Conformational analysis of 3,4-dihydropyridine and its alkyl derivatives

The geometry of dihydropyridine and its alkyl derivatives was studied by the molecular mechanics method. The dihydrocycle was found to be mobile; however, substituents exert little effect on its distorted sofa conformation. The alkyl groups attached to the saturated carbon atoms occupy pseudo-equatorial position in monosubstituted and pseudo-axial positions in disubstituted 3,4-dihydropyridines. Unusually high barriers to inversion of the dihydrocycle were observed incis-3,4-dialkyl-3,4-dihydropyridines caused by the eclipse of the substituents in the transition state.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1009–1012, June, 1994.     

Conformational analysis of 2-oxo-1,2,3,4,-tetrahydropyridine and its alkyl- and phenyl-substituted derivatives

The molecular geometries and inversion barriers of the rings in 2-oxo-1,2,3,4-tetrahydropyridine and its alkyl-substituted (Me, Et, Prⁱ, or Bu^t) and phenyl-substituted derivatives were calculated by the molecular mechanics method. The introduction of substituents has no substantial effect on the equilibrium conformation of the heterocycle (a distorted sofa). For 4-alkyl- and 3-alkyl-substituted derivatives (except for 4-Me and 4-Et derivatives), an axial orientation of the alkyl group is more favorable. The phenyl substituents have equatorial and axial orientations at postions 4 and 3, respectively. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1584–1586, September, 1997.     

Conformational analysis of sesquiterpene lactones of germacrane type

The structure of 1(10)Z,4Z-germacranolides was studied by the method of molecular mechanics. Possible conformers, the probability of their existence, and barriers to conformational transitions were determined. For Part 1, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 268–271, February, 1997.     

The effect of substituents on the conformational mobility of the heterocycle in 1,4-dihydropyrimidine and its derivatives

The equilibrium geometry of 1,4-dihydropyrimidine, 4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine, and their alkyl (Me, Et, Prⁱ, Bu^t) and phenyl derivatives has been calculated by molecular mechanics method. The equilibrium conformation of unsubstituted molecules is planar, but it is easily transformed to the boat conformation with a small change in the conformational energy. The effect of substituents on the geometry and conformational mobility of the dihydropyrimidine ring has been studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1394–1397, August, 1994.     

Cycle mobility in 1,4-dihydropyridine and its monoalkyl and phenyl derivatives

The conformational mobility of the 1,4-dihydropyridine cycle has been studied by the molecular mechanics method. It was shown that the N(1) and C(4) atoms are displaced asymmetrically from the plane of the double bonds. The asymmetry is the result of conjugation between the nitrogen lone pair and the systems of the double bonds. The influence of alkyl and phenyl substituents at the carbon atoms on the equilibrium conformation and cycle mobility has been investigated.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1217–1219, July, 1993.     

Conformational analysis of sesquiterpene lactones of the germacrane type 1. 1(10)E,4E-Germacranolides

The structure of 1(10)E,4E-germacranolides was studied by a molecular mechanics method. Possible conformers, the probabilities of their occurrence, and the barriers to conformational transitions were determined.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No, 12, pp, 2890–2893, December, 1996.     

Conformational mobility of the six-membered ring in 5-oxo-1,3-cyclohexadiene and its derivatives

Molecular mechanics and MNDO calculations showed that the six-membered ring in the molecule of 5-oxo-1,3-cyclohexadiene possesses high conformational mobility. The transition from a planar equilibrium conformation to a distorted sofa conformation in which the C(sp²)-C(=O)-C(sp³)-C(sp²) torsion angle is equal to ±30° increases the energy of the molecule by less than 1 kcal mol^–1. The influence of steric (R = Me, Et, Prⁱ, Bu^t) and electronic (R = NH₂, NO₂) effects of substituents R on the equilibrium conformation and mobility of the carbocycle has been analyzed. Both types of substituents at unsaturated C atoms do not change the equlibrium conformation or flexibility of the six-membered ring. Substituents at saturated C atoms cause the transition of the carbocycle to the distorted sofa conformation and significantly restrict its mobility. The electronic structures of 5-oxo-1,3-cyclohexadiene and its amino and nitro derivatives have been analyzed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 849–854, May, 1995.     

Conformational analysis and steric effects of substituents in derivatives of 3-oxo-, 3-imino-, and 3-methylenecyclohexene

The equilibrium conformations and the inversion barriers of the rings in 3-oxo-, 3-imino-, 3-methylenecyclohexenes and in their methyl,tert-butyl, and phenyl derivatives were calculated by molecular mechanics. The unsubstituted molecules adopt a sofa conformation. The nonbonded interactions between substituents at positions 2 and 4 and the exocyclic double bond lead to a change in the conformation of the ring to a half-chair. The effect is enhanced as the volume of the substituent increases in the series of the oxo, imino, and methylene derivatives. Substituents at other positions of the ring affect only slightly the equilibrium conformation. The results of calculations were confirmed by X-ray structural analysis of 2-(4-benzoyloxybenzyl)-6-isopropyl-3-methylcyclohex-2-enone. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1995–2000, November, 1997.     

Cycle inversion in 1,3-cyclohexadiene and its 5-alkyl derivatives

Cycle inversion in 1,3-cyclohexadiene and its 5-alkyl derivatives is studied by means of the MMP2 molecular mechanics procedure. The choice of a torsion angle between single bonds as a reaction coordinate is justified. Substituents at the C(5) atom (R=Me, Et,i-Pr,t-Bu) are shown to have little effect on the cycle shape, and the equatorial conformer is preferable to the axial one.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1142–1144, June, 1993.     

Conformational searching of transition metal compounds

To date, no conformational search of inorganic complexes has been reported that searches for all the conformations and configurations available to the complex. This is due to the various coordination geometries that transition metal ions can adopt and the difficulties in conducting conformational searches with systems that have connected ring systems, such as the ones formed when a metal ion binds a multidentate ligand. Using three test complexes {[Co(dien)₂]³⁺, [Co(dien)(dpt)]³⁺, and [Co(hexamethylcyclam)(Cl)} the ability of the random kick (Cartesian stochastic Monte Carlo search) method and the Monte Carlo dihedral and positional method to find all conformations and geometric isomers was tested (dien, diethylenetriamine; dpt, di(3-aminopropyl)amine; hexamethylcyclam: tet-a, meso-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; tet-b, racemic-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane). Both methods are significant improvements on the current method by which all possible isomers are entered graphically and minimized individually. The major difficulty that was encountered was how to differentiate between the large number of similar conformations found. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1549–1558, 1999     

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     

Conformational analysis ofortho-substituted diphenyl ethers and diphenylmethanes with linear substituents

Conformational analysis of di-ortho-substituted diphenylmethanes and Biphenyl ethers containing I, CCH, and CCCCH substituents was carried out by the molecular mechanics method using the MM3 program. Several minima on the potential energy surface, which correspond to thegg, gt, tg, andort conformations, were found. An increase in the length of the linear substituent results in a substantial decrease in the difference in the relative energies of conformers. Barriers to conformational transitions between thegt, tg, andort conformers are less than 2 kcal mol^–1. The transitionort-gg requires expenditure of energy of up to 5 kcal mol^–1. Two valleys of centrosymmetric pairs of thegt, tg, andort conformers are separated by a barrier of up to 6 kcal mol^–1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No, 12, pp, 2882–2885, December, 1996.     

Pyrrolizidine alkaloids necine bases: II. Conformational analysis of free bases

Molecular mechanics calculations were applied to the conformational analysis of two diasteroisomers, the pyrrolizidine alkaloids (PAs) retronecine and heliotridine. The application of reoptimized parameters for H bonding corrected the tendency of MM3(92) calculations to give unrealistic H(DOTTED BOND)O distances for intramolecular OH interactions occurring in both diasterisomers. Inversions in the H-bond direction of exo-retronecine and in the relative stability of heliotridine endo–exo conformers were also observed with the application of the new parameters. A set of probable conformers was obtained for each diasterisomer, based on conformational and Boltzmann population analysis. Only exo-puckered conformers were found in the retronecine set, whereas both exo- and endo-puckered conformers were obtained for heliotridine. Transition state conformations supplied arguments supporting the design of models for H-bond interconversion in the case of exo-retronecine and for the exo–endo interconversion of heliotridine. Reactivity behaviors and ¹H-NMR data of both diasterisomers were elucidated in light of the theoretical results. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1853–1861, 1998     

Configuration and conformation of alfentanil hydrochloride. Conformational study by NMR and theoretical calculations

The configurational and conformational structure of alfentanil hydrochloride (1) was studied by nuclear magnetic resonance and theoretical calculations. Compound 1 is best described by equilibrium between two stereoisomeric piperidinium rings with the N‐substituent always being in equatorial position. Nuclear magnetic resonance spectra demonstrate that, depending on the solvent, 1 adopts the conformation with an axial methoxymethylene group. Computations were crucial in determining the importance of the transannular attractive interaction between the positive charge at the piperidinium N‐atom and the methoxymethyl group in position 4. Copyright © 2014 John Wiley & Sons, Ltd.     

Conformational analysis of gossypol and its derivatives by molecular mechanics

Conformations and inversion pathways leading to racemization of all the tautomers of gossypol, gossypolone, anhydrogossypol, and a diethylamine Schiff's base of gossypol were investigated with MM3(2000). All forms have hindered rotation because of clashes between the methyl carbon atom and oxygen-containing moieties ortho to the bond linking the two naphthalene rings. Inversion energies generally agree with available experimental data. Gossypol preferentially inverts in its dihemiacetal tautomeric form through the cis pathway (where similar groups clash). Gossypolone inverts more easily than gossypol, and preferentially through the trans pathway (where dissimilar groups clash) when one of its outer rings has an enol-keto group and the other has an aldehyde group. Anhydrogossypol racemizes through the cis pathway. The bridge bond and the ortho exo-cyclic bonds in all the structures bend from planarity, and the inner naphthalene rings pucker to accommodate the inversion. For gossypol, the transition is achieved through greater bending of the exo-cyclic bonds (up to 12°) and less distortion of the inner benzyl rings (q≤0.34 Å), (up to 12.7°) . For gossypolone the transition occurs with greater distortion of the inner benzyl rings (q≤0.63 Å) and less out-of-plane bending (up to 8.4°). By isolating individual clashes, their contribution to the overall barrier can be analyzed, as shown for the dialdehyde tautomer of gossypol.     

Energetics of Stretching of Conformational Defects in Extended Poly(methylene) Chains

The deformation energetics of highly extended poly(methylene) segments with conformational defects of the kink and jog types, is investigated by molecular mechanics calculations. The deformation potential displays abrupt discontinuities as a result of sudden gauche‐to‐trans conformational transitions accompanied by a release of the elastic energy stored in all valence parameters. By stretching, the chain defects are sequentially annihilated, with the weakest elements interconverting first. Due to sudden drops in force the calculated force–length curves F(R) display a sawtooth‐like profile. The force jumps define a maximum load F_c that defect chains can bear prior to conformational “yielding”. The F_c in the range about 0.7–1.1 nN is found in highly extended multikink chains. The results suggest that the sawtooth‐like profile can be a common feature of mechanochemistry of bridging polymers with the restricted number of available conformations. A similar pattern of F(R) curves were previously observed at stretching and sequential unfolding of compact structural domains in biomacromolecules. Further, the calculations predict a distinct reduction of the longitudinal Young's modulus E with increasing concentration of kinks in molecules.     

计算机化学模拟—分子构象识别的新方法

简介了几种利用计算机图形技术研究化合物分子构象的新方法。重点介绍了分子力学计算方法中的系统搜索、随机搜索方法和分子动力学计算方法中的模拟淬火、模拟退火等新技术 ,为药物分子设计中受体与配体分子构象的识别提供了合理可行的方法。     

Conformational analysis of hydrogen polyoxides

The semiempirical AM I method was used for the calculation of conformational potential energy surfaces of hydrogen trioxide and tetraoxide. The most stable conformation of trioxide is itsanti-form, which is characterized by the torsion angle = 82.3°, and that of tetraoxide is theanti, anti-form with = 80.7° (H-O-O-O) and 74.1° (O-O-O-O). The structures of the stable conformers are determined by the interaction between lone clectron pairs of oxygen atoms. The dipole-dipole interaction of OH groups is weaker than that in hydrogen peroxide. The results were used for the estimation of the polyoxide increment of the Benson's additivity scheme, _f H°[O-(O)₂] = 48±6 k1 mol^–1.Translated from lzveshyn Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1356-1361, June, 1996.     

谷胱甘肽分子伞的构象分析及VolSurf表征

使用分子动力学模拟迟火和半经验AMl方法对谷胱甘肽分子伞进行了构象分析 ，结果表明，真空下屏蔽构象和暴露构象的最低能量值相差很小(26.00kJ/mol)。 考虑溶剂效应后，屏蔽构象的能量值最高，暴露构象的能量值最低。屏蔽构象的能 量最低值高于暴露构象的能量最低值89.24kJ/mol，从理论上解释了谷胱甘肽分子 伞在水溶液中呈现暴露构象的原因。利用VolSurf参数分析了分子伞以屏蔽构象穿 透磷脂双分子层的影响因素，结果表明屏蔽构象较小的两亲矩及较大的分子褶皱程 度是其能够穿透细胞膜的主要影响因素，与构象的绝对疏水区域无关。     

Analysis of the Conformational Composition of 2-Alkyl-4-phenyl-1,3,2-oxazaborinanes

The empirical MM2 and semiempirical AM1 methods were used to calculate the energy of model 2-methyl-4-phenyl-1,3,2-oxazaborinane with full optimization of the molecular geometry. Comparison of the experimental coupling constants for the 2-isobutyl analog and calculated coupling constants as well as the data for the relative energy of the individual conformers indicated that these compounds form a multicomponent equilibrium system containing sofa and a family of half-chair forms.