Design and synthesis of multicomponent antimalarial cocrystals through structural inequivalence and combinatorial approaches

Structural inequivalence is a state-of-the-art molecular architecture (strategy) that allows increasing the number of components in a single cocrystal from a binary precursor to higher order cocrystal (HOC) levels by replacing a weakly bound molecule in crystallographic space with another molecule with greater binding energy and directionality. Recent advances in crystal engineering and supramolecular chemistry present the possibility (prospect) of designing and synthesizing HOCs of important pharmaceutical drugs with optimized solid-state properties through the knowledge and application of structural inequivalence. Thus, the strategy aims to design an ABB* precursor of “stoichiometric binary cocrystal” from the cocrystallization of molecules selected as A + B with two B molecules located in crystallographically distinct positions (Z’greater than or equal to two) with different binding strengths. for B and B*. This provides the opportunity to selectively replace the B* molecule located at a weak binding site with a different molecule (C) with stronger non-covalent binding energy and create a ternary HOC with ABC stoichiometry. The successful inclusion of C and others to design ternary, quaternary, etc. systems. requires the exploration of chemical differences using combinatorial synthesis, shape-size mimicry, and synthon hierarchy approaches.

External Reference Name

Drug-based Strategies
Product Development

Nov 2023 — Oct 2024

Brazil