Synthesis and characterisation of phenanthroline-oxazine ligands and their Ag(I), Mn(II) and Cu(II) complexes and their evaluation as antibacterial agents.

A series of phenanthroline-oxazine ligands were formed by a cyclisation reaction between L-tyrosine amino acid esters and 1,10-phenanthroline-5,6-dione (phendione). The methyl derivative of the phenanthroline-oxazine ligand 1 was complexed with Ag(I), Mn(II) and Cu(II) to form [Ag(1)2]ClO4, [Mn(1)3](ClO4)2 and [Cu(1)3](ClO4)2. The activity of these metal complexes was tested against the bacteria Escherichia coli and Staphylococcus aureus. Each of the metal complexes was more active than 1 against S. aureus and the Mn(II) and Cu(II) complexes also showed greater activity than 1 towards E. coli. The effect of increasing the length of the alkyl moiety on the phenanthroline-oxazine ligands and their corresponding tris homoleptic Cu(II) complexes was investigated. In all cases both the ligands and their complexes were more active against Gram-positive S. aureus than against Gram-negative E. coli. Differences in the lipophilicity of the ligands and their corresponding Cu(II) complexes did alter the antibacterial activity, with the hexyl and octyl derivatives and their complexes showing the greatest activity and comparing well with clinically used antibiotics. The most active Cu(II) complexes and their respective ligands were also active against Methicillin-resistant S. aureus (MRSA). In vivo toxicity studies, conducted using the Galleria mellonella model, showed that all of the compounds were well tolerated by the insect larvae.