Conformational analysis of dimethylphosphate with quantum-mechanical and classical methods

In order to shed light on the conformational behavior of polynucleotide chains, and in particular to clarify the origins of the barriers to internal rotation in the phosphodiester linkage, we computed, with a quantum-mechanical ab initio procedure, the energies associated to 86 combinations of the two torsion angles in the dimethylphosphate anion (CH₃O)₂PO₂ ^–, and then we sought for an analytical expression apt to reproduce these energies with the highest possible accuracy. An excellent agreement (standard deviation of the fitted energies from the ab initio energies 0.28 kcal/mole) with the quantum-mechanical calculations was reached with a potential consisting of four terms: 1) a 6–12 Lennard-Jones contribution, in which different parameters are used to describe the interactions of methyls with the ester oxygens and with the anionic oxygens; 2) a contribution with twofold periodicity, accounting for the anomeric effects connected to the interactions between the lone pair electrons and the polar bonds of phosphorus with the anionic oxygens; 3) a contribution with threefold periodicity, representing the usual bond-staggering term; and 4) a Coulombic contribution, arising from electrostatic interactions between partially charged atoms.     

Effect of water on the tautomeric equilibrium of uracil monoanions. A PCILO study

The PCILO method is used to calculate the stabilization energies of the anionic forms of uracil by water molecules forming the first hydration shell of the tautomers. The results show that the 1-HU^– tautomer is more stabilized by the solvent effect than the 3-HU^– tautomer by about 8 kcal/mole. The effect brings closer together the energies of the two tautomers which differ intrinsically by about 13 kcal/mole in favour of the 3-HU^– form. It operates in the direction inferred from experimental studies.This work was supported in part by R.C.P. 173 of the Centre National de la Recherche Scientifique of France and in part by the Polish Academy of Sciences within the project 09.3.1.     

Theoretical studies on the conformation of saccharides

Conformations of 2-methoxytetrahydropyran as a model for the six-membered ring in aldopyranosides have been calculated by the PCILO method using the algorithm of the conjugated gradient to optimize the geometry. The calculated geometry of the fourteen basic forms of 2-methoxytetrahydropyran was found to be in agreement with the available data obtained by X-ray diffraction of pyranosides. The results indicate differences in the geometry of 2-methoxytetrahydropyran resulting from the change of the axial vs. equatorial position of the methoxyl group. These changes are particularly meaningful in the values of bond angles and they are in agreement with the anomeric and exoanomeric effects. The experimentally found differences in the energies of an axial (⁴ C ₁) and equatorial (¹ C ₄) conformer, G = 2.9–3.7 kJ/mol, and the dipole moment, = 1.20 ± 0.05 D (1D = 3.33 10^–30mAs) agree well with the calculated values E = 3.18 kJ/mol and <> = 1.18 D which, in turn, suggest that the axial conformer is preferred over the equatorial one by a ratio a:e = 78:22.     

Non-empirical calculations and basis set effects on the inversion geometry of the aniline molecule

The geometry of the amine group and the barrier to internal conversion in aniline have been studied by single-determinantab initio SCF calculations using several basis sets from minimal to double-zeta quality. The results obtained from different types and sizes of basis sets are discussed. Calculations performed with the two most flexible basis sets yield inversion barriers of 0.9–1.1 kcal/mole and angles of pyramidalization at the nitrogen atom of 38–39 ° which are in good agreement with the experimental results (1.3 kcal/ mole and 38 °). Orbital and overlap population analyses are performed and compared with the expected mesomeric and inductive effect. The calculated dipole moment 1.48–1.49 D also agrees with the experimental values (1.48–1.50 D).Dedicated to Professor O. E. Polansky, Mülheim/Ruhr, on the occasion of his 60th birthday.     

Quantum chemical studies on electrophilic addition

The geometries of the 2-aminoethyl cation and the isomeric protonated aziridine have been optimized using ab initio molecular orbital calculations employing the split-valence shell 4-31G basis set. The protonated aziridine is computed to be the more stable ion by 46.5 kcal/mole (4-31G level) and 44.9 kcal/mole (double-zeta basis set). The profile to interconversion is found to have a barrier of less than 15 kcal/mole (relative to the 2-aminoethyl cation) and this profile is compared with those computed for the similar ions XCH₂CH ₂ ⁺ where X=OH, F, SH and Cl.     

A theoretical study of electrophilic reactions

The electronic structures of protonated formyl and acetylium cations and their deprotonation paths leading to HCO⁺, COH⁺ and CH₃CO⁺have been studied by means of ab initio calculations. The results support Olah's theory that dipositive species can be the de facto reagents in electrophilic reactions.     

Quantum chemical studies on electrophilic addition

The geometries of the 2-hydroxyethyl and isomeric oxiranium cations have been fully optimized using ab initio molecular orbital calculations employing the split valence shell 4-31G basis set. These species are possible intermediates in both the electrophilic addition of OH to ethylene and in the acid catalysed ring opening of oxirane. The optimized structures were then used to compute more accurate wave functions using Dunning's double-zeta basis set, and with this large basis set the bridged oxiranium ion was found to be the more stable by 7.2 kcal/mole. The barrier to interconversion of these two C₂H₄OH ions was computed to be 25.0 kcal/mole above the oxiranium ion.     

Molecular orbital studies on the conformation of GABA (γ-aminobutyric acid)

In distinction to Extended Hückel Theory which predicts as the most stable conformation of free zwitterionic GABA a totally extended form, PCILO and SCF ab initio studies show that the intrinsically preferred conformation of the isolated molecule is a highly folded one, resulting from strong interactions between the two charged ends. Computations are also carried out for hydrated GABA in the supermolecule approach allowing moreover for the flexibility of binding of some of the water molecules of the first hydration shell. They predict the coexistence in solution of a large number of conformations showing different degrees of folding (or extension), a result confirmed by recent NMR studies. This and a number of similar results show that we have to adapt our thinking on the role of conformations in pharmacological activity to this situation, which was frequently obscured by the more abundant results of X-ray crystallography yielding a single conformation.     

Effect of the crystalline environment upon the rotational conformation about the N-C and C-C′ bonds (Φ andΨ) in amides and peptides

SCFab initio and PCILO computations indicate the intrinsic preference of the torsion angle for 60 °. In the crystal structure of simple methylamides and peptides the observed values for this torsion angle lie between 0 °–30 °. Different procedures for computing lattice energies and total crystallographic conformational energies (lattice + torsional) utilized by other authors, failed to account for this situation. We show that the procedure developed recently in our laboratory for computing lattice energies indicates that the minima of these energies for in acetamide and N-methylacetamide correspond well to 0 °–30 °. Because of the low value of the barrier of the torsional potential for this angle, the total crystallographic conformational energy corresponds also to = 0 °–30 ° in agreement with the experimental data.     

Hydration scheme of uracil and cytosine

The comparison of a pure electrostatic approximation and complete supermolecule SCF ab initio computations on the hydration scheme of uracil and cytosine shows that the electrostatic procedure is capable to reproduce the general aspects of the results of the supermolecule treatment provided that different distances of shortest approach be adopted for the distances between the oxygen of water and the nitrogen of NH₂ or NH groups or the oxygen of C-O groups on the one hand and the oxygen of water and pyridine-type nitrogens on the other hand.     

Ab initio crystal orbital studies on linear chains of H atoms

Anab initio crystal orbital method is used to calculate the energies of an infinite chain of H atoms and of linear arrangements of H₂ molecules with different interatomic distances. The H₂ arrangements are not stable in respect to isolated molecules. The cohesive energy of an optimized arrangement of H atoms chain is 0.0354 a.u.     

Theory of isomer shift in hemin

Using the self-consistent charge extended Hückel procedure, the charge density difference at Fe⁵⁷ nucleus, between hemin and Fe⁺³ ion is calculated. This is combined with the recent value of the calibration constant, –0.23±0.02a ₀ ³ mm/sec to obtain an isomer shift of –0.374 mm/sec between hemin and Fe⁺³ in good agreement with the value –0.392 mm/sec derived from experimental data and the calculated value of the isomer shift of Fe⁺³ with respect to K₃FeF₆ from first principle covalency investigations in the latter compound. is composed of contributions from core and valence electrons of the same order of magnitude, with the latter being more than one-half of the former. The core contribution is composed of a number of terms of comparable magnitude and differing signs, whose significance is discussed.Supported by grant HL 15196-02 from the Heart and Lung Institute of National Institute of Health.     

Ab initio study of hydrazoic acid

SCF and CI calculations were carried out on the ground^1A state of HN₃. The equilibrium geometry and vibration frequencies were computed. The results point to a planar structure (groupC _s) but to a non-linear (170 °) N-N-N conformation. The calculated vibration frequencies are in fair agreement with experimental assignments.The dissociation path of the molecule to NH and N₂ products was investigated and compared to the isoelectronic reaction of diazomethane. The dissociation energy of hydrazoic acid is estimated to be about –8 kcal/mole, with a potential barrier to dissociation of about 30 kcal/mole.Boursier IRSIA     

Cation-binding to biomolecules

Ab initio SCF computations indicate that Mg²⁺ should bind essentially to the oxygen atoms of uracil, the remaining part of the base being rather repulsive towards such an interaction. The Coulombic component predominates in the interaction, the essential feature of which may thus be deduced from the study of the molecular electrostatic potential of uracil. These ab initio results contradict an earlier CNDO prediction that the binding of uracil and Mg²⁺ should occur preferentially at the C₅=C₆ double bond of the base. It is shown that the CNDO result is an artifact due to an exaggeration by this method of the charge transfer between the ligand and the cation. The small amount of available experimental data seem in favor of the ab initio results.     

Ab initio Calculations of the potential energy surface of the reaction of singlet methylene with the hydrogen molecule

The potential energy surface for the insertion of singlet methylene into H₂ has been computed on theab initio SCF level as well as with inclusion of electron correlation by means of the CEPA method. The results are compared with those of previous semiempirical,ab initio SCF and CI calculations. The system is a prototype of a reaction where an allowed and a symmetry-forbidden path can compete. The electron correlation energy was found to be very different for different regions of the surface, but did not have much influence on the optimum reaction path. From the computed heat of the reaction, the heat of formation of singlet methylene was estimated to be 101.5 kcal/mol. According to the calculations the reaction does not need any activation energy.     

Theoretical study of the electronic structure of diazomethane

The least-energy dissociation path of the ground state of CH₂N₂ was determined fromab initio calculations using in a complementary way basis sets of minimal size (STO-3G) and double-zeta (DZ) quality. The results indicate that the least-energy point of attack of the N₂ molecule on CH₂ (¹ A ₁) is roughly perpendicular to the molecular plane (93 °), the C and N atoms being almost co-linear (angle C-N-N203 ° with outermost N atom pointing away from CH₂). The potential barrier of 1.2 eV found previously on theC _2v dissociation path, disappears completely along the least-energy dissociation path (point groupC _s (out-of-plane)). These findings corroborate the Woodward-Hoffman rules for this process since the outermost orbitals of the two intersecting states found in point groupC _2v (...2b ₁ and ...8a ₁) both correlate to the same irreducible representation (10á) in point groupC _s (out-of-plane).Larger basis set calculations (DZ + polarization functions on all centers, 3d _c and 3d _N developed here), were also carried out on CH₂N₂ (¹ A ₁,³ A ₂ and¹ A ₂) at the¹ A ₁ equilibrium geometry and on CH₂ (³ B ₁) and N₂ (¹ _g ⁺ ) at their respective equilibrium geometries. These calculations, together with consideration of correlation energy differences, yieldD ₀ ⁰ (CH₂N₂,¹ A ₁) = 19 kcal/mole and vertical excitation energies of 67 and 73 kcal/mole for the³ A ₂ and¹ A ₂ states respectively. The latter value is in good agreement with the measured experimental value: 72.4 kcal/mole corresponding to the maximum of intensity in the¹ A ₂¹ A ₁ absorption band.     

A non-empirical molecular orbital study on the relative stabilities of adenine and guanine tautomers

The relative stabilities of a series of adenine and guanine tautomers have been calculated using anab initio Hartree-Fock-Roothaan SCF MO method. The calculated relative stabilities agree in general with the results of earlier semiempirical studies. According to the present study, tautomeric forms with regular Kekulé structure for the six-membered purine ring are the most stable. The amine-imine tautomerization of purine bases is not likely to be responsible for spontaneous mutations in DNA.     

Ab initio MP2 calculations of the products of acetylene addition to HgCl2

Gas-phase reaction of acetylene with HgCl₂ resulting in -chlorovinylmercury derivatives and their interaction with Cl^– and I^– anions and KI molecule was studied by the ab initio MP2 method with the Dunning—Hay double zeta basis set and LanL pseudopotential for Hg, K, and I atoms. The reaction was shown to proceed via a -complex of acetylene and HgCl₂ (the calculated enthalpy of formation is –6.5 kcal mol^–1). According to calculations, the activation energy of formation of cis--chlorovinylmercury chloride from acetylene and HgCl₂ is 31 kcal mol^–1. Chloride and iodide anions and KI molecule are readily added to both cis- and trans-isomer of -chlorovinylmercury chloride to give stable species.     

The physical nature of the lone pair

Despite the large number of experimental and theoretical studies on the size, shape, and orientation of lone pairs and their resulting stereochemical character, lone pairs still remain poorly defined in terms of quantitative observable properties of a molecule. Using the conformation of saturated molecules and barriers to internal rotation, experimental chemists have arrived at conflicting sizes and orientations for lone pairs. Most theoretical attempts to define lone pair properties have centered on such non-observables as localized molecular orbitals or have been based on studies on isolated molecules.The use of observable properties to construct a consistent set of physical models to analyze the physical nature of lone pairs is discussed. Much as one probes an electric field with a test charge, probes such as H⁺, H^–, He and H could be used to probe regions of molecules such as NH₃ and H₂O where lone pairs are often postulated to exist.Ab initio quantum mechanical studies can be analyzed using electron density (and resulting changes during interaction), total pair density of electrons, the electrostatic potential about the molecule and bond energy analysis to study lone pair properties. A simple study of NH₃ using an H⁺ probe is presented to clarify the approach.