2D Chemical Drawings Correlate to Bioactivities: MIA-QSAR Modelling of Antimalarial Activities of 2,5-Diaminobenzophenone Derivatives

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Two-dimensional chemical structures of a series of 2,5-diaminobenzophenone derivatives, some farnesyltransferase inhibitors, have shown to correlate with the corresponding antimalarial activities. The descriptors in this QSAR analysis are pixels of the chemical structures (two dimensional images) transformed into binaries and, therefore, the data variance explaining the variance in the activities block corresponds to the coordinates of each pixel in each molecule. This method, named multivariate image analysis applied to quantitative structure-activity relationship (MIA-QSAR), was applied to model the antimalarial activities of the titled compounds and the results were compared to well known three-dimensional QSAR techniques for the same class of compounds. In addition to the simplicity and high predictive performance of the MIA-QSAR modelling, this 2D image-based method has the potential of working well when equally simple, classical analysis fails. Overall, the present QSAR analysis based on 2D chemical drawings (constrained structures) dispensed conformational screening and 3D alignment to provide a reliable QSAR model; the physicochemical description about e.g. steric effects and chiral centers is all contained in the way in which substituents in a congeneric series are drawn, and the method can serve as a tool to introduce those who are planning to deal with drug design.224637U326Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Conformational analysis, stereoelectronic interactions and NMR properties of 2-fluorobicyclo[2.2.1]heptan-7-ols

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Four diastereoisomers of 2-fluorobicyclo[2.2.1]heptan-7-ols were computationally investigated by using quantum-chemical calculations, and their relative energies were analyzed on the basis of stereoelectronic interactions, particularly the presence or otherwise of the F center dot center dot center dot HO intramolecular hydrogen bond in the syn-exo isomer. It was found through NBO and AIM analyses that such an interaction contributes to structural stabilization and that the (1h)J(F),(H(O)) coupling constant in the syn-exo isomer is modulated by the n(F)->sigma*(OH) interaction, i.e., the quantum nature of the F center dot center dot center dot HO hydrogen bond.812271232Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

A Theoretical View on the Conformer Stabilization of Butane

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The rotational barrier and conformer energies of butane are well-known, but the contributing effects to its conformational isomerism are Still Unclear. Calculated potential energy surfaces for the relaxed and vertical (bond distances and angles frozen) structures, together with NBO, analysis, Suggest that approaching or distancing methyl groups involve: substantial energy costs between the gauche and anti isomers, while hyperconjugative interactions play an important, but not prevalent, role for the conformational isomerism of butane.742183848387Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

The lack of intramolecular hydrogen bonding and the side chain effect in alanine conformers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Although amino acids are considered one of the most important classes of compounds found in Nature, the literature has few reports that have been made to understand the intramolecular interactions that govern their conformational energies and geometries. Actually, it has been arbitrarily assigned that possible intramolecular hydrogen bonding is the responsible force that dictates amino acid conformational preferences. In this paper, calculations at B3LYP/aug-cc-pVDZ level of theory within the NBO and QTAIM frameworks have shown that hyperconjugation and steric effects interplay, not H-bonding, are the intramolecular interactions that govern alanine conformational preferences. It is also shown that the steric interactions between the alanine methyl group side chain and its main chain influences its energies and geometries. (C) 2012 Elsevier B.V. All rights reserved.10141216Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Are hydrogen bonds responsible for glycine conformational preferences?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Glycine conformational preferences have mostly been explained as due to the formation of intramolecular hydrogen bonding, despite other possible relevant intramolecular interactions that may be present in this molecular system. This paper, within the framework of the quantum theory of atoms in molecules and natural bond orbital analysis, at the B3LYP/aug-cc-pVDZ level, shows that hydrogen bonding formally stabilizes just one of the glycine conformers. Indeed, these theoretical calculations suggest that both steric hindrance and hyperconjugative effects rule conformational preferences of this model compound and may not be ignored in discussions of amino acid conformational analyses. (C) 2011 Elsevier B.V. All rights reserved.387416998591Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2009/02715-1, 2010/15765-4

Phenylalanine and tyrosine methyl ester intramolecular interactions and conformational analysis by H-1 NMR and infrared spectroscopies and theoretical calculations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Amino acid conformational analysis in solution are scarce, since these compounds present a bipolar zwitterionic structure (+H3N-CHR-COO-) in these media. Also, intramolecular hydrogen bonds have been classified as the sole interactions governing amino acid conformational behavior in the literature. In the present work we propose phenylalanine and tyrosine methyl ester conformational studies in different solvents by H-1 NMR and infrared spectroscopies and theoretical calculations. Both experimental and theoretical results are in agreement and suggest that the conformational behavior of the phenylalanine and tyrosine methyl esters are similar and are dictated by the interplay between steric and hyperconjugative interactions. (C) 2014 Elsevier B.V. All rights reserved.123482489Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2012/03933-5]FAPESP [2011/01170-1, 2010/15764-4

The F center dot center dot center dot HO intramolecular hydrogen bond forming five-membered rings hardly appear in monocyclic organofluorine compounds

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)This paper emphasizes that fluorine atoms in organic molecules need special geometric requirements to experience intramolecular hydrogen bonds (H-bonds). Calculations at the B3LYP/aug-cc-pVDZ theoretical level and using the quantum theory of atoms in molecules applied over a series of monocyclic compounds, which have similar C = C(F)-C(OH)= C fragments, predict that the F center dot center dot center dot HO intramolecular H-bond does not exist when forming five-membered rings. Indeed, it is shown that the geometric restrictions imposed by the rigid rings are the main reasons in preventing fluorine participating in such a F center dot center dot center dot HO intramolecular H-bond.21041694174Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

A theoretical and experimental 1H NMR spectroscopy study of the stereoelectronic interactions that rule the conformational energies of alanine and valine methyl ester

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Amino acids exhibit a bipolar zwitterionic structure (+H3N-CHR-COO-) in solution; hence, conformational studies of these compounds have been limited to the gas phase. The conformational preferences of amino acids have been widely attributed to intramolecular hydrogen bonding, despite steric and hyperconjugative effects. In this work, we propose the conformational study of alanine and valine methyl esters, which do not show zwitterionic structures in solution, by1H NMR and theoretical calculations. The 3JHH spin-spin coupling constants and theoretical calculations were found to be in agreement, showing that the interplay between steric hindrance and hyperconjugation is the forces that are responsible for determining the conformational preferences of alanine and valine methyl esters. Copyright (c) 2013 John Wiley & Sons, Ltd.2610849857Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Conformational Analysis and Intramolecular Interactions in Aminofluorobenzoic Acids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Some aminofluorobenzoic acids were studied to evaluate the power of the F center dot center dot center dot HO hydrogen bond and other interactions as driving forces of the conformational isomerism of these compounds. Despite the occurrence of this hydrogen bond in the 2-fluorinated derivatives, as well as attractive O/F nonbonding interactions and NH center dot center dot center dot O = C hydrogen bond, the O/O repulsion dictates the orientation of the carboxyl group. Unlike 2-fluorophenol, which is reported to not experience a F center dot center dot center dot HO hydrogen bond, 2-fluorobenzoic acid derivatives were calculated to exhibit such interaction, but it could not be monitored experimentally by means of F/H(O) coupling constant, because of the low solubility of these compounds in nonpolar solvents, the acidity of the carboxyl hydrogen, the small population of some conformers capable of exhibiting hydrogen bond, and the solute self-association in solution, which make their conformational equilibrium different from that in gas phase.117716591664Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq