MM2 Force Field Research Articles

Photochemistry of valerophenone in solid solutions

Photoreactivity of valerophenone was investigated in frozen solid solvents: benzene, cyclohexane, t-butanol, hexadecane, and water. Different product and mass distributions were followed during the course of the photoreaction. It was evidenced that a portion of ketone molecules is almost unreactive in the solid state due to physical restraints of the solid solvent cavity. Free rotation along the C–C bonds becomes difficult inside the cavity and it is probable that larger conformational changes are totally restricted. It was shown that a fraction of molecules having the favorable conformation for hydrogen abstraction reacts with the same photochemical efficiency no matter what solvent was used. The elimination/cyclization ratio of the Norrish Type II reaction was studied as a function of temperature. Variation of the ratios, characteristic for each solvent, diminished with decreasing temperature what has been rationalized in terms of the effective reaction cavity. The semi-empirical PM3 method and molecular mechanics MM3 force field calculations were performed to evaluate stabilities of the ground state valerophenone conformations.

Chemical Sensors for Solvent Vapors: Enthalpic and Entropic Contributions to Host-Guest Interactions

Chemical sensors, based on the mass-sensitive quartz micro balance (QMB) or the surface acoustic wave device (SAW), that are coated with thin cyclophane layers allow the detection of harmful organic vapors. The sensor signal of these supramolecular analyte-receptors can be predicted by a method that uses estimated free energies of the host-guest complex formation. From MM3 force field calculations, the reaction enthalpies ΔH° of host-guest interaction between the macrocycle and the analyte can be calculated, whereas the entropy changes are taken from condensation data. The validity of this condensation model is proven by an excellent linear correlation of the logarithm of the experimental equilibrium constant with the estimated Gibbs energy DG°. In this way promising sensor materials can be selected, even before they are synthesized.

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 studies of coenzyme B12 complexes with constrained Co-N(axial-base) bond lengths: introduction of the universal force field (UFF) to coenzyme B12 chemistry and its use to probe the plausibility of an axial-base-induced, ground-state corrin butterfly conformational steric effect

The universal force field (UFF) is used to minimize a series of cobalamins to (i) test the applicability of UFF to model unstrained cobalamin structures in comparison with the literature force field MM2′, a force field parameterized using a set of 19 cobalamin X-ray crystal structures, and (ii) to probe the steric-based, ground-state corrin butterfly effect, a literature hypothesis aimed at explaining the observed 1012 enzymic acceleration of adenosylcobalamin (AdoCbl) Co-C bond homolysis. The results obtained show that UFF is at least as good as MM2′ in modeling the five cobalamins which were originally used to test the accuracy of MM2′. Next, by using UFF to constrain the Co-N(bzm) bond length in adenosylcobalamin (AdoCbl) to bond lengths ranging from 4.5 to 1.44 Å, the putative axial-base-induced corrin butterfly conformation effect was modeled. The results show that while a short Co-N(bzm) bond length does lengthen the Co-C bond and increase the Co-C-C bond angle, the maximum magnitude of the predicted distortions appears, at least when considering steric effects alone, to be at most ∼1/3 that needed to accomplish the observed Co-C bond homolysis acceleration. Equivalent results were obtained in analogous studies of base-free adenosylcobinamide (AdoCbi+) in the presence of an exogenous N-methylimidazole base, [AdoCbi·N-MeIm]+. Overall, literature precedent, and now UFF molecular mechanics, all provide evidence against a solely axial-base-driven, sterically-induced corrin butterfly conformation effect as the dominant mechanism in the enzymic acceleration of AdoCbl Co-C bond homolysis. Serious consideration must now be given to a combination of effects: an enzyme-induced rack mechanism (which can contain an enzyme-induced corrin butterfly conformational effect), and a coupling of Co⋯C cleavage, substrate or cysteine S⋯H bond cleavage, and Ado⋯H bond formation steps.

Characterization of Interaction between Butylbenzene Sulfonates and Cetyl Pyridinium Chloride in a Mixed Aggregate System

Surface active short chain alkyl benzene sulfonates, which are known as hydrotropes, interact electrostatically as well as hydrophobically with cationic surfactants. The mixtures of butyl benzene sulfonate (BBS-) with cetyl pyridinium chloride (CPyCl), as shown by surface tensiometry, rheological techniques, and IR and NMR spectroscopy form rodlike micelles or vesicles. These microstructures give rise to highly viscous solutions even at very low concentrations in the millimolar region. The CPy+/BBS- complexes also show similar behavior in the absence of electrolytes. The steric hindrance due to the butyl group to the interaction with CPyCl is at a maximum with tert-butyl benzene sulfonate (TBBS-) as compared to n-butyl benzene sulfonate (NBBS-) and iso-butyl benzene sulfonate (IBBS-). The molecular interactions between surfactant/hydrotrope pairs are simulated using the MM2 force field in the presence and absence of water. The presence of water reduces the electrostatic interaction by solvation and reinfo...

Conformational Analysis of Neocarrabiose and its Sulfated and/or Pyruvylated Derivatives using the MM3 Force-Field

ABSTRACT The adiabatic conformational surfaces of neocarrabiose (3,6-An-α-D-Galp-(1→3)-β-D-Galp) and of nine sulfated and/or pyruvylated derivatives were obtained using the MM3 force-field. These maps indicate greater flexibility of the glycosidic linkage than found for similar compounds that are based on α-D-galactose instead of 3,6-anhydrogalactose units. Sulfation of the β-D-galactose unit on position 2 shifts the global minimum to negative ΨH (θC1'-03-C3-H3) angles, whereas sulfation at either position 4 of the same unit or at position 2 of the 3,6-anhydro-α-D-galactose unit has less effect. The results are consistent with the X-ray diffraction data on crystalline neocarrabiose and carrageenan fibers. Free energy calculations show that entropy is not uniformly distributed among confomers.

Conformational Analysis of C-Disaccharides using Molecular Mechanics Calculations

ABSTRACT Relaxed-residue energy maps based on the MM3 force field were computed for the methyl glycosides of eight C-linked D-glucosyl disaccharides: the two-bond axial-equatorial linked disaccharides β-kojibioside [(1→2)α–], β-nigeroside [(1→3)α–] and β-maltose [(1→4)α–], the two-bond equatorial-equatorial linked disaccharides β-sophoroside [(1→2)β–], β–laminarabioside [(1→3)β-], β–cellobioside [(1→4)β–] and the three-bond-linked (1→6) disacharides C-isomaltoside and C-gentiobioside. Optimized structures were calculated on a 20° grid spacing of the torsional angles about the C-glycosidic bonds and the final isoenergy surfaces were based on 11664 conformations, for the two-bond-linked disaccharides and 69984 conformations for the three-bond-linked disaccharides. Boltzmann-weighted 3J coupling constants were calculated and compared to the experimental values. They are satisfactory except for maltose where hydrogen bonds cause an over-estimation of the energy differences between the conformers. The energy maps are similar to maps of the corresponding O-disaccharides, but there are differences in the locations and the relative energies of the minima. The preferred conformations of the C-glycosidic bonds are as if they were conforming to the exo-anomeric effect but are closer to staggered conformations than shown by the MM3 results for the O-linkages.

A priori crystal structure prediction of native celluloses

The packing of beta-1,4-glucopyranose chains has been modeled to further elaborate the molecular structures of native cellulose microfibrils. A chain pairing procedure was implemented that evaluates the optimal interchain distance and energy for all possible settings of the two chains. Starting with a rigid model of an isolated chain, its interaction with a second chain was studied at various helix-axis translations and mutual rotational orientations while keeping the chains at van der Waals separation. For each setting, the sum of the van der Waals and hydrogen-bonding energy was calculated. No energy minimization was performed during the initial screening, but the energy and interchain distances were mapped to a three-dimensional grid, with evaluation of parallel settings of the cellulose chains. The emergence of several energy minima suggests that parallel chains of cellulose can be paired in a variety of stable orientations. A further analysis considered all possible parallel arrangements occurring between a cellulose chain pair and a further cellulose chain. Among all the low-energy three-chain models, only a few of them yield closely packed three-dimensional arrangements. From these, unit-cell dimensions as well as lattice symmetry were derived; interestingly two of them correspond closely to the observed allomorphs of crystalline native cellulose. The most favorable structural models were then optimized using a minicrystal procedure in conjunction with the MM3 force field. The two best crystal lattice predictions were for a triclinic (P(1)) and a monoclinic (P2(1)) arrangement with unit cell dimensions a = 0.63, b = 0.69, c = 1.036 nm, alpha = 113.0, beta = 121.1, gamma = 76.0 degrees, and a = 0.87, b = 0.75, c = 1.036 nm, gamma = 94.1 degrees, respectively. They correspond closely to the respective lattice symmetry and unit-cell dimensions that have been reported for cellulose Ialpha and cellulose Ibeta allomorphs. The suitability of the modeling protocol is endorsed by the agreement between the predicted and experimental unit-cell dimensions. The results provide pertinent information toward the construction of macromolecular models of microfibrils.

Synthesis of Optically Active Polyarylates Having Axially Chiral Binaphthylene Unit.

Novel optically active polyarylates having axially chiral 6, 6’-binaphthylene units in the main chain have been synthesized by the reaction of (R)- or (S)-2, 2’-bisalkoxy-6, 6’-dibromo-1, 1’-binaphthyl (1a, 1b) and aromatic diols with carbon monoxide in the presence of palladium catalyst. The resulting polyarylates had molecular weights up to 20000 and were soluble in a variety of organic solvents including N, N-dimethylformamide, 1-methyl-2-pyrrolidone, m-cresol, tetrahydrofuran, and pyridine. Circular dichroism (CD) spectra of these polyarylates showed large Cotton effects compared with those of the model compounds and were the complete mirror images of each enantiomer, suggesting the existence of an ordered conformation. The most stable structure of the optically active polyarylates indicated helical conformation by MM2 force field calculation. No change in the specific rotation of the optically active polyarylates was observed on heating at 100°C for 5h, suggesting thermal stability of the ordered conformation such as helix.

Crystal and molecular structure of augustamine

The crystal and molecular structure of augustamine (1), C17H19NO4 an amaryllidaceae alkaloid of the tazettine group has been determined by direct methods from single crystal x-ray diffractometer data and refined by full-matrix least squares. The alkaloid (1) crystallizes in the space group P212121, with cell parameters: a = 7.833(8) b = 11.08(2) a, c = 16.69(6) A, Z = 4, Dc = 1.381 g/cm−3, R = 7.6% for 1115 observed reflections. The molecule, having a hexacyclic ring system, is very rigid with the ring B in a chair conformation. Molecular mechanics calculations have been made using MM3(2000) force field.

Predicted Influence of N-Acetyl Group Content on the Conformational Extension of Chitin and Chitosan Chains

ABSTRACT Conformational analysis of chitosan molecules has been performed using the MM3(92) force field to investigate the role played by the acetamido groups on the stiffness of these chains. A high dielectric constant value was needed to model an aqueous environment and to reproduce the distribution of the N-acetyl glucosamine group orientation that is observed by NMR. Disaccharidic fragments, differently substituted at C2, were selected as models for chitin and chitosan chains. Their conformational space has been explored by means of adiabatic mapping of the glycosidic Φ,Ψ torsion angles. Although the overall features of all the potential energy surfaces created appear similar, the accessible conformational space of a glycosidic bond is affected by the nature of the substituent at C2 on the non-reducing residue of the disaccharide unit. This is illustrated by the differences in the calculated partition functions together with the predicted average homonuclear and heteronuclear coupling constants. Computed maps were used to predict polymeric unperturbed dimensions, characteristic ratio and persistence length of idealized chitin and chitosan chains, by Monte Carlo methods. Pure chitosan is predicted to be more coiled than pure chitin chains. At low N-acetyl group contents, chain extension appears to be dependent on the degree of substitution. Average chain dimensions increase monotonically for increases in content up to 60% of N-acetyl groups, but show no significant variation at higher contents. For molecules consisting of 50% amino and 50% N-acetylated residues, random, alternate and block patterns of substitution have been investigated. It has also been shown that the spatial extension of the polymer chains is dependent on the primary structure. Comparison with the literature experimental data is difficult because of the extreme diversity of the reported conformationally dependent values. However, such study provides a unique insight into the dependence of these two factors (degree of acetylation and distribution of acetyl groups) on the stiffness and flexibility of different chitin and chitosan chains.

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.

Convenient synthesis of propane aminophosphonic acids, aminodiphosphonic acids and their structural analogues, mediated by azetidinium salts

The reactions of azetidinium salts with phosphorus nucleophiles R 2P(O)H have been investigated. Treatment of O-benzyl-N,N-diethyl-3-hydroxyazetidinium salt 2 with R 2P(O)H in the presence of sodium hydride gave the corresponding γ-N,N-diethylamino-β-benzyloxypropylphosphonate 6a or phosphine oxide 6b. After debenzylation γ-N,N-diethylamino-β-hydroxypropylphosphonate 3a and phosphine oxide 3b were obtained. The compound 6a was converted into its sulfonate ester 8 which underwent elimination to yield 4. The structure 4 has been employed in Michael addition of R 2P(O)H to form compounds 5 containing two phosphorus centers. Further compounds of type 3 have been transformed into compounds 5 by reaction with R 2P(O)H in the presence of 1.1 equivalents of NaH in boiling toluene. Finally, azetidinium salts 1 have been converted into compounds 5a by reaction with two equivalents of R 2P(O)H in the presence of 2.1 equivalents of NaH. Molecular mechanics with implementation of the Allinger MM2 force field and semiempirical AM1 and PM3 methods were used to investigate structures 5d and 5f.

Molecular Mechanics (MM3) Calculations on Oxygen-Containing Phosphorus (Coordination IV) Compounds.

An MM3 force field has been developed for small oxygen-containing phosphorus (coordination IV) compounds. Experimental electron and neutron diffraction, X-ray, and infrared spectral data were utilized in parametrization when available. Results from previous ab initio calculations at both the restricted Hartree-Fock (RHF) and second-order Møller-Plesset (MP2) levels of theory with the standard 6-31G basis set supplemented missing structural data, rotational profiles, and vibrational frequencies. Negative hyperconjugation (the anomeric effect) affects the structures and energies of the molecules under study which contain one or more sp(3)-hybridized oxygen atoms. Natural bond order (NBO) analysis was helpful in identifying the key orbital interactions involved in this effect.

Characterization of Interaction between Butyl Benzene Sulfonates and Cetyl Trimethylammonium Bromide in Mixed Aggregate Systems

Surface-active short-chain alkyl benzene sulfonates which are known as hydrotropes interact electrostatically as well as hydrophobically with cationic surfactants in the same manner as salicylate. The interaction in mixed aggregates of the three isomers of butyl benzene sulfonate (BBS-) and cetyl trimethylammonium bromide (CTAB) has been studied by surface tensiometry and rheological techniques. These mixed aggregates form rodlike micelles, giving rise to highly viscous solutions even at low concentrations. To study the interactions in the absence of electrolytes, CTA/BBS complexes were also obtained separately and characterized by similar techniques. The steric effect due to the structure of the butyl group in butyl benzene sulfonates on the interaction with CTAB has been emphasized during these investigations. The interactions are also characterized by infrared and ultraviolet absorption and nuclear magnetic resonance spectroscopy. Molecular modeling was carried out using an MM2 force field for molecula...

A Test of the Single-Conformation Hypothesis in the Analysis of NMR Data for Small Polar Molecules: A Force Field Comparison

A tricyclic ketone with seven stereogenic centers produced in >95:5 diastereomeric excess by an asymmetric Diels−Alder reaction has been subjected to a careful 2-D NMR(CDCl3)/MD analysis by Reggelin and co-workers and interpreted in terms of a single conformation in CDCl3 solution. The present work examines the validity of this interpretation. Specifically, the conformational profile of the endo isomer of the tricyclic ketone was examined by Monte Carlo searches with both the MM2* and MMFF force fields in MacroModel using the GB/SA CHCl3 solvent continuum model. The two sets of conformations were then combined and optimized with the MM3(96) force field. The structures of the resulting conformations and the NMR-derived geometric variables were together subjected to a NAMFIS analysis (NMR analysis of molecular flexibility in solution). Ideally, the procedure deconvolutes the thermally averaged NMR data into a small family of conformations that optimally represents the J-derived torsions and the NOE-derived ...

Synthesis and Properties of Chiral Self-Assembling Lamellar Polydiacetylene Systems with Very-Long-Range Order

Two new, very accessible, chiral, self-assembling phospholipid analogues containing diacetylenic units in the middle of their acyl chains were prepared by very simple and highly efficient routes. Films were cast and then polymerized by activation with UV light or doped with iodine. X-ray diffraction, NMR spectroscopy measurements, and molecular mechanics analyses using the MM3 force field indicated that the acyl chains are closely packed in a parallel fashion. The new molecules and the polymerized films derived from them were characterized by a variety of physical methods including confocal polarized light microscopy, atomic force microscopy, and near-infrared spectroscopy. These analytical methods showed that the unpolymerized molecules are able to form lamellar systems with very-long range order. They formed very uniform, extremely flat, thin films which are readily polymerized to give extensively conjugated systems which absorbed well out into the near-infrared region unlike typical polydiacetylenes. The propensity of the new molecules to form such well-packed structures arises from their resemblance to diacyl glycerolipids, with the π-stacking interaction from the diacetylene units giving extra stabilization. The results indicate that this is an excellent approach for preparing ordered polydiacetylene systems for use in designing advanced materials.

Conformational interconversions of partially dehydroxylated calix[4]arenes. A molecular mechanics study 1†

The rotational pathways of the cone↔cone topomerisation for a series of dehydroxylated calix[4]arenes 2–5 have been calculated using the MM3 force field. The key intermediates and rate-limiting steps have been identified and characterised. The low barriers obtained for phenyl residue rotation suggest that the compounds should be partially flexible at low temperatures. The results are discussed in relation to available experimental data.

Synthesis of Medium-Sized Bicyclic Compounds by Intramolecular Cyclization of Cyclic β-Keto Radicals Generated from Cyclopropanols Using Manganese(III) Tris(pyridine-2-carboxylate) and Its Application to Total Synthesis of 10-Isothiocyanatoguaia-6-ene

Abstract Bicyclic cyclopropanols having an olefinic side chain are oxidized with manganese(III) tris(pyridine-2-carboxylate) to generate cyclic β-keto radicals with ring-expansion. These cyclize intramolecularly, affording bicyclic radical intermediates. The cyclized radicals are trapped with various radical-trapping reagents such as electron-rich or -deficient olefins, tributylstannane and diphenyl diselenide to give the corresponding functionalized products. Stereochemistries of the bicyclic products are well predicted by MM2 force field calculation. A stereoselective total synthesis of an isothiocyano sesquiterpene, 10-isothiocyanatoguaia-6-ene, is achieved using this reaction.

Molecular Mechanics: The Cross-conjugated Carbonyl Group in Heterocyclic Compounds. 1. Parameterisation (MM2) of the >C=O Bond

A new type of carbon atom has been included in the MM2 force field when it is part of a carbonyl group cross-conjugated in a heterocyclic molecule. This carbon atom is fully included in the π system calculation. New stretching parameters for the C=O bond have been estimated by a statistical process from X-ray molecular structures recorded in the Cambridge Structural Database System. The proposed parameters have been found appropriate for compounds in which the atoms adjacent to the carbonyl are a carbon and a heteroatom i.e. mainly for the α-pyrone ring and the conjugated "lactams". They are inappropriate for carbonates and oxazo-ones but should be valid for quinones provided that they are not involved in a charge transfer complex. The mean unsigned deviation for 111 bond lengths (89 cyclic molecules) is 0.01A but the maximum deviation can reach ± 0.03A. Part of the observed dispersion could be the result of the variation of the effective dielectric constant D from one crystal to another.