X-Ray and infrared spectral studies of the ionic structure of trimethoprim–sulfamethoxazole 1 : 1 molecular complex

Abstract

The crystal structure of the title compound (I) has been refined. Those of trimethoprim (TMP) hydrochloride (II) and sulfamethoxazole (SMZ) sodium salt (III) have been determined. In (I) the proton participating in the hydrogen bond between the pyrimidine (TMP) and sulfonamide (SMZ) nitrogen atoms is transferred from SMZ to TMP (NH⁺⋯ N^–), with the molecules being ionized. This was verified by comparing the geometrical features exhibited around the nitrogen atoms in (I)–(III). The N–H stretching vibration bands observed in the i.r. (3500–2 500 cm ^–1) for (I)–(III) have been assigned taking into consideration the deuterium isotope effects, Raman spectra, and the hydrogen-bonding configuration. The band at 2 520 cm^–1(broad) in (I) was assigned to a specific N⁺–H unit in the hydrogen bond. The ionization of the components in (I) was thus confirmed, contrary to the non-ionic structure previously proposed.