Rosana M. Lobayan

A search for C–H⋯O type hydrogen bonds in Lamivudine (3TC). An exploratory conformational and electronic analysis

Abstract A conformational study of the molecule Lamivudine (3TC), or cis-1-[2′-hydroxymethyl-5′-(1,3-oxathiolanyl)] cytosine, was carried out. Rotation about the C–N bond (ϕ1) and about the C–CH2(OH) bond (ϕ2), which connects the hydroxymethyl group to the five member ring, led to a conformational potential energy surface. The conformational potential energy 2D map, obtained at the HF/3-21G level of theory, had several minima. A topological analysis of the electron density was carried out on four selected ab initio minimum energy conformations, using judiciously constructed hartree–fock (RHF) wave functions. In order to see all possible hydrogen bonding, the DFT wave function was generated using a mixed basis set; a 6-311++G∗∗ basis was employed on atoms involved in hydrogen bonding interactions and a 3-21G basis on all other atoms. For this analysis the theory of atoms in molecules, developed by Bader, was used. The stability of the intramolecular hydrogen bonding interactions was analyzed in terms of the results obtained.

NMR-K REDUCED COUPLING CONSTANTS WITHIN THE CLOPPA-PM3 APPROACH. II : SHORTCOMINGS AND HOW TO OVERCOME THEM

Abstract The shortcomings encountered in the CLOPPA-PM3-RPA coupling constant calculations shown in part I of this work are analyzed. These are: (i) the Hartree–Fock quasi-instabilities of the non-singlet type in PM3 wavefunctions; and (ii) the erroneous PM3-derived description of the hybridization of some localized molecular orbitals. It is shown that these problems arise from: (a) the parameters optimization procedure used within the PM3 scheme, which apparently takes into account some effects at the nuclear sites in an inappropriate way; and (b) the selected set of properties chosen to be reproduced by the parameters optimization procedure. Properties do not critically depend on the electronic surroundings of the nuclei. Hence, some effects at nuclear sites are badly produced when the PM3 wavefunction is used. We have found three parameters which are mainly involved: the one-center two-electron integrals; the β s or β p parameters; and the U ss one-electron energies. The FC electronic mechanism is the most affected by the problems analyzed here.

NMR-K reduced coupling constant calculations within the CLOPPA-PM3 approach: I. General results

Abstract A new version, i.e. PM3, of the CLOPPA model modified to make indirect nuclear spin coupling calculations for molecules containing heavy atoms is presented. Its performance compared with previous CLOPPA-MNDO-RPA and CLOPPA-AM1-RPA calculations is discussed. The PM3 approach gives better results than its predecessors for couplings where one of the coupled nuclei is P or Cl, and permits one to reproduce qualitatively experimental trends for some other nuclei that are not parametrized within the MNDO and AM1 methods; for example As, Sb, Bi, Ga, In and Tl. However, the general performance of the new version does not achieve the level of the two previous ones.

Conformational and electronic (AIM/NBO) study of unsubstituted A-type dimeric proanthocyanidin

The conformational space of the unsubstituted A-type dimeric proanthocyanidin was scanned using molecular dynamics at a semiempirical level, and complemented with functional density calculations. The lowest energy conformers were obtained. Electronic distributions were analysed at a higher calculation level, thus improving the basis set. A topological study based on Bader’s theory (AIM: atoms in molecules) and natural bond orbital (NBO) framework was performed. Furthermore, molecular electrostatic potential maps (MEPs) were obtained and analysed. NMR chemical shifts were calculated at ab initio level and further compared with previous experimental values; coupling constants were also calculated. The stereochemistry of the molecule is thoroughly discussed, revealing the key role that hyperconjugative interactions play in defining experimental trends. These results show the versatility of geminal spin–spin coupling 2J(C-1′,O) as a probe for stereochemical studies of proanthocyanidins.

Topology of the electron density in open-shell systems.

This work describes the decomposition of the electron density field of open-shell molecular systems into physically meaningful contributions. The new features that the open-shell nature of the wave function introduces into these fields are topologically studied and discussed, showing the charge concentration and depletion regions within the system. The localized character (field concentration only close to the nuclear positions of the system) or the nonlocalized character (concentration in other regions of the system) is used to study the reliability of the Lewis model of bonding to describe chemical bonding phenomenon in open-shell systems. Numerical examples are reported for molecular systems at a correlated level of approximation, in the single-double configuration interaction wave function approach.

Theoretical study of Z isomers of A-type dimeric proanthocyanidins substituted with R=H, OH and OCH3: stability and reactivity properties

The stereochemistry of A-type dimeric proanthocyanidins was studied, focusing on the factors that determine it, and the changes that occur with R = OCH3, R′ = H, and R = OH, R′ = H as substituents, starting with the study of the conformational space of each species. Using molecular dynamics at a semiempirical level, and complementing with functional density calculations, two conformers of lowest energy were characterized for R = H, eight conformers for R = OH, and three conformers for R = OCH3. Electronic distributions were analyzed at a higher calculation level, thus improving the basis set. Intramolecular interactions were examined and characterized by the theory of atoms in molecules (AIM). Detailed natural bond orbitals (NBO) analysis allowed the description of subtle stereoelectronic aspects of fundamental importance for understanding the stabilization and antioxidant function of these structures. The study was enriched by a deep analysis of maps of molecular electrostatic potential (MEP). The coordinated analysis of MEP, together with the NBO and AIM results, allowed us to rationalize novel distribution aspects of the potential created in the space around a molecule.

Electronic Structure and Effectively Unpaired Electron Density Topology in closo-Boranes: Nonclassical Three-Center Two-Electron Bonding.

This article provides a detailed study of the structure and bonding in closo-borane cluster compounds X2B3H3 (X = BH(-), P, SiH, CH, N), with particular emphasis on the description of the electron distribution using the topology of the quantum many-body effectively unpaired density. The close relationship observed between the critical points of this quantity and the localization of the electron cloud allows us to characterize the nonclassical bonding patterns of these systems. The obtained results confirm the suitability of the local rule to detect three-center two-electron bonds, which was conjectured in our previous study on boron hydrides.

Topology of the Effectively Paired and Unpaired Electron Densities for Complex Bonding Patterns: The Three-Center Two-Electron Bonding Case.

Our previously reported local formalism of the electron density decomposition into effectively paired and unpaired densities is applied to electron deficient molecular systems possessing complex bonding patterns. It is shown that the unpaired density is not only near the nuclear positions, like in classical bonds, but also spills out over the bonding regions, to compensate the electron deficiency. Topological information obtained from the effectively unpaired density, which may not be directly observed from the total density, allows us to establish a procedure to detect complex interactions. This study is complemented with results arising from nonlocal formalism of topological population analyses. The conclusions from both formalisms are in complete agreement and permit to interpret the well-known structural information from Lipscomb styx numbers going beyond it in cases where the electronic description becomes ambiguous, pointing out the subtle information contained in the unpaired density. Numerical results for three-center two-electron bondings in the boranes B2H6, B4H10, B5H9, and B5H11 are reported.

Conformational and stereoelectronic investigation of tryptamine. An AIM/NBO study

Due to the free radical scavenger properties of Tryptamine (TRA), as well as of others indole derivatives, it is in our interest to explore deeply the stereoelectronic aspects that would be relevant in their stabilization and antioxidant activity. In this work the conformational space of TRA was scanned using molecular dynamics complemented with functional density calculations at B3LYP/6-31 + G** level. Twenty one conformers of lowest energy were obtained, their electronic distributions were analyzed at a higher calculation level, thus improving the basis set (B3LYP/6-311++G**). A topological study based on Bader’s theory (AIM: atoms in molecules) and natural bond orbital (NBO) framework was performed. The study was enriched by a deep analysis of maps of molecular electrostatic potential (MEP) through a coordinated NBO/AIM analysis. The conformational preferences were explained by hyperconjugative interactions, which were revealed by NBO data. Because radical scavenging by indolic compounds is strongly modulated by their functional residues our study was related to similar analysis done previously on Indole and 1H-indole-3-acetic acid (IAA). Therefore, the conformational space of TRA was studied from a new perspective focusing on a deep analysis of the geometric and electronic properties of TRA conformers. The changes of the electronic distribution introduced by the substituent and the conformational flexibility of the side chain were addressed. The results reported contribute to the understanding of the structure, stability and reactivity of TRA and others indole derivatives.

Electronic structure and conformational properties of 1H-indole-3-acetic acid

The conformational space of 1H-Indole-3-Acetic Acid (IAA) was scanned using molecular dynamics at semiempirical level, and complemented with functional density calculations at B3LYP/6-31G** level, 14 conformers of lowest energy were obtained. Electronic distributions were analyzed at a higher calculation level, thus improving the basis set (B3LYP/6-311++G**). A topological study based on Bader’s theory (AIM: atoms in molecules) and natural bond orbital (NBO) framework performed with the aim to analyze the stability and reactivity of the conformers allowed the understanding of electronic aspects relevant in the study of the antioxidant properties of IAA. Intramolecular hydrogen bonds were found and were characterized as blue-shifting hydrogen bonding interactions. Furthermore, molecular electrostatic potential maps (MEPs) were obtained and analyzed in the light of AIM and NBO results, thus showing subtle but essential features related not only to reactivity but also with intramolecular weak interactions, charge delocalization and structure stabilization.