The use of variable temperature C-13 solid-state MAS NMR and GIPAW DFT calculations to explore the dynamics of diethylcarbamazine citrate

Autor(es)

Venancio, Tiago ^{[1, 2]} ; Oliveira, Lyege Magalhaes ^[2] ; Pawlak, Tomasz ^{[1, 3]} ; Ellena, Javier ^[4] ; Boechat, Nubia ^[5] ; Brown, Steven P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Warwick, Dept Phys, Coventry, W Midlands - England

^[2] Univ Fed Sao Carlos, Dept Quim, Rodovia Washington Luis, Km 235, BR-13565905 Sao Carlos, SP - Brazil

^[3] Polish Acad Sci, Ctr Mol & Macromol Studies, Lodz - Poland

^[4] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP - Brazil

^[5] Fundacao Oswaldo Cruz FioCruz, Inst Tecnol Farmacos FarManguinhos, Rio De Janeiro, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Magnetic Resonance in Chemistry; v. 57, n. 5, p. 200-210, MAY 2019.
• Citações Web of Science: 1

Resumo

Experimental 13C solid-state magic-angle spinning (MAS) Nuclear Magnetic Resonance (NMR) as well as Density-Functional Theory (DFT) gauge-including projector augmented wave (GIPAW) calculations were used to probe disorder and local mobility in diethylcarbamazine citrate, (DEC)+(citrate)-. This compound has been used as the first option drug for the treatment of filariasis, a disease endemic in tropical countries and caused by adult worms of Wuchereria bancrofti, which is transmitted by mosquitoes. We firstly present 2D 13C. 1H dipolar-coupling-mediated heteronuclear correlation spectra recorded at moderate spinning frequency, to explore the intermolecular interaction between DEC and citrate molecules. Secondly, we investigate the dynamic behavior of (DEC)+(citrate)-by varying the temperature and correlating the experimental MAS NMR results with DFT GIPAW calculations that consider two (DEC)+ conformers (in a 70: 30 ratio) for crystal structures determined at 293 and 235 K. Solid-state NMR provides insights on slow exchange dynamics revealing conformational changes involving particularly the DEC ethyl groups. (AU)

• Processo FAPESP: 09/13860-2 - Aplicação da ressonância magnética nuclear no estado sólido aliada a ferramentas quimiométricas na caracterização de polimorfismo em fármacos
• Beneficiário: Tiago Venancio
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/21708-7 - Caracterização de complexos supramoleculares de sólidos farmacêuticos por Ressonância Magnética Nuclear no estado sólido e abordagens computacionais
• Beneficiário: Tiago Venancio
• Modalidade de apoio: Bolsas no Exterior - Pesquisa