Modular synthesis of antimalarial quinoline-based PGM metallarectangles

Area of Science:

• Coordination Chemistry
• Supramolecular Chemistry
• Medicinal Chemistry

Background:

• The quinoline scaffold is a key component in antimalarial drugs.
• Developing novel metal complexes for therapeutic applications is an active research area.
• Supramolecular self-assembly offers new avenues for designing complex molecular architectures.

Purpose of the Study:

• To synthesize novel ditopic quinoline-based ligands and their metal complexes.
• To construct supramolecular metallarectangles through coordination-driven self-assembly.
• To evaluate the antiplasmodial activity of these compounds against Plasmodium falciparum.

Main Methods:

• Suzuki cross-coupling reaction for ligand synthesis.
• [2 + 2] coordination-driven self-assembly for metallarectangle formation.
• Single-crystal X-ray diffraction, DFT calculations, NMR, IR, and ESI-MS for characterization.
• In vitro antiplasmodial assays against chloroquine-sensitive and resistant strains.

Main Results:

• Successful synthesis and characterization of a quinoline-based ligand, iridium(III), and ruthenium(II) complexes.
• Formation of metallarectangles via self-assembly, confirmed by structural analyses.
• Significant in vitro antiplasmodial activity observed for the synthesized compounds.
• Correlation between increased nuclearity of metallarectangles and enhanced antiplasmodial potency.
• Selected metallarectangles demonstrated inhibition of haemozoin formation, similar to chloroquine.

Conclusions:

• The synthesized quinoline-based metallarectangles represent a promising class of antiplasmodial agents.
• Supramolecular design can be effectively utilized to enhance antimalarial drug efficacy.
• These metallosupramolecular structures offer a potential new strategy for combating malaria.