Indium(III) 8-hydroxyquinolinates: Activity and selectivity towards multi-drug resistant strains of Klebsiella pneumoniae

A series of dimethyl indium(III) 8-hydroxyquinolinates; [InMe₂(Q")] (1), [InMe₂(Q'Cl)] (2), [InMe₂(QCl₂)] (3), [InMe₂(QBr₂)] (4), [InMe₂(QI₂)] (5), [InMe₂(QICl)] (6), and a series of indium(III) tris(8-hydroxyquinolinates); [In(Q")₃]•H₂O (7), [In(QCl₂)₃] (8), [In(QBr₂)₃] (9), [In(QI₂)₃] (10), and [In(QICl)₃] (11), (where Q"-H = C₉H₇NO; Q'Cl-H = C₉H₆NOCl, QCl₂-H = C₉H₅NOCl₂; QBr₂-H = C₉H₅NOBr₂; QI₂-H = C₉H₅NOI₂; and QICl-H = C₉H₅NOICl) were synthesised, characterised, and evaluated for their antibacterial activity against Gram-positive bacteria (vancomycin-resistant E. faecalis, S. aureus, methicillin-resistant S. aureus), Gram-negative bacteria (K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli) and mammalian cell inhibition of L929 fibroblasts. Single crystal X-ray diffraction data of 2-4 indicates the dimethylindium complexes are dimeric in the solid-state through 'In₂O₂' bridging. Complexes 1-6 exhibit significant activity and selectivity against three multi-drug resistant strains of K. pneumoniae, with MIC (minimum inhibitory concentration) values as low as 49 nM and selectivity indices as high as 159 against carbapenem-resistant strain RH201207. The antibacterial activity and selectivity against K. pneumoniae is generally enhanced upon complexation of the 8-hydroxyquinolinate ligands to indium(III).