A comparative molecular field analysis (CoMFA) study using semiempirical, density functional, ab initio methods and pharmacophore derivation using DISCOtech on sigma 1 ligands

The Comparative Molecular Field Analysis (CoMFA) was developed to investigate a three-dimensional quantitative structure activity relationship (3D-QSAR) model of ligands for the sigma 1 receptor. The starting geometry of sigma-1 receptor ligands was obtained from the Tripos force field minimizations and conformations were decided from DISCOtech using the SYBYL 6.8. program. The structures of 48 molecules were fully optimized at the ab initio HF/3-21G* and semiempirical AM1 calculations using GAUSSIAN 98. The electrostatic charges were calculated using several methods such as semiempirical AM1, density functional B3LYP/3-21G*, and ab initio HF/3-21G*, MP2/3-21G* calculations within GAUSSIAN 98. Using the optimized geometries, the CoMFA results derived from the HF/3-21G method were better than those from AM1. The best CoMFA was obtained from HF/3-21G* optimized geometry and charges (R2 = 0.977). Using the optimized geometries, the CoMFA results derived from the HF/3-21G methods were better than those from AM1 calculations. The training set of 43 molecules gave higher R2 (0.989-0.977) from HF/3-21G* optimized geometries than R2 (0.966-0.911) values from AM1 optimized geometries. The test set of five molecules also suggested that HF/3-21G* optimized geometries produced good CoMFA models to predict bioactivity of sigma 1 receptor ligands but AM1 optimized geometries failed to predict reasonable bioactivity of sigma 1 receptor ligands using different calculations for atomic charges.     

Performance of semiempirical methods in fullerene chemistry: relative energies and nucleus-independent chemical shifts

Semiempirical MNDO, AM1, and PM3 calculations are reported for 153 fullerene isomers in an attempt to assess the reliability of these methods through comparisons with ab initio and density functional results. B3LYP/6-31G^* relative energies are generally reproduced quite well by these calculations. Qualitative trends in ab initio nucleus-independent chemical shifts at the cage centers are captured by the semiempirical GIAO-MNDO approach while underestimating their absolute values. The agreement between the semiempirical results and the ab initio or density functional reference data is generally better for the larger fullerenes (C₆₀–C₁₀₂) than for the smaller ones (C₂₀–C₅₀). These systematic comparisons clarify the accuracy that may be expected from semiempirical computations in fullerene chemistry.     

Computational chemistry of the silicon nitride surface. 1. Water,ammonia, and water-ammonia complex

This paper deals with computational modeling of structure and properties of the silicon nitride surface zone using combined computational and real experiments. The computational experiment implies quantum chemical calculations of structure and vibrational spectra of polyatomic clusters. The real experiment suggests measurement and analysis of vibrational spectra. For quantum chemical calculations, semiempirical methods (MNDO and AM1) were chosen. In most calculations, the MNDO/H method was preferred because of the presence of many H-bonds in the surface zone. For verification of calculations, we calculated the structures and vibrational spectra of water and ammonia molecules and the water-ammonia complex and compared the results with experimental and ab initio (extended basis) data; MNDO/H proved to be an optimal method giving reliable results. Russian Peoples' Friendship University. Translated fromZhurnal Strukturnoi Khimii, Vol. 36, No. 1, pp. 58–69, January–February, 1995. Translated by L. Smolina     

Comparison of AM1 and PM3 semiempirical to ab initio methods in the study of Diels-Alder reactions of butadiene and cyclopentadiene with cyanoethylenes

Assuming a concerted synchronous mechanism with one transition state of the Diels-Alder reactions, the structures of the transition states and the activation energies for the reactions of butadiene and cyclopentadiene with cyanoethylenes were calculated by AM1 and PM3 semiempirical methods. The structural parameters were compared with those obtained by high level Gaussian calculations, whereas the activation energies were compared both with the ab initio calculations and those obtained experimentally. The structural properties calculated with PM3 methods are in general in better agreement with the ab initio calculations. The low level ab initio calculations are in many cases worse than the semiempirical methods. All predicted activation energies with both semiempirical methods are up to 300% higher than the experimental values. The predicted reactivity is also opposite to the experimental data. Only the very high level Gaussian calculations are in good correlation with experimental results. The predicted selectivity of the reaction is also opposite to the experimental facts. Two explanations are offered for this discrepancy: AM1 and PM3 methods cannot handle the calculation of the concerted Diels-Alder transition states and are not recommended to be used for that purpose, or this Diels-Alder reaction is not concerted but is stepwise.     

FTIR and FT-Raman spectra, molecular geometry, vibrational assignments, first-order hyperpolarizability, ab initio and DFT calculations for 3,4-dimethoxybenzonitrile

Quantum chemical calculations of energies, geometrical structure and vibrational wave numbers of 3,4-dimethoxybenzonitrile (DMBN) were carried out by the ab initio Hartree-Fock (HF) and density functional theory (DFT) with complete relaxation in the potential energy surface using 6-311++G(d,p) basis set. The computed values of frequencies are scaled using a suitable scale factor to yield good coherence with the observed values. Making use of the recorded data, the complete vibrational assignments are made and analysis of the observed fundamental bands of molecule is carried out. The geometries and normal modes of vibrations obtained from ab initio HF and B3LYP calculations are in good agreement with the experimentally observed data. The electric dipole moment (μ) and the first hyperpolarizability (β) values of the investigated molecule have been computed using ab initio quantum mechanical calculations. The calculated HOMO and LUMO energies show that charge transfer occur within the molecule. The theoretical FTIR and FT-Raman spectra for the title molecule have been constructed.     

Ab initio and DFT studies of the vibrational spectra of benzofuran and some of its derivatives

The vibrational spectra of benzofuran and some of its derivatives have been systematically investigated by ab initio and density functional B3LYP methods. The harmonic vibrational wavenumbers and intensity of vibrational bands were calculated at ab initio and DFT levels invoking different basis sets up to 6-311++g**. Vibrational assignments have been made and it has been found that the calculated DFT frequencies agree well in most cases with the observed frequencies for each molecule. Conformational studies have also been carried out and it is evident from ab initio calculations that 2(3H) benzofuranone is more stable than 3(2H) benzofuranone in support to our earlier semiempirical results.     

Ab initio and semiempirical study of structure and electronic spectra of hydroxy substituted naphthoquinones

The geometries of hydroxy derivatives of 1,4-naphthoquinone (NQ), viz., 2-hydroxy-1,4-naphthoquinone (2HNQ), 5-hydroxy-1,4-naphthoquinone (5HNQ), and 5,8-dihydroxy-1,4-naphthoquinone (DHNQ), have been optimized using the semiempirical and ab initio theoretical methods. Semiempirical methods used for the optimization are Austin Model 1 (AM1) and Zerner's Intermediate Neglect of Differential Overlap/1(ZINDO/1). For ab initio calculations the 6-31G* basis set is used. The electronic spectra of 1,4-naphthoquinone and its hydroxy derivatives are calculated using the semiempirical Zerner's Intermediate Neglect of Differential Overlap/Spectroscopy (ZINDO/S) method employing the geometries optimized at AM1, ZINDO/1 and ab initio levels and compared with their electronic absorption spectra measured by us. For hydroxy substituted systems, such calculations for spectral assignments are made for the first time. It is found that though the predictions of the three theoretical methods for the geometries are similar, the predictions of the ZINDO/S method using the ZINDO/1 optimized geometries, are better for the transition wavelengths in the visible region of the hydroxy substituted naphthoquinones, especially for 5HNQ and DHNQ.     

Structures and energies of D-galactose and galabiose conformers as calculated by ab initio and semiempirical methods

Optimized geometries and total energies of some conformers of alpha- and beta-D-galactose have been calculated using the RHF/6-31G* ab initio method. Vibrational frequencies were computed at the 6-31G* level for the conformers that favor internal hydrogen bonding, in order to evaluate their enthalpies, entropies, Gibbs free energies, and then their structural stabilities. The semiempirical AM1, PM3, MNDO methods have also been performed on the conformers GG, GT, and TG of alpha- and beta-D-galactose. In order to test the reliability of each semiempirical method, the obtained structures and energies from the AM1, PM3, and MNDO methods have been compared to those achieved using the RHF/6-31G* ab initio method. The MNDO method has not been investigated further, because of the large deviation in the structural parameters compared with those obtained by the ab initio method for the galactose. The semiempirical method that has yielded the best results is AM1, and it has been chosen to perform structural and energy calculations on the galabiose molecule (the disaccharides constituted by two galactose units alpha 1,4 linked). The goal of such calculations is to draw the energy surface maps for this disaccharide. To realize each map, 144 different possible conformations resulting from the rotations of the two torsional angles psi and phi of the glycosidic linkage are considered. In each calculation, at each increment of psi and phi, using a step of 30 degrees from 0 to 330 degrees, the energy optimization is employed. In this article, we report also calculations concerning the galabiose molecule using different ab initio levels such as RHF/6-31G*, RHF/6-31G**, and B3Lyp/6-31G*.