A theoretical study of malonate ion and its metal binding by ab initio and semiempirical techniques

STO-3G and CNDO calculations have been performed on malonate ion and its Mg²⁺ complexes. The parallel carboxyl group arrangement is found to be the single minimum energy conformation with both techniques. In the metal binding studies, the binding of a Mg²⁺ to a single carboxyl is preferred over binding symmetrically to both carboxyls in their parallel conformation. These results are consistent with X-ray structure results on calcium malonate.     

Vibrational study of dialkylphosphonates: di-n-propyl- and di-i-propylphosphonates by semiempirical and ab initio methods

Fourier transform infrared and Fourier transform Raman spectra of n-C(3)H(7) and i-C(3)H(7) dialkylphosphonates have been obtained. Semiempirical AM1 and the ab initio orbital molecular RHF/6-31G* theories have been used to study the molecular geometry, and the harmonic vibrational spectra with the purpose to assist the experimental assignments of these compounds. An extensive discussion on the assignment of the C-C, C-O, P-O and P=O stretching is carried out based on experimental data of compounds which have the propyl and isopropyl groups, as well as comparing the vibrational spectra of propane. Most of the RHF/6-31G* and AM1 results, once applied the appropriate scaling factor, showed an excellent agreement with the experimental wavenumbers. A few calculated frequencies related to CC and CO stretching do not agree well with the experimental trends.     

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.     

A theoretical ab initio study on the H(2)NO + O(3) reaction

The deviation of the NH(2) pseudo-first-order decay Arrhenius plots of the NH(2) + O(3) reaction at high ozone pressures measured by experimentalists, has been attributed to the regeneration of NH(2) radicals due to the subsequent reactions of the products of this reaction with ozone. Although these products have not yet been characterized experimentally, the radical H(2)NO has been postulated, because it can regenerate NH(2) radicals through the reactions: H(2)NO + O(3) --> NH(2) + O(2) and H(2)NO + O(3) --> HNO + OH + O(2). With the purpose of providing a reasonable explanation from a theoretical point of view to the kinetic observed behaviour of the NH(2) + O(3) system, we have carried ab initio electronic structure calculations on both H(2)NO + O(3) possible reactions. The results obtained in this article, however, predict that of both reactions proposed, only the H(2)NO + O(3) --> NH(2) + O(2) reaction would regenerate indeed NH(2) radicals, explaining thus the deviation of the NH(2) pseudo-first-order decay observed experimentally.     

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*.     

A theoretical study of malonate and formate calcium binding by ab initio techniques

Ab initio calculations at the STO—3G level have been performed on the binding of CA(II) ion to malonate and formate with and without d orbitals in the basis set for the CA(II) ion. The malonate and formate binding results with CA(II) are similar. The addition of d orbitals to CA(II) has little effect on the conformational minimum. The results are qualitatively similar to those from our previous calculations on the Mg²⁺—malonate interaction: a single carboxyl interaction with the metal ion appears to be preferred over a conformation in which two carboxyl groups bind to Ca(II). Moreover, the single carboxyl group interaction with CA(II) appears to be favored over the binding of CA(II) to a single oxygen of a carboxyl group.     

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.     

Electronic structure of testosterone: A semiempirical and ab initio assessment

Testosterone (17β-hydroxy-4-androsten-3-one) was studied by the semiempirical AM1 and PM3 and ab initio STO-3G^*, 3–21G^*, and 6–31G^* methods. The goals were to compare those methods and to know the electronic structure of the hormone. Full geometry optimization was performed, and two crystal conformers (T1 and T2), and experimental dipole moment in solution were used for comparison. One conformer with a dipole moment similar to the solvated conditions was generated. Total energy, entalphies, dipole moments, charges, electrostatic potentials, and highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbital (LUMO) were calculated. Root-mean-square (RMS) index of the theoretical molecules against T1 and T2 showed best results with the 3–21G^* and 6–31G^* methods, while AM1 gave better energies than PM3. Dipole moments were directed toward the OH group and the botton face of the A ring. The frontier orbitals were located along the C4–C5 π bond, particularly the LUMO was split between C4 and C5, predicting the action of enzymes at C5 yielding to 5α and 5β-reduced androgens. Electrostatic potentials might be also of biological importance since they are coincidental with the dipole-moment orientation. Finally, it is interesting that the solvatedlike conformer, its properties, and the OH group laid between the same group of T1 and T2 and with a total energy between the crystals and the gas phase or in vacuo conditions. This results might also explain the biology of testosterone and use them to model the hormone-receptor interaction. © 1997 John Wiley & Sons, Inc.     

A comparative AM1 and ab initio study of the intramolecular proton transfer in tautomeric organic compounds

The proton-transfer barriers along the intramolecular hydrogen bond in a series of substituted salicylaldehyde anils were calculated using the AM1 SCF semiempirical method. The reliability of this method for the calculation of proton-transfer barriers was analyzed by the comparison of AM1 barriers for a series of different tautomeric organic compounds with those calculated using ab initio SCF and second-order perturbation theory with extended basis sets. In general, the AM1 method systematically overestimates the barrier height. However, this error is approximately constant for given pairs of groups involved in the intramolecular proton transfer. © 1996 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.     

A semiempirical and ab initio MO study of the tautomers ofN-unsubstituted pyrazolones [hydroxy pyrazoles]

Semiempirical (MNDOC, MINDO/3, AM1, and MNDO) and ab initio (STO-3G and 4-31G basis sets) calculations on the relative stabilities, structures, and dipole moments of the 8 theoretically possible tautomeric forms of pyrazolone are reported. It is shown that MNDO + CI and MINDO/3 predict that 5-hydroxy pyrazole, 3-hydroxy pyrazole, and 2-pyrazolin-5-on are the most stable. These results correspond to the known experimental data. Of all used quantum chemical methods, the MINDO/3 results for the dipole moments of the investigated tautomers are in best agreement with the known experimental data. The electronic excitation energies were calculated using the CNDO/S-CI method. The results are in good agreement with the experimental UV spectra.     

The prediction of (1)H chemical shifts in amines: a semiempirical and ab initio investigation

Twenty one conformationally fixed amines and their N,N-dimethyl derivatives were obtained commercially or synthesized. These included cis and trans 4-t-butyl cyclohexylamine, 2-exo and 2-endo norbornylamine, 2-adamantylamine, 4-phenylpiperidine, 1-napthylamine and tetrahydro-1-napthylamine. The (1)H NMR spectra of these amines were measured in CDCl(3) solution, assigned and the (1)H chemical shifts given. This data was used to investigate the effect of the amino group on the (1)H chemical shifts in these molecules. These effects were analyzed using the CHARGE model. This calculates the electric field and steric effects of the amino group for protons more than three bonds removed, together with functions for the calculation of two-bond and three-bond effects. The rotational isomerism about the C--N bond of the amino group was investigated by ab initio calculations of the potential energy surface (PES) about this bond at the HF/3-21G level. The resulting conformers were then minimized at the B3LYP/6-311 + + G (d,p) level. These geometries were then used to calculate the (1)H chemical shifts in the above compounds by CHARGE and the ab initio gauge-invariant atomic orbital (GIAO) method at the B3LYP/6-311 + + G(d,p) level and the shifts were compared with those observed. The compounds investigated gave 170 (1)H chemical shifts ranging from 0.60 to 8.2 ppm. The rms errors (obs.-calc.) were ca 0.1 ppm (CHARGE) and ca 0.2 ppm (GIAO). Large deviations of ca 1.0 ppm were observed for the NH protons in the GIAO calculations. The complex spectra of alkyl and aryl amines can thus be successfully predicted by both ab initio and semiempirical methods except for the NH protons, for which the ab initio calculations are not sufficiently accurate.     

An ab initio theoretical study of the stereoisomers of tetrahydrocannabinols

An extensive theoretical study of the stereoisomers of tetrahydrocannabinols has been performed at the ab initio HF/6-31G^* and B3LYP/6-31G^* levels. Effects of solvation were calculated with the Onsager model (with full geometry optimization), SCRF with Tomasi's PCM, and isodensity polarization continuum models. Single-point MP2//HF/6-31G^* calculations were carried out. Frequency calculations for all the isomers at the HF/6-31G^* level and for two natural isomers ¹-THC-RR and ⁶-THC-RR at the B3LYP/6-31G^* level were performed. Our results support the findings of the previous AM1 studies that the orientation of the carbocyclic ring and its C1 substituent with respect to the phenyl group hydroxyl oxygen play the major role in the activity. The calculated values of the LUMO energy (lowest unoccupied molecular orbital) and the hardness of the stereoisomers show that for the trans isomers it is easier to remove one electron from its HOMO (highest occupied molecular orbital) to the LUMO and easier to accept an electron from the receptor binding site than for the cis isomers. Combining geometric features (the orientation of the carbocyclic ring and its C1 substituent with respect to the phenyl group hydroxyl oxygen) with electronic features (LUMO and hardness), we explain the activity differences among the stereoisomers.     

The valence isomers of (CH)8 and (SiH)8: An ab initio MO study

The 22 possible valence isomers of the (CH)₈ and (SiH)₈ systems have been studied by ab initio molecular orbital calculations at the MP2/6-31G*//6-31G* + ZPE level. Optimized geometries, relative energies, and, for some selected compounds, vibrational frequencies are reported. The systematic differences between the carbon and silicon compounds are analyzed. © 1994 by John Wiley & Sons, Inc.     

Copolymers of carbon dioxide and nitrogen: an AM1 and ab initio computational study

Extending work by various groups on possible dimers, trimers, etc. of dinitrogen and of carbon dioxide, the authors have studied analogous copolymers of N₂ and CO₂ computationally. Twelve cyclic structures were examined with the AM1, HF/3-21G, HF/6-31G* and MP2(FC)/6-31G* methods, and the acyclic “monomer” to “tetramer” HO(C(O)O–N= N–)_nH, n=1–4, were studied at the AM1 and HF/3-21G levels; the cyclic species included 2-oxa-3,4-diazacyclobut-3-ene-1-one, 2-oxa-3,4,5,6-tetraazacyclohexa-3,5-diene-1-one, and various aza/oxa bicyclo[2.2.0] and bicyclo[2.2.2] systems. For the cyclic species, it was concluded that only the MP2(FC)/6-31G* results, which differ considerably from those at the other three levels, are likely to be reliable. These MP2 calculations indicate that only seven of the 12 cyclic structures studied are stationary points (one is a transition structure), and none of them is kinetically stable at room temperature. Although some have high energy densities (ca. 7–10 kJ g⁻¹), their expected low kinetic stabilities seems to make this of little practical value. The acyclic “copolymers” were all relative minima at the AM1 and HF/3-21G levels; unlike the cyclic species, their kinetic stabilities were not investigated directly by comparing the energies of reactants and decomposition transition states. The energy density of the infinite acyclic polymer was found by extrapolation to be 5.1 (AM1) or 5.6 (3-21G) kJ g⁻¹. The calculated vibrational spectra of the MP2 stationary points and of the acyclic molecules gave some indication of instability by the presence of low-frequency modes leading in the limit to decomposition.     

Prediction of geometries and interaction energies of complexes formed by small molecules using semiempirical and ab initio methods

The accuracy of the semiempirical quantum mechanics methods (AM1 and PM3), and the ab initio methods (6-31G^** and MP2/6-31G^**) in predicting intermolecular geometries and interaction energies have been evaluated by detailed studies of 17 bimolecular complexes formed by small molecules. Comparisons between calculated and experimental geometries for 12 complexes are presented. It was found that AM1 gave reasonably good predictions of the geometries of complexes such as CH₄ · CH₄, which have very weak interactions, but it is not as good as other methods in predicting intermolecular geometry for complexes where hydrogen bonding interactions play an important role. This is consistent with its inability to reproduce the charge transfer in the formation of hydrogen bonds in these complexes.

PM3 is able to predict intermolecular geometries for most complexes, including those with hydrogen bonding; its major flaw is its tendency to overestimate the strength of the interactions between hydrogen atoms. Care should be taken therefore in using PM3 to study complicated molecular systems with multiple hydrogen atom interactions and the method's weakness in handling complexes in which electrostatic forces are important should also be noted.

Among ab initio methods, both the 6-31G^** and the MP2/6-31G^** were found to outperform AM1 and PM3 in prediction of intermolecular geometry. Both of these ab initio methods showed excellent consistency in geometry prediction for most of the complexes studied, although MP2/6-31G^** is better than 6-31G^**. It is noted that the MP2/6-31G^** did not produce the correct geometry for the CO₂· HF complex.

For 12 complexes for which experimental geometry data are available, AM1, PM3, 6-31G^**, and MP2/6-31G^** successfully predicted the geometry in 10, 12, 12, and 11 cases, respectively. The average errors given by AM1 in the predicted intermolecular distances were 0.264, 0.272, 0.091, and 0.061 Å, respectively. In comparison to the ab initio methods, AM1 and PM3 commonly underestimated the molecular interaction energy in such complexes by ˜ 1–2 kcal mol⁻¹.     

Semiempirical AM1 electrostatic potentials and AM1 electrostatic potential derived charges: A comparison with ab initio values

Electrostatic potentials calculated from AM1 wave functions have been compared with ab initio STO-3G values and qualitative agreement has been found. Atomic charges derived from AM1 electrostatic potentials for both experimental and AM1 optimized geometries are of comparable quality with STO-3G potential derived charges. These results suggest that the AM1 electrostatic potential may be useful both in its own right and also for deriving atomic charges for use in molecular dynamics studies.     

The structure of potassium hydrogentartrate: A combined X-ray,semiempirical, and ab initio study

Single crystals of potassium hydrogentartrate, (2R,2R)-KO₂C(CHOH)₂CO₂H, were taken from a three-year-old wine bottle. The structure was determined by low-temperature single-crystal X-ray diffraction analysis using a Siemens SMART diffractometer. (2R,2R)-KO₂C(CHOH)₂CO₂H crystallizes in the orthorhombic space group P2₁2₁2₁ with Z = 4 and unit cell dimensions a = 7.6065(5), b = 7.7599(5), and c = 10.6054(7) Å. The structure of an isolatedhydrogentartrate anion, (2R,2R)-[O₂C(CHOH)₂-CO₂H]⁻, was calculated at the semiempirical AM1 and PM3 levels of theory with a VSTO-3G* basis set and in addition ab initio at the self-consistent level of theory using a standard 6-31G(d, p) basis set (Non-SI units employed: kcal ≈ 4.184 kJ, Å = 10⁻¹⁰ m).© 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:307–310, 1998     

An ab initio study of the geometry and rotational barrier of 4-phenylimidazole

The molecular design of several synthetic artificial enzymes, which mimic the action of the serine protease-chymotrypsin, incorporates the phenylimidazole molecular fragment to play the role of the His-57 residue in the native enzyme active site. Study of these artificial enzymes by molecular modeling techniques requires accurate torsional force field parameters for the phenylimidazole interring bond. This, in turn, requires accurate characterization of the barrier to rotation around this bond. Previous semiempirical calculations of this rotational barrier have neglected geometry optimization of the molecule at the points along the rotational pathway. The 4-phenylimidazole rotational barrier (5.6 kcal mol^–1] presented here was obtained by full ab initio geometry optimization at the 3–21G level at each of the points along the rotational pathway.     

Internal rotation in squaramide and related compounds. A theoretical ab initio study

The structural and energetic changes associated with C–N bond rotation in a squaric acid derivative as well as in formamide, 3-aminoacrolein and vinylamine have been studied theoretically using ab initio molecular orbital methods. Geometry optimizations at the MP2(full)/6-31+G* level confirmed an increase in the C–N bond length and a smaller decrease in the C=O length on going from the equilibrium geometry to the twisted transition state. Other geometrical changes are also discussed. Energies calculated at the QCISD(T)/6-311+G** level, including zero-point-energy correction, show barrier heights decreasing in the order formamide, squaric acid derivative, 3-aminoacrolein and vinylamine. The origin of the barriers were examined using the atoms-in-molecules approach of Bader and the natural bond orbital population analysis. The calculations agree with Pauling's resonance model, and the main contributing factor of the barrier is assigned to the loss of conjugation on rotating the C–N bond. Finally, molecular interaction potential calculations were used to study the changes in the nucleophilicity of N and O (carbonyl) atoms upon C–N rotation, and to obtain a picture of the abilities of the molecules to act in nonbonded interactions, in particular hydrogen bonds. The molecular interaction potential results confirm the suitability of squaramide units for acting as binding units in host–guest chemistry. Received: 13 March 2002 / Accepted: 23 June 2002 / Published online: 21 August 2002