MM2 Molecular Mechanics Research Articles

Equilibrium constants for noble-gas fullerene compounds

We have calculated equilibrium constants for the reaction of noble gas atoms becoming trapped inside C60 molecules. Two models of the potential were used: a Lennard-Jones (12,6) potential between the noble gas atom and each carbon atom and the MM3 molecular mechanics program. We assume that the vibration of the noble gas atom is uncoupled to the cage vibrations and calculate the corresponding partition function classically. The results for the two potentials agree for helium and neon but disagree strongly for krypton and xenon, with the MM3 results being much smaller than the Lennard-Jones results.

Comparison of modelling and experimental values of non-linear optical coefficients of SCE13(*)

Abstract Second order non-linear optical properties of tilted smectic liquid crystalline phases with chiral molecules have been recently measured 1,2. This paper describes experimental measurement of non-linear optical coefficients of a commercial FLC mixture, SCE13*3 and comparison with values derived from molecular modelling. Using a thin cell geometry and in-plane electrodes, Maker fringes were detected. From the SHG signal, the bulk coefficients were calculated to be deff = 0.0008 prnV-1, d21 = 0.0001 pmV-1, and d22 = 0.003 pmV-1 at 50°C. Molecular modelling of the chiral components of SCE13* was carried out using MM2 molecular mechanics and the semi-empirical MOPAC 5 and 6 packages. The d22 coefficient was calculated to be 0.0004 prnV-1 using simple geometric arguments, and was 0.0027 pmV-1 using an extended theory.

Conformational Characteristics and Unperturbed Chain Dimensions of the Oxygen-Containing Polymers [−OCH2CR2CH2−]n with R = H, CH3, and CH2CH3

MM3 molecular mechanics calculations reveal that poly(3,3‘-diethyloxetane) (PDEO) differs sharply from poly(3,3‘-dimethyloxetane) (PDMO) and poly(trimethylene oxide) (POM3) in terms of conformational preferences, notwithstanding the similarity of these three polymers as successive members of the homologous series [OCH2CR2CH2]n where R = CH2CH3, CH3, and H, respectively. Within the four-bond repeat unit OCH2CR2CH2, POM3 and PDMO both prefer ttgg while PDEO prefers tttt. These conformational differences are reflected in the predicted values of the characteristic ratio CR = 〈r2〉0/nl2 for the unperturbed chain dimensions (after allowance for the oxygen gauche effect) obtained from rotational-isomeric-state (RIS) calculations: 3.9 for POM3, 4.7 for PDMO, and 23 for PDEO. These CR values for POM3 and PDMO are consistent with experiment (3.9 and 4.3, respectively) and with previous theoretical treatments. The larger R substituent of PDEO compared with PDMO and POM3 imposes steric demands that offset the otherwise strong preference of the C−C backbone bonds for gauche states. This reversal in preference from gauche to trans causes the abrupt increase in CR since now the almost exclusively all-trans backbone of PDEO lacks the distinctive conformational randomness of POM3 and PDMO. In terms of Eσ = Et − Eg for the focal C−C bond in these polymers, comparison of the MM2, MM3, and Discover (plus a variant Discover‘) force fields reveals a wide disparity of values for Eσ and more so for the constituent energy components Estretch, Ebend, Etorsion, EvdW, and Eelectrostatics. The preference of the focal C−C bond in PDEO for trans over gauche involves a surprising degree of interplay among these energy components; hence the conformational analysis of PDEO would represent a stringent test of any existing or prospective force field.

Hydration of α-maltose and amylose: molecular modelling and thermodynamics study

Hydration of α-maltose and amylose were investigated using molecular modelling and thermodynamics methods. The structure and energy of hydration of three low-energy conformers of α-maltose were determined by the MM3 molecular mechanics method. The hydration structure was found to be sensitive to the conformation of α-maltose and hydration numbers 10 or 11 were estimated for the different conformers. Differential scanning calorimetry and thermogravimetric analysis were used to determine the number of water molecules specifically bonded (non-freezing water) to amylose and different samples of α-maltose. Due to high crystallinity of α-maltose samples, the observed non-freezing water content was lower than predicted by molecular modelling. In contrast, the experimental number of non-freezing molecules of water per d-glucopyranose residue for amorphous amylose ( n h = 3.8) is in good accordance with the value of 3.8 extracted from our calculations.

Calculations of the phi-psi conformational contour maps for N-acetyl alanine N'-methyl amide and of the characteristic ratios of poly-L-alanine using various molecular mechanics forcefields.

We generated phi- psi conformational energy contour maps for the N-acetyl alanine N'-methyl amide using the molecular mechanics forcefields AMBER, AMBER3, BIO85, CFF91, CVFF, MM2, MM3, MM+, AND SYBYL. With MM2, MM3, and MM+ we used a dielectric constant of epsilon = 1.5, the default effective value for these forcefields. With the other forcefields we used epsilon = 1 and 4, except with SYBYL, which, in Spartan 3.1, has no electrostatic term. All forcefields yielded the C7eq conformation as a low-energy minimum or the global minimum. Most of the forcefields also yielded a minimum-energy conformation in the C5, alpha R, and alpha L regions of the phi-psi contour map. Fewer of the forcefields yielded a minimum in the C7ax region; however, adiabatic relaxation frequently lowered the relative energy of this region. Based on the appearance of the phi-psi maps, the following pairs of forcefields were broadly similar (but not identical) to each other but dissimilar to the other pairs: AMBER3 and AMBER, BIO85 and CHARMM, MM+ and MM2, SYBYL and ECEPP, and CFF91 and MM3. We used the data from the phi-psi contour maps to compute the characteristic ratio of poly-L-alanine. Most of the computed values deviated significantly from the experimental value. Only the computed characteristic ratio of CFF91 without adiabatic relaxation at epsilon = 4 and MM3 without adiabatic relaxation at epsilon = 1.5 agreed with the experimental value.

Empirical relationship between structure and molecular optical rotation in cyclohexane derivatives (Part 2)

Dihedral angle sines have been related to the molecular rotation values of some di-, tri- and tetrasubstituted cyclohexane derivatives. For every compound, dihedral angles were obtained by optimization of their geometry using a molecular mechanics MM2 program. In general, a good concordance with experimental values was obtained.

Crystal-Nematic Transition Temperature Depend on Energy of the Torsion Deformation for Nematogene Molecules

Abstract The linear regression equation determining a dependence between crystal-nematic mesophase transition temperature, TN, and energy of the torsion deformation, ET, of the nematogene molecules has been obtained on the strength of calculations by the MM2 molecular mechanics method. It has been perfomed this transition occurs on reach such value TN which corresponds to the average quantity of the heat kinetic energy <EK> in respect to the two short molecule axes exceeding ET. The methods of consideration of the intermolecular association have been examined.

Molecular mechanics study of zirconocenium catalyzed isospecific polymerization of propylene

AbstractStereocontrol energy (ΔE0) is investigated as a measure of enantioselectivity of ansa‐zircoocenium catalyst in propylene polymerization; it was calculated with MM2 (molecular mechanics) force field using π complex (°C) and transition state (TS) geometries obtained by ab initio molecular orbital methods. Both rac‐ethylenebis (1‐η5‐indenyl) ‐ (1) and rac‐ethylenebis (1‐η5‐4,5,7,8‐tetrahydroindenyl) (2) zirconocenium species are isospecific in either the π‐complexes or the transition states. The stereoselectivity is greater if there is α‐agostic interaction; it is lowered in the cases of β and γ agostic interactions. The 13C‐NMR steric pentad distribution indicates the poly(propylene) to be much less stereoregular than that predicted by ΔE0. Following the occurrence of a regiochemical insertion error, the addition of another monomer via any mode is prohibitively unfavorable. The catalyst suffers loss of stereospecificity as temperature of polymerization increases. Insertion via transition states involving different agostic interactions could be one explanation for the observed loss. © 1995 John Wiley &amp; Sons, Inc.

Conformation and dynamics of a cyclic (1 → 2)-β- d-glucan

A molecular modelling and nuclear magnetic resonance spectroscopic study was performed in order to gain insight into the conformational preferences of cyclosophoroheptadecaose. MM3 molecular mechanics calculations predicted a non-symmetric conformer with a small cavity of 3.7 Å diameter as the lowest energy form. Molecular dynamics simulations gave insight into the dynamics of the free cyclosophoroheptadecaose and also supported the results of molecular mechanics calculations. A fair agreement was found between experimental data and corresponding average values predicted by molecular modelling

14N and 15N NMR studies of highly sterically hindered tertiary amines

14 N 15 N NMR and molecular mechanics MM2 have been applied to study the structural changes in a series of highly sterically hindered amines. The NMR parameters, chemical shifts, 15N- 1H coupling constants and the 14N linewidths, are sensitive to the variations in sterical hindrance about the nitrogen. In particular, the chemical shift of the extremely hindered tri-isopropylamine ( 4) has been shown to deviate from the correlation calculated from the substitution parameters and from the correlation with the 13C chemical shift of the corresponding hydrocarbon. These results are consistent with the results of a gas phase electron diffraction study which showed that 4 exhibits a trigonal planar structure.

The conformational equilibrium of [2.2]paracyclophanes in solution

AbstractA conformational equilibrium exists in solution between two skew forms (s+ and s−) of [2.2]paracyclophane (1a). The vicinal coupling constants in the 1H‐NMR spectra of the bridge protons in the six ar‐monosubstituted derivatives 1b–1g (RCN, NO, Br, CH3, CHO, and NO2) indicate an increasing shift of the equilibrium towards one side in the order mentioned. The s+ form (positive CCCC torsional angles of the bridges) is favored in the (S) enantiomer. MM2(91) and MM3(89) molecular mechanics computations suggest that this is largely caused by increasing unfavorable nonbonded interactions in the s− conformer between the substituent and the syn proton on the ortho bridge carbon atom. Thus the „effective size”︁ of the substituent increases from 1b towards 1g.

Directional hydrogen bonding in the MM3 force field. I

AbstractThe MM3 molecular mechanics program calculates a fair representation of hydrogen bonding interactions, but to improve the MM3 hydrogen bond potential, a directional term has been added to the hydrogen bonding function. The resulting total function was reoptimized. Comparisons of the hydrogen bonding potential functions from ab initio, the original MM3, the current MM3(92) force field and the reoptimized MM3 force field MM3(94) for a variety of C,N,O systems are described.

Modeling of arabinofuranose and arabinan, II. Nmr and Conformational analysis of arabinobiose and arabinan

AbstractThe disaccharide arabinobiose (5‐O‐α‐L‐arabinofuranosyl‐α‐L‐arabinofuranose) constitutes the basic repeating structures found in such polysaccharides as arabinan or in the side chains of the hairy regions of pectins. The conformational behavior of aqueous arabinobiose has been investigated by high resolution nmr and computerized molecular modeling. The complete conformational analysis of the, disaccharide has been achieved with the MM3 molecular mechanics methods using the flexible residue method. In this study, both the puckering of the arabinofuranose, rings and the orientations about the glycosidic torsion angles ϕ, ψ, and ω; were considered. Some insights into conformational transitions were obtained through molecular dynamics simulation using the CHARMM force field. In parallel, transient nuclear Overhauser effects at 400.13 MHz and long‐range vicinal homonuclear and heteronuclear coupling constants have been measured. The theoretical nmr data were calculated taking into account all accessible conformations and using averaging methods for both slow and fast internal motions models. The data do not support a single conformational model, and only conformational averaging yields the excellent agreement between the observed and simulated parameters. Within the potential energy surfaces computed for the disaccharide, several low energy conformers can be identified. When these conformations are extrapolated to regular polysaccharide structures, they generate chains of arabinan displaying right‐ and left‐handed chirality and a wide range of repeating units per turn of helix. © 1994 John Wiley &amp; Sons, Inc.

Empirical relationship between structure and molecular optical rotation in cyclohexane derivatives

Abstract A simple empirical relationship between geometrical parameters and molecular optical rotation experimental values exists for a series of cyclohexane derivatives. By an MM2 molecular mechanics program, geometrical and energetic parameters for these compounds are obtained. As a result of this study, a method of calculating the magnitude and the sign of the molecular optical rotation for compounds similar to those studied is proposed.

Skeletal conformations and receptor binding of some 9,11-modified estradiols

The effect of the modification of the 9–11 positions on the skeletal confirmation of estradiol (E 2) has been analyzed by X-ray crystallography and MM2 molecular mechanics. The 11β-hydroxyl and 11-keto analogs of E 2 maintained ring conformations which were similar to the natural hormone (E 2). Introduction of a double bond at position 9–11 induced a flattening of the entire steroid molecule. An 11α-hydroxyl group brought about significant changes in the alicyclic rings of E 2. 9β-Estradiol and 11-keto-9β-estradiol formed ring conformations which were significantly bent from E 2 (below the plane of the A-ring). Examination of the affinity of these C-ring analogs of E 2 for the human estrogen receptor has shown extreme variations. A hydroxyl group placed either α or β at the 11-position yielded ligands with vastly different and reduced affinities for the receptor. The low affinity of 11α-hydroxyestradiol (1/300th of E 2) may be due to the drastic structural change induced in the alicyclic portion of the molecule, as well as, to the steric or electrostatic effects of the α-hydroxyl group upon the receptor protein. An 11β-hydroxyl group diminished the receptor binding to 1/60th that of E 2 without alicyclic ring distortions, whereas a 9–11 unsaturation reduced the binding to 1/5th although this steroid displayed a flattening of rings B, C, and D. The 11-keto function, which had little effect on the conformation of the estrogen nucleus, reduced the affinity of this ligand to 1/1000th that of E 2. The negative bend at the C-ring of 11-keto-9β-estradiol and 9β-estradiol prevented these ligands from binding receptor. Some of the observed receptor interactions were related to structural alterations in the estrogen ring system induced by modifications on the 9–11 region.

Syn‐ar,ar′‐Difluorometacyclophanes: Strong 19F,19F Spin—Spin Interactions Transmitted through Space

AbstractThe close approach of the fluorine nuclei in the difluorinated syn‐[3.3]metacyclophanes 1, 2 and their [2.2] analogues 3, 4 leads to strong 19F,19F spin‐spin interactions which obey a through‐space mechanism. The geometries of 1–4 were estimated by MM2 molecular mechanics computations, those of 1 and 3 were also determined by X‐ray structural analyses. The decrease of the F,F internuclear distance in the series 1, 2, 3, 4 (2.78–2.48 Å) correlates with an increase of J(FF) from +42.1 to +99.2 Hz. It follows that, for a given distance d(FF), J(FF) is up to twice as large as a previous empirical correlation has assumed and even larger with respect to earlier theoretical calculations. Only weak F,F spin interaction occurs in 8, the anti isomer of 4.

A modified MM2 program for molecular mechanics calculations on coordination compounds

The MM2 molecular mechanics program has been modified to allow the treatment of molecules containing atoms with up to six connections. A term to allow for the periodicity of ligand-metal-ligand angles has also been included. Calculations have been performed successfully on various octahedral metal complexes, but it was necessary to replace the default value of the stretch-bend force constant in order to obtain satisfactory results.

A 3D QSAR approach to the search for geometrical similarity in a series of nonpeptide angiotensin II receptor antagonists

A 3D QSAR methodology based on the combined use of conformational analysis and chemometrics was applied to perform a comparative analysis of the 3D conformational features of 13 nonpeptide angiotensin II receptor antagonists showing different levels of binding affinity. Conformational analysis by using a molecular mechanics MM2 method was carried out for each of these structures to obtain conformational minima. These minima were described by ten interatomic distances which define the relative spatial disposition of five significant atoms belonging to relevant functional groups present in all the 13 molecules. The structure-activity relationship between the interatomic distances and the biological activity was then assessed by using chemometric methods (cluster analysis, principal component analysis, classification methods). With our indirect approach based on the search for geometrical similarity it was possible, even though structural information on the receptor active site was lacking, to identify the 3D geometrical requirements for the binding affinity of nonpeptide angiotensin II receptor inhibitors.

Steric and electronic requirements for chloroflavone congeners as hepatic microsomal monooxygenase inducers.

We previously classified chloroflavone congeners into 3-methylcholanthrene (MC)-type, phenobarbital (PB)-type and mixed (MC plus PB)-type inducers of hepatic microsomal monooxygenases in rats. In the present study, we examined the structure-activity relationship involved in the capability of congeners to induce the described regioselective O-demethylation activity of scoparone. The steric and electronic parameters of congeners were calculated by the MM2 molecular mechanics and Extended Hückel MO methods, respectively. The molecular rectangle-area/depth ratios related well to the ratios of scoparone 6-/7-O-demethylation activities induced by the congeners. The molecular dimensions characterized the MC-type congeners as nearly planar molecules and the PB-type congeners as bulky and nonplanar. Moreover, the ratio of scoparone 6-/7-O-demethylation activities had significant correlation with both the LUMO energy (ELUMO) and the difference (delta E) between ELUMO and HOMO energy for the congeners. The ELUMO and delta E were less in the MC-type congeners than in the PB-type. These correlations suggest that the steric and electronic features of chloroflavone congeners are responsible for the induction of cytochrome P450 isozymes and associated monooxygenase activities.

Conformational study of the cholinergic agonist pilocarpidine, isopilocarpidine, and related species

A conformational study on the energies and geometries of the stable conformers of the cholinergic agonist pilocarpidine and of its inactive isomer, isopilocarpidine, has been carried out by molecular mechanics MM2 and by semiempirical quantum chemical AM1. The former predicts an envelope conformation of the γ-lactone nucleus, whereas AM1 predicts a planar conformation. The relative energies of the different conformations of both isomers are strongly dependent on the relative orientation of the imidazole moiety. Other related species, intermediate steps in their synthesis, and the anion intermediate in the epimerization are also discussed.