Structural properties of methanol-water binary mixtures within the quantum cluster equilibrium model.

Density functional theory (B3LYP-D3, M06-2X) has been used to calculate the structures, interaction energies and vibrational frequencies of a set of 93 methanol-water clusters of different type (cubic, ring, spiro, lasso, bicyclic), size and composition. These interaction energies have been used within the framework of the Quantum Cluster Equilibrium Theory (QCE) to calculate cluster populations as well as thermodynamic properties of binary methanol-water mixtures spanning the whole range from pure water to pure methanol. The necessary parameters amf and bxv of the QCE model were obtained by fitting to experimental isobars of MeOH-H2O mixtures with different MeOH content. The cubic and spiro motifs dominate the distribution of methanol-water clusters in the mixtures with a maximum of mixed clusters at x(MeOH) = 0.365. Reasonable agreement with experimental data as well as earlier molecular dynamics simulations was found for excess enthalpies H(E), entropies S(E) as well as Gibbs free energies of mixing G(E). In contrast, heat capacities Cp and C showed only poor agreement with experimental data.

Comparison of Chirasil-DEX CB as gas chromatographic and ULMO as liquid chromatographic chiral stationary phase for enantioseparation of aryl- and heteroarylcarbinols.

For a broad spectrum of simple chiral alcohols, incorporating a (substituted) (het)aryl building block, enantiomer separation characteristics are reported for both gas chromatography on a Chirasil-DEX phase, and liquid chromatography on an (S,S)-ULMO phase. On this chiral Pirkle-type phase, homochiral enantiomers (mostly R) are eluted first without exception. The elution order R before S appears conserved as a rule also for gas chromatographic separations on Chirasil-DEX, though with some remarkable exceptions indicating a change in the dominant discriminative mechanism. This was shown in the homologous series 1-phenylethanol to 1-phenylhexanol having the point of reversal at C4, while the o-methoxy analogues elute from C1 to C4 already in the reversed order.

Absolute configuration in 4-alkyl- and 4-aryl-3,4-dihydro-2(1H)-pyrimidones: a combined theoretical and experimental investigation.

Structural features (orientation of the carboxyl group, ring puckering), electronic absorption, and circular dichroism spectra of 4-alkyl- and 4-aryl-dihydropyrimidones 1-5 are calculated by semiempirical (AM1, INDO/S), ab initio (HF/6-31G, CIS/6-31G, RPA/6-31G), and density functional theory (B3LYP/6-31G) methods. These calculations allow an assignment of the absolute configuration by comparison of simulated and experimental CD spectra. Although the ab initio methods greatly overestimate electronic transition energies, the general appearance of the experimental CD spectra is quite nicely reproduced by these calculations. Thus, comparison of experimental with calculated CD spectra is a reliable tool for the assignment of the absolute configuration. For 4-methyl derivatives 1, the first enantiopure DHPM examples with no additional aromatic substituent, the stereochemistry at C4 provided by the theoretical results is confirmed by X-ray structure determination of the diastereomeric salt 6. Additional support is the consistent HPLC elution order found for all investigated DHPMs on a cellulose-derived chiral stationary phase.

Quantitative structure-enantioselective retention relationships for chromatographic separation of arylalkylcarbinols on Pirkle type chiral stationary phases.

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.

Nucleophilic substitution by a hydroxide ion at a vinylic carbon: ab initio and density functional theory studies on methoxyethene, 3-methoxypropenal, 2,3-dihydro-4H-pyran-4-one, and 4H-pyran-4-one.

Nucleophilic substitutions by a hydroxide ion at vinylic carbons of methoxyethene (system A), 3-methoxypropenal (system B), 2,3-dihydro-4H-pyran-4-one (system C), and 4H-pyran-4-one (system D) were calculated by Becke's three-parameter hybrid density functional-HF method with the Lee-Yang-Parr correlation functional (B3LYP//B3LYP) and the second-order Møller-Plesset theory (MP2//B3LYP) using the 6-31+G(d) and AUG-cc-pVTZ basis sets. In addition, bulk solvent effects (aqueous solution) were estimated by the polarized continuum (overlapping spheres) model (PCM-B3LYP//B3LYP) and the polarizable conductor PCM model (CosmoPCM-B3LYP//B3LYP). The mechanisms as well as the influence of resonance, cyclic strain, aromatic, and polar effects on the reactivity of the calculated systems were determined. In the gas phase the rate-determining step of nucleophilic vinylic substitutions by a hydroxide ion may be either addition of hydroxide ion at the vinylic carbon (systems A and B) or elimination of the leaving group (systems C and D). In aqueous solution, for all four systems investigated, addition of hydroxide ion at the vinylic carbon is rate determining.

Classical QSAR and comparative molecular field analyses of the host-guest interaction of organic molecules with cyclodextrins.

The application of classical QSAR and molecular modeling analysis using Comparative Molecular Field Analysis (CoMFA) to the complexation of some natural and modified cyclodextrins (CDs) with guest molecules was examined. For 1:1 complexation systems between natural beta-CD, modified alpha-, beta-, and gamma-CD that bear one p-(dimethylamino)benzoyl (DMAB) moiety (DMAB-alpha-, beta-, and gamma-CDs) and guest molecules of widely varying chemical structures and properties, the binding constants of the complexes were successfully fitted using multiple linear regression (MLR) with hydrophobic descriptor log P (the partition coefficient between 1-octanol and water phases) and molecular connectivity indices. A non-linear dependency of binding constants on the zero-th and/or first order molecular connectivity index as a measure of size becomes apparent. The modeling performance of the CoMFA models with steric/electrostatic fields to DMAB-alpha- and beta-CD systems was comparable to those of MLR models. However, statistically significant CoMFA models for gamma-CD systems which have higher conformational flexibility of the ring could not be obtained. The CoMFA models obtained for DMAB-alpha- and beta-CD systems showed that the predominant effects were steric for the DMAB-alpha-CD system and electrostatic for the DMAB-beta-CD system, respectively.

Combined use of NMR, distance geometry and MD calculations for the conformational analysis of opioid peptides of the type [D(L)-Cys2, D(L)-Cys5]enkephalin.

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-D-Cys2-Gly3-Phe4-D-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-Tyr1-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.