Synthesis, characterisation and antibacterial activity of novel Ga(III) polypyridyl catecholate complexes

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Materials Science

Background:

• Gallium(III) complexes are explored for therapeutic applications.
• Polypyridyl and catecholate ligands offer versatile coordination possibilities.
• Developing novel antibacterial agents is a global health priority.

Purpose of the Study:

• To synthesize and characterize novel Gallium(III) polypyridyl catecholate complexes.
• To evaluate the in vitro antibacterial efficacy of these complexes against pathogenic bacteria.
• To assess the in vivo toxicity and protective effects of a lead complex against Pseudomonas aeruginosa infection.

Main Methods:

• Synthesis of Ga(III) complexes using Ga(NO3)3, catecholate ligands (2,3-DHBA, 3,4-DHBA, 2,3,4-THBA, CafA), and bipyridine (bipy) or phenanthroline (phen).
• Characterization using X-ray crystallography to confirm coordination geometry.
• In vitro antibacterial assays against Gram-negative (E. coli, K. pneumoniae, P. aeruginosa) and Gram-positive (S. aureus, MRSA) bacteria.
• In vivo toxicity and efficacy studies in Galleria mellonella larvae infected with P. aeruginosa.

Main Results:

• Successfully synthesized and characterized Ga(III) polypyridyl catecholate complexes.
• X-ray crystallography confirmed bidentate coordination of catecholate ligands to Ga(III) centers.
• All complexes demonstrated significant in vitro antibacterial activity against Gram-negative bacteria.
• Complexes were inactive against Gram-positive bacteria, including MRSA.
• [Ga(bipy)2(2,3-DHBA-2H)](NO3)·1.5H2O showed no in vivo toxicity in Galleria mellonella larvae up to 2000 μg mL-1.
• This lead complex provided protection against P. aeruginosa infection in vivo at doses of 100 and 250 μg mL-1.

Conclusions:

• Novel Ga(III) polypyridyl catecholate complexes possess potent antibacterial activity against key Gram-negative pathogens.
• The lead complex exhibits favorable in vivo safety profile and therapeutic potential against P. aeruginosa infections.
• These findings highlight the potential of tailored Ga(III) complexes as a new class of antibacterial agents.