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

• Grant number: 23/04534-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2023
• End date: October 31, 2024
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Gabriel Lima Barros de Araujo
• Grantee: Bolaji Charles Dayo Owoyemi
• Supervisor: Stephen R. Byrn
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Purdue University, United States
• Associated to the scholarship: 21/14683-9 - DESIGN AND SYNTHESIS OF MULTICOMPONENT ANTIMALARIAL COCRYSTALS THROUGH STRUCTURAL INEQUIVALENCE AND COMBINATORIAL APPROACHES, BP.PD

Abstract

Structural inequivalence is a state-of-the-art molecular architecture (strategy) that allows increasing the number of components in a simple co-crystal from a binary precursor to a higher order cocrystal (HOC) levels by substituting a weakly bonded molecule in the crystallographic space by another molecule with higher bonding energy and directionality. Recent advances in crystal engineering and supramolecular chemistry present the possibility (prospect) to design and synthesize HOCs of important pharmaceutical drugs with optimized solid-state properties through knowledge and application of structural inequivalence. Thus, the strategy aims to design a "stoichiometry binary cocrystal" ABB* precursor from the cocrystallization of selected molecules as A + B with two molecules B being located in crystallographically distinct positions (Z' greater or equal 2) with different bonding strengths for B and B*. This offers the opportunity to selectively substitute molecule B* located at a weak bonding point with a different molecule (C) with stronger non-covalent bonding energy and create a ternary HOC with stoichiometry ABC. The successful inclusion of C and others to design ternary, quaternary, etc. systems requires exploiting chemical differences using combinatorial synthesis, shape-size mimicry, and synthon hierarchy approaches. Therefore, this project aims to design, synthesize, and characterize HOCs of antimalarial drugs as fixed-dose formulations with improved drug properties through the application of structural inequivalence and combinatorial synthesis methods in line with crystal engineering and supramolecular design. (AU)