Crystal engineering strategies against antimicrobial resistance: a solid contribution to a contemporary problem

This PhD thesis sets its goal in the application of crystal engineering strategies to the design, formulation, synthesis, and characterization of innovative materials obtained by combining well established biologically active molecules and/or GRAS (generally recognized as safe) compounds with co-formers able to modulate specific properties of the molecule of interest. The solid-state association, via non-covalent interactions, of an active ingredient with another molecular component, a metal salt or a complex, may alter in a useful way the physicochemical properties of the active ingredient and/or may allow to explore new ways to enhance, in a synergistic way, the overall biological performance. More specifically this thesis will address the threat posed by the increasing antimicrobial resistance (AMR) developed by microorganisms, which call for novel therapeutic strategies. Crystal engineering provides new tools to approach this crisis in a greener and cost-effective way. This PhD work has been developed along two main research lines aiming to contribute to the search for innovative solutions to the AMR problem. Design, preparation and characterization of novel metal-based antimicrobials, whereby organic molecules with known antimicrobial properties are combined with metal atoms also known to exert antimicrobial action. Design, preparation and characterization of co-crystals obtained by combining antibacterial APIs (active pharmaceutical ingredients) with natural antimicrobials.