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.     

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.     

Triaziridines. Part V. A semiempirical MNDO study of nitrogen inversion and amide rotation in Formyltriaziridines

Since we found certain structural features of triaziridine ( 1 ) obtained by MNDO calculations to be in qualitative agreement with those derived earlier from ab initio calculations, we used the MNDO method to derive properties of formyltriaziridine ( 2 ) and 1-formyl-2,3-diisopropyltriaziridine ( 3 ) as models for the preparatively known 2,3-dialkyl-triaziridine-1-carboxylates 4 and 5 . The main results are: (a) The triaziridine N-atoms with H, alkyl, or formyl as substituents (see 2 and 3 ) are pyramidal. N(1) carrying the formyl group is flatter than N(2) and N(3) with H or alkyl substitent. Bond lengths and angles at N(2) and N(3) are almost identical with those calculated for the N-atoms of 1 . (b) The MNDO inversion barriers at the H-substituted N(2) and N(3) of 2 are higher than those at the formyl-substituted N(1), but similar to the ab initio barriers at the N-atoms of 1 . (c) The MNDO inversion barriers at N(1) of 2 and 3 are 53 to 92 kJ/mol, whereas the rotation barriers around the N(1)–C(4) bond are 7 to 23 kJ/mol; thus, the previously observed dynamic NMR phenomena in trans-2,3-diisopropyltriaziridine-carboxylates ( 5 ) can now be assigned to the slowing down of N(1) inversion rather than N(1)–C(4) rotation.     

MNDO Calculations of silicon-containing molecules

A comparison is made of MNDO and MINDO /3 calculations for saturated silicon-containing molecules, and with experimental values, for heats of formation, molecular geometries, charge distributions, and ionization potentials. Except for bond angles, it is found that with the published parameter values the MINDO /3 program gives more reliable results than MNDO . For unsaturated molecules, a comparison of bond lengths and stabilities of Si multiple bonds as given by the two programs and ab initio methods is made, and large discrepancies between predicted structures are pointed out. Some reasons for the dicrepancies are discussed.     

Ring opening of the molecular ion of 5(4H)-oxazolone

Quantum chemical calculations were carried out at several theoretical levels (semi-empirical, MNDO; ab initio, 3–21G SCF, 6–311G** SCF and DZP CISD) to investigate the ring-opening process of and the loss of CO from the molecular ion of 5(4H)-oxazolone. The ring-opening process is predicted to be slightly endothermic and the loss of CO from the open-ring molecular ion to be slightly exothermic. Detailed population analysis calculations suggest the weakening of the lactonic C? O bond in the closed-ring molecular ion and weak carbon—carbon and nitrogen—(formy)—carbon bonds in the open form. Both the open-ring molecular ion and the [M–CO]^+· ion are suggested to be of distonic type.     

“Spectroscopic” Calculations of CH Bond Dissociation Energies for Ethane, Propane, Butane, Isobutane, Pentane, Hexane, and Neopentane Using Fundamental Vibration Frequencies

The fundamental spectrum and the parameters of the potential function of a number of saturated hydrocarbon molecules are calculated in an anharmonic approximation. The calculation is performed by the variational technique using a minimal Morse-harmonic basis. The potential function is taken as the sum of the Morse function for CH bonds and the harmonic function for the skeletal and deformation vibrations. The initial approximation for the potential function is found by ab initio calculations in a 6-31G basis and refined by solving the inverse problem. The calculated CH bond dissociation energies depend significantly on the molecular structure and on the position of CH bonds in the molecule. These energies correlate well with the experimental cleavage energies of these bonds. The changes in the dipole moment of the molecule induced by vibrations were found by ab initio calculations in a 6-31G basis. The calculated IR transmission curves are in good agreement with the experimental curves.     

Solvation free energies calculated using the GB/SA model: Sensitivity of results on charge sets,protocols, and force fields

The sensitivity of aqueous solvation free energies (SFEs), estimated using the GB/SA continuum solvent model, on charge sets, protocols, and force fields, was studied. Simple energy calculations using the GB/SA solvent model were performed on 11 monofunctional organic compounds. Results indicate that calculated SFEs are strongly dependent on the charge sets. Charges derived from electrostatic potential fitting to high level ab initio wave functions using the CHELPG procedure and “class IV” charges from AM1/CM1a or PM3/CM1p calculations yielded better results than the corresponding Mulliken charges. Calculated SFEs were similar to MC/FEP energies obtained in the presence of explicit TIP4P water. Further improvements were obtained by using GVB/6-31G** and MP2/6-31+G** (CHELPG) charge sets that included correlation effects. SFEs calculated using charge sets assigned by the OPLSA* force field gave the best results of all standard force fields (MM2*, MM3*, MMFF, AMBER*, and OPLSA*) implemented in MacroModel. Comparison of relative and absolute SFEs computed using either the GB/SA continuum model or MC/FEP calculations in the presence of explicit TIP4P water showed that, in general, relative SFEs can be estimated with greater accuracy. A second set of 20 mono- and difunctional molecules was also studied and relative SFEs estimated using energy minimization and thermodynamic cycle perturbation (TCP) protocols. SFEs calculated from TCP calculations using the GB/SA model were sensitive to bond lengths of dummy bonds (i.e., bonds involving dummy atoms). In such cases, keeping the bond lengths of dummy bonds close to the corresponding bond lengths of the starting structures improved the agreement of TCP-calculated SFEs with energy minimization results. Overall, these results indicate that GB/SA solvation free energy estimates from simple energy minimization calculations are of similar accuracy and value to those obtained using more elaborate TCP protocols. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 769–780, 1998     

Tautomeric equilibria of heterocyclic molecules. A test of the semiempirical AM1 and MNDO-PM3 methods

Tautomeric equilibria (mainly of the lactam-lactim type) for a rather large number of six-membered heterocyclic molecules are calculated by the semiempirical AM1, MNDO-PM3, and MNDO methods. Except for compounds with adjacent pyridine-like lone pairs both AM1 as well as MNDO-PM3 give rather reliable predictions for relative stabilities of the various tautomeric species–comparable to quite high level ab initio calculations. The known errors associated with MNDO in the treatment of heterocyclic tautomerism are thus largely corrected in AM1 as well as MNDO-PM3. For 2-hydroxypyridine-pyrid-2(1H)-one the effect of self-association is less satisfactorily described by MNDO-PM3 than by AM1. MNDO-PM3 calculated relative stabilities of methylated derivatives are, however, in considerably closer agreement with experimental values than those obtained by AM1. Ionization potentials, especially those for lone-pair orbitals, are overestimated by all three semiempirical methods. MNDO-PM3 results for nitrogen lone-pair orbital energies are slightly better than those obtained by the AM1 or MNDO method.     

The value of the π-bond order–bond length relationship in geometry prediction and chemical bonding interpretation

The π-bond order–bond length relationship is reintroduced to the literature and extended to heteronuclear bonds by presenting graphs derived solely by theoretical methods. π-bond order and overlap population results for carbon–carbon, carbon–nitrogen, and carbon–oxygen bonds obtained from ab initio STO -3G calculations using theoretically-optimized geometries are reported for a series of pteridines and for a wide range of small organic molecules. The order–length correlation graphs are used in predicting the “intrinsic” single bond lengths for sp² – sp² and sp – sp hybridized C? C, C? N, and C? O bonds, and in evaluating the relative importance of hybridization, π-electron delocalization and bond polarization effects in causing bond shortening in conjugated and hyperconjugated molecules. The calculated value of the π-bond order for a given bond in a molecule is shown to be relatively insensitive to moderate geometry changes: Hence, a use for the correlation graphs in geometry prediction is suggested. Some results for the extended 4-21G basis set are also presented.     

Comparison of the use of the MNDO and MINDO/3 methods with ab initio methods to study tautomerism in histamine, 2- and 4-methylhistamine

The semiempirical MNDO and MINDO/3 methods are used to study the various tautomeric forms of histamine, 2-methylhistamine, and 4-methylhistamine. Comparisons of the optimized structures and tautomerization energies are made with values obtained from ab initio Hartree-Fock calculations using the 3-21G and STO-3G basis sets. Based on these results and previous comparisons of STO-3G results with x-ray structures, the present results indicate that while there are some differences in the values of the structural parameters, the changes in structure upon tautomerization and/or protonation are very similar. Further analysis of the MNDO and MINDO/3 structures by means of their utilization in 3-21G and STO-3G calculations indicates that either of these semiempirical methods provides reliable values for the structural parameters. Both methods give good qualitative agreement with the ab initio calculations for the relative energies of the various tautomers in the three compounds. In these studies the MNDO method appears to give better quantitative agreement with the 3-21G and STO-3G results than the MINDO/3 method.     

Quantum study of the ground state of a series of unsaturated boron–nitrogen compounds by the MNDO method. I. Geometries and stabilities

A MNDO study of molecular geometries, enthalpies, formation, atomization, bond separation, and hydrogenation of a series of unsaturated boron–nitrogen compounds, linear with two and three members and cyclic with three, four, five, and six members are presented. For all these molecules, MNDO calculations are in excellent agreement with available ab initio calculations or experimental data. The high rotational barrier in aminoborane H₂BNH₂, 30.6 kcal/mol, and the length of bond in iminoborane HBNH, 1.183 Å, imply strong double and triple BN bond character in these two molecules. In the odd membered heterocycles, examination of the molecular geometries and energies of equilibrium states shows that in all cases, the stability of the compounds grows with the number of boron atoms and decreases with that of the nitrogen atoms. Moreover, compared study of the two BN-fulvenes with their homologous hydrocarbon shows that only BN (BB)-fulvene has a polyenic structure similar to that of fulvene.     

Calculations on the diphenylmethyl anion

Semiempirical and ab initio calculations for the diphenylmethyl anion and related species are reported. MINDO/3 calculations indicate a coplanar anion with an enlarged bond angle of ～139° to counteract the steric repulsions. MNDO calculations reveal an expanded bond angle with somewhat greater twist (21°). The ab initio calculations (STO -3G level) reveal an expanded central bond angle with an intermediate degree of phenyl twist. The results are compared with experimental data for this and related anions.     

MNDO calculations on hydrogen bonds. Modified function for core-core repulsion

The MNDO method has been modified to calculate the properties of the structures involving hydrogen bonds X···H—Y, X, Y = N, O and F. A new method (referred to as MNDO/H) has been tested by calculation of a wide range of molecular systems with weak and strong (ionic) hydrogen bonds. The results obtained are in good agreement with the experimental data. In the cases where direct comparisons are possible, the MNDO/H method seems to give more accurate values of hydrogen bond energy than the ab initio method using STO-4-31G basis set.     

On Feasibility of “Spectroscopic” Calculations of XH Bond Dissociation Energies for Polyatomic Molecules from Fundamental Vibration Frequencies Using the Anharmonic Molecular Model

This paper discusses the applicability of the variational technique using a minimal Morse-harmonic basis set to calculations of the fundamental spectrum and the potential function parameters for polyatomic molecules. The potential function is assumed to be the sum of the Morse function for XH bonds and the harmonic function for the skeletal and deformation vibrations. The initial approximation for the potential function is found by ab initio calculations and refined by solving the inverse mechanical problem (selecting the scaling indices). The thus selected harmonic part of the potential function gives equally good agreement between the experimental and calculated transition frequencies in both harmonic and anharmonic approximations. The anharmonic (Morse) term of the potential function (bond dissociation energy) is selected by solving the inverse mechanical problem until the best agreement between the experimental and calculated CH bond stretching frequencies has been achieved. Problem solving ends with the construction of a transmission curve in the IR spectrum. Variations of the dipole moment of the molecule induced by vibrations are found by ab initio calculations.     

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.     

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.     

Comparative Study of the Structure of Rhodanine, Isorhodanine, Thiazolidine-2,4-dione, and Thiorhodanine

Ab initio (HF and MP2 level) and semiempirical (AM1, PM3, MNDO) calculations on the relative stabilities and structures of the potential tautomeric forms of rhodanine, isorhodanine, thiazolidine-2,4-dione, and thiorhodanine are reported. Ab initio calculations predict that the thiooxo, oxothio, dioxo, and dithio tautomers are the most stable. These results correspond to the known experimental data. Infrared spectra of the investigated compounds were recorded for the region 4000-150 cm^-1, and the characteristic bands were compared with ab initio calculated frequencies at the HF/3-21G^(*)* level.     

Raman intensities of liquids: Absolute scattering activities and electro-optical parameters of the halate ions ClO3−, BrO3−, and IO3− in aqueous solutions

Absolute Raman scattering activities of aqueous solutions of sodium bromate and lithium iodate have been measured against NaClO₄ as an external standard. Electro-optical parameters (EOPs) for the BrO and IO bonds were calculated. Equilibrium bond polarizabilities were estimated from refractive index measurements in connection with Raman intensities of the bending modes. Relations between Bragg—Slater radii and EOPs are discussed. EOPS calculated from experimental data are compared with those from ab initio calculations.     

Use of molecular dynamics simulations with ab initio SCF calculations for the determination of the deuterium quadrupole coupling constant in liquid water and bond lengths in ice

The deuterium quadrupole coupling constant and asymmetry parameter in heavy water were determined using ab initio SCF calculations. Snapshots from a molecular dynamics simulation were used to give liquid water cluster configurations and the influence of simulation parameters on the quadrupole coupling constant was investigated. The electronic potential model and the number of molecules in the molecular dynamics simulation and the pressure of the system were found to have only a small influence on the quadrupole coupling constant. The average value of the quadrupole coupling constant at room temperature, corrected for the known deficiency of the ab initio calculation in the gas phase, yields a quadrupole coupling constant of 253 kHz, in perfect agreement with the most recent experiments. The oxygen—deuterium bond lengths in ice Ih, ice II, and ice IX were determined using experimental quadrupole coupling constants and a model equation. An averaged bond length of 98.9 pm was obtained for the Ih form, which is approximately 2 pm shorter than that determined by neutron diffraction studies, whereas the bond lengths for the four deuterium sites in ice II and the three sites in ice IX are in fair agreement with experiment. © John Wiley & Sons, Inc.