DESAFIOS ESTRUTURAIS NO MINOXIDIL: TAUTOMERISMO IMINA-ENAMINA

Abstract

Minoxidil is a vasodilator drug widely used in the treatment of hair loss, whose chemical structure in solution still presents poorly explored aspects, with possible impact on spectral interpretation and on the quantification of the active compound in pharmaceutical formulations. This study aimed to investigate structural characteristics of minoxidil in solution by means of 1H and 13C Nuclear Magnetic Resonance (NMR) spectroscopy. Initially, solubility tests were performed in different solvents, with tetradeuterated methanol (CD3OD-d4) being the medium that showed the best performance for the analysis. In the experiments conducted in CD₃OD-d4, a selective reduction in the integral of the aromatic hydrogen was observed over time, with greater intensity at 25 ºC than at 5 ºC; Additionally, the progressive emergence of a triplet in the 13C NMR spectra, compatible with C-D coupling was observed. In contrast, in the experiments performed in hexadeuterated dimethyl sulfoxide (DMSO-d₆), the proportion between the integrals of the 1H NMR signals remained stable for approximately 59 h, and the 13C NMR spectra did not show the emergence of the triplet or other relevant changes. Taken together, the results indicate that the behavior of minoxidil in solution is strongly dependent on the solvent and temperature, being compatible with the occurrence of imine-enamine tautomerism and H/D exchange in a deuterated protic solvent, providing support for more consistent structural interpretations and for the development of analytical methodologies applied to quality control and quantification of this drug.