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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Amino-Imino Tautomerism in the Salt Formation of Albendazole: Hydrobromide and Nitrate Salts

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Autor(es):
Carvalho Jr, Paulo de S. ; Diniz, Luan F. [1] ; da Silva, Gelson T. S. T. [2] ; Coutinho, Nayara Dantas [3] ; dos Santos, Priscila Gomes [4] ; Carvalho-Silva, Valter Henrique [4] ; Ribeiro, Caue [2] ; Ellena, Javier [5]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Fed Minas Gerais, Fac Farm, Dept Prod Farmaceut, Lab Controle Qualidade Med & Cosmet, BR-31270901 Belo Horizonte, MG - Brazil
[2] EMBRAPA Instrumentacao, Natl Nanotechnol Lab Agribusiness LNNA, BR-13560970 Sao Carlos, SP - Brazil
[3] Univ Brasilia IQ UnB, Lab Bioact Cpds Synth NTS, Campus Univ Darcy Ribeiro, Brasilia, DF - Brazil
[4] Goias State Univ, Modeling Phys & Chem Transformat Div, Theoret & Struct Chem Grp, BR-75132903 Anapolis, Go - Brazil
[5] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Crystal Growth & Design; v. 21, n. 2, p. 1122-1135, FEB 3 2021.
Citações Web of Science: 0
Resumo

Albendazole (ABZ) is a poorly soluble anthelmintic drug that can exist in amine and imine desmotropic forms. These facts can affect the solubility and bioavailability of the drug product. Here, we investigate the salt formation of ABZ with the acids HCl, HBr, and HNO3 associated with the tautomerism of the ABZ molecule. The reaction of ABZ with an excess of the acids HCl, HBr, and HNO3 results in the protonation of the imidazole ring, hiding the occurrence of tautomeric states. Thus, the ABZ HCl, ABZ HBr, and ABZ HNO3 salts were obtained and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, FT-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and aqueous solubility measurements. Furthermore, static and dynamic DFT calculations were carried out to understand how the albendazolium cation (ABZ-H+) is obtained from ABZ in amine and imine forms. An analysis of crystal structures reveals that cations and anions aggregate in 1D chains stabilized by NH...X (X = Cl, Br, O) interactions, generating layered structures. In solution, the intramolecular amine ? imine conversion (?G? similar to 50 kcal mol1) and the solvent-mediated deprotonation of the ABZ-H+ cation (?G? similar to 20 kcal mol1) requires a higher energy barrier to occur, allowing the independence between tautomers to propitiate the crystallization process. Consequently, the process is dependent on the tautomer population in the starting material. All salts were demonstrated to be more soluble than pure ABZ. Given the good physicalchemical profile of these salts, our results show a notable effect on the multicomponent crystal design, manufacturability, and processing of the drug ABZ. (AU)

Processo FAPESP: 16/09198-6 - Desenvolvimento e caracterização de modificações sólidas de ingredientes agroquímicos de ação herbicida com menor impacto ambiental
Beneficiário:Paulo de Sousa Carvalho Júnior
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 12/05616-7 - Caracterização no estado sólido de fármacos de ação anti-convulsionantes e antidepressivos: Planejamento de novas formas cristalinas.
Beneficiário:Paulo de Sousa Carvalho Júnior
Modalidade de apoio: Bolsas no Brasil - Doutorado