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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 oxidation of the renewable diols isosorbide and isomannide was successfully achieved using a TEMPO/laccase system. Furthermore, various TEMPO-derivatives were tested leading to conversions of up to >99% for the oxidation of isosorbide, isomannide, indanol and a halohydrin to the corresponding ketone.

Scalar coupling constants and signal splitting patterns in NMR spectra contain a wealth of short-range structural information. The extraction of these parameters from (1)H NMR spectra is often prohibited by simultaneous scalar coupling interactions with several other protons. Here we present a high-resolution NMR experiment where scalar coupling to only one selected signal is visible. All other couplings are removed from the spectrum. This real-time selectively refocused NMR experiment is achieved by spatially selective homonuclear broadband decoupling combined with selective refocusing during acquisition. It allows the unperturbed extraction of scalar coupling constants from the highly resolved acquisition dimension of NMR spectra.

Prochiral bicyclic diketones were transformed to a single diastereomer of 3-substituted cyclohexylamine derivatives via three consecutive biocatalytic steps. The two chiral centres were set up by a CC hydrolase (6-oxocamphor hydrolase) in the first step and by an ω-transaminase in the last step. The esterification of the intermediate keto acid was catalysed by a lipase in the second step if possible. For two substrates the CC hydrolytic step as well as the esterification could be run simultaneously in a one-pot cascade in an organic solvent. In one example, the reaction mixture of the first two steps could be directly subjected to bio-amination in an organic solvent without the need to change the reaction medium. Depending on the choice of the ω-transaminase employed and the substrate the cis- as well as the trans-diastereomers could be obtained in optically pure forms.

Textile dyeing has economical and ecological implications. Our application of QSAR techniques to dye–cellulose binding is based on the hypothesis of specific dye–fibre interactions. As an alternative to classical QSAR studies, comparative molecular field analysis was previously used to predict technical dye adsorption properties. This paper presents a structure-affinity study of heterocyclic azo dye adsorption on cellulose fibre by multiple linear regression (MLR), comparative molecular field (CoMFA) and comparative molecular similarity index (CoMSIA) analysis. Structural descriptors, derived from the minimum energy conformers, obtained by molecular mechanics and semiempirical level quantum chemical calculations, were correlated with dye affinity for cellulose by MLR. Models with predictive power were obtained. Despite these good results 3D-QSAR CoMFA and CoMSIA approaches gave a deeper insight into dye–cellulose interactions. Dye conformers obtained by the AM1 and ab initio approaches were aligned using atom per atom superposition of a common frame. A comparative analysis on statistic performances and predictive model power was performed for the AM1 and DFT variants of CoMFA and CoMSIA models. Statistically significant models were established for 16 molecules and validated by an external test set of 5 compounds, yielding the best predictive DFT CoMFA model [ r 2 = 0.960, with 4 components, q 2 = 0.707 and SEE = 1.12] and several CoMSIA models for AM1 and ab initio cases [ r 2 = 0.935 ÷ 0.947, q 2 = 0.688 ÷ 0.739 and SEE = 1.32 ÷ 1.46]. The contour maps obtained from 3D-QSAR studies were appraised for affinity trends for the investigated dye molecules. Results indicate a predominant hydrogen donor ability of the dye molecules for both AM1 and ab initio variants to play a significant role in dye binding to cellulose. Electrostatic interactions derived from DFT charges bring an important contribution to dye affinity, too. The information obtained from both CoMFA and CoMSIA 3D contour maps may be used in the design of new heterocyclic azo dyes.

In this work we studied the capability of several diene/dienophile pairs to undergo Diels-Alder (DA) reactions leading to benzo[b]thiophenes. A variety of synthetically and commercially available nitrothiophenes were chosen as dienophiles. Methyl 5-nitro-3-thiophenecarboxylate was selected as a potential strong electrophilic candidate based on some DFT-based properties and the substitution pattern of the expected product. The mechanistic details concerning the participation of this dienophile in polar DA reactions were investigated through a theoretical point of view. The results were compared with the experimental outcomes. This methodology should allow synthetic chemists to analyze DA reactions in detail in a stage prior to the synthetic job. Fil: Brasca, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. 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.. Karl-franzens-universitat Graz; Austria

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) model was applied to the liquid phase for the first few members of the homologous series of unbranched aliphatic primary alcohols, methanol, ethanol, propan-1-ol, and butan-1-ol. Cluster structures and energies were calculated by density functional theory [B3LYP/6-311++G(2d,2p)]. For butan-1-ol the dispersion interaction was also considered with the B3LYP-D method. In agreement with previous findings, cyclic cluster structures are the most probable ones. In addition, weak C-H...O interactions as well as dispersion interactions between the longer alkyl chains were found to be important in the cluster formation. The reliability of the model was assessed by the calculated constant pressure heat capacity (C(p)) values. Larger deviations between theory and experiment were found for higher homologes (propan-1-ol, butan-1-ol) with the B3LYP method. When the B3LYP-D method was applied for butan-1-ol, adequate agreement was found between experimental and calculated C(p) values.

The asymmetric bioreduction of activated alkenes catalyzed by flavin-dependent enoate reductases from the OYE-family represents a powerful method for the production of optically active compounds. For its preparative-scale application, efficient and economic NADH-recycling is crucial. A novel enzyme-coupled NADH-recycling system is proposed based on the concurrent oxidation of a sacrificial sec-alcohol catalyzed by an alcohol dehydrogenase (ADH-A). Due to the highly favorable position of the equilibrium of ene-reduction versus alcohol-oxidation, the cosubstrate is only required in slight excess.

Diels-Alder reactions between the substituted furans 1a-1c and Danishefsky's diene (2), yielding 5-hydroxybenzofurans, were studied by density functional theory [B3LYP/6-31G(d) level] in benzene as solvent (SP/CPCM). The mechanistic details of these reactions, especially with respect to regio-, site-, and stereochemistry were analyzed in detail. Moreover, the extrusion of nitrous acid from the Diels-Alder cycloadducts and the formation of the aromatic products were also explained in order to give a total description of the complete domino processes. Some Diels-Alder reactions leading to 5-hydroxybenzofurans were studied at the B3LYP/6-31G(d) level of theory in benzene as solvent (SP/CPCM). DFT calculations on the transition structures were carried out for all the possible reaction channels (site, regio-, and stereoisomeric channels were included in this study). Additionally, a description of the complete domino processes was performed. Fil: Brasca, Romina. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Kneeteman, Maria Nelida. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mancini, Pedro Maximo Emilio. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Departamento de Química; Argentina Fil: Fabian, Walter M. F.. Karl Franzens Universität Graz,; Austria

Aqueous acid dissociation constants of substituted areneseleninic, areneselenenic, arenesulfinic, and benzoic acids are calculated by ab initio (MP2) and DFT (B3LYP) methods in combination with bulk solvation models (IEFPCM, CRSrad) from appropriate thermodynamic cycles. Mean absolute deviations (MAD) between experimental and calculated pK(a) values are quite large for basis sets without diffuse functions; however, trends are reasonably well described. Best agreement with experiment as described by MAD as well as correlation coefficient and slope of the correlation equation pK(a) = a*ΔG(calc)/RT ln(10) + b is obtained with the CPCM solvation model using the defaults optimized within COSMO-RS (CRSrad; MAD = 1.54, R(2) = 0.94, a = 0.83). Sulfenic (selenenic) acid tautomers are significantly more stable than the corresponding sulfoxide (selenoxide) forms.

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.

Three approaches of computational chemistry [quantum mechanics (QM) calculations, docking, and molecular dynamics (MD) simulations] were used to investigate the redox cycle of bovine erythrocyte glutathione peroxidase from class 1 (GPx1, EC 1.11.1.9). The pKa calculations for two redox states of the active-site selenocysteine of GPx1 (selenol, Sec45-SeH, and selenenic acid, Sec45-SeOH) were estimated using a bulk solvent model (B3LYP-IEFPCM and B3LYP-CPCM-COSMO-RS). The calculated pKa values of Sec45-SeH and Sec45-SeOH were corrected via a simple linear fit to a training set of organoselenium compounds, which consisted of aliphatic selenols and aromatic selenenic acids with available experimental pKa values. Based on docking calculations, binding sites for both molecules of the cofactor glutathione (GSH) are described. MD simulations on the dimer of GPx1 have been performed for all chemical states of the redox cycle: without GSH and with one or two molecules of GSH bound at the active site. Conformational analyses of MD trajectories indicate high mobility of the Arg177 and His79 residues. These residues can approach the vicinity of Sec45 and take part in the catalytic mechanism. On the basis of the calculated data, new atomistic details for a generally accepted mechanism of GPx1 are proposed.

A biocatalytic redox-neutral reaction cascade was designed for the deracemisation of racemic mandelic acid to yield optically pure L -phenylglycine employing three enzymes. The cascade consisted of three steps: a racemisation, an enantioselective oxidation and a stereoselective reductive amination. The enantioselective oxidation of D -mandelic acid to the corresponding oxo acid was coupled with the stereoselective reductive amination of the latter; thus the oxidation as well as the reduction reactions were performed simultaneously. The formal hydrogen abstracted in the first step -the oxidation - was consumed in the reductive amination allowing a redox-neutral cascade due to a cascade-internal cofactor recycling. The enantiomers of the starting material were interconverted by a racemase (mandelate racemase) ensuring that in theory 100% of the starting material can be transformed. Using this set-up racemic mandelic acid was transformed to optically pure L -phenylglycine (ee > 97% ) at 94% conversion without the requirement of any additional redox reagents in stoichiometric amounts.

The adsorption of aniline on SWCNTs has been investigated using three different DFT methods, PW91LYP, the hybrid m-GGA MPWB1K, and the dispersion-corrected BP86-D functionals. The BSSE-corrected adsorption energies for top orientation of aniline to the nanotube surface are Eads = 9.7 kcal mol−1 and Eads = 1.4 kcal mol−1 with BP86-D/SVP and MPWB1K/6-311+G(d), respectively. Results validated that the adsorption energy of aniline depends on the diameter of the nanotube with a pronounced manner, especially for small diameters. The TDDFT calculations of UV/vis spectra predict two electronic transitions resulting from nanotube excitations in the visible spectra (>500 nm) and one imperceptible aniline → SWCNT excitation at ca. 1200 nm. Inclusion of solvent effects (MeOH) by explicit solvent molecules leads to a pronounced red shift of the weak longest wavelength aniline → nanotube transition, whereas the strong intratube excitations are only a little influenced. Fluorescence excitation spectra (λem = 586 nm) of ...

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.

Dwindling petroleum feedstocks and increased CO(2)-concentrations in the atmosphere currently open the concept of using CO(2) as raw material for the synthesis of well-defined organic compounds. In parallel to recent advances in the chemical CO(2)-fixation, enzymatic (biocatalytic) carboxylation is currently being investigated at an increased pace. On the one hand, this critical review provides a concise overview on highly specific biosynthetic pathways for CO(2)-fixation and, on the other hand, a summary of biodegradation (detoxification) processes involving enzymes which possess relaxed substrate specificities, which allow their application for the regioselective carboxylation of organic substrates to furnish the corresponding carboxylic acids (145 references).

Biscarbostyrils (4,4′-bisquinolones) can be synthesized from 4-chloro-2-quinolinones using a Pd-catalyzed one-pot borylation/Suzuki cross-coupling protocol or via Ni(0)-mediated reductive homocoupling. The electronic spectra of biscarbostyrils 4b–8 exhibit unusual properties in comparison to the corresponding carbostyrils 1–3. Similar absorption spectra are accompanied by red-shifted emission maxima up to 520 nm. Unsubstituted biscarbostyril 4b displays the unusual property of a 2500 cm−1 fluorescence redshift in water as compared to dimethylsulfoxide instead of an expected 800 cm−1 blueshift. In order to further improve redshifts and fluorescence quantum yields, varying substitution patterns were created. In bisquinolone 7, an additional diphenylphosphinoxide substitution in position 3 and 3′ (15c) increased the quantum yield to 20% and the epsilon value to 25,000. A crown ether linkage from position 6 to 6′ in biscarbostyrils improved the emission maximum from 470 to 500 nm, but the fluorescence quantum yield was raised only from 3% to 6%. Time-dependent density functional calculations of absorption and emission spectra of selected derivatives show good agreement with the corresponding experimental data. Especially, the unusual large Stoke’s shift observed for biscarbostyrils as well as their rather low fluorescence quantum yields can be rationalized on the basis of these calculations. Like 1,1′ binaphthalenes the biscarbostyril structures are axially chiral and can be functionalized in position 3 and 3′ with diphenylphosphine. Most of the racemates were baseline HPLC separated on the Pirkle type ULMO column, with separation factors of up to 2.4 for BINAP type intermediate 15a.

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.

The answer to the title question is definitely “yes” – at least for fairly small molecules. Computational procedures, namely the Weizmann (Wn) and Gaussian-3 (G3) family of methods, the complete basis set extrapolation scheme (CBS-x), the “high accuracy extrapolated ab initio thermochemistry” (HEAT) as well as the “correlation consistent composite approach” (ccCA), aimed at energies with chemical accuracy or even better (sub kJ mol−1) are described and several applications illustrating the level of accuracy that can be achieved are presented.

Density functional theory calculations on complexes of 4C1, 1C4 and 2SO ring conformations of methyl beta-D-xylopyranoside 1 with divalent metal cations, M = Mg2+, Ca2+, Zn2+, and Cd2+, are presented. Bridging and pendant cationic, [M(H2O)41]2+ and [M(H2O)(5)1]2+, as well as neutral complexes, [M(OH)2(H2O)(2)1] and [M(OH)2(H2O)(3)1], and neutral complexes involving a doubly deprotonated sugar, [M(H2O)(4)1(2-)], are considered. In aqueous and chloroform solution the stability of cationic and pendant neutral complexes is greatly diminished compared with gas-phase results. In contrast, bridging neutral complexes [M(OH)2(H2O)(2)1] and those of type [M(H2O)(4)1(2-)], are stabilized with increasing solvent polarity. Solvation also profoundly influences the preferred binding position and ring conformation. Compared with complexes of bare metal cations, additional ligands, e.g., H2O or OH-, significantly reduce the stability of 1C4 ring complexes. Irrespective of the cation, the most stable structure of bridging complexes [M(H2O)(4)1]2+ results from coordination of the metal to O3 and O4 of methyl beta-D-xylopyranoside in its 4C1 ring conformation.

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 .

The mechanism of reaction of isothiocyanates with diazopyrazoles to 4-imino-4H-pyrazolo[5,1-d] [1,2,3,5]thiatriazines was investigated. It was suggested that the reaction proceeds via a pseudopericyclic cycloaddition with activation barrier of ∼31 kcal mol−1 (B3LYP/6-31G*). The mechanism was confirmed by NBO and ACID schemes. The question of regioselectivity was also explored. It was shown that an acyl substituent on the isothiocyanate led to a stabilization of the final product due to S… O interaction. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007

The first reaction step of the redox cycle of bovine erythrocyte glutathione peroxidase from class 1 (GPX1) was investigated using hybrid quantum mechanics/molecular mechanics (QM/MM) calculations using the ONIOM methodology. The reduction of hydrogen peroxide by the active-site selenocysteine in selenolate form assisted by the Arg177 residue was modeled based on a proposal from previous molecular dynamics simulations and pKa calculations (J. Chem. TheoryComput. 2010, 6, 1670-1681). The redox reaction is predicted as a concerted SN2 nucleophilic substitution with a concomitant proton transfer from Arg177 onto leaving hydroxide ion upon reduction of hydrogen peroxide. The height of the reaction barrier was predicted in range of 6-11 kcal mol(-1), consistent with an experimental rate constant of ca. 10(7) M(-1) s(-1). The proposed GPX1-Se(-)-Arg177H(+) mechanism for GPX1 is compared with the GPX3-SeH-Gln83 one proposed for human glutathione peroxidase from class 3 (GPX3) and with the solvent-assisted proton exchange mechanism proposed for GPX-like organic selenols. The structural and energetic parameters predicted by various density functional theory methods (B3LYP, MPW1PW91, MPW1K, BB1K, M05-2X, M06-2X, and M06) are also discussed.

The tautomeric enol imine--enaminone (phenol--quinone) equilibrium of the 1-hydroxy-2-naphthaldehyde Schiff base (2-phenyliminomethyl-naphthalen-1-ol) was investigated by density functional theory (B3LYP) and ab initio (MP2) methods in the IEF-PCM polarizable continuum dielectric solvent approximation and by a combined ab initio + FEP/MC study by considering an explicit solvent model. Special emphasis was put on the effect of solvation on this equilibrium by using an apolar (CCl4), polar aprotic (CH3CN), and polar protic (CH3OH) solvent. Compared with experimental tautomerization Gibbs free energies, the IEF-PCM/B3LYP calculations apparently overestimate the stability of the quinone form both when the 6-31G(d,p) and the 6-311++G(d,p) basis sets are applied. IEF-PCM/MP2 studies with the above basis sets predict the preference of the aromatic phenol tautomer, in contrast to the experiment in methanol and acetonitrile solvent. Calculation of the total relative free energy as DeltaG(tot) = DeltaE(int)(IEF-PCM/QCISD(T)/6-31G(d)) + DeltaG(solv, FEP/MC) + DeltaG(thermal) provided agreement with the experimental values up to 0.6 kcal/mol in the three solvents, and the predominant tautomer was always correctly predicted. In-solution relevant atomic charges, derived by a fit to the molecular electrostatic potential generated by the IEF-PCM/B3LYP/6-31G(d,p) wave function, show strong dependence on the fitting procedure (CHELPG or RESP) and are fairly insensitive to the chemical nature of the actual solvent. Use of the CHELPG charges in FEP/MC simulations revealed to be superior in comparison with the use of the RESP charge set.

The product of the reaction between o-phenylenediamine and 4-dimethylaminobenzaldehyde, mp=179°, is unambiguously shown to be 1-(4-dimethylaminobenzyl)-2-(4-dimethylaminophenyl)-benzimidazole by X-ray crystallography. It crystallises in the monoclinic space group P21/c, with a=18.327(5) A, b=6.318(15) A, c=18.204(4) A, β=110.73(2)°, R1=0.0647. Quantum chemical calculations [density functional theory, B3LYP/6-31G(d)] are used to propose a reaction mechanism for the rearrangement of the initially formed bis-Schiff base via a two-step process involving cyclization (TS1, ΔG≠=32 kcal mol–1) to a tetrahedral intermediate (3, ΔGreact=30 kcal mol–1). A formal (1,3)-shift (TS2, ΔG≠=38 kcal mol–1 with respect to 3) then yields in a strongly exothermic reaction (ΔGreact=−17 kcal mol–1) the rearranged product, 1-(4-dimethylaminobenzyl)-2-(4-dimethylaminophenyl)-benzimidazole (2).

A detailed conformational search for 4C1,1C4, and 2SO ring structures of methyl s-D-xylopyranoside is performed by density functional theory calculations. For low energy structures in addition a composite energy approach is used. Complexation by divalent metal cations (Mg2+, Ca2+, Zn2+, Cd2+) induces a conformational interconversion 4C1 → 1C4. Relative Gibbs’ free energy differences between these two forms of the complexes roughly follow the respective ionic radii. In addition, for each ring conformation different binding sites of the cation are considered. In CHCl3 (PCM approximation for solvation), the shift toward the 1C4 chair form is substantially reduced or, in the case of the Cd2+ complexes, even reversed.

For a set of 7 selected stable intermediates and derived radicals for the formation of 1,3,6,8- and 1,3,7,9-tetrachlorodibenzo- p -dioxins from 2,4,6-trichlorophenol, energy minimum structures, total atomic spin densities ρ , harmonic vibrational wavenumbers ν ˜ , principal moments of inertia I A , I B , and I C , heat capacities C p o ( T ) , entropies S o ( T ) , enthalpy increments H o ( T ) − H o ( 0 ) , and standard enthalpies of formation Δ f H o ( T ) were calculated at the G3MP2B3 level of theory and presented for T = 298.15 K . A set of 7 reaction paths is characterized by means of enthalpies of reaction Δ r H o ( 298.15 ) .

A new approach to dissociable chromoionophores 5, 6a–e, 7 and 8 by reaction of (dicyanomethylene)indandione 1 and (dicyanomethylene)pyrazolones 2a–e, respectively, with aminophenyl crowns 3 and 4 is described. The complexation constants were determined by 1H-NMR spectroscopy. For the chromoionophores 5 and 6a–e bearing a benzo[15]crown-5 moiety, Kc values between 1100 and 1900 were found, while the chromoionophores 7 and 8 bearing the N-phenylaza[15]crown-5 provided binding constants which are about twenty times lower. These differences depending on the nature of the crown (aza-crown or benzo-crown with the same ring size) are discussed by comparison with a series of known crowns and also on the basis of molecular modelling techniques. The ability of the chromophore 6a as extractant for sodium and potassium ions in its ionic form is shown.

Semi-empirical (ZINDO-SOS), time-dependent density functional theory and ab initio quadratic response function (DDRPA) calculations on a series of donor–acceptor substituted salen-type Schiff bases are used to aid in the design of dyes with useful optical nonlinearities (molecular quadratic hyperpolarizabilities β vec ). 4-Phenylazo-2-phenyliminomethylphenols 1 are calculated to be less suitable as nonlinear optical materials than the isomeric 5-phenylazo-2-phenyliminomethylphenols 2 . The largest hyperpolarizabilities are predicted for compounds with an acceptor-containing phenylazo and a donor-substituted phenyliminomethyl moiety. The calculations also clearly indicate the intramolecular charge transfer nature of the first ππ ∗ -transition in the investigated Schiff bases.

1,7-Dipolar cyclizations of 1-diazo-2,4-pentadiene 1a and its heteroanalogues 1b,c and 4c were studied using density functional theory (DFT). Although the heteroanalogue 1c has an appropriate electronic structure to allow for pseudopericyclic cyclization, natural bond order (NBO) analysis has provided evidence for the electrocyclic ring closure. Magnetic criteria (anisotropy of the induced current density [ACID], nucleus-independent chemical shifts [NICS]) confirmed the pericyclic character of the located transition states 2a,c and 5c. The activation barriers for the cyclization of 1-diazo-2,4-pentadiene 1a and its aza analogues 1c, 4c are 3.3, 8.2, and 12.3 kcal/mol at the B3LYP/6-31G(d) level, respectively. The higher barrier of the 1c3c and 4c3c reactions compared with 1a3a is in line with the Hammond postulate. The out-of-plane distorted geometry of the cyclic product is an additional factor arguing against a pseudopericyclic mechanism. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006

A set of small radicals SiF, SiCl, F– C O, C N–O , O3H, NO3, CH2NC, CF3O , and O3 exhibit pronounced discrepancies between different experimental as well as experimental and calculated values of the respective enthalpies of formation ΔfHo(298.15). For stable molecules, this quantity is well established and reliable values are available. However, for free radicals and other short-lived intermediates, the situation is not nearly as favorable. Consequently, critical evaluation of thermodynamic properties of free radicals is necessary, both originating from experiment and computation. Calculated enthalpies of formation for the above systems are based on the ab initio methods G3MP2B3 and CCSD(T)–CBS (W1U) for which mean absolute deviations are known.

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 (four minimum and three transition structures) on the •O3H 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 (MAD) of 3.9 kJ mol−1 and 2.3 kJ mol−1, respectively, between experimental and calculated standard enthalpies of the formation of a set of 32 free radicals. For CCSD(T)-CBS (W1U) the well depth from O3 + H• to trans-•O3H, ΔHowell(298.15) = −339.1 kJ mol−1, as well as the reaction enthalpy of the overall reaction O3 + H•→O2 + •OH, ΔrHo(298.15) = −333.7 kJ mol−1, and the barrier of bond dissociation of trans-•O3H → O2 + •OH, ΔHo(298.15) = 22.3 kJ mol−1, affirm the stable short-lived intermediate •O3H. In addition, for radicals cis-•O3H and trans-•O3H, the thermodynamic functions heat capacity Cop(T), entropy So (T), and thermal energy content Ho(T) − Ho(0) are tabulated in the range of 100 − 3000 K. The much debated calculated standard enthalpy of the formation of the trans-•O3H resulted to be ΔfHo(298.15) = 31.1 kJ mol −1 and 32.9 kJ mol −1, at the G3MP2B3 and CCSD(T)-CBS (W1U) levels of theory, respectively. In addition, MR-ACPF-CBS calculations were applied to consider possible multiconfiguration effects and yield ΔfHo(298.15) = 21.2 kJ mol −1. The discrepancy between calculated values and the experimental value of −4.2 ± 21 kJ mol−1 is still unresolved.

Two alternative directions for thermal transformation of 6-amino-4-oxopyrano[3,4-d] [1,2,3]thiadiazoles 1, leading either to 6-hydroxy-4-oxo-[1,2,3]thiadiazolo[4,5-c]pyridines 2 or 2-cyano-2-(1,2,3-thiadiazol-5-yl)acetamide 4b, were observed. The first one represents a new, Dimroth-type rearrangement and proceeds by thermal opening of the pyrane ring, followed by the simultaneous rotational isomerization of the ketene intermediate 7 (s-cis) to 7 (s-trans) and its recyclization onto the amido group to form the pyridin-2-one cycle.The first step of the rearrangement has a calculated [B3LYP/6-31G(d)] activation barrier of 24–34 kcal/mol, the involvement of amines reduces it by ca. 5 kcal/mol [PCM-B3LYP/6-31G(d), DMSO]. In contrast, the recyclization step onto the amido group is calculated to occur essentially barrierless (ΔE < 2 kcal/mol). The influence of substituents, in particular of those capable of intramolecular hydrogen bonding, on the preferred reaction path was also studied. The alternative ring opening of the pyrane cycle was calculated to be at least 5 kcal/mol [B3LYP/6-31G(d)] less favorable than the Dimroth rearrangement. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)