Copper(II)-photocatalyzed Hydrocarboxylation of Schiff bases with CO₂: antimicrobial evaluation and in silico studies of Schiff bases and unnatural α-amino acids

Abstract

We synthesized and characterized two copper(II) complexes: [CuL2Cl]Cl and [CuL′2Cl]Cl, where L = 2,2'-bipyridine and L′ = 4,4'-dimethyl-2,2'-bipyridine. We evaluated their photocatalytic hydrocarboxylation properties on a series of synthesized Schiff bases (SBs): (E)-1-(4-((5-bromo-2-hydroxybenzylidene)amino)phenyl)ethanone (SB1), (E)-N-(4-(dimethylamino)benzylidene)benzo[d]thiazol-2-amine (SB2), (E)-4-Bromo-2-((thiazol-2-ylimino)methyl)phenol (SB3), and (E)-4-((5-bromo-2-hydroxybenzylidene)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (SB4). Under mild photocatalytic reaction conditions (room temperature, 1 atm CO₂, 30-watt Blue LED light), the derivatives of α-amino acids UAA1-4 were obtained with yields ranging from 5% to 44%. Experimental results demonstrated that [CuL2Cl]Cl exhibited superior photocatalytic efficiency compared to [CuL′2Cl]Cl, attributed to favourable electronic properties. In silico studies revealed strong binding strengths with E. faecalis DHFR (4M7U) for docked Schiff bases (SB) and unnatural α-amino acids (UAAs). In vitro studies further demonstrated significant antimicrobial and antifungal activity for SB2, SB3, and SB4, while none of the synthesized UAAs exhibited such properties, primarily due to the electronic and binding properties of these molecules.

Communicated by Ramaswamy H. Sarma

Keywords:

• Schiff bases (SB)
• unnatural α-amino acid (UAAs)
• hydrocarboxylation
• Cu(II) complexes
• antimicrobial studies

Acknowledgements

The authors thank Nelson Mandela University and National Research Foundation (NRF), South Africa (Grant No: 129887) and Royal Society of Chemistry (R22-3427614666) for co-funding the research work. The authors would also like to thank the Centre for High Performance Computing (CHPC) for providing access to the Schrödinger computational platform.

Disclosure statement

The authors declare no conflict of interests.

Additional information

Funding

The authors thank Nelson Mandela University and National Research Foundation (NRF), South Africa (Grant No: 129887) and Royal Society of Chemistry (R22-3427614666) for co-funding the research work. The authors would also like to thank the Centre for High Performance Computing (CHPC) for providing access to the Schrödinger computational platform.