Modulating the crystalline forms of silver-sulfadiazine complexes by mechanochemistry

Abstract

Mechanochemical synthesis of pharmaceutical compounds has gained significant attention due to its potential to overcome traditional synthetic challenges while offering the possibility of improving the physicochemical properties of drugs. This study delves into the mechanochemical synthesis of silver sulfadiazine (AgSD) coordination compounds, obtained under different mechanochemical stress and processing conditions. The aim of this work was to investigate the influence of mechanochemical conditions on the selectivity in the preparation of AgSD coordination compounds. Through a series of experiments, we demonstrate the successful synthesis of two different AgSD coordination networks, using high-energy ball milling. By strategically manipulating the starting materials and milling parameters — including milling time, milling frequency, type of mechanical stress (as determined by different milling devices), and the presence of co-milling agents — we were able to control the product outcome. As a result, we achieved two different forms of silver-sulfadiazine metal frameworks, one of which was not previously disclosed. The crystal structure of the new form, obtained recurring to high resolution PXRD synchrotron data, was compared with the previously known structure of a silver sulphadiazine compound. The in-depth antimicrobial activity systematic study of these AgSD forms on the generic systems showed increased antibacterial activity when compared to sulfadiazine. This research sheds light on the mechanochemical synthesis of silver sulfadiazine complexes. The obtained knowledge may guide the development of novel synthetic strategies for other drug molecules, leading to improved drug performance, stability, and therapeutic outcomes.