Experimental and DFT studies of sulfadiazine ‘piano-stool’ Ru(ii) and Rh(iii) complexes

While sulfadiazine (HL(SZ)) is extensively used to elaborate complexes of intriguing biological applications (e.g. topical antibiotic silvadene; silver sulfadiazine), the molecular structure modification of sulfadiazine or even other sulfa drugs by coordination to either η(6)-cymene Ru(ii) or η(5)-Cp* Rh(iii) motif has not been investigated. Here, half-sandwich organoruthenium(ii) and organorhodium(iii) compounds of the type [(η(6)-p-cymene)Ru(L(SZ))(2)] (1) and [(η(5)-C(5)Me(5))Rh(L(SZ))(2)] (2) are synthesized, characterized and evaluated for their potential antimicrobial activity. Spectroscopic and single crystal X-ray analysis showed that L(SZ) is coordinated to Rh(iii) via both the sulfonamide and pyrimidine nitrogen atoms forming “piano-stool” geometry. In 2, the NMR equivalence clearly pointed to participation of two L(SZ) molecules in a fluxional process in which the third bond of the base of the stool is oscillating between two equivalent sulfonamide nitrogen atoms. While 1 was biologically inactive, complex 2 was potent against Gram-positive bacteria, Candida albicans and Cryptococcus neoformans. Hen white egg lysozyme (HEWL), a model protein, reacted covalently with 2via the loss of one L(SZ) molecule, while compound 1 decomposed during the interaction with that protein.