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The reactions of N-unsubstituted triazoles with sulfonyl chlorides afforded mixtures of regioisomeric 1- and 2-sulfonyl-1,2,3-triazoles. In some cases, pure regioisomers were obtained by crystallization of mixtures of isomers. 1,2,3-Triazoles bearing thiadiazole, isoxazole and benzene rings react with mesyl chloride and tosyl chloride to form mainly 1-substituted 1,2,3-triazoles. Conversely, reactions of triazoles 1a,b and oxadiazolyl triazole 1h with more bulky 1-(2,4-dimethylphenyl)sulfonyl chloride affords mainly 2-substitued products. Oxadiazole 1b furnishes an equal mixture of the regioisomeric products 3 and 4 as a result of the reaction with mesyl and tosyl chlorides. Higher temperatures increase the ratio of isomers in favor of the 2-substituted triazole. The ratio of isomers depends on both the nature of the azolyl ring and on the size of the substituent in the sulfonyl chloride. Based on the results of experimental and theoretical data, 1-substituted and 2-substituted 1,2,3-triazoles can be considered as the kinetic and thermodynamic products.

We have used computational chemistry methods to aid the rational design of long-wavelength absorbing and emitting organic materials. For this purpose, the vertical electronic transition energies of 3,4-dicyano carbostyrils (quinolone-2(1H)-ones) substituted by electron-donating substituents (methoxy, methylamino, dimethylamino) at positions 6 and 7, are calculated by time-dependent density functional theory (B3LYP) within the Tamm–Dancoff approximation. Bulk solvent effects (DMSO, CH 3 CN, H 2 O) were taken into account by the CPCM solvation model. Particular long-wavelength absorptions (∼540 nm) are predicted for derivatives containing an amino group in position 6 irrespective of whether a 7-methoxy or a 7-amino group is present. In contrast, considerably shorter wavelength absorption (∼440 nm) can be expected for 6-methoxy-7-amino substituted 3,4-dicyano carbostyrils. Optimization of the first excited singlet state of 6-dimethylamino substituted carbostyrils leads to a perpendicular arrangement of the (CH 3 ) 2 N-group with respect to the heterocyclic ring system accompanied by an extremely low electronic transition energy (1000–1500 nm) with vanishingly small intensity (oscillator strength f

Macrolide antibiotics, such as azithromycin and erythromycin, are in widespread use for the treatment of bacterial infections. Macrolides are taken up and excreted mainly by bile. Additionally, they have been implicated in biliary system diseases and to modify the excretion of other drugs through bile. Despite mounting evidence for the interplay between macrolide antibiotics and bile acids, the molecular details of this interaction remain unknown. Herein, we show by NMR measurements that macrolides directly bind to bile acid micelles. The topology of this interaction has been determined by solvent paramagnetic relaxation enhancements (solvent PREs). The macrolides were found to be bound close to the surface of the micelle. Increasing hydrophobicity of both the macrolide and the bile acid strengthen this interaction. Both bile acid and macrolide molecules show similar solvent PREs across their whole structures, indicating that there are no preferred orientations of them in the bile micelle aggregates. The binding to bile aggregates does not impede macrolide antibiotics from targeting bacteria. In fact, the toxicity of azithromycin towards enterotoxic E. coli (ETEC) is even slightly increased in the presence of bile, as was shown by effective concentration (EC50 ) values.

The conformational properties (C-4(1), C-1(4), and skew ring structures, side chain torsion) of methyl 2,4-(1) and 3,4-O-diacetyl (2) as well as 2,4-(3) and 3,4-O-dibenzoyl (4)-SS-D-xylopyranoside are calculated by dispersion-corrected density functional theory (B3LYP-D3) and LPNO-CEPA/1-def2-TZVPP. Derivatives with acyl groups in positions 2 and 4 (1 and 3) prefer the 1C4 chair conformation of the pyranose chair; 3,4-di-O-acyl compounds 2 and 4 show nearly equal or even dominating amounts of the C-4(1) chair. Intramolecular hydrogen bonding of the type O3-H center dot center dot O1 (1 and 3) and O2-H center dot center dot center dot O4 are characteristic for the lowest energy conformations of 1C4 chairs. With increasing solvent polarity a shift towards 4C1 chair structures is calculated. B3LYP-D3 conformer populations show fairly good agreement with CEPA/1 results (R-2 = 0.992).

The absolute configuration of a series of 4(R)-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones is assigned by comparison of experimental and calculated CD spectra using time-dependent density functional theory (TDDFT) in combination with four different functionals (B3PW91, CAM-B3LYP, M06-2X, BMK). Closest agreement with experiment is obtained with B3PW91. All compounds except those bearing an acyl group at N5 exist in two nearly isoenergetic conformations of the seven-membered ring (G ⩽ 0.5 kcal mol−1 with the local pair natural orbital coupled-electron pair approximation LPNO-CEPA/1/def2-TZVPP//B3LYP/6-311G(d,p)). Agreement between simulated and experimental CD spectra was found to critically depend on a proper description of conformer population as well as the position of the calculated longest-wavelength transitions of the individual conformers.

The absolute configuration of axially chiral bisquinolones is established by comparison of experimental CD spectra and those simulated on the basis of TDDFT calculation. Specifically, the previous ambiguous assignment for 3,3′-dibromo-6,6′,7,7′-tetramethoxy-4,4′-biscarbostyril could be resolved as aR axial chirality for the first eluted enantiomer. The computational findings are corroborated by X-ray crystallography.

Density functional theory (M06-2X) calculations on divanadium complexes [(VO)2(bpbp)(A)]2+ of the oxo anions formate, phosphate, and arsenate (A = HCOO−, H 2 PO 4 - , H 2 AsO 4 - ) as well as the diaquo complex [(VO)2(bpbp)(OH2)2]3+ indicate increased binding in the series H2O H 2 PO 4 - H 2 AsO 4 - . Aqueous solvation enhances the experimentally observed selective recognition of arsenate over phosphate indicating differences in hydration enthalpies of the respective complexes as the main reason for the surprising differentiation between dihydrogenphosphato and dihydrogenarsenato by the divanadyl complex [(VO)2(bpbp)(OH2)2](ClO4)3·H2O. Deprotonation of the dihydrogenphosphato/arsenato complexes to [(VO)2(bpbp)(HXO4)]+ further increases preferential solvation of the arsenato over the phosphato complex.

The quantum cluster equilibrium (QCE) theory was applied for liquid methanol using MP2(fc)/6-31+G(d,p) cluster geometries and MP2/6-311++G(d,p) energies. Three approaches for the determination of the empirical parameters inherent in the QCE model, amf and bxv, were considered, while the molar volumes of both the liquid and the vapor were obtained from experiment. Model 1, in which amf and bxv were optimized for the vapor and liquid phase, respectively, gave the best results for thermochemical parameters (constant pressure heat capacity C and entropy S) of methanol, especially for the liquid state. In line with Pauling’s suggestions concerning the structure of liquid methanol, cyclic hexamers cyclo-(MeOH)6 are the dominant species, even near the boiling point (∼50%) increasing to ∼90% at the freezing temperature.

Fast semipreparative HPLC enantioseparation of four axially chiral biscarbostyrils (4,4'-bisquinoline-2-ones) using ULMO as a pi-acidic Pirkle type chiral stationary phase leads to two racemizing pairs (1,2; k(obs) 1.6x10(-4) and 3.0x10(-4)s(-1) at 28 degrees C) and two stable ones (3,4). 3 was stabilized by a crown ether linkage from pos. 6 to 6', and 4 had sterically demanding bromo substituents in pos. 3 and 3'. On-column generated temperature-dependent chromatograms of 1 and 2 were fitted with Auto-DHPLCy2k and DCXplorer. For cpd 2 both programs delivered similar DeltaG values of 90 and 93kJ/mol, well comparable with the 99kJ/mol calculated with the B3LYP/6-31G (d) procedure. At temperatures of high conversion DCXplorer delivered inconsistent series of rate constants for the more tailing and less resolved tetramethoxy derivative 1. We connect this problem with an almost impossible halfwidth calculation of tailing peak pairs which are weakly resolved. However, this problem could be observed only in the case of tetramethoxy derivative 1. Stochastic generated data of Auto-DHPLCy2k could be used at a lower percentage of conversion only while the theoretical plate model did not deliver useful data at temperatures of very low conversion but fitted well high conversion chromatogram series of 1 and 2.

Various types of biocatalysts like oxidases, alcohol dehydrogenases, and microbial cells were tested for the oxidation of benzyl alcohol. Oxidases in combination with molecular oxygen led to low conversion. Alcohol dehydrogenases and microbial cells were tested in a hydrogen transfer reaction employing acetaldehyde, chloroacetone, and acetone as hydrogen acceptor. Excellent conversion (95%) could be achieved employing lyophilised cells of Janibacter terrae DSM 13953 at a substrate concentration of 97 mM.

Quasi-irreversible oxidation of sec-alcohols was achieved via biocatalytic hydrogen transfer reactions using alcohol dehydrogenases employing selected ketones as hydrogen acceptors, which can only be reduced but not oxidized. Thus, only 1 equiv of oxidant was required instead of a large excess. For the oxidation of both isomers of methylcarbinols a single nonstereoselective short-chain dehydrogenase/reductase from Sphingobium yanoikuyae was identified and overexpressed in E. coli.

Density functional theory [B3LYP/6-31G(d) with inclusion of solvent effects by the Onsager SCRF approximation] is used to investigate the mechanism of the hydrogen halide induced cyclisation of α-diazonitriles to 5-halo-1,2,3-triazoles. The reaction occurs stepwise. The first step, addition of the hydrogen halide onto the nitrile group to form diazo imidoyl halides, is rate determining. Barriers are calculated to be in the range 20–30 kcal mol −1 . The largest ones were found for 2-diazomalononitrile and 2-trifluoroacetyl-2-diazoacetonitrile. The second step, cyclisation of these intermediates to the triazoles, has a significantly lower barrier, −1 .

Nucleophilic vinylic substitutions of 4 H -pyran-4-one and 2,6-dimethyl-4 H -pyran-4-one with hydroxide ion in aqueous solution were calculated by the density functional theory (B3LYP) and ab initio (MP2) methods using the 6-31+G(d) and 6-31G(d) basis sets. The aqueous solution was modelled by a supermolecular approach where 11 water molecules were involved in the reaction system. The calculations confirmed a different addition-elimination mechanism of the reaction compared with that in the gas phase or non-polar solution. Addition of hydroxide ion at the C2 vinylic carbon of the pyranone ring with activation barrier of 10–11 kcal mol −1 (B3LYP) was shown to be rate determing in good quantitative and qualitative agreement with experimental kinetics. Solvent effects increase the activation barrier of the addition step, and in opposite, decrease the barrier of the elimination step.

The relative enthalpies, ΔHo(0) and ΔHo(298.15), of stationary points (seven minimum and five transition structures) on the CHO 2 · potential energy surface were calculated with the aid of the G3MP2B3 as well as the CCSD(T)-CBS (W1U) procedures from which we earlier found mean absolute deviations of 3.9 and 2.3 kJ mol–1, respectively, between experimental and calculated enthalpies of formation of a set of 32 free radicals. For CCSD(T)-CBS (W1U) both the well depth of trans-HOCO, Δ H well o ( 298.15 ) = − 110.9 kJ mol − 1 , as well as the reaction enthalpy of the overall reaction, OH+CO→H +CO2, ΔrHo(298.15)=−102.5 kJ mol–1, are in close agreement with the most recent experimental values, Δ H well o ( 298.15 ) = − 108.4 kJ mol − 1 and ΔrHo(298.15)=−102.3 kJ mol–1, respectively. In addition, for radicals trans-HOCO, cis-HOCO, and formyloxy HC(O)O , the thermodynamic functions heat capacity C p o ( T ) , entropy So(T), thermal energy content Ho(T) – Ho(0), and enthalpy of formation ΔfHo(T) are tabulated in the range of 50 – 3000 K. The reaction OH+CO→H +CO2 via rotation of the initially formed trans-HOCO to cis-HOCO proceeds over a quite small barrier (TS3, ΔHo(298.15)=1.1 kJ mol–1 with respect to the asymptote OH+CO), considerably lower than that for rearrangement to the formyloxy radical HC(O)O (TS4, ΔHo(298.15)=36.0 kJ mol–1). The first electronically excited state (2B2) of HC(O)O is found to lie just 7.0 kJ mol–1 above the 2A1 ground state (experimental T0=2.6 kJ mol–1). For HC(O)O (2A1) the CCSD(T)-CBS (W1U) method gives ΔfHo(298.15)=−127.1 kJ mol–1 (experimental ΔfHo(298.15)=−129.7±12.6 kJ mol–1).

Primary amino groups of di- or triaminoaryl compounds add a remarkably stable dioxinyl-alpha-oxoketene affording bis- or tris-[trioxabicyclo[3.3.1]nona-3,7-dienyl (bridged bisdioxine)] systems which can be converted into the corresponding bis- or tris-[2,4,6,8-tetraoxadamantanes] by acidic hydrolysis. Stereochemical peculiarities as well as preliminary host-guest abilities of these molecules are investigated with aid of NMR-spectroscopy, an X-ray analysis and ESI-mass spectrometry. (C) 2004 Elsevier Ltd. All rights reserved.

The synthesis and photophysical data of new carbostyrils (quinoline-2(1H)-ones) with the longest hitherto observed absorption- and emission wavelengths are described. Introduction of 6-amino, 7-MeO, and 4-(CF3) substituents enabled us to rise the absorption and fluorescence maxima up to 414 and 557 nm, respectively. Supported by semi-empirical and ab initio calculations, the 6,7-(1,4-diazine)-fused carbostyril 23b displayed absorption maxima at up to 440 nm, with quantum yields of up to 0.9 and large Stokes shifts (>100 nm), comparable to the best coumarin chromophores known. The new fluorophore is neither pH-sensitive between pH 6 and 10 nor susceptible to O2 quenching. At pH 3, the emitted light appears greenish-white, which arises from three different stages of protonation.

Quantitative structure-retention (QSRR, retention factors log k1 and log k2 for the first and second eluted enantiomer) as well as enantioselective retention relationships (QSERR, separation factor log a) for a series of 42 chiral arylalkylcarbinols on four brush-type chiral stationary phases are derived by multiple linear regression analyses and artificial neuronal network calculations using 2D and 3D molecular descriptors including those obtained by quantum chemical calculations. Separation factors are in addition modeled by the 3D-QSAR method of comparative molecular field analysis (CoMFA). For the retention factors the LUMO energy turns out to be the most important descriptor, whereas for log a it is the hydrophobicity of the analytes. With CoMFA both the steric and electrostatic field are found to be of almost comparable significance.

The effect of structural variations of either the donor (number and position of methoxy groups, replacement of the aryl by Fischer's base) or the acceptor moiety (bisacylation of the amino group, extension of the conjugated system by condensation with dimethylformamide–dimethylacetale) of a series of dyes containing malononitrile dimer as acceptor is investigated both experimentally and computationally. Semiempirical (AM1) and ab initio (HF/6-31G ∗ and HF/3-21G) calculations are used for a conformational analysis of the acceptor groups and model systems thereof. Electronic excitation energies are obtained by ZINDO, ab initio CIS/6-31+G ∗ and time-dependent density functional theory (TDDFT(B3LYP)/6-31+G ∗ ) computations. Inclusion of solvent effects is important for a reliable description of the trends observed in the experimental absorption spectra by ZINDO. Methoxyaryl, even polysubstituted, derivatives absorb at significantly shorter wavelengths than the corresponding p-dimethylamino compounds. Replacement of the p-dimethylaminoaryl donor by Fischer's base leads to a bathochromic shift, as does the bisacylation of malononitrile dimer's amino group. Functionalization by condensation with dimethylformamide–dimethylacetale generally has only a small and irregular effect on absorption spectra.

Semiempirical computational methods (AM1 for geometries, ZINDO for electronic transition energies) were used to calculate the absorption and fluorescence spectra of a series of oligophenylenes, their heteroaromatic substituted derivatives, and aryl substituted open-chain and bridged polyenes. The calculations were calibrated on a series of 61 (for absorption) and 42 (for fluorescence) compounds and are shown to reproduce experimental data with an accuracy of −1 . Based on these results, calculations on possible synthetic targets for compounds to be used as scintillating fluors in high-energy particle detection were performed, whereby absorption and emission wavelengths were predicted for 15 and 34 compounds, respectively.

Synthesis, absorption and fluorescence spectra, as well as quantum yields of a series of donor-acceptorsubstituted carbostyrils (a quinolin-2(1H )-ones), are reported. Unprecedented strong absorption maxima (ea 10000 ‐ 20000) close to the visible spectrum, large Stokes shifts up to 130 nm, and quantum yields up to 0.7 are obtained with derivatives containing donor substituents at C(6) and C(7), and either one Ph substituent at C(3) or one CF 3 residue at C(4). For analytical applications in biochemistry and medicine, N(1)-functionalization, or amidoacylation at C(3) in the case of the CF 3 derivatives, is possible without a concomitant hypsochromic shift of their absorption and emission maxima. Semiempirical molecular-orbital calculations ( AM1 for structures, ZINDO for electronic transition energies) prove to be a suitable tool for the prediction of absorption properties of these compounds. The crystal-structure analysis of 6,7-dimethoxy-1-methyl-3-nitro-4-(trifluoromethyl)quinolin-2-(1H )-one (7 )( C 13H11F 3N2O5, monoclinic, P21/c, aa 12.372(2), ba 12.154(2), ca 10.119(2)a, ba 112.95(2)8) shows that the NO2 group, squeezed between the CF 3 and the CaO group, is oriented almost perpendicularly (87.8(4)8) to the ring plane. The intramolecular F ··· N distance between the CF 3 and the NO2 group is only 2.513(4)a.

Ab initio (RHF and MP2) and density functional (B3LYP) calculations with basis sets ranging from 3–21G( ∗ ) up to 6–31 + G ∗∗ on dihydropyrimidine-5-carboxylates 4 are performed. At all levels of theory a slight preference (≈1 kcal mol −1 ) for a cis ester orientation ( 4a ) is found, as proposed for the receptor-bound geometry in biologically active dihydropyrimidine derivatives. For the ring conformation a strong dependence on the computational procedure is observed. Calculations with basis sets lacking polarization functions on first row heavy atoms (3–21G( ∗ ), 6–31G, 6–311G) lead to planar ring geometries. Inclusion of polarization functions yields puckered boat conformations. The puckering amplitudes increase in the order Q (RHF) Q (B3LYP) Q (MP2). With MP2 unrealistically strong deviations from planarity are predicted. By single-crystal X-ray analysis an almost planar ring conformation is found. Energy differences between planar and puckered geometries are negligible with RHF and B3LYP ( −1 ), whereas with MP2 somewhat larger ΔE values (1.5–2.6 kcal mol −1 ) are calculated, especially when diffuse functions are included.

Geometries of the 12 possible cycloaddition products between ketenimine and acrolein as well as of the respective transition states have been obtained by ab initio calculations at the MP2/6-31G* le...

The title compounds, a mixture of anti and syn diastereomers, were prepared by Pd-catalyzed coupling of areneboronic acids with hetaryl halides. Energy barriers for the interconversion of the diastereomers obtained by kinetic and computational studies show a dependence on the location of the annular nitrogen atom, the ortho providing a smaller barrier than the meta nitrogen atom.

The conformational features of 4-aryl-dihydropyrimidine calcium channel modulators were investigated by computational and X-ray crystallographic studies. The geometries of dihydropyrimidines 8–11 were fully optimized using ab initio (HF/3-21G) and semiempirical (AM1, AM1/MM, PM3, PM3/MM) methods, and rotational barriers for important functional groups determined. All computational treatments predict the lowest energy conformation to be identical with the recently proposed receptor-bound geometry.

The title compound prepared by Pd-catalyzed coupling of 1,8-dibromonaphthalene and diethyl(3-pyridyl)borane shows syn-anti diastereoisomerism due to restricted rotation at ambient temperatures. AM1 and PM3 computations indicate the preferred T-shaped transition state for rotation has a highly deformed naphthalene ring. There is a slight preference for H4′ and not the nitrogen lone electron pair to be directed at the face of the other pyridyl ring.

The heterocyclic 2,3-diones 1 and 11 together with Lawesson reagent (LR) afford novel isoindigoide dyes 4 and 12 , respectively. 4a can thermally be isomerized into the pyrano[4,3-c]pyrane 6, accompanied by a significant hypsochromic shift which was corroborated by quantum chemical calculations. The phoshporanylidene derivative 13 was obtained via Wittig reaction of 1 . All structural assignments were based on X-ray studies of 4a and 13 .

The method of comparative molecular field analysis (CoMFA) has been applied to a series of symmetrical bisazo dyes containing H-acid or J-acid as coupling component to obtain quantitative structure-activity relationships with respect to the affinity of the dyes towards cellulose fibres. An excellent correlation between the CoMFA descriptors and experimental dye affinities has been obtained (r2 = 0.999 and r2 = 0.988 for sp3 carbon, charge + 1, and sp3 oxygen, charge −1, respectively, as probe atom). The electrostatic contribution is found to be the dominant factor in the dye-fibre interaction. The CoMFA equations were successfully applied to the prediction of the affinities of two further compounds. The differences in the dye affinities can be interpreted with the aid of plots of steric and electrostatic fields. In addition, semiempirical molecular orbital calculations (PM3 method) have been made for all the molecules.

Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity approach, was used to interpret the affinity of a series of anthraquinone vat dyes to cellulose fibres. The excellent correlation obtained by this method — even when using a quite small number (five) of components in the partial least-squares analysis (crossvalidated rcv2 = 0.841, conventional r2 = 0.992) — indicates that the dye-fibre interaction is largely dominated by steric and even more important electrostatic effects. Based on the CoMFA field contributions, suggestions for further activity enhancements can be made. Inclusion of molecular orbital (AM1) derived quantitative structure-activity relationship (QSAR) descriptors (ϵHOMO, ϵLUMO and dipole moments μ) does not alter the picture derived from CoMFA fields alone. Of the molecular orbital descriptors, the LUMO orbital energy is found to yield the most important contribution. In addition, a multiconformational minimal steric difference (MTD) analysis, including several low-energy conformations of the investigated compounds, was done. This approach also indicated a good correlation with dye affinity (rcv2 = 0.827, r2 = 0.941). The optimized receptor map is in accordance with the CoMFA electrostatic contour maps.

The electronic and geometric structures of benzocyclobutadiene ( 1 ), biphenylene ( 2 ) and their protonated forms are studied by the ab initio HF 6-31G * and MP2(fc)/6-31G * //HF/6-31G * methods. It is shown that β -protonated species are more stable in both cases indicating greater susceptibility of the β -positions towards electrophilic substitutions. This finding is rationalized by the lower π -electronic energy estimated by the valence bond resonance structures and a decreased antagonism between σ - and π -electrons in β -Wheland intermediates. The inherent generalized strain energies in the parent compounds ( 1 ) and ( 2 ) are estimated by homodesmic reactions. It is found that the intrinsic destabilization energy is ≈ 8 kcal mol −1 higher in 1 , which is interpreted as the inability of the peripheral double bond to escape the cyclobutadiene antiboding pattern in an efficient way. The semiempirical AMI calculations give correct qualitative results, but fail at the quantitative level.

An unexpected, redox-neutral C=C bond isomerization of a γ-butyrolactone bearing an exo-methylene unit to the thermodynamically more favoured endo isomer (k(cat) =0.076 s(-1) ) catalysed by flavoproteins from the Old Yellow Enzyme family was discovered. Theoretical calculations and kinetic data support a mechanism through which the isomerization proceeds through FMN-mediated hydride addition onto exo-Cβ, followed by hydride abstraction from endo-Cβ', which is in line with the well-established C=C bond bioreduction of OYEs. This new isomerase activity enriches the catalytic versatility of ene-reductases.

Dibenzoylketene has been found to dimerize in the usual way, i.e. [4 + 2] cycloddittion of the ketene C=C double bond as dienophile with a second acylketene molecule, to 3-acl-α-pyrones. In contrast, dipivaloyketene reacts with its carbonyl C=O double bond to a 1,3-dioxin-4-(2H)-one which contains an unusually inert α-oxo ketene functionality. This difference in site-selectivity is rationalized with the aid of semiempirical molecular orbital (AM1) calculations. Although both the dibenzyol- and the dipivaloylketene reactions of the ketene C=C double bond are predicted to lead to thermodynamically more stable products, cycloaddition of the carbonyl group should be favoured in the case of dipivaloylketene because of its lower activation energy. A different cycloaddition pathway involving the ketene C=O group as dienophile should also be feasible.

The regioselectivity for a series of experimentally studied Diels–Alder reactions between furan derivatives and Danishefsky’s diene has been rationalized within the framework of local DFT-based descriptors (i.e. electrophilicity and nucleophilicity indexes). The importance of the solvent in the calculations has been studied. It has been shown that the relative trend of an atomic center to behave as an electrophile is affected by the medium (gas phase or benzene solution) and the basis set used in the calculation of the reactivity descriptors. The local electrophilicity (xk) and nucleophilicity (Nk) indexes properly account for the observed regioselectivity only when B3LYP/LANL2DZ and HF/LANL2DZ levels of theory have been used. Fil: Brasca, Romina. Universidad Nacional del Litoral; Argentina Fil: Kneeteman, Maria Nelida. Universidad Nacional del Litoral; Argentina Fil: Mancini, Pedro Maximo Emilio. Universidad Nacional del Litoral; Argentina Fil: Fabian, Walter M.F.. Universität Graz; Austria

Four derivatives of schisandrin, a major dibenzo[a,c]cyclooctadiene lignan of Schisandra chinensis (Turcz.) Baillon were synthesized and structurally characterized by means of NMR and mass spectroscopy. Furthermore, axial chirality of the biphenyl system was determined by comparison of calculated with measured circular dichroism (CD) spectra. Three of the obtained derivatives showed a ring contraction during chemical modification. While the original lignans were inactive on the performed bioassays, the compounds which showed the cycloheptadiene skeleton revealed remarkable activities. For the inhibition of LTB(4) production the IC(50) values of aR-6,7-dihydro-6-(1'-hydroxyethyl)-3,9-dimethoxy-6-methyl-5H-dibenzo[a,c]cycloheptene-1,2,10,11-tetraol (6) and aR-6-(1'-iodoethyl)-1,2,3,9,10,11-hexamethoxy-6-methyl-5H-dibenzo[a,c]cycloheptene (8) were 4.2+/-0.3microM and 4.5+/-0.2microM, respectively. aR-6,7-Dihydro-6-(1'-hydroxyethyl)-6-methyl-5H-dibenzo[a,c]cycloheptene-1,2,3,9,10,11-hexaol (5) revealed dual inhibition on COX-2 (IC(50) 32.1+/-2.5microM) and on LTB(4) production (37.3+/-5.5% inhibition at 50microM).

2-Substituted derivatives of the antihistaminic agents Bamipine, Diphenylpyraline and of their 1-phenyl analogues were tested for their antimycobacterial and H1-antagonistic activities. They are strong H1-receptor antagonists and also inhibit the growth of mycobacterials with a maximum MIC of 6.25 μg/mL against Mycobacterium tuberculosis H37Rv. H1-receptor antagonistic potency was slightly decreased by substitution in ring position 2 and distinctly diminished by N-aryl substitution. The antimycobacterial potency of Diphenylpyraline was in general increased by substitution in ring position 2, whereas only a few Bamipine derivatives showed markedly improved activity. A correlation between the two activities was not detected for those compounds.

Semiempirical (AM1, MNDO and MINDO/3) and ab initio (3-21G basis) calculations on relative stabilities, dipole moments, structures, and ionization potentials of the different tautomers of 3-hydroxypyridazine (1), 3,5-dihydroxypyridazine (2), and 3,6-dihydroxypyridazine (maleic hydrazide, 3) are reported. According to the ab initio calculations (including 6-31G∗ results for 1), for 1 the lactam tautomer, for 2 the 4-hydroxy-6-oxo and for 3 the 3-hydroxy-6-oxo form should have the greatest stability. The only available gas phase experimental investigation on 3 is in complete agreement with these ab initio results. In contrast, the semiempirical methods used erroneously predict in each case the greatest stabilities for the lactim (dilactim) tautomers. Errors are least for the AM1 method. N-N bond lengths obtained by the semiempirical methods are significantly shorter and C-N bonds longer than either ab initio or experimental values. Calculated dipole moments and ionization potentials (except MINDO/3) are in satisfactory agreement for the different quantum chemical methods. Electronic excitation energies were calculated using the CNDO/S-CI method; these agree quite well with experimental UV spectra, especially when ab initio geometries are used.

The solution structures of a series of conformationally restricted pentapeptides with a sequence H-Tyr1-Cys2-Gly3 Phe4-Cys5-OH cyclic (2-5) disulfide, where the cysteines possess either the D or L configuration, were examined by a combined approach including NMR measurements as well as MD calculations. It turned out that at least one low energy conformer of H-Tyr1-Cys2-Gly3-Phe4-Cys5-OH cyclic (2-5) disulfide (DCDCE), as well as one conformer out of the group of calculated conformers for H-Tyr1-D-Cys2-Gly3-Phe4-Cys5-OH cyclic (2-5) disulfide (DCLCE), satisfies the NMR data obtained in this study, whereas for the derivative H-Tyrl-Cys2-Gly3-Phe4-Cys5-OH cyclic (2-5) disulfide, which contains solely L-Cys (LCLCE), there is no single structure compatible with the NMR data. © Munksgaard 1996.

A novel reductive biotransformation pathway for β,β-disubstituted nitroalkenes catalyzed by flavoproteins from the Old Yellow Enzyme (OYE) family was elucidated. It was shown to proceed via enzymatic reduction of the nitro-moiety to furnish the corresponding nitroso-alkene, which underwent spontaneous (non-enzymatic) electrocyclization to form highly strained 1,2-oxazete derivatives. At elevated temperatures the latter lost HCN via a retro-[2 + 2]-cycloaddition to form the corresponding ketones. This pathway was particularly dominant using xenobiotic reductase A, while pentaerythritol tetranitrate-reductase predominantly catalyzed the biodegradation via the Nef-pathway.

The proton affinities of cycloalkanones and some open chain ketones have been calculated by means of the MINDO/3 method. The marked ring size effect on the proton affinities of cyclic ketones as opposed to their open chain counterparts is rationalized in terms of a model for protonation of carbonyl compounds proposed by Del Bene, as well as in terms of the energy partitioning scheme within MINDO/3.

The pars-orbital method has been used to explain the absorption and fluorescence properties of a series of coumarins and carbostyrils on the basis of molecular subunits, and to evaluate the changes of molecular structure on excitation to the fluorescent state.

The remarkable regioselectivity of the photochemical reaction of alkenes with enaminecarbaldehydes yielding dihydropyridines is discussed on the basis of biradical stability, perturbational molecular orbital theory as well as dipole—dipole controlled interactions. To this end theoretical calculations (semi-empirical as well as ab initio) were employed. In addition, the geometrical relaxation, especially rotation around the CC double bond, in the excited T 1 state of the enaminecarbaldehydes, are discussed on the basis of quantum chemical calculations.

The recently discovered [4+2] cycloaddition of ketenimines to the oxa-1,3-diene system of carbonyl substituted furandiones is investigated by means of the semiempirical AM1 method. Heats of formation for the four regioisomeric primary cycloadducts as well as a number of potential rearrangement products are calculated. In combination with perturbational MO arguments these calculations provide a consistent rationalization of the proposed reaction mechanism involving special and rather novel rearrangements of the primary cycloadduct to give the isolable endproduct.