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.     

Molecular mechanics (MM3) parameterization for oxocarbenium ions

The physical properties of a diverse group of 12 oxocarbenium ions have been studied with ab initio calculations at the MP2/6‐31+G* level of theory. Based on theoretically derived properties such as molecular equilibrium geometry, dipole moment, and vibrational frequencies, a molecular mechanics (MM3) force field has been developed with the assistance of the programs TORSMART and MPMSR, components of our artificial parameter development and refinement method. The MM3 force field is now able to reproduce bond lengths, bond angles, moments of inertia, dipole moments, torsional energy profiles, and vibrational frequencies of oxocarbenium ions, which will allow further studies of glycoside hydrolysis and their rates of reaction. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 329–339, 2000     

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 (MM2) calculations and cone angles of phosphine ligands

Molecular mechanics (MM2) calculations were performed on 54 conformations of 18 phosphines (PH₃; PH_3−nR_n, where n = 1,…3, and R = Me and Et, n = 1 or 2 and R =ⁱPr, and n = 1 and R =^tBu, PMe₂Et, PMeEt₂, and PPhMe₂, and PPh₂R where R = Me, Et, ⁱPr, ^tBu and Ph). The results are compared to those previously obtained from MINDO/3 and MNDO calculations, and to experimental data. Single conformer cone angles and weighted average cone angles were calculated from MM2 optimized geometries employing Tolman's general definition, and they are compared to Tolman's values, MINDO/3 results, and T.L. Brown's E_R values. Of the cone angle definitions used, the weighted average values are suggested as the best single representation of phosphine ligand sizes. The steric parameters (cone angle and E_R values) alone, and in conjunction with electronic parameters, are correlated with experimental data.     

Molecular mechanics (MM4) study of fluorinated hydrocarbons

A molecular mechanics study of small saturated hydrocarbons (up to C-6) substituted by up to six fluorines has been carried out with the MM4 force field. A parameter set has been developed for use in the calculation of bond lengths, bond angles, torsion angles, conformational energies, barriers to rotation, dipole moments, moments of inertia, and vibrational frequencies for these compounds. The results are mostly in fair to good agreement with experiment and ab initio calculations. The high electronegativity of fluorine leads to serious geometric consequences in these compounds, but these consequences can be dealt with adequately by suitable cross-terms in the force constant matrix, and by recognizing that some of the reference bond lengths and angles (l(0), theta(0)) and the corresponding stretching and bending constant parameters (k(s), k(theta)) that are usually thought of as constants must in fact be treated as functions of the electronegativity of the substituents. Additionally, the heavy mass of the fluorine (relative to the mass of hydrogen in alkanes) leads to large values for other cross-terms that were found to be unimportant in hydrocarbons. Conformational equilibria for polyfluorinated compounds are affected by the delta-two effect well-known in carbohydrates. A few larger fluorinated and polyfluorinated alkanes, including perfluoropropane, perfluorobutane, and Teflon, have also been studied.     

Rotational barriers of disilane,hexafluorodisilane, and hexamethyldisilane: Ab initio,density functional,and molecular mechanics (MM3) studies

We investigated structures, vibrational frequencies, and rotational barriers of disilane (Si₂H₆), hexafluorodisilane (Si₂F₆), and hexamethyldisilane (Si₂Me₆) by using ab initio molecular orbital and density functional theories. We employed four different levels of theories (i.e., HF/6–31G*, MP2/6–31G*, BLYP/6–31G*, and B3LYP/6–31G*) to optimize the structures and to calculate the vibrational frequencies (except for Si₂Me₆ at MP2/6–31G*). MP2/6–31G* calculations reproduce experimental bond lengths well, while BLYP/6–31G* calculations largely overestimate some bond lengths. Vibrational frequencies from density functional theories (BLYP/6–31G* and B3LYP/6–31G*) were in reasonably good agreement with experimental values without employing additional correction factors. We calculated the ΔG^‡(298 K) values of the internal rotation by correcting zero-point vibration energies, thermal vibration energies, and entropies. We performed CISD/6–31G*//MP2/6–31G* calculations and found the ΔG^‡(298 K) values for the internal rotation of Si₂H₆, Si₂F₆, and Si₂Me₆ to be 1.36, 2.06, and 2.69 kcal/mol, respectively. The performance of this level was verified by using G2 and G2(MP2) methods in Si₂H₆. According to our theoretical results, the ΔG^‡(298 K) values were marginally greater than the ΔE^‡(0 K) values in Si₂F₆ and Si₂Me₆ due to the contribution of the entropy. In Si₂H₆ the ΔE^‡(0 K) and ΔG^‡(298 K) values were coincidently similar due to a cancellation of two opposing contributions between zero-point and thermal vibrational energies, and entropies. Our calculated ΔG^‡(298 K) values were in good agreement with experimental values published recently. In addition, we also performed MM3 calculations on Si₂H₆ and Si₂Me₆. MM3 calculated rotational barriers and thermodynamic properties were compared with high level ab initio results. Based on this comparison, MM3 calculations reproduced high level ab initio results in rotational barriers and thermodynamic properties of Si₂H₆ derivatives including vibrational energies and entropies, although large errors exist in some vibrational frequencies. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1523–1533, 1997     

Molecular mechanics calculations (MM3) on sulfones

The structures of several sulfones, including dimethyl sulfone, methyl ethyl sulfone, methyl vinyl sulfone, and diphenyl sulfone, have been fit with the MM3 force field to existing experimental data from electron diffraction and microwave spectroscopy. The vibrational spectra have also been fit for six of these compounds. The torsional parameters for the aliphatic sulfones were fit to ab initio 6-31G data. Heats of formation were also fit. © 1993 John Wiley & Sons, Inc.     

A molecular mechanics (MM3) study of fluorinated hydrocarbons

A molecular mechanics study of small saturated hydrocarbons (up to C-6), substituted by up to six fluorines was carried out with the MM3 force field. Perfluorobutane and Teflon were also studied. A parameter set was developed for use in the calculation of bond lengths, bond angles, torsion angles, conformational energies, barriers to rotation, dipole moments, moments of inertia and vibrational frequencies for these compounds. The results are in good agreement with experiment when only one or two fluorines are present, but some rather large discrepancies were noted when the F/H ratio becomes high. These can be taken into account only by using a force field more complicated than MM3. Some of the requirements of such a force field are delineated. Some pertinent ab initio results are also reported in this article.     

Conformational analysis of synthetic neolignans active against leishmaniasis,using the molecular mechanics method (MM2)

Conformational analysis of 20 neolignans was performed to determine the most probable conformer that may fit the receptor. The molecular mechanics method (MM2) was employed to construct conformational maps in both a vacuum and a biological environment. Boltzmann's distribution among several local minima was calculated. © 1997 by John Wiley & Sons, Inc. J Comput Chem 18: 712–721, 1997     

Efficient treatment of out-of-plane bend and improper torsion interactions in MM2, MM3, and MM4 molecular mechanics calculations

Simple and very efficient formulas are presented for four-body out-of-plane bend (used in MM2 and MM3 force fields) and improper torsion (used in the MM4 force field) internal coordinates and their first and second derivatives. The use of a small set of bend and stretch intermediates allows for order of magnitude decreases in calculation time for potential energies and their first and second derivatives, which are required in molecular mechanics calculations. The formulas are eminently suitable for use in molecular simulations of systems with complicated bond networks. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1804–1811, 1997     

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 calculations (MM2 and MM3) on enamines and aniline derivatives

The MM2 and MM3 force fields have been extended to cover this class of compounds. Structures, vibrational spectra, and other data for 13 compounds were examined and can be reproduced satisfactorily by MM3. Except for the spectra, the other data can be reproduced somewhat less well by MM2. © 1994 by John Wiley & Sons, Inc.     

Molecular mechanics (MM3) calculations on alkyl radicals

The MM3 force field has been extended to cover alkyl radicals. Structures, conformational energies, vibrational spectra, and heats of formation have been well fit, mostly to ab initio data. © 1994 by John Wiley & Sons, Inc.     

Molecular mechanics (MM3) calculations on azoxy compounds

The MM3 force field has been extended to include azoxy compounds and also the related amine oxides, both aliphatic and aromatic. The structures of nine molecules were all well fit. The heats of formation for the aliphatic compounds were also well fit, and the vibrational spectra of eight compounds were also fit to the accuracy expected for such calculations. Because many of the experimental data needed to derive the force field were either lacking or were inadequate, ab initio calculations on structures, optimized at the MP2/6-31G* level, were used as needed. © 1994 by John Wiley & Sons, Inc.     

Molecular mechanics (MM3) calculations on conjugated hydrocarbons

The MM3 molecular mechanics program has been extended to conjugated systems. A VESCF method is applied to the pi-system to calculate bond orders, from which various stretching and torsional parameters are obtained. The procedure gives somewhat better results than the analogous MM2 calculations. It has been applied to a study of 81 compounds of aromatic and other conjugated hydrocarbons, as well as 45 alkenes and unconjugated polyenes. The structures calculated are generally in good agreement with experiment, and the heats of formation of these compounds can be calculated with a rms value of 0.62 kcal/mol, which may be compared with the average experimental error of 0.61 kcal/mol. In addition, vibrational frequencies for five representative conjugated model structures are calculated, with an rms value of 46 cm^?1, and from these, other properties such as entropy can be calculated.     

Molecular mechanics calculations (MM3) on bicycloalkyl hydrocarbons

A series of bicycloalkyl hydrocarbons were studied using molecular mechanics methods (MM3), and the results were compared with the experimental data available. Five compounds were studied: bicyclopropyl, bicyclobutyl, bicyclopentyl, bicyclohexyl and 2,3-dimethylbutane. In general, the MM3 results are in good agreement with experimental values. Predicted structures and conformations are given for the bicyclopentyl previously uninvestigated experimentally.     

Ab initio calculations and molecular mechanics (MM3) force field development for ammonium and protonated aliphatic amines

The geometries and vibrational frequencies of 11 training molecules containing the ammonium ion moiety were calculated at the MP2/6-31+G* level of theory. Various torsional energy profiles were also calculated using this basis set. From those ab initio calculations, a molecular mechanics (MM3) force field was developed using our Parameter Analysis and Refinement Toolkit System (PARTS). Using this set of parameters, the MM3 force field was found to well reproduce the molecular geometries and vibrational spectra for the all training molecules. CPU time was reduced from days to seconds. The availability of this new force field dramatically increases the feasibility of the computer-assisted drug design involving ammonium and protonated amino groups. © 1997 by John Wiley & Sons, Inc. J Comput Chem 18 : 1371–1391, 1997     

Molecular mechanics (MM3) parameterization of hydroxylamine and methyl derivatives

Based on results of electron diffraction, gas phase infrared spectroscopy (IR), and MP2/6-31 + G* ab initio calculations, a set of molecular mechanics (MM3) parameters was developed for molecules containing the N(sp³)—O(sp³) moiety. Using this set of parameters, MM3 is able to reproduce structures (bond lengths and bond angles) and vibrational spectra satisfactorily. © 1994 by John Wiley & Sons, Inc.     

Halogenation of dichloro- and dibromovinyl(phenyl) sulfides

Bromination of 2,2-dichlorovinyl(phenyl) sulfide with bromine afforded a product that, upon heating or addition of zinc, cleaved the bromine to form the original sulfide. Chlorination of 2,2-dibromovinyl(phenyl) sulfide with chlorine resulted in substitution of a bromine atom by chlorine and/or hydrogen at the double bond as well as cleavage of the C-S bond to form polyhaloethenes, polyhalosulfides, and chlorinated dithioethenes. The chlorine addition product was absent.Irkutsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Irkutsk 664033. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 4, pp. 955–957, April, 1992.