Molecular mechanics calculations on carbonyl compounds. III. Cycloketones

Molecular mechanics (MM4) calculations were carried out on cycloketones for ring sizes ranging from 4 to 11 carbon atoms. The MM4 relative energies for the various conformations of the cycloketones were compared to density functional theory (DFT) calculations (B3LYP/6‐31G*), which were also carried out in this work. For small ring sizes (n=4–6), calculated molecular geometries, dipole moments, moments of inertia, and vibrational spectra were compared to experimental data. The axial–equatorial energy differences in methyl‐substituted cyclohexanones were also calculated by MM4 and compared to ab initio, DFT, and experimental results. The results of the MM4 studies on cycloketones showed significant improvement from those of MM3 calculations performed in parallel with the MM4 calculations. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1451–1475, 2001     

Molecular mechanics calculations on carbonyl compounds. IV. Heats of formation

Molecular mechanics (MM4) calculations on the heats of formation of aldehydes and ketones were carried out for a total of 59 compounds (10 aldehydes and 49 ketones). Optimization of the heat of formation parameters was obtained by a least squares fit to the experimentally known heats of formation. With the optimized MM4 heat of formation parameters, the MM4 calculated heats of formation showed significant improvement over those of MM3. The standard and weighted root mean square deviations for the MM4 values were 0.35 and 0.31 kcal mol^?1, respectively, whereas for the MM3 values they were 0.42 and 0.39 kcal mol^?1, respectively. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1476–1483, 2001     

Molecular mechanics (MM4) calculations on carbonyl compounds part I: aldehydes

Aliphatic aldehydes have been studied with the aid of the MM4 force field. The structures, moments of inertia, vibrational spectra, conformational energies, barriers to internal rotation, and dipole moments have been examined for six compounds (nine conformations). MM4 parameters have been developed to fit the indicated quantities to the wide variety of experimental data. Ab initio (MP2) and density functional theory (B3LYP) calculations have been used to augment and/or replace experimental data, as appropriate. Because more, and to some extent, better, data have become available since MM3 was developed, it was anticipated that the overall accuracy of the information calculated with MM4 would be better than with MM3. The best single measure of the overall accuracy of a force field is the accuracy to which the moments of inertia of a set of compounds (from microwave spectroscopy) can be reproduced. For all of the 20 moments (seven conformations) experimentally known for the aldehyde compounds, the MM4 rms error is 0.30%, while with MM3, the most accurate force field presently available, the rms error over the same set is 1.01%. The calculation of the vibrational spectra was also improved overall. For the four aldehydes that were fully analyzed (over a total of 78 frequencies), the rms errors with MM4 and MM3 are 18 and 38 cm^?1, respectively. These improvements came from several sources, but the major ones were separate parameters involving the carbonyl carbon for formaldehyde, the alkyl aldehydes and the ketones, and new crossterms featured in the MM4 force field that are not present in the MM3 version. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1396–1425, 2001     

Molecular mechanics (MM3) calculations on lithium amide compounds

The MM3 force field has been extended to deal with the lithium amide molecules that are widely used as efficient catalysts for stereoselective asymmetric synthesis. The MM3 force field parameters have been determined on the basis of the ab initio MP2/6-31G* and/or DFT (B3LYP/6-31G*, B3-PW91/6-31G*) geometry optimization calculations. To evaluate the electronic interactions specific to the lithium amides derived from the diamine molecules properly, the Lewis bonding potential term for the interaction between the lithium atom and the nonbonded adjacent electronegative atom such as nitrogen was introduced into the MM3 force field. The bond dipoles were evaluated correctly from the electronic charges on the atoms calculated by fitting to the electrostatic potential at points selected. The MM3 results on the molecular structures, conformational energies, and vibrational spectra show good agreement with those from the quantum mechanical calculations.     

Molecular mechanics (MM4) study of amines

The MM4 force field has been extended to include aliphatic amines. About 20 amines have been examined to obtain a set of useful molecular mechanics parameters for this class. The vibrational spectra of seven amines (172 frequencies) calculated by MM4 have an overall rms error of 27 cm(-1), compared with corresponding MM4 value of 24 cm(-1) for alkanes. The rms and signed average errors of the moments of inertia of nine simple amines compared with the experimental data were 0.18% and -0.004%, respectively. The heats of formation of 30 amines were also studied. The MM4 weighted standard deviation is 0.41 kcal/mol, compared with experiment. Electronegativity effects occur in the hydrocarbon portion of an amine from the nitrogen, and are accounted for by including electronegativity induced changes in bond lengths and angles, and induced dipole-dipole interactions in the molecule. Negative hyperconjugation results from the presence of the lone pair of electrons on nitrogen, and leads to the Bohlmann bands in the infrared, and also to strong and unusual geometric changes in the molecules (Bohlmann effect), all of which are fairly well accounted for. The conformational energies in amines appear to be less straightforward than those for most other classes of molecules, apparently because of the Bohlmann effect, and these are probably not yet completely understood. In general, the agreement between the MM4 calculated results and the available data is reasonably good.     

Alcohols,ethers, carbohydrates,and related compounds. I. The MM4 force field for simple compounds

Simple alcohols and ethers have been studied with the MM4 force field. The structures of 13 molecules have been well fit using the MM4 force field. Moments of inertia have been fit with rms percentage errors as indicated: 18 moments for ethers, 0.28%; 21 moments for alcohols, 0.22%. Rotational barriers and conformational equilibria have also been examined, and the experimental and ab initio results are reproduced substantially better with MM4 than they were with MM3. Much of the improvement comes from the use of additional interaction terms in the force constant matrix, of which the torsion-bend and torsion-torsion are particularly important. Induced dipoles are included in the calculation, and dipole moments are reasonably well fit. It has been possible for the first time to fit conformational energetic data for both open chain and cyclic alcohols (e.g., propanol and cyclohexanol) with the same parameter set. For vibrational spectra, over a total of 82 frequencies, the rms error is 27 cm(-1), as opposed to 38 cm(-1) with MM3. Both the alpha and beta bond shortening resulting from the presence of the electronegative oxygen atom in the molecule are well reproduced. The electronegativity of the oxygen is sufficient that one must also include not only the alpha and beta electronegativity effects on bond lengths, but also on angle distortions, if structures are to be well reproduced. The heats of formation of 32 alcohols and ethers were fit overall to within experimental error (weighted standard deviation error 0.26 kcal/mol).     

Atomistic insight into chondroitin‐6‐sulfate glycosaminoglycan chain through quantum mechanics calculations and molecular dynamics simulation

Chondroitin‐6‐sulfate (C6S) is a glycosaminoglycan (GAG) constituent in the extracellular matrix, which participates actively in crucial biological processes, as well as in various pathological conditions, such as atherosclerosis and cancer. Molecular interactions involving the C6S chain are therefore of considerable interest. A computational model for atomistic simulation was built. This work describes the design and validation of a force field for a C6S dodecasaccharide chain. The results of an extensive molecular dynamics simulation performed with the new force field provide a novel insight into the structure and dynamics of the C6S chain. The intramolecular H‐bonds in the disaccharide linkage region are suggested to play a major role in determining the chain structural dynamics. Moreover, the unravelling of an additional H‐bond involving the sulfate groups in C6S is interesting as changes in sulfation have been claimed to be an important factor in several diseases. The force field will prove useful for future studies of crucial interactions between C6S and various nanoassemblies. It can also be used as a basis for modeling of other GAGs. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

d‐electron count,ion‐pairing and diagonal twist angles in metallo‐bis(dithiolene) complexes

Electronic structure calculations for late transition metals coordinated by two dithiolene ligands are found to be consistent with existing structures and also predict the geometries of Ni(I) species for which no solid state structures have been reported. Of particular interest are the compounds [M(mnt)₂]^{n −} (M = Ni, Pd, and Pt with n = 1, 2, 3; M = Cu with n = 2). Calculations have been performed with and without ion‐paring with M(diglyme)⁺ (M = Li, Na, K) and R₄N⁺ (R = Me, Bu). The diagonal twist angle between two NiS₂ planes is found to depend on (i) the metal's d‐electron count, spanning from 0° (planar d⁷ and d⁸), to 42° (d⁹), to 90° (pseudo‐tetrahedral d¹⁰), and (ii) the identity of the ion‐paired cations. Calculated ion‐pairing energies are functions of the cation size and charge‐density, being larger for alkali‐metal coordinated diglyme and smaller for tetra‐alkyl ammonium cations. © 2016 Wiley Periodicals, Inc.     

A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations

Molecular mechanics models have been applied extensively to study the dynamics of proteins and nucleic acids. Here we report the development of a third-generation point-charge all-atom force field for proteins. Following the earlier approach of Cornell et al., the charge set was obtained by fitting to the electrostatic potentials of dipeptides calculated using B3LYP/cc-pVTZ//HF/6-31G** quantum mechanical methods. The main-chain torsion parameters were obtained by fitting to the energy profiles of Ace-Ala-Nme and Ace-Gly-Nme di-peptides calculated using MP2/cc-pVTZ//HF/6-31G** quantum mechanical methods. All other parameters were taken from the existing AMBER data base. The major departure from previous force fields is that all quantum mechanical calculations were done in the condensed phase with continuum solvent models and an effective dielectric constant of epsilon = 4. We anticipate that this force field parameter set will address certain critical short comings of previous force fields in condensed-phase simulations of proteins. Initial tests on peptides demonstrated a high-degree of similarity between the calculated and the statistically measured Ramanchandran maps for both Ace-Gly-Nme and Ace-Ala-Nme di-peptides. Some highlights of our results include (1) well-preserved balance between the extended and helical region distributions, and (2) favorable type-II poly-proline helical region in agreement with recent experiments. Backward compatibility between the new and Cornell et al. charge sets, as judged by overall agreement between dipole moments, allows a smooth transition to the new force field in the area of ligand-binding calculations. Test simulations on a large set of proteins are also discussed.     

New rhodium(II) catalyzed synthesis of 1,4-dicarbonyl compounds from α-diazo ketones using vinyl ethers as two-carbon synthons

Rhodium(II) acetate catalyzed reactions of various α-diazo ketones, and vinyl ethers afforded γ-ketoaldehydes or 1,4-diketones in a facile manner. In this process, oxycyclopropanes are formed as intermediates, and are subsequently ring opened in the presence of the rhodium(II) acetate catalyst to furnish the corresponding 1,4-dicarbonyl compounds. The scope of this protocol has been demonstrated with the synthesis of a serotonin antagonist.     

Metal and solvent‐free cyanosilylation of carbonyl compounds with tris(pentafluorophenyl)borane

A highly effective method of the cynaosilylation of aldehydes and ketones with TMSCN in the presence of catalytic amount of B(C₆F₅)₃ [tris(pentafluorophenyl)borane] has been developed. Cyano transfer from TMSCN to carbonyl group proceeds at room temperature under solvent‐free conditions. Various alehydes and ketones have been converted into the corresponding trimethylsilylether within short reaction times with excellent yield under mild conditions. Copyright © 2008 John Wiley & Sons, Ltd.