Conformational study of the electronic interactions and nitric oxide release potential of new S-nitrosothiols esters derivatives of ibuprofen, naproxen and phenyl acids substituted (SNO-ESTERS): Synthesis, infrared spectroscopy analysis and theoretical calculations

Autor(es)

Reginato, Marcelo Mota ^[1] ; Paiva, Derisvaldo Rosa ^[1] ; Sensato, Fabricio Ronil ^[1] ; Monteiro, Hugo Pequeno ^[2] ; Cardoso Amorim Reis, Adriana Karla ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Chem, Inst Environm Chem & Pharmaceut Sci, Campus Diadema, Diadema, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Biochem, Ctr Cellular & Mol Therapy, Campus Sao Paulo, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY; v. 207, p. 132-142, JAN 15 2019.
• Citações Web of Science: 1

Resumo

The conformational study on the new S-nitrosothiols esters (SNO-ESTERS): pars-substituted (X = H, OMe, Cl and NO2) S-nitrosothiol derivatives 2-methyl-2-(sulfanyl)propyl phenylacetates (R1), 2-(4-isobutylphenyl) propanoate (ibuprofen, R2), and 2-(4-isobutylphenyl)propanoate of 2-methyl-2-(nitrososulfanyl)propyl (naproxen, R3) was performed using infrared spectroscopy (IR) in solvents with increasing polarity (CCl4, CH3Cl, and CH3CN), and theoretical calculations, to determine the preferential conformer and the potential of these compounds to release nitric oxide (NO). S-Nitrosothiols were synthesized by esterification reactions, using chlorides of the corresponding carboxylic acids, with good yields (similar to 60%). IR results showed that these compounds presented only one conformation, and the experimental data were supported by the theoretical results obtained by density functional theory (DFT) calculations using the 6311+G (2df, 2p) basis set. The calculations revealed that all S-nitrosothiols presented one preferential anticlinal (ac) geometric conformation, which agrees with the data obtained experimentally in CCl4. These conformers are stabilized by intramolecular hydrogen bonds. Examination of the geometry with regard to the R-SNO group revealed that these compounds are preferentially in the trans (anti) conformation. The calculation of the orbital interactions using the Natural Bond Orbital (NBO) method showed that the n(O(NO)) -> sigma((S-N)){*} hyper-conjugative interaction increases the S-N bond length. The strong n(s) -> pi((NO)){*} interaction and electronic delocalization induces a partial pi character to the S-N bond. The weak sigma(S-N) bond indicates strong delocalization of the electron pair in O (NO) by the n(O(NO)) -> sigma((S-N)){*} interaction, thereby increasing the capacity of NO release from SNO-ESTERS. (C) 2018 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 10/51784-3 - Estudo conformacional e das interacoes eletronicas de s-nitrosotiois com potencial atividade biologica
• Beneficiário: Adriana Karla Cardoso Amorim Reis
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/16644-4 - S-nitrosotióis derivados de Aril-amidas e Aril-pirimidin-2-onas(tionas) - potenciais inibidores duplos de HIV-1-PR e renina: síntese, análise estrutural e ensaios biológicos
• Beneficiário: Adriana Karla Cardoso Amorim Reis
• Modalidade de apoio: Auxílio à Pesquisa - Regular