Ab initio self-consistent field study of deoxyguanosine

The rotational energy of deoxyguanosine around the C₁–N₉ bond is calculated using the Hartree-Fock method with an STO-3G basis set.     

Ab initio calculations on the thermodynamic properties of azaborospiropentanes

Following our recent studies of the thermodynamic properties of azaspiropentane and borospiropentane, in consideration of their usefulness as new potential high energy materials, we follow up with ab initio calculations on the thermodynamic properties of azaborospiropentanes. Properties reported in this study include optimized structural parameters, vibrational frequencies, enthalpies of formation, specific enthalpies of combustion, proton affinities, and hydride affinities. Our results indicate that azatriborospiropentane gives off most energy when combusted, as evidenced by its specific enthalpy of combustion of about −52 kJ per gram. Figure Optimized geometry for R-azatriborospiropentane (10) Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Ab initio molecular orbital studies of closed shell flavins

Ab initio calculations with a (7 s 3 p) basis set are performed on uracil, lumazine, alloxazine and various isoalloxazines. The results as total energies and charge distributions are discussed in relation to the biochemical behaviour of the flavins. The calculations correctly predict equilibrium situations in the alloxazine-isoalloxazine system and explain the high affinity for nucleophilic addition at N₅ in the flavins. The reduction of flavins and their reoxidation by oxygen are discussed.     

Ab initio calculations of the pyrophosphate hydrolysis reaction.

Ab initio quantum mechanical calculations were used to study the hydrolysis reaction H4P2O7 + H2O in equilibrium with 2H3PO4, as well as some molecular properties of the reactants and products. SCF calculations with several basis sets ranging from minimal to extended with polarization functions were used to look at the basis dependency of the reaction enthalpies and optimized geometries. Although the minimal basis sets yield erratic predictions of the enthalpy, when a more extended basis (3-21G*) was used for the geometry optimization, and the total energies of the reactants and products were computed with this and larger basis sets, we obtained more consistent predictions of the structural properties of the P-O-P bridge and of the heat of the hydrolysis reaction (delta E = -7.39 kcal/mol at the SCF/6-31G** level). A comparison is made with previous estimates performed with smaller basis sets and without taking into account the electron correlation effects, which are calculated in the present work. The inclusion of the zero point energy calculated using the harmonic approximation, and of the electronic correlation energy determined at the MBPT(2) level, raised the computed heat of the reaction to -3.83 kcal/mol, and when an estimate for the thermal energy was added, the value obtained was of -3.38 kcal/mol. In conclusion, we found that the hydrolysis of pyrophosphate should be exothermic in the gas phase. The implications of this result in relation to some recent theories about enzyme catalysis are discussed.     

Ab initio calculations of electron distributions in heme-CO models

We have, by the use of ab initio calculations, found a back-bonding state of pi symmetry close to the Fermi level for CO bound to FeN5C14. We thus find it likely that small shifts of the redox potential magnitude of EF - EV magnitude of will cause relatively large changes of the CO vibrational frequency. The separation of Fe 3d orbitals in our heme model is found to agree with what is predicted by ligand field theory for Oh symmetry. This paper presents nonrelativistic Hartree-Fock-Slater calculations of the 5 sigma bonding and 2 pi back-bonding between CO and Fe. The effects of up to 19 additional atoms are discussed for models of heme (COFe to COFeN5C14). The filled back-bonding state is found to be strongly influenced by second nearest neighbor atoms. By use of symmetry orbitals we have resolved the Fe 3d orbitals into the T2g and Eg representations of the Oh point group and find the former states to be occupied whereas the latter are unoccupied. The difference in occupancy is reduced when the CO ligand is removed which also causes an increased density of states at the Fermi level, i.e., the highest occupied and lowest unoccupied orbitals. Possible correlations between our data and experimental results are discussed for heme proteins as well as for metal surfaces.     

Ab initio molecular dynamics study of the hydration of the formohydroxamate anion

We apply ab initio molecular dynamics (AIMD) to study the hydration structures and electronic properties of the formohydroxamate anion in liquid water. We consider the cis- nitrogen-deprotonated, cis- oxygen-deprotonated, and trans- oxygen-deprotonated formohydroxamate tautomers. They form an average of 6.3, 6.9, and 6.0 hydrogen bonds with water molecules, respectively. The predicted pair correlation functions and time dependence of the hydration numbers suggest that water is highly structured around the nominally negatively charged oxime oxygen in O-deprotonated tautomers but significantly less so around the nitrogen atom in the N-deprotonated species. Wannier function analysis suggests that, in the O-deprotonated anions, the negative charge is concentrated on the oxime oxygen, while in the N-deprotonated case, it is partially delocalized between the nitrogen and the adjoining oxime oxygen atom.     

Ab initio calculations on hidden modulators of theta class glutathione transferase activity

The glutathione transferases decrease the pKa of glutathione, allowing its deprotonation and the formation of the more reactive thiolate anion. The thiolate is maintained in the active site through a weak conventional hydrogen bond first sphere interaction donated by a Tyr hydroxyl in the Alpha, Mu, Pi, and Sigma glutathione transferase classes that can be modified by other second sphere or indirect thiolate contacts. However, the Theta and Delta class isoforms use a Ser hydroxyl for stabilizing the GSH thiolate, and as such, have a different chemical system compared with that of the Tyr possessed by other classes. We have used high level ab initio methods to investigate this interaction by using a simple methanol methanethiol system as a model. The hydrogen bond strength of this initial first sphere interaction was calculated to be less than that of the Tyr interaction. A putative second sphere interaction exists in the Theta and Delta class structures between Cys or Ser-14 and Ser-11 in the mammalian Theta subclass 1 and 2, respectively. The effect of this interaction on the first sphere interaction has also been investigated and found to significantly increase the energy of the bond.     

Effects of non-aqueous solvents on CO2 absorption in monoethanolamine: Ab initio calculations

Monoethanolamine (MEA) is the most typical alkanolamine and its aqueous solutions are widely used for CO₂ absorption with mature technology, but the regeneration process is energy consuming. To reduce the energy demand, non-aqueous solvents, such as methanol and ethanol are proposed to substitute water in amine solutions. To understand the influence of the aqueous and non-aqueous solvents on CO₂ capture process, the chemical reactions of MEA absorbing CO₂ were conducted via ab initio calculations. The non-aqueous solvents discussed in this paper are methanol, ethanol, 1-propanol and 2-propanol. The reaction patterns were investigated and energy barriers were observed. The results show that zwitterion formation and the followed intermolecular hydrogen transfer are proven to be the most possible reaction pattern in both aqueous and non-aqueous solvents. The energy analysis shows that the forward reaction energy barriers increase while the backward barriers decrease as the solvent changes from water to methanol, ethanol, 1-propanol and 2-propanol in turn. The decreases of the energy barriers for backward processes are much higher than the corresponding increases for forward processes. These results indicate that lower energies are required in non-aqueous solvents than in water during the desorption reactions and the non-aqueous solvents are very promising to reduce the regeneration energy consumption in MEA capturing CO₂ process. Moreover, the reaction energy gaps between different solvation effects were found to have linear relationship with the logarithm of the dielectric constant difference, which could provide an easy way to theoretically predict the reaction energies of monoethanolamine absorbing CO₂ in other solvation effect and can be used to screen appropriate CO₂ capture solvent.     

Ab initio vibrational calculations on ara-T molecule: application to analysis of IR and Raman spectra

The FTIR and FT-Raman spectra are reported for the arabinonucleoside ara-T (1-beta-D-arabinofuranosylthymine), which shows antiviral activity. The accurate knowledge of the vibrational modes is a prerequisite for the elucidation of drug-nucleotide and drug-enzyme interactions. The FTIR and FT-Raman spectra of ara-T were recorded from 4000 to 30 cm(-1). A tetradeuterated derivative (deuteration at N3, and hydroxyl groups O'2, O'3, and O'5) was synthesized and the observed isotopic shifts in its spectra were used for the vibrational analysis of ara-T. The theoretical frequencies and the potential energy distribution (PED) of the vibrational modes of ara-T were calculated using the ab initio Hartree-Fock/3-21G method. An assignment of the vibrational spectra of ara-T is proposed considering the scaled PED and the observed band shifts under deuteration. The scaled ab initio frequencies were in reasonable agreement with the experimental data.     

Ab initio molecular orbital calculations on the conformations of some unsaturated fragments of lipid molecules: 1-Butene, cis-2-pentene and 1,4-pentadiene

Conformational energies have been calculated for the title compounds which are basic fragments of physiologically active polyunsaturated fatty acids. For 1-butene extremely good accordance has been obtained with experimental data. In cis-2-pentene a strong influence of the cis methyl group on the potential energies for internal rotation has been found. For 1,4-pentadiene no great influence has been found from a possible coupling of the two rotors on the relative stabilities of the two stable conformations. Reasonable agreement has been observed with similar calculations published recently.     

Ab initio parameterization of YFF1, a universal force field for drug-design applications

The YFF1 is a new universal molecular mechanic force field designed for drug discovery purposes. The electrostatic part of YFF1 has already been parameterized to reproduce ab initio calculated dipole and quadrupole moments. Now we report a parameterization of the van der Waals interactions (vdW) for the same atom types that were previously defined. The 6–12 Lennard-Jones potential terms were parameterized against homodimerization energies calculated at the MP2/6-31 G* level of theory. The Boys-Bernardi counterpoise correction was employed to account for the basis-set superposition error. As a source of structural information we used about 2,400 neutral compounds from the ZINC2007 database. About 6,600 homodimeric configurations were generated from this dataset. A special “closure” procedure was designed to accelerate the parameters fitting. As a result, dimerization energies of small organic compounds are reproduced with an average unsigned error of 1.1 kcal mol^-1. Although the primary goal of this work was to parameterize nonbonded interactions, bonded parameters were also derived, by fitting to PM6 semiempirically optimized geometries of approximately 20,000 compounds.     

Ab initio predictions of structural and elastic properties of struvite: contribution to urinary stone research

In the present work, we carried out density functional calculations of struvite – the main component of the so-called infectious urinary stones – to study its structural and elastic properties. Using a local density approximation and a generalised gradient approximation, we calculated the equilibrium structural parameters and elastic constants C _ijkl . At present, there is no experimental data for these elastic constants C _ijkl for comparison. Besides the elastic constants, we also present the calculated macroscopic mechanical parameters, namely the bulk modulus (K), the shear modulus (G) and Young's modulus (E). The values of these moduli are found to be in good agreement with available experimental data. Our results imply that the mechanical stability of struvite is limited by the shear modulus, G. The study also explores the energy-band structure to understand the obtained values of the elastic constants.     

Ab initio predictions of structural and elastic properties of struvite: contribution to urinary stone research

In the present work, we carried out density functional calculations of struvite--the main component of the so-called infectious urinary stones--to study its structural and elastic properties. Using a local density approximation and a generalised gradient approximation, we calculated the equilibrium structural parameters and elastic constants C(ijkl). At present, there is no experimental data for these elastic constants C (ijkl) for comparison. Besides the elastic constants, we also present the calculated macroscopic mechanical parameters, namely the bulk modulus (K), the shear modulus (G) and Young's modulus (E). The values of these moduli are found to be in good agreement with available experimental data. Our results imply that the mechanical stability of struvite is limited by the shear modulus, G. The study also explores the energy-band structure to understand the obtained values of the elastic constants.     

Ab initio calculations on (-)-calicheamicinone and some of its reactions involved in its activation and interaction with DNA

Ab initio calculations were performed on (-)-calicheamicinone, and on the product (Z or E) of the Michael addition via a reaction with methanethiol. It is found that the sulfur moiety position versus the rest of the molecule is quite flexible. The Michael adduct featuring the carbamate group E to the sulfur moiety is more stable than the Z isomer. The Bergman reaction of the diradical formation is strongly exothermic.     

Ab initio (CASPT2) excited state calculations, including circular dichroism, of helically twisted cyanine dyes

Ab initio calculations at the CASSCF/CASPT2 level were performed on helically twisted mono-, tri-, and pentamethine cyanine dyes in the all-Z-configurations. Excitation energies and oscillator and rotatory strengths were calculated for the five lowest energy singlet states. Both the long wavelength methine band and the cis-band could be identified unambiguously from their configurational parentage. The calculated state energies are within 0.09 eV of the experimental value for the methine band and within 0.16 eV for the cis-band. The calculated rotatory strengths of the methine band shows sign inversion as the length of the chromophore increases: negative for the short monomethine, strongly positive for the pentamethine. The trimethine presents a borderline case: the measured rotatory strength is almost nil, the calculated one depends on the geometry. There is good agreement between rotatory strengths calculated in the velocity and in the length formalism.     

The effects of vitronectin on specific interactions between urokinase-type plasminogen activator and its receptor: ab initio molecular orbital calculations

Binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) on the surface of a cancer cell is considered to be a trigger for starting cancer invasions. In addition, the somatomedin B (SMB) domain of vitronectin binds simultaneously to uPAR to construct a ternary complex of uPAR–uPA–SMB. Here we present stable structures of the solvated complexes of uPAR–uPA and uPAR–uPA–SMB obtained by classical molecular mechanics simulations, and the specific interactions between uPAR, uPA and SMB are investigated by ab initio fragment molecular orbital calculations. The result indicates that the SMB binding enhances the binding affinity between uPAR and uPA, although there is no direct contact between SMB and uPA. In particular, the specific interaction between uPAR and the Lys36 residue of uPA is significantly affected by the SMB binding. The positively charged Lys23, Lys46 and Lys61 residues of uPA have strong attractive interactions to uPAR in both the uPAR–uPA and uPAR–uPA–SMB complexes, demonstrating the importance of these residues in the specific binding between uPAR and uPA. The current results on the specific interactions are informative for proposing potent antagonists, which block the uPA and SMB bindings to uPAR.     

Ab initio multiconfiguration reference perturbation theory calculations on the energetics of low-energy spin states of iron(III) porphyrins

Although a major goal of inorganic spectroscopy is to determine the energetics of the low-lying spin states of transition metal complexes, surprisingly little has been accomplished in this respect by means of accurate ab initio calculations. Against this context, we present ab initio multiconfiguration reference perturbation theory (CASPT2) calculations with large basis sets on the low-lying spin states of Fe(III)(P)Cl and [Fe(P)Cl](+) (P(2-)=porphinato). The CASPT2 results on the energetics of various low-lying spin states studied differ significantly, sometimes even dramatically, from those obtained from density functional theory calculations.     

All-valence-shell molecular orbital calculations on the chiroptical properties of substituted and unsubstituted 2,5-diketopiperazine structures

The chiroptical properties of L -3-methyl-2,5-diketopiperazine (L -alanylglycyl anhydride) are examined on a theoretical model in which the electronic wave functions are obtained from semi-empirical all-valence-shell molecular orbital calculations. The INDO molecular orbital model is used to perform SCF-MO calculations on the ground states of six conformation isomers of L -3-methyl-2,5-diketopiperazine and two chiral conformational isomers of unsubstituted 2,5-diketopiperazine. Excited-state wave functions are constructed in the virtual orbital-configuration interaction approximation. The rotatory strengths, dipole strengths, oscillator strengths, and dissymmetry factors of the first eight singlet–singlet transitions for each of the eight structures are calculated and reported. Additionally, ground-state dipole moments, net atomic charges, and the first four ionization potentials (calculated according to Koopman's theorem) are computed for each structure. The signs and the magnitudes of the rotatory strengths are found to be extremely sensitive to the conformation of the piperazine ring as well as to methyl substitution at the α carbon of the ring. Spectra–structure relationships based on the calculations reported here are discussed, and the available experimental CD data on dissymmetric 2,5-diketopiperazine are examined in terms of our theoretical results.