Structural and functional implications of the interaction between macrolide antibiotics and bile acids.

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.

Disentangling scalar coupling patterns by real-time SERF NMR.

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.

Spectroscopic and quantum mechanical investigation of N,N'-bisarylmalonamides: solvent and structural effects.

The UV absorption spectra of ten N,N'-bisarylmalonamides have been recorded in the range 200-400 nm in a set of selected solvents. The solute-solvent interactions have been analyzed on the basis of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The effects of substituents on the absorption spectra have been interpreted by correlating absorption frequencies with Hammett substituent constants.

Long wavelength absorbing carbostyrils as test cases for different TDDFT procedures and solvent models.

The vertical excitation energies of 3,4-dicyano-6-methoxy and 3,4-dicyano-6,7-dimethoxy carbostyril have been computed with different approximations for the time-dependent density functional theory (TD-DFT) procedure and with different implementations of the continuum solvation model COSMO. Different DFT functionals were tested in TD-DFT and Tamm-Dancoff approximations (TDA) for the excitation energies in the gas phase. TDA-B3LYP showed the best agreement with the experimental data.

Phenol-quinone tautomerism in (arylazo)naphthols and the analogous Schiff bases: benchmark calculations.

Tautomerization energies of a series of isomeric [(4-R-phenyl)azo]naphthols and the analogous Schiff bases (R = N(CH3)2, OCH3, H, CN, NO2) are calculated by LPNO-CEPA/1-CBS using the def2-TZVPP and def2-QZVPP basis sets for extrapolation. The performance of various density functionals (B3LYP, M06-2X, PW6B95, B2PLYP, mPW2PLYP, PWPB95) as well as MP2 and SCS-MP2 is evaluated against these results. M06-2X and SCS-MP2 yield results close to the LPNO-CEPA/1-CBS values.

Spectroscopic behavior of loratadine and desloratadine in different aqueous media conditions studied by means of TD-DFT calculations.

In this study, we explained the influence of the stepwise protonation of two antihistaminic drugs on their experimental absorption spectra. We demonstrated the capability of the TD-CAM-B3LYP method, combined with a polarizable continuum model, to produce good performance for the calculated spectra. The lowest energy transitions and the molecular orbital plots were analyzed in detail.

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione.

The reaction of cyclobutane-1,2-dione with hydroxide was studied by a variety of ab initio (MP2, SCS-MP2, CCSD(T), CEPA/1) and density functional (M06-2X) methods. Three possible reaction paths of the initially formed tetrahedral adduct leading to either 1-hydroxycyclopropane-1-carboxylate (benzilic acid type rearrangement, path A), α-oxobutanoate (path B) or γ-oxobutanoate (path C) were considered. Although the latter two products show similar or even more negative Gibbs free energies of reaction than calculated for the benzilic acid type rearrangement, the Gibbs free energies of activation are substantially higher.

Unusual C=C bond isomerization of an α,β-unsaturated γ-butyrolactone catalysed by flavoproteins from the old yellow enzyme family.

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.

A substrate-driven approach to determine reactivities of α,β-unsaturated carboxylic esters towards asymmetric bioreduction.

The degree of C=C bond activation in the asymmetric bioreduction of α,β-unsaturated carboxylic esters by ene-reductases was studied, and general recommendations to render these "borderline-substrates" more reactive towards enzymatic reduction are proposed. The concept of "supported substrate activation" was developed. In general, an additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates, and α-cyano groups showed little effect.

Coordination of methanol clusters to benzene: a computational study.

Benzene-methanol cluster structures were investigated with theoretical chemistry methods to describe the microsolvation of benzene and the benzene-methanol azeotrope. Benzene-methanol (MeOH) clusters containing up to six methanol molecules have been calculated by ab initio [MP2/6-311++G(d,p)//MP2/6-31+G(d,p) + BSSE correction] method. The BSSE was found quite large with this basis set, hence, different extrapolation schemes in combination with the aug-cc-pVxZ basis sets have been used to estimate the complete basis set limit of the MP2 interaction energy [ΔE(MP2/CBS)].

Hybrid QM/MM Calculations on the First Redox Step of the Catalytic Cycle of Bovine Glutathione Peroxidase GPX1.

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.

Application of the Quantum Cluster Equilibrium (QCE) model for the liquid phase of primary alcohols using B3LYP and B3LYP-D DFT methods.

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.

Reductive biotransformation of nitroalkenes via nitroso-intermediates to oxazetes catalyzed by xenobiotic reductase A (XenA).

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.

A highly efficient ADH-coupled NADH-recycling system for the asymmetric bioreduction of carbon-carbon double bonds using enoate reductases.

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).

Theoretical prediction of pKa values of seleninic, selenenic, sulfinic, and carboxylic acids by quantum-chemical methods.

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.

Dibenzocyclooctadiene lignans from Magnolia and Talauma (Magnoliaceae): their absolute configuration ascertained by circular dichroism and X-ray crystallography and re-evaluation of previously published pyramidatin structures.

Twelve pyramidatins, i.e., dibenzocyclooctadiene-type lignans, together with Machilin G, were isolated from the dichloromethane extracts of aerial material of Talauma gloriensis, Magnolia fraseri, and Magnolia pyramidata (Magnoliaceae).

Theoretical Study on the Redox Cycle of Bovine Glutathione Peroxidase GPx1: pKa Calculations, Docking, and Molecular Dynamics Simulations.

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.

Derivatives of schisandrin with increased inhibitory potential on prostaglandin E(2) and leukotriene B(4) formation in vitro.

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.

Biocatalytic carboxylation.

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).

On- and off column enantiomerization of 4,4'-bisquinolin-2-ones: A comparison of Auto-, DHPLcy2k and DCXplorer calculated thermodynamic data generated by dynamic high, performance liquid chromatography with theoretically calculated data.

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).

Absolute configuration of eremophilane sesquiterpenes from Petasites hybridus: comparison of experimental and calculated circular dichroism spectra.

In-depth conformational analyses of 10 known eremophilane (= (1S,4aR,7R,8aR)-decahydro-1,8a-dimethyl-7-(1-methylethyl)napththalene) sesquiterpenes, 1-10, from Petasites hybridus were performed with molecular mechanics as well as density functional theory methods. Electronic transition energies and rotational strengths of these eight eremophilane lactones and two petasins were calculated by time-dependent density functional theory (B3PW91/TZVP). The absolute configurations of the constituents could be assigned by comparison of their simulated and experimental circular dichroism (CD) spectra in methanol as (4S,5R,8S,10R) (1, 2), (2R,4S,5R,8S,10R) (3, 4, 5), (2R,4S,5R,8R,9R,10R) (6), (2R,4S,5R,8R,10R) (7, 8), and (3R,4R,5R) (9, 10).

Antimycobacterial and H1-antihistaminic activity of 2-substituted piperidine derivatives.

2-Substituted derivatives of the antihistaminic agents Bamipine, Diphenylpyraline and of their 1-phenyl analogues were tested for their antimycobacterial and H(1)-antagonistic activities. They are strong H1-receptor antagonists and also inhibit the growth of mycobacterials with a maximum MIC of 6.25 microg/mL against Mycobacterium tuberculosis H(37)Rv.

One-way biohydrogen transfer for oxidation of sec-alcohols.

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.

Interaction of methyl beta-D-xylopyranoside with metal ions: density functional theory study of cationic and neutral bridging and pendant complexes.

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.

Structure-acidity-IR spectra correlations for p-substituted N-phenylsulfonylbenzamides.

The wavenumbers of the IR absorption bands of the C=O, S=O and N-H stretching vibrations for a series of p-substituted N-phenylsulfonylbenzamides were measured in trichloromethane. The bond orders, Mulliken charges, charge densities and heats of formation were calculated using the PM3 method. Fifty significant mutual mono parameter (MP) and six dual parameter (DP) correlations were found for the IR spectral, theoretical structural data, substituent constants and previously reported dissociation constants in five polar organic solvents.