Vibrational circular dichroism and theoretical study of the conformational equilibrium in (-)-S-nicotine.

We report an extensive study of the molecular and electronic structure of (-)-S-nicotine, to deduce the phenomenon that controls its conformational equilibrium and to solve its solution-state conformer population. Density functional theory, ab initio, and molecular mechanics calculations were used together with vibrational circular dichroism (VCD) and Fourier transform infrared spectroscopies. Calculations and experiments in solution show that the structure and the conformational energy profile of (-)-S-nicotine are not strongly dependent on the medium, thus suggesting that the conformational equilibrium is dominated by hyperconjugative interactions rather than repulsive electronic effects. The analysis of the first recorded VCD spectra of (-)-S-nicotine confirmed the presence of two main conformers at room temperature. Our results provide further evidence of the hypersensitivity of vibrational optical activity spectroscopies to the three-dimensional structure of chiral samples and prove their suitability for the elucidation of solution-state conformer distribution.

Study of the chelating properties of Ge(OH)2 functionality as metal binding group for Zn2+ cation in simplified protease-like environments: a DFT analysis.

The development of protease's inhibitors is an active field of research in the pharmaceutical industry. As concerns the design of new inhibitors, the theoretical study of the binding patterns and energies of known metal binding groups (MBGs) toward Zn(2+) using quantum-chemical calculations may offer a better understanding of their interaction models and may be useful for the improvement and design of novel ZBGs. Here the properties of gem-Ge(OH)(2)-based compounds as ZBG were assessed theoretically using DFT calculations. [Zn(Imdz)(2) R - OH(2)](2+) complexes (Imdz =imidazole rings; R = imidazole ring, acetic acid molecule or acetate anion) were used to partially reproduce the coordination sphere in metalloproteases (ACE, amgiotensin converting enzyme, and TLN, thermolysine) being inhibited by related compounds (i.e., silanediols). The MBG- Zn(2+) interaction was analyzed through the energy of the reaction: [Zn(Imdz)(2) R - OH(2)](2+) + L → [Zn(Imdz)(2) R - L](2+) + H(2)O using DFT (M06L/cc-pVDZ) in gas-phase and in solution (IEF-PCM). Although the functional used (M06L) has proven its efficiency to study systems containing transition metal governed by non-covalent interactions, dispersion effects were implemented by the correction of the computed energies using the DFT-D3 program. Accounting for dispersion effects produced a systematic increase of c.a. 13 kJ mol(-1) on the energies, whereas the effect of solvent goes in the opposite direction (i.e., BE under the IEF-PCM model are on average 125 kJ mol(-1) lower). The Ge(OH)(2) - Zn(2+) interaction seems to be similar (or even stronger) than the Si(OH)(2) -Zn(2+). Their better performance as ZBG is explained by the combined NBO-AIM analysis. The results of this work may encourage the preparation, isolation, and experimental assay of the chelating properties of these compounds, which may propose a new family of protease's inhibitors.

Quartic canonical force field in curvilinear internal coordinates for XY3 (D3h) molecules. The case of the BH3 molecule.

Using the canonical force field theory, expressions of quadratic, cubic, and quartic canonical force constants are obtained for XY3 (D3h) molecules in curvilinear redundant coordinates, i.e., simple valence internal coordinates (VICs), in terms of force constants in normal coordinates and in independent symmetry coordinates. To carry out this task, it was previously necessary to obtain for the first time the non-linear redundancy relation and the corresponding orthogonal projection onto the pure vibrational manifold for XY3 (D3h) molecules corresponding to a set of seven VICs. As an application, the quartic canonical force field in curvilinear redundant internal coordinates of BH3 is determined from ab initio force fields in normal coordinates calculated at the coupled-cluster singles and doubles level with perturbative treatment of the triples in conjunction with a triple- and quadruple-ζ size basis set. This anharmonic force field so obtained for the borane molecule, and in general for XY3 (D3h) molecules, is uniquely defined (therefore in an unambiguous form) and depending on the same number of parameters, i.e., force constants, when independent coordinates (natural or symmetry) are used in its description.

Quantum chemical study of silanediols as metal binding groups for metalloprotease inhibitors.

DFT (B3LYP and M06L) as well as ab initio (MP2) methods with Dunning cc-pVnZ (n=2,3) basis sets are employed for the study of the binding ability of the new class of protease inhibitors, i.e., silanediols, in comparison to the well-known and well-studied class of inhibitors with hydroxamic functionality (HAM). Active sites of metalloproteases are modeled by [R3M-OH2]²âº complexes, where R stands for ammonia or imidazole molecules and M is a divalent cation, namely zinc, iron or nickel (in their different spin states). The inhibiting activity is estimated by calculating Gibbs free energies of the water displacement by metal binding groups (MBGs) according to: [R3M-OH2]²âº + MBG → [R3M-MBG]²âº + H2O. The binding energy of silanediol is only a few kcal mol(-1) inferior to that of HAM for zinc and iron complexes and is even slightly higher for the triplet state of the (NH3)3Ni²âº complex. For both MBGs studied in the ammonia model the binding ability is nearly the same, i.e., Fe²âº(t) > Ni²âº(t) > Fe²âº(q) > Ni²âº(s) > Zn²âº. However, for the imidazole model the order is slightly different, i.e., Ni²âº(t) > Fe²âº(t) > Fe²âº(q) > Ni²âº(s) ≥ Zn²âº. Equilibrium structures of the R3Zn ²âº complexes with both HAM and silanediol are characterized by the monodentate binding, but the bidentate character of binding increases on going to iron and nickel complexes. Two types of intermediates of the water displacement reactions for [(NH3)3M-OH2]²âº complexes were found which differ by the direction of the attack of the MBG. Hexacoordinated complexes exhibit bidentate bonding of MBGs and are lower in energy for M=Ni and Fe. For Zn penta- and hexacoordinated complexes have nearly the same energy. Intermediate complexes with imidazole ligands have only octahedral structures with bidentate bonding of both HAM and dimethylsilanediol molecules.

Effect of substituents and hydrogen bonding on barrier heights in dehydration reactions of carbon and silicon geminal diols.

Activation barrier heights for the dehydration reaction of geminal carbinols and silanediols R'R″X(OH)(2) (X = C, Si) were estimated at the B3LYP and MP2 levels of theory employing Dunning's correlation-consistent triple-zeta basis sets. It was shown that the barrier height for carbon derivatives steadily decreases upon substitution by R groups, usually termed as electron-donating, such as alkyl and amino groups. Substitution by electron-withdrawing groups leads, however, only to small changes in barrier heights compared to that of methanediol. A similar tendency was also found for silicon derivatives, but high activation barriers of this reaction remain even for amino group substituted silanediols. Introduction of additional water molecules into the reactive space of carbinol dehydration drastically reduces barrier heights and brings the transition state energy for methanediol close to the experimental value. The difference between dehydration barrier heights for both methanediol and carbinols with electron-rich substituents becomes well-defined for dimeric species. The higher acidity of the hydroxyl group protons in molecules containing halogens and C==O groups brings about a noticeable growth in the dehydration barrier heights of these compounds. This difference in barrier heights for oligomeric species may be the reason for the stability of carbinols with electron-rich substituents.

Conformational preference of a chiral terpene: vibrational circular dichroism (VCD), infrared and Raman study of S-(-)-limonene oxide.

S-(-)-Limonene oxide (4-isopropenyl-1-methyl-7-oxabicyclo[4.1.0]heptane) is a secondary metabolite and an atmospheric pollutant product of oxidation of other terpenes, such as limonene and alpha-pinene, among others. For the first time, a theoretical study of the molecular structure and a theoretical and experimental analysis of the infrared and Raman spectra of this chemical species are presented. Theoretical calculations reveal the existence of two conformers depending on the position of the isopropenyl group (axial and equatorial) and twelve rotamers (six equatorials and six axials), with the six equatorial ones as the most stable (around 97%) on the basis of Boltzmann's distribution law. In the current work, from a reliable assignment of the IR and Raman spectra and with the help from the study of the VCD spectrum of the title compound, five rotamers have been detected experimentally in the liquid phase. The present work reveals that IR, Raman and VCD are helpful complementary techniques to characterize flexible systems, as terpenes, which present several conformers.

Structure and vibrational spectra of Ti(IV) hydroxides and their clusters with expanded titanium coordination. DFT study.

Equilibrium structures of H(4-n)Ti(OH)n (n = 2-4) molecules and the Ti(OH)4 dimer and trimers were optimized at the B3LYP level of theory. Theoretical vibrational frequencies of TiO stretching modes obtained with several basis sets were compared with the existing experimental frequencies of these vibrations, and the 6-31+G(d) set was chosen for cluster calculations. Only one energy minimum was found for the [Ti(OH)4](2) dimer, but two isomers without symmetry elements stabilized by internal hydrogen bonds and two isomers, belonging to C(s) and C(i) point groups, with free OH groups were found as minima at the [Ti(OH)4](3) potential energy surface. The structure with the linear arrangement of hexacoordinated titanium atoms in the Ti3O12 skeleton may be proposed for trimeric species observed in liquid titanium alkoxides as the only structure satisfying experimental spectroscopic evidence about the presence of center of inversion in these species. Frequency changes of TiO4 modes which accompany the oligomer formation are predicted and discussed.

Validation of the existence of tetrameric species of potassium trimethylsilanolate in the gas phase with a theoretical cluster model: role of the counterion as charge localizer in the structure.

We have investigated, theoretically, the structural properties of potassium trimethylsilanolate in the gas phase at a B3LYP/6-31+G* level. For this purpose, a simplified ionic cluster model based on potassium trimethylsilanolate tetramers, proposed in the literature as the structural units of this compound in the solid state, was developed. Furthermore, we compared the validity of the model with two simpler ones: a monomer of potassium trimethylsilanolate and a trimethylsilanolate anion in the gas phase. The developed ionic cluster model was found to be best in reproducing the experimental structure of potassium trimethylsilanolate, supporting, at the same time, the existence of such tetrameric species (previously identified experimentally from mass spectrometry data by Weiss et al.) in the gas phase. Finally, NBO calculations highlighted the important role of the potassium counterion as a charge localizer in the structure of these chemical species.