Allinger's MM2 Research Articles

ChemInform Abstract: Convenient Synthesis of Propane Aminophosphonic Acids, Aminodiphosphonic Acids and Their Structural Analogues, Mediated by Azetidinium Salts.

Abstract The reactions of azetidinium salts with phosphorus nucleophiles R2P(O)H have been investigated. Treatment of O-benzyl-N,N-diethyl-3-hydroxyazetidinium salt 2 with R2P(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 R2P(O)H to form compounds 5 containing two phosphorus centers. Further compounds of type 3 have been transformed into compounds 5 by reaction with R2P(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 R2P(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.

Ab Initio Molecular Modeling of 13C NMR Chemical Shifts of Polymers. 2. Propene−Norbornene Copolymers

A methodology based on ab initio DFT computations as well as on molecular mechanics has been devised for helping the elucidation of the microstructure of polymers through the interpretation of their C-13 NMR spectra and has been applied to the case of propene-norbornene (P-N) copolymers. In a first step, a rotational-isomeric-state model of the chain of these copolymers has been achieved. The results of molecular mechanics calculations on various model compounds were checked and corrected by means of ab initio DFT computations at high level of theory. In general, good agreement was found between the results obtained with Allinger's MM2 force field and with the quantum-mechanical method B3LYP/ 6-31G**. Then, theoretical C-13 chemical shifts for two basic compounds were obtained according to the GIAO (gauge including atomic orbitals) method, using a large basis set and Adamo and Barone's functional. The theoretical chemical shifts averaged over the RIS populations provided rather unambiguous indications for interpreting the C-13 NMR signals observed in spectra of isotactic (P-N) copolymers with mid-low norbornene content. Thus, only with the help of these calculations was it possible to achieve a first unambiguous assignment of each of the seven major N signals in the complex spectra of P-N copolymers. This methodology may turn out to be of general utility, in particular for those macromolecular systems where empirical relationships between conformation and chemical shifts are not available.

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 Study of Organophosphorus Compounds

Molecular Mechanics calculation (Allinger's force field and MM2 1985 program) was successfully applied for the structure-reactivity studies of organophosphorus compounds in our laboratory.

Dielectric and molecular mechanics study of the γ relaxations of poly(chloroethyl methacrylate) and poly(chloropropyl methacrylate)

Cryogenic dielectric measurements corresponding to the γ-relaxation zone have been made for poly(chloroethyl methacrylate) and poly(chloropropyl methacrylate). Molecular mechanics calculations using the Allinger MM2 force field have been carried out on monomer and trimer model compounds in an attempt to gain some insight into the possible origin of the γ-relaxation process which occurs in these polymers at low temperatures. In both cases, we found that the molecular mechanism of oxylcarbonyl side group rotation combined with reasonable constraints on movements of the neighbouring side groups gave theoretical activation energy requirements which were in good agreement with those determined from the experiment.

An improved force field for conformational analysis of sulfated polysaccharides

A force field to be used in molecular mechanics studies of sulfated polysaccharides with explicit account of water and counterion interactions was derived from the analysis of six crystal structures of sulfated monosaccharide salts. The force field is based on Allinger's MM2, and was developed starting from the parameters used in previous studies of heparin and related oligosaccharides. While the novel parameters have been derived empirically, use of the atomic charge distribution obtained from ab initio quantum-mechanical computations, at the 6–31 + G** level, improves the quality of structural fitting significantly. The overall discrepancy between the positions of the nonhydrogen atoms determined by X-ray diffractometry and those corresponding to the minimum-energy structure is 0.21 A. While most geometrical features of both carbohydrate and sulfate moieties are reproduced satisfactorily, in some cases (particularly in the case of the Na+ salt of α-methyl-4-O-sulfogalactopyranoside) the hydrogen bond pattern is altered by energy minimization, probably due to errors in the balance of the strong electrostatic forces. © 1997 by John Wiley & Sons, Inc.

Molecular Arrangement Simulation of Pentacosadiynoic Acid Langmuir-Blodgett Films

A simulation of the molecular arrangement of 10,12-pentacosadiynoic acid (PDA) Langmuir-Blodgett (LB) films has been carried out. The PDA molecules were optimized to local minimum energy structures by the molecular mechanics technique using Allinger's MM2 force field. The optimized molecules were arranged in the close-packed structures in a two-dimensional area where the closest atomic distances of the contacting molecules were restricted by the Van der Waals radii. The simulation results showed successful agreement with the reported experimental data.

Searching conformational space with molecular mechanics method. Dihedral angle random increment search

A computational method for finding different molecular conformations of organic molecules is described. The method is based on Allinger's MM2 (MMP2) force-field program where DRIVER subroutine was supplemented by Monte Carlo type routine for generation of new conformations by random variation of the randomly selected torsional angles. The method works in two directions: conformational search (using torsional or energetic criteria) providing conformational geometries, energies and molar fractions, and search for global minimum using simulated annealing procedure. The use of “temperature shaking” procedure facilitates escape from deep local minima. The method works for open chain as well as for cyclic molecules of any size acceptable by MM2 (MMP2) program. It has been tested by searching conformational space for several acyclic and cyclic (medium- and large- ring) molecules.

Theoretical conformational analysis of seven-membered rings (VI). Perhydroazepine

Conformational analysis of perhydroazepine has been carried out within the Allinger MM2 and MM3 force fields. The chair/twist-chair and boat/twist-boat transitions have been studied as have the transitions between both forms. The compound shows a conformational preference for the twist-chair conformation which can be explained on the basis of non-bonded interactions between hydrogen atoms. In addition, the energy values have been calculated for the inversion of the amine hydrogen.

Ab initio study of bond stretching: Implications in force‐field parametrization for molecular mechanics and dynamics

AbstractWe report a theoretical study of the stretching of chemical bonds and its implications on the force‐field parametrization. Computations were performed at the SCF and MCSCF levels by using minimal, split‐valence, and large extended and polarized basis sets. The stretching energy profiles were determined considering up to 25 perturbed geometries of 11 different bonds (6 singles, 2 doubles, and 3 triples). The energy profiles and stretching parameters are compared with the experimental data compiled in the most popular force fields. MCSCF stretching energy profiles are mainly anharmonic and can be only roughly reproduced by quadratic equations. The use of Allinger's MM2 quasiharmonic expression appears as the best choice because it fits with reasonable accuracy a large percentage of the stretching profile without increasing the complexity of the formalism and of the parametrization procedure. MCSCF computations are needed to obtain reliable stretching force parameters. In this respect, MCSCF calculations considering as active space only the bonded and nonbonded orbitals of the perturbed bond seems to be the best strategy to obtain good results at a minimum computational cost, especially if small split‐valence basis sets like the 3‐21G are used. Results obtained at this level of sophistication are completely comparable to stretching parameters compiled on empirical force fields. © 1993 John Wiley & Sons, Inc.

Modified MM2 scheme for computation of OCN‐containing systems

AbstractA modification of Allinger's MM2 force field for the anomeric effect in OCN systems is presented. For optimal consistency, it was parameterized by alternate use of ab initio (3‐21G level) and X‐ray results to account for the energetic and structural manifestations of the effect in the gas or condensed phase, respectively. The results obtained with the modified force field are in good agreement with those from both theoretical and experimental methods. The parameterization scheme explicitly treats all structural parameters of the COCNC moiety as well as CN bond lengths in tertiary amines contained within an anomeric unit. In addition, it includes directional H‐bond type interactions. A limited number of parameters is put forward, in accord with the general MM2 force‐field approach. © 1993 John Wiley & Sons, Inc.

(MM2) theoretical conformational analysis of seven-membered rings (IV)1: thiepane and 1,4-oxathiepane

Abstract The theoretical conformational analysis of thiepane 9 and 1,4-oxathiepane 10 has been carried out by molecular mechanics (Allinger's MM2 force field), studying both chair/twist chair (C/TC) and boat/twist boat (B/TB) families as well as the transitions between the families. Both compounds show a conformational preference for the twist chair conformations. The B/TB family has a smaller number of stationary points than the corresponding one in cycloheptane, the existing boat forms are of minimum energy and twist boat forms have proved to be energetic maxima. Non-bonding interactions between the hydrogen atoms of the rings seem to control the stability of the different conformations in both compounds.

Computation of O-C-F and N-C-F systems: AB-initio calculations and a MM2 parameterization study. Theory vs. experiment

A parameterization scheme of Allinger's MM2 force field for the anomeric effect in O-C-F and N-C-F systems is presented. The scarcity of experimental data, in particular for the N-C-F case, dictated the use of ab-initio calculations to account for the energetic and structural manifestations of the effect. The resulting modified force field was tested against available X-ray, microwave and NMR results leading to a very good agreement between calculations and experiment. In addition, ab-initio results were used to demonstrate the role of the anomeric effect in lowering barriers to N-inversion and elevating barriers for rotation around single CN bonds. The results for the fluoro compounds, when juxtaposed to other systems, provide a complete treatment of the anomeric effect for the first row elements.

Molecular mechanics calculations on the differentiation of diastereomeric complexes ofcis-decalin with?-cyclodextrin

Molecular mechanics calculations with the latest available version of Allinger's MM2 force field (MM2(91)) on the diastereomeric complexes of both enantiomeric conformations ofcis-decalin with β-cyclodextrin show a small preference (1.67 kJ mol−1) for one of them, in agreement with the available13C-NMR results. Calculations were found to be sensitive to the procedure used.

Empirical force field models for the transition states of intramolecular Diels-Alder reactions based upon ab initio transition structures

A quantitative model based upon Allinger's MM2 force field has been devised to calculate the diastereoselectivity of intramolecular Diels-Alder (IDA) reactions. The parameters for the modified MM2 force field were derived whenever possible from ab initio calculations on the intermolecular transition structure for the Diels-Alder reactions of butadiene plus ethylene, acrolein, and acrolein coordinated to BH 3 . The force field reproduces the ab initio 3-21G transition structures for the intramolecular Diels-Alder reactions of 1,3,8-nonatriene and 1,3,9-decatriene

Force field modeling of transition structures of intramolecular ene reactions and ab initio transition structures for an activated enophile

A modification of Allinger's MM2 force field has been developed to rationalize and predict the stereochemistries of intramolecular ene reactions. This force field reproduces the stereochemical trend observed for intramolecular ene reactions with unactivated enophiles, but gives poor results with activated enophiles. Ab initio molecular orbital calculations on the ene reaction of acrylonitrile with propene were performed to investigate the change in the transition structure caused by activating substituents

Locating minima on seams of intersecting potential energy surfaces. An application to transition structure modeling

It is proposed that the equivalent of a transition structure within a force field model can be defined as the lowest energy structure on the seam of the two intersecting potential energy surfaces valid for the reactant and product. The present paper describes a method for locating such minima and compares the obtained results with ab initio transition structures and with experimental activation energies for closely related systems. Using Allinger's MM2 force field, it is shown that the method generates transition structures with overall features close to those obtained by ab initio calculations, and Yends in activation energies are also reproduced reasonably well

Molecular mechanics: Use of an extended version of the MM2 program for pentacoordinated phosphorus compounds. 2. Conformational analysis of substituted bicyclic phosphoranes with a PH2 group

Allinger's program MM2 extended to pentacoordinated phosphorus compounds was used for a conformational study of substituted bicyclophosphoranes containing a PH2 group. The results agree with NMR data and show that the difference in steric energies between the conformations of lowest energies determines whether the rings are in a single conformation or not.

Comparative molecular mechanics study of the low-spin nickel(II) complexes of an extended series of tetraaza macrocycles

Molecular mechanics calculations of metal complex structures are often not straight forward because of uncertainties concerning the appropriate force-field parameters for structural elements involving the metal. A systematic study aimed at extending the Allinger MM2 force field for use with N 4 -macrocyclic complexes of low-spin Ni(II) is reported. The application of the extended force field to the re-examination of the configurational isomers of [Ni(cyclam)] 2+ and their N,N,N,N-tetramethylated derivatives is reported

Molecular mechanics: Extension of the MM2 program to pentacoordinate phosphorus compounds. 1. Conformational study of the bicyclic phosphoranes of the type R-P(H)N(CH2-CH2-O2 (R=H, Me, Ph)

Extension of Allinger's program MM2 [21] to pentacoordinate phosphorus compounds has been performed, tested, and used for a conformational study of the bicyclic phosphoranes R-P(H)N(CH2-CH2-O)2 with R = H, Me, and Ph. Conformations of low energy and barriers between them agree well with the interpretation of NMR results in terms of flexibility of the rings with an exception for R = Ph. In that case, one possible explanation could be the lack of modeling of a special stereoelectronic interaction of the oxygen lone pairs with the phenyl ring.