Pyrrolizidine alkaloids necine bases: Ab initio,semiempirical, and molecular mechanics approaches to molecular properties

The structural stabilities of endo and exo conformations of retronecine and heliotridine molecules were analyzed using different ab initio, semiempirical, and molecular mechanics methods. All electron and pseudopotential ab initio calculations at the Hartree-Fock level of theory with 6-31G* and CEP-31G* basis sets provided structures in excellent agreement with available experimental results obtained from X-ray crystal structure and ¹H-NMR (nuclear magnetic resonance) studies in D₂O solutions. The exo conformations showed a greater stability for both molecules. The most significant difference between the calculations was found in the ring planarity of heliotridine, whose distortion was associated with the interaction between the O(11)H group and the C(1)-C(2) double bond as well as with a hydrogen bond between O(11)H and N(4). The discrepancy between pseudopotential and all-electron optimized geometries was reduced after inclusion of the innermost electrons of C(1), C(2), and N(4) in the core potential calculation. The MNDO, AM1, and PM3 semiempirical results showed poor agreement with experimental data. The five-membered rings were observed to be planar for AM1 and MNDO calculations. The PM3 calculations for exo-retronecine showed a greater stability than the endo conformer, in agreement with ab initio results. A good agreement was observed between MM3 and ab initio geometries, with small differences probably due to hydrogen bonds. While exo-retronecine was calculated to be more stable than the endo conformer, the MM3 calculations suggested that endo-heliotridine was slightly more stable than the exo form. © 1996 by John Wiley & Sons, Inc.     

A theoretical study on the structure and properties of phenothiazine derivatives and their radical cations

Semiempirical CNDO, AM1, PM3 and ab initio HF/STO-3G, HF/3-21G(d), and HF/6-31(d) methods were employed in the geometry optimization of the phenothiazine and the corresponding radical cation. The results obtained from the PM3 performances were as good as those from the ab initio calculations in the structure optimization of both phenothiazine and phenothiazine radical cation. The PM3 method was used to optimize the structures of a series of N-substituted phenothiazine derivatives and their radical cations. The PM3-optimized results were then analyzed with the ab initio calculation at the 6-311G(d,p) level, which yielded the total energy, frontier molecular orbitals, dipole moments, and charge and spin density distributions of the phenothiazine derivatives and their radical cations.     

Study of hydrogen bonding interactions relevant to biomolecular structure and function

Ab initio molecular orbital calculations were used to study hydrogen bonding interactions and interatomic distances of a number of hydrogen bonded complexes that are germane to biomolecular structure and function. The calculations were carried out at the STO-3G, 3-21G, 6-31G*, and MP2/6-31G* levels (geometries were fully optimized at each level). For anionic species, 6-31 + G* and MP2/6-31 + G* were also used. In some cases, more sophisticated calculations were also carried out. Whenever possible, the corresponding enthalpy, entropy, and free energy of complexation were calculated. The agreement with the limited quantity of experimental data is good. For comparison, we also carried out semiempirical molecular orbital calculations. In general, AM1 and PM3 give lower interaction enthalpies than the best ab initio results. With regard to structural results, AM1 tends to favor bifurcated structures for O? H-O and N? HO types of hydrogen bonds, but not for hydrogen bonds involving O-H? S and S-H? O, where the usual hydrogen bond patterns are observed. Overall, AM1 geometries are in general in poor agreement with ab initio structural results. On the other hand, PM3 gives geometries similar to the ab initio ones. Hence, from the structural point of view PM3 does show some improvement over AM1. Finally, insights into the formation of cyclic or open formate–water hydrogen bonded complexes are presented. © 1992 by John Wiley & Sons, Inc.     

Unusual conformational-determining interactions in oxymethylpyridines: An ab initio study and an improved method for refining molecular mechanics parameters

The conformational preferences of oxymethylpyridines have been investigated by ab initio calculations and compared to similar calculations for oxymethylbenzene. The C? O bond in the pyridine compounds was found to prefer eclipsing with a C? C bond in the ring, in agreement with previous observations but in disaccord with tentative MM2 calculations. The effect was most pronounced in the 2-substituted pyridine. The benzene compound, on the other hand, showed good agreement between the energies from MM2, MM3, and ab initio calculations. The conformational preferences are discussed in terms of stereoelectronic interactions. New MM2 and MM3 parameters were determined from ab initio calculations on nonstationary points on the energy hypersurface. The parameterization method is discussed. © 1995 by John Wiley & Sons, Inc.     

Theoretical study of “protonated pyruvate”: A methylhydroxycarbene—carbon dioxide complex—implications for the decarboxylation of pyruvic acid

Two conformers of protonated pyruvate, CH₃C⁺(OH)COO, with the OH group either trans or cis to the methyl group and the carboxylate group in the C? C? C plane have been studied using the ab initio SCF/3-21G method, as well as by some semiempirical AM1 calculations. Both ab initio SCF and AM1 curves for the potential energy as a function of the C? COO distance exhibit a minimum corresponding to a complex of methylhydroxycarbene, CH₃COH, associated with carbon dioxide, but only the AM1 curves predict an inner minimum corresponding to a covalently bonded protonated pyruvate molecule with a C? COO distance of 1.6–1.7 Å. The two models also disagree on the dissociation pathway for pyruvic acid, with the AM1 calculations predicting formation of acetyl and HOCO radicals while the ab initio method predicts dissociation into methylhydroxycarbene and carbon dioxide following an initial intramolecular proton transfer. The weakly bound complexes of methylhydroxycarbene and carbon dioxide have been studied in some detail using ab initio SCF and MP2 methods in conjunction with 6-311G** basis sets, obtaining equilibrium geometries and vibrational frequencies. In addition, the lactone-type isomer of protonated pyruvate, which contains a C? C? O ring, was also studied. The conclusions of these calculations are consistent with those from earlier work using the smaller 3-21G basis set. The most stable complex is predicted to occur between trans-methylhydroxycarbene and carbon dioxide where substantial stabilization is provided by an OH ? OC hydrogen bond. © 1993 John Wiley & Sons, Inc.     

Ab initio studies of structural features not easily amenable to experiment. 38. Structural and conformational investigations of propanoic, 2-methylpropanoic,and butanoic acid

The structures and conformational energies of several conformations of propanoic acid, 2-methylpropanoic acid, and butanoic acid were determined by geometrically unconstrained ab initio gradient geometry refinement on the 4-21G level. The O?C? C? C torsional potentials of propanoic acid and butanoic acid are found to be practically identical. There are energy minima at 0° and 120°, and maxima in the 60° region and at 180°. In 2-methylpropanoic acid there are energy minima at H? C? C?O dihedral angles of 0° and 120°, and maxima at 60° and 180°. The exact positions of the maxima and minima of the H? C? C?O torsional potential of 2-methylpropanoic acid are found to be predictable from propanoic acid rotational-potential parameters. Some conformationally dependent, local geometry trends are discussed.     

Conformation energy around the N(sp3)?O single bond

A detailed conformational analysis was performed on simple substituted hydroxylamines using either ab initio (from HF/6-31G* to RQCISD/6-311G**) or popular semiempirical (MNDO, AM1, PM3) methods to ascertain the allowed conformations and to establish the influence of the level of theory on the results. All the ab initio results (provision being made for their expected divergences) are similar and show a simple twofold character for the > N? O? rotational energy, without any appreciable populations of the cis conformer. On the other hand, the predictive value of the semiempirical methods for structural and energetical parameters of molecules bearing > N? O? moieties is limited, a situation like that prevailing for peptide bonds. The inversional barriers for the methyl-substituted hydroxylamines were also calculated and compared to the corresponding rotational energy barriers. Rotation is generally favored over inversion for hydroxylamine and its methylated derivatives. © 1994 by John Wiley & Sons, Inc.     

Comparative study between ab initio and semiempirical electrostatic potentials on molecular surfaces

The electrostatic potentials of 21 molecules containing different functional groups has been computed at the ab initio RHF/6-31G* level on a series of solvent accessible surfaces and compared with MNDO, AM1, and PM3-derived pontentials. We analyzed in detail the distribution of electrostatic potentials on the surfaces around their maximum and minimum values and found out that consistently MNDO gives results similar to ab initio potentials. The actual values of the MNDO electrostatic potentials show a systematic deviation from the “correct” results, but the pattern of the MEP distribution on the surface is similar to that of the ab initio results. In contrast, PM3 fails in some cases to give even the correct number or distribution of “hot spots” of potential (low MEP) on the surface. AM1 behaves somewhere between these two semiempirical methods. As a conclusion, MNDO would be suggested as the best approach to analyses requiring a fast and efficient mapping of electrostatic potentials on simplified models of molecular surfaces. © 1993 John Wiley & Sons, Inc.     

Semiempirical study of compounds with intramolecular O?H…︁O hydrogen bonds. II. Further verification of a modified MNDO method

In the forerunner of this article, we described a MNDO modification designed for studies of compounds with intramolecular O? H…?O hydrogen bonds. Here, we report the further verification of the modification by means of its application to 14 compounds not considered in its development. Comparison of the calculated structural parameters and proton transfer characteristics with available experimental or ab initio results, and with those obtained using MNDO, AM1, MNDO/H, MNDO/M, and PM3, supports the validity of the new modification for prediction of hydrogen bond characteristics. © 1994 by John Wiley & Sons, Inc.     

Comparison of AM1 and ab initio calculation of the carbon-carbon bond rotation in ethylene glycol diacetate

The C-C glycol bond rotational energy in ethylene diacetate as a polyester model was compared using the semiempirical method AM1 and an ab initio method with an STO-3G basis set. The results were qualitatively much different depending on the method used. Ab initio calculations showed the expected minima at 180 and near 60 (69.6) degrees dihedral angle with maxima at 0 and 120 degrees. The AM1 rotational curve indicated an apparent minimum at a 90 degree dihedral angle, a shallow, apparent maximum at 180 degrees and an apparent maximum at 0 degrees which could not be confirmed as minima or maxima via frequency calculations. Ethylene diacetate analog compounds with one or two ester oxygens replacing methylene group(s) gave curves with AM1 having the general shape for ethylene diacetate by the ab initio method, indicating a parameterization problem for the otherwise very useful AM1 to correctly handle a compound with only two carbons between the two electronegative oxygen atoms thus rendering this method currently unsuitable for examination of rotational energy barriers of such polyester model compounds.     

Molecular structures and intramolecular interactions in dimethyl cyclohexane isomers

The geometries of ten isomers of dimethyl cyclohexane were determined by ab initio gradient geometry refinement with the 4-21G basis set. It is found that many intramolecular interactions are clearly manifested by correlated structural trends, and that they are consistent with strain energies calculated by employing previously defined ab initio group equivalents. Specifically, non-bonded interactions are found between two adjacent methyl groups in some of the forms, and between axial methyl groups and adjacent axial C? H bonds in others. Unperturbed axial C? H and C? C bonds are consistently longer than equatorial bonds. In general, C? H bonds which are involved in non-bonded repulsive interactions are shortened, i.e., strengthened, and the corresponding H? C? C angles are large, compared to non-interacting parameters.     

Suitability of the PM3-derived molecular electrostatic potentials

A systematic study of the suitability of PM3-derived molecular electrostatic potentials (MEPs) is presented. Forty-six MEP minima, 81 electrostatic charges, and 17 electrostatic dipoles were determined at the PM3 level and compared with those obtained from the ab initio 6-31G* wave function, as well as from the semiempirical MNDO and AM1 wave functions. The statistical results of the comparison analysis between semiempirical and ab initio 6-31G* MEPs show that PM3 is in general reliable for the study of the MEP minima but a mediocre method as a source of electrostatic charges. © 1993 John Wiley & Sons, Inc.     

含苯并五元环方酸衍生物的二阶非线性光学性质的理论研究

利用从头算HF/6-31G*方法对用苯并五元环取代的方酸衍生物体系SQ1～SQ15进行几何构型优化和电子结构计算. 以优化后的构型为基础, 应用ZINDO方法计算电子光谱. 同时应用从头算CPHF/6-31G*方法和半经验FF/AM1, FF/PM3, FF/MNDO等有限场方法计算了分子的二阶非线性光学系数β_μ. 研究几何结构、电子结构和前线分子轨道能与β_μ之间的关系, 为设计性能优良的有机非线性光学材料提供理论指导, 并对这四种计算方法的结果进行了比较.     

Structure of disiloxane: A semiempirical and Post-Hartree–Fock study

The semiempirical (MNDO, AM1, and PM3) and ab initio predicted structure of disiloxane is studied with a series of basis sets and inclusion of electron correlation at MP2, MP3, MP4, CCD, CCSD, and CCSD(T) levels. The calculated molecular geometry and barrier to linearization of the Si? O? Si bond angle are compared with previous theoretical and experimental values. Our results show that the calculated barrier to linearization is very sensitive to the number of polarization functions in the basis set. We also investigate the coupling between the Si? O? Si bond angle and the Si? O bond length and calculate the Mulliken and electrostatic potential-derived charges. For comparison purposes we also calculate the molecular geometry, the barrier to linearization of the Si? O? Si bond angle, and the atomic charges in hexamethyldisiloxane. © 1994 by John Wiley & Sons, Inc.     

MO-Studies of enzyme reaction mechanisms. I. Model molecular orbital study of the cleavage of peptides by carboxypeptidase A

Ab initio and semiempiridal (AM1) molecular orbital theory has been used to model the cleavage of formamide at the active site of carboxypeptidase A. The model active site consists of a zinc dication coordinated to two imidazoles, an acetate, a water with a hydrogen-bonded formate, and a formamide molecule as model substrate. AM1 has been compared with ab initio theory for the coordination of water and formamide to Zn⁺⁺ and found to give excellent energetic results. The course of the amide cleavage was therefore calculated with AM1. The first step of the reaction is the dissociation of the zinc-coordinated water to give an active ZnOH⁺ species. The remote formate acts as proton acceptor. This process has an activation energy of only 4.6 kcal mol^?1. The next and rate-determining step is the concerted addition of the ZnOH⁺ moiety to the formamide C?O bond. The Zn? O distance in the transition state is more than 3 Å. In four further steps, the amide nitrogen is protonated and the C? N bond cleaved. The net activation energy for the entire process is 15.5 kcal mol^?1 relative to the active site model and 19.6 kcal mol^?1 relative to the most stable point on the calculated reaction profile.     

Conformational energetics of 1,3-dichloropropane as predicted by several calculations methods

Two semiempirical methods (MNDO and AM1), a molecular mechanics technique (MM2) and two ab initio approaches (6–31G* full optimization and 3–21G/6–31G*) were used to calculate the ordering of and energy difference between conformers in 1,3-dichloropropane. The semiempirical methods did not order the conformers properly or predict correct energy differences. Both ab initio methods ordered the conformers and predicted energy differences correctly, with the 6–31G* full optimization performing slightly better. The MM2 results were presented for calculations involving a force field with no hydrogens and a full force field of all atoms. The full force field properly ordered the conformers but did not correctly predict the energy differences. The nonhydrogen field ordered the conformers based on the Cl…Cl nonbonded distance. The data show that conformer stability is not a simple matter of maximizing the Cl…Cl nonbonded distance, but is also related to some other stabilizing interaction(s).     

A theoretical study of the rotational isomers of nitrosomethanol by semiempirical (AM1) and ab initio methods

The conformational potential energy surface as a function of the two internal torsion angles in C-nitrosomethanol has been obtained using the semiempirical AM1 method. Optimized geometries are reported for the local minima on this surface and also for the corresponding points on the HF/6-31G, 6-31G*, and 6-31G** surfaces. All methods predict cis and trans minima which occur in degenerate pairs, each pair being connected by a transition state of C_s symmetry. The AM1 structures are found to compare well with the corresponding ab initio structures. Ab initio HF/6-31G and HF/6-31G* harmonic vibrational frequencies are reported for the cis and trans forms of nitrosomethanol. When scaled appropriately the calculated frequencies are found to compare well with experimental frequencies. The ab initio calculations predict the energy barrier for cis → trans isomerization to be between 5.8 and 6.5 kcal/mol with the trans → cis isomerization barrier lying between 2.3 and 6.5 kcal/mol. The corresponding AM1 energy barriers are around 1 kcal/mol lower in energy. The ab initio calculations predict the barrier to conversion between the two cis rotamers to be very small with the AM1 value being around 1 kcal/mol. Both AM1 and ab initio calculations predict interconversion between trans rotamers to require between 1.2 and 1.4 kcal/mol.     

Molecular mechanics of peroxides. I. Parametrization and conformational analysis of linear compounds

A force field has been developed for use in MM2 calculations of geometric and energy data for linear peroxides R₁? O? O? R₂ and tested in some of them (R₁, R₂ = H, Me, Et, Prⁱ, Bu^t). The field obtained yield results that agree considerably better with experimental and ab initio data than those afforded by the only set of estimated parameters hitherto available.     

Comparison of NDDO and quasi-ab initio approaches to compute semiempirical molecular electrostatic potentials

The suitability of the two most widely used strategies to compute semiempirical MEPs is examined. For this purpose, MEP minima, electrostatic charges, and dipoles for a large number of molecules were computed at the AM1, MNDO, and PM3 levels using both the NDDO strategy developed by Ferenczy, Reynolds, and Richards and our own quasi-ab initio method. Results demonstrate that the quasi-ab initio is preferred over the NDDO method for the computation of MEP minima. It is also found that the best set of semiempirical charges and dipoles are obtained using either the AM1 NDDO or the MNDO quasi-ab initio methods. In these two cases, the quality of the results is fully comparable with 6-31G* values. © 1994 by John Wiley & Sons, Inc.