induced an increased infiltration of macrophages, and then of giant cells, both with high lipid formation. AaDSC degraded at least twice as slowly as HDSC and GDSC, finally leaving a matrix of newly formed rat collagen. Samples crosslinked with 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide hydrochloride and N‐hydroxysuccinimide (ENDSC) induced the same mild cellular reaction as HDSC; whereas, similar to AaDSC, the degradation rate was slow and an optimal rat collagen matrix was formed. Of the crosslinked DSC samples, ENDSC seems most promising for tissue regeneration. © 1994 John Wiley & Sons, Inc.
Mathematical modeling of water permeability of surgical fabrics for vascular use
Authors: Chu C. C. , Rawlinson Jeremy
Published: December 2004

The purpose of this study was to derive new mathematic formulae that could be used reliably to predict water permeability of surgical fabrics before they are made and tested for water permeability. Such a theoretical prediction of water permeability, Qprd, of surgical fabrics is needed for not only timely characterization but also for assisting in more efficient future design and development of better surgical fabrics. Two mathematic formulae, Qw and Qk, were derived from the Buckingham Pi Theorem, in which relevant fiber and fabric parameters were placed into dimensionless π groups and computed for 25 commercial and experimental vascular fabrics. Linear regression analysis of the relationship between these π groups with water permeability on the woven and knitted grafts yielded coefficients for the corresponding π groups that were required for constructing appropriate mathematic formulae to predict water permeability of vascular fabrics. When proper sources of the experimentally determined water permeability, Qexp, were chosen for comparison, we found that 86% of woven fabrics (6 of 7) and 77% of knitted fabrics (14 of 18) had their Qprd within 10% of their Qexp. This high percentage of close matching (within 10%) between Qprd and Qexp should be considered satisfactory because the experimental error for obtaining Qexp is generally higher than 10%. The difference between Qprd and Qexp ranged from as small as 0.27% to as high as 74.2%, depending on the type of fabrics and source of Qexp. It appeared that the formulae worked well with fabrics of simpler structure such as those experimental woven vascular fabrics that showed 100% close match between Qprd and Qexp. Nonlinear relationship among the parameters and additional new parameters are required to fine‐tune for existing mathematic formulae to improve their accuracy of predicting water permeability for more complex fabric structures such as knitted fabrics. A computer program had been written that uses these theoretical formulae for predicting water permeability of vascular fabrics. Users could simply input five major fabric and fiber parameters of a surgical fabric and the computer would calculate its water permeability instantaneously. © 1994 John Wiley & Sons, Inc.
AM‐1 molecular orbital calculations of silica–alanine–nitrogen interaction
Authors: West Jon K. , Hench Larry L.
Published: December 2004

Chemical binding of proteins with bioactive surfaces is modeled using a semi‐empirical molecular orbital theory (AM‐1). The model calculates the optimized molecular structures of an amino acid (L‐alanine) interacting with a cyclotetrasiloxane silica cluster (a four‐membered hydrated silica ring). The calculated heats of formation for various orientations of alanine show +5 kcal/mol difference for binding via the −NH2 group following a condensation reaction with a pentacoordinate Si intermediate. Hydrogen bonding of the alanine via the COOH group occurs with +13 to +15 kcal/mole differences in heats of formation and imposes a highly specific geometric orientation on the amino acid. Association of a diatomic N2 molecule with the silica cluster before interaction with alanine inhibits formation of an intermolecular bond, as is observed experimentally in studies of silicaalanine epitaxy. © 1994 John Wiley & Sons, Inc.
On the possibility of improving the integral evaluation section in ab initio Hartree–Fock calculations on large molecules
Authors: Karlström Gunnar
Published: December 2004

A modified integral package for evaluation of two‐electron integrals over Gaussian basis functions is described. Modifications are implemented in the MOLECULE program system and are especially suited for the study of large molecules and molecular complexes.
Molecular potential, cation binding, and hydration properties of the carboxylate anion. Ab initio studies with an extended polarized basis set
Authors: Berthod H. , Pullman A.
Published: December 2004

The carboxylat anion, involved in the structure of numerous compounds of biological interest, participates in a number of intermolecular interactions involving water, cations, and other cellular constituents. A set of ab initio SCF computations have been carried out with an extended polarized basis set on HCOO–, its molecular electrostatic potential, and its interaction with Li+, Na+, K+, and H2O. The results are compared with those of a minimal good quality basis set. An evaluation of the basis set superposition error is made in the two basis as well as that of the contribution of the dispersion energy to the hydration. The analogies and differences in the nucleophilic character of the formate and the phosphate groups are discussed.
Ab initioMO calculations for the oxides, oxyacids, and oxyanions of S(IV) and S(VI)
Authors: Baird N. Colin , Taylor Kathleen F.
Published: December 2004

Ab initio molecular orbital (MO) calculations for two series of sulfur–oxygen compounds are reported: the S(IV) system of SO2, H2SO3, HSO, and SO, and the S(VI) system of SO3, H2SO4, HSO, and SO. Geometries about the sulfur atoms were optimized using the STO‐3G* basis set; energies at these geometries were computed by the STO−3G and 44‐31G basis sets both with and without five Gaussian d orbitals on S. The sulfur–oxygen bond lengths and the angles about the central atoms agree fairly well with experiment. The stabilization energy associated with the addition of the d orbitals was found to be a constant amount per bond (ca. 54 and 28 kcal mole−1 in the minimal and extended bases, respectively) in hypervalent compounds. The isomer HSO was predicted to be more stable than SO2(OH)−, but the reverse was true for HSO2(OH) compared to SO(OH)2. The deprotonation energies for the acids and the hydration energies for the oxides also were computed and discussed with reference to experimental data.
A computerized structure–activity correlation program for relating bacterial mutagenesis activity to chemical structure
Authors: Tinker John F.
Published: December 2004

The program employs a substructure recognition process based on the procedure of Hodes et al. Structural information is accepted from connection tables (Chemical Abstracts Registry II or III) or MCC‐TSS ciphers. Typically in this program the basic substructure unit (ganglion) is an atom triplet. Data for correlation are provided by over 1000 results from mutagenesis tests run in the Ames Salmonella typhimurium test, obtained from the literature. Activity may be calibrated in two to eight levels. Statistical weights for ganglia are calculated from the program of Hodes et al. The results of the program reveal the dependence of biological data on chemical structure, the self‐consistency of the data, and the level of activity to be expected of an unknown structure, with an estimate of confidence. The value of the program was shown with 34 unknowns simultaneously tested for activity in the Ames test and submitted to structure–activity analysis. Of these 74% were correctly predicted for the level of activity, and 88% to within one level of activity. It is expected that experience with the program in a trial application setting will enable us to restrict the number of activity calibrations to two. This will allow a simple selection of an inactive or active prediction to be made.
Ab initio study of 4‐monosubstituted pyrimidines in ground and excited n → π* states
Authors: Del Bene Janet E.
Published: December 2004

Ab initio SCF and SCF‐CI calculations have been performed to investigate substituent effects on ground‐ and excited‐state properties of 4‐R‐pyrimidines, and to compare these with substituent effects in 2‐ and 4‐R‐pyridines, with R including the π donating and σ withdrawing groups CH3, NH2, OH, F, and C2H3 and the σ and π electron‐withdrawing groups CHO and CN. Substitution leads to significant changes in the internal angles of the pyrimidine ring, which are independent of the nature of the substituent. The geometry of the pyrimidine ring is more sensitive to substitution in the 4 position than the pyridine ring geometry is to substitution in either the 2 or the 4 position. The isodesmic reaction energies for substituent transfer from the 4 position of pyrimidine to the 2 or 4 position of pyridine indicate that all R groups except CN have a relative stabilizing effect in pyrimidine. The presence of a π donating group leads to an increase in the n→π* transition energy of 4‐R‐pyrimidines, while the π withdrawing group CN leads to a decrease in the transition energy relative to pyrimidine. Orbital energy differences and virtual excitation energies tend to correlate with n→π* transition energies of 4‐R‐pyrimidines with saturated R groups, but such correlations are masked by π conjugation, n orbital interaction, and configurational mixing when the unsaturated groups C2H3, CHO, and CN are present. The electronic effects of a π donating group are stronger when the group is bonded to pyrimidine than to pyridine, but those of a π withdrawing group are weaker when the group is bonded to pyrimidine.
A systematic preparation of new contracted Gaussian‐ type orbital sets. VII. MINI‐3, MINI‐4, MIDI‐3, and MIDI‐4 sets for transition metal atoms
Authors: Tatewaki Hiroshi , Sakai Yoshiko , Huzinaga Sigeru
Published: December 2004

Two minimal contracted Gaussian‐type orbital (CGTO) sets are developed for the transition metal atoms. The expansion terms for the first set, MINI‐3, are 4, 3, 3, and 3 for s‐type CGTOs and others are all three. The abbreviation would be (4333/33/3) where the slash divides symmetry. The expansion terms for the other set, MINI‐4, is (4333/43/4). The split‐type basis sets, MIDI‐3 and MIDI‐4, are derived directly from MINI‐3 and MINI‐4, MINI‐3 and MIDI‐3 provide the outer‐shell orbital energies which are far better than those by single‐zeta (SZ) STOs. MINI‐4 and MIDI‐4 provide the outer‐shell orbital energies which are almost as good as those by double‐zeta (DZ) STOs. The total energies given by the present sets are better than those of SZ except for MINI‐3 for Sc and Ti: the energies by MINI‐4 and MIDI‐4 are only 0.8–1.7 a.u. higher than DZ. The basis sets were tested on the Cu2 molecule, where a large basis set was also used.
Force field and self‐consistent field calculations on a trans coplanar disulfide: Bis(2‐pyrimidyl)disulfide
Authors: Boyd Donald B. , Lipkowitz Kenny B.
Published: December 2004

Two diaryl disulfides, bis(2‐pyrimidyl)disulfide and diphenyldisulfide, have been characterized by molecular mechanics and molecular orbital calculations. When complexed with Cu(I), the pyrimidyl disulfide is known to have a unique 180° CSSC dihedral angle and to be coplanar. Our analysis of the conformational energies of the rotamers suggests that copper–ring interactions are primarily responsible for altering the molecular and electronic structure of the disulfide such that the trans barrier to rotation about the SS bond is effectively overcome. In contrast, the phenyl and uncomplexed pyrimidyl disulfides prefer the usual CSSC torsional angle near 85° and have trans barriers greater than 7 kcal/mol. The barrier to rotation about SC bonds (2–3 kcal/mol) is low and consistent with ab initio calculations and experiments on other molecules. The force field calculations were done using MMP1. A serious problem was encountered in the use of the MMP1 computer program on molecules with N‐type atoms that contribute only one electron to the π‐electron system. A solution is to modify the variable electronegativity self‐consistent field (VESCF) part of the MMP1 calculation to use another set of parameters in the program that pertain to a type of nitrogen with one π electron. CNDO/2 was used for most of the MO calculations, although INDO and extended Hückel were also used.
Semiempirical spin–orbit coupling calculations. I. Theory and method. Benzophenone as a test case
Authors: Pasternak R. , Wagnière G.
Published: December 2004

The molecular spin–orbit coupling operator is brought into a simplified form through a convenient choice of origin for the orbital angular momentum operator. The eigenvalue problem of the Hamiltonian that includes the spin–orbit (SOC) operator as a perturbation is solved by means of a linear variational procedure in the basis of the spin‐pure molecular eigenstates. Test calculations on benzophenone are presented and the results are compared to experiment. We discuss the minimal size of the spin‐pure variational basis needed to achieve stable results as well as the amount of single‐excitation configurational mixing needed to describe the spin‐pure molecular eigenstates.
An ab initio study of the guanidinium fragments in tetrodotoxin and saxitoxin
Authors: Sapse A. M. , Santoro A.
Published: December 2004

SCF Hartree–Fock calculations are used to predict properties of the guanidinium fragment present in tetrodotoxin and saxitoxin, toxins known to block the sodium channels of the nerve cell membrane. The results, in terms of net atomic charges and geometries, are compared to similar calculation results obtained for the Na+–H2O complex.
On efficient integration techniques for oscillatory integrals in periodic system calculations
Authors: Schneider W. J. , Ladik J. J.
Published: December 2004

Quantum chemical calculations of polymers and solids, especially on an ab initio level, represent a large computational task and therefore necessitate efficient computing methods. This is particularly true for the oscillatory integrals appearing in such calculations. For these integrals efficient integration methods based both on the Chebyshev series and the spline representation of the nonoscillatory part of the integrand are considered; they are found far superior compared with more standard integration rules. In two‐ and three‐dimensional systems, directions with maximum oscillatory behavior can be selected along which these new efficient integration techniques can be used advantageously. The ideas are illustrated by Hückel crystal orbital (HCO) bond orders for the polyacetylene chain and the graphite layer. In the latter example, also, a method for the integration of oscillatory integrands with a singularity is given.
On the construction of self‐avoiding chains
Authors: Mom V.
Published: December 2004

In this article an algorithm to generate self‐avoiding chains fitting a predefined lattice is described. The lattice has to fulfill some mild conditions but can be one, two, or many dimensional. The chains are random in the sense that they are calculated in such a way that every chain fitting the lattice has the same chance to be constructed.
Space modification: An alternative approach to chemistry problems involving geometry
Authors: Silver G. L.
Published: December 2004

The sequential simplex optimization algorithm has been translated into non‐Euclidean space. A study of the algorithm in this space suggests that the path of convergence of the simplex depends on the properties of the space so that different convergence paths can be obtained even with the same starting points. The path of convergence approaches the path observed in Euclidean space as the metric constant of the hyperbolic space increases.
An ab initioCI calculation of the triplet–triplet absorption spectrum of naphthalene
Authors: Ha Tae‐Kyu , Wild Urs P.
Published: December 2004

The triplet–triplet absorption spectrum of naphthalene (3B1g ← 3B2u; 3Ag ← 3B2u) was calculated using an ab initio method with a STO‐3G basis set and moderately large configuration interaction. Eight bands were found in the region 18,000–45,000 cm−1 and compared with those of the experimental spectrum. The strongest band observed at about 44,000 cm−1 was assigned to a 3Ag ← 3B2u tansition. The excited triplet and singlet ground‐state electronic charge distributions are compared.
Theory of lone pairs. IV. Molecular ion hole states of ten‐electron hydrides. Molecular ionization potentials and proton affinities by direct SCF calculations
Authors: Kozmutza C. , Kapuy E. , Robb M. A. , Daudel R. , Csizmadia I. G.
Published: December 2004

Closed‐shell SCF calculations on the ground states and direct SCF calculations on the ionized doublet states were carried out for a series of ten‐electron hydrides. The correlation of ionization potentials with the degree of protonation and the nuclear charge has been studied for hole states derived from excitation out of both the core and valence molecular orbitals. Calculated proton affinities of the ground states and hole states derived from a given symmetry orbital show a similar trend to that of the ionization potentials.
Iterative calculation of eigenvalues and eigenvectors of large, real matrix systems with overlap
Authors: Gallup G. A.
Published: December 2004

An improved method for obtaining a few eigenvalues and eigenvectors of the symmetric matrix system is presented:

where S ≠ I. The method allows us to handle larger systems more easily than any other known to the author. It requires the inversion of S, and N3 step, but thereafter each eigenvector and eigenvalue is obtained in a length of time proportional to N2. The relation of this method to the MOR and MMOR methods developed recently for handling the case, S = I, is discussed.
An open‐ended self‐consistent field method. A simulation of a molecular orbital technique for small memory computers
Authors: Benzel Mark A. , Dykstra Clifford E.
Published: December 2004

The steps in a nonconventional algorithm for self‐consistent field calculations are outlined, and calculations on cumulenes are given to demonstrate the convergence properties of the method. The approach is essentially open ended and is likely to be cost effective on computer systems with minimal core.
Empirical penetration functions and two‐center electron repulsion integrals for semiempirical calculations of electronic structure
Authors: Parry D. E. , Whitehead M. A.
Published: December 2004

Explicit functional forms for both the two‐electron Coulomb integral, (aa∣bb), and the one‐center core–orbital integrals, Z (aa∣ZA), are derived which permit the penetration integrals to be fully derived and calculated. With these forms the 3Σ of the H2 molecule is unstable. These forms are generalized so that they are suitable for optimizing semiempirical predictions of experimental one‐electron properties.