How does methylation suppress the electron-induced decomposition of 1-methyl-nitroimidazoles?

• Autor(es): Kossoski, Fábris, 1988-
• Data: 2017
• Identificador Persistente: https://hdl.handle.net/20.500.12733/1665214
• Origem: Oasisbr
• Assunto(s): Elétrons; DNA; Metilação; Electrons; DNA; Methylation; Artigo original
• Tipo de Documento: Artigo científico
• Idioma: Inglês

Descrição

Agradecimentos: F.K. acknowledges financial support from São Paulo Research Foundation (FAPESP), under Grant No. 2015/23792-5. M.T. do N.V. acknowledges financial support from FAPESP (Grant No. 2014/10012-9) and also from the Brazilian National Council for Scientific and Technological Development (CNPq), Grant No. 305672/2014-2. This work used computational resources from LCCA-USP

Abstract: The efficient decomposition of nitroimidazoles (NIs) by low energy electrons is believed to underlie their radiosensitizing properties. Recent dissociative electron attachment (DEA) measurements showed that methylation at the N1 site unexpectedly suppresses the electron-induced reactions in 4(5)-NI. We report theoretical results that provide a clear interpretation of that astounding finding. Around 1.5 eV, DEA reactions into several fragments are initiated by a pi* resonance, not considered in previous studies. The autoionization lifetime of this anion state, which limits the predissociation dynamics, is considerably shorter in the methylated species, thereby suppressing the DEA signals. On the other hand, the lifetime of the pi* resonance located around 3 eV is less affected by methylation, which explains why DEA is still observed at these energies. Our results demonstrate how even a simple methylation can significantly modify the probabilities for DEA reactions, which may be significant for NI-based cancer therapy

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ

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