The antimicrobial properties of some copper(ii) and platinum(ii) 1,10-phenanthroline complexes

Abstract

Copper(II) (1(Cu)-21(Cu)) and previously established experimental anticancer platinum(II) metallointercalator complexes (1(Pt)-16(Pt)) have been prepared and investigated for their antimicrobial properties. These complexes are of the general structure [M(I(L))(A(L))](2+) where I(L) represents functionalised 1,10-phenanthrolines (1(IL)-10(IL)), and A(L) represents 1,2-diaminoethane, 1S,2S- or 1R,2R-diaminocyclohexane. The structures of synthesised complexes were confirmed using a combination of elemental analysis, UV spectrometry, circular dichroism, (1)H and [(1)H-(195)Pt]-HMQC NMR, X-ray crystallography, and electrospray ionisation mass spectrometry and where appropriate. Crystallisation attempts yielded single crystals of [Cu(4-methyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)](ClO(4))(2) (4(Cu)), [Cu(5,6-dimethyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)(H(2)O)](ClO(4))(2)·1.5H(2)O (10(Cu)) and [Cu(5,6-dimethyl-1,10-phenanthroline)(3)](ClO(4))(2)·5,6-dimethyl-1,10-phenanthroline·2H(2)O (21(Cu)). Growth inhibition of liquid cultures of bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), and yeast (Saccharomyces cerevisiae) discerned the most antimicrobially potent metal complexes ≤20 μM, as well as that of their intercalating ligands alone. To further investigate their mode of antimicrobial activity, membrane permeabilisation caused by selected complexes was visualised by means of a cell viability kit under fluorescence microscopy.

The antimicrobial and antibiofilm activities of copper(II) complexes

“…The antibacterial activity of the Cu(II) complexes chosen for this study has been reported before [16,24], but because the activity was not determined on the same panel of bacterial isolates, we re-evaluated their activity (Table 1). This was compared with the activity of two antibiotics, vancomycin (compound 12) and chloramphenicol (compound 13).…”

“…Activity against Gram-negative bacteria is lower, with the compounds still showing some activity against E. coli but no significant activity against P. aeruginosa. Note that neither the ligands [16], nor CuCl2 (compound 14; Table 1) have a high antimicrobial activity on their own; these have sublethal activity at the concentrations tested, and significant antimicrobial activity is only observed for the complexes of Cu(II) with the ligands.…”

“…As recently reviewed by us, these complexes interact with DNA through intercalation [14]. It is important to note that complex formation is important, as the biological activity is significantly enhanced when compared to ligands or metals alone [15,16]. In addition, copper(II) complexes may also have chemical nuclease activity [17], and several groups have designed and explored complexes which facilitate DNA transformations [18][19][20].…”

“…In recent years we have investigated the antimicrobial activity of compounds containing iron, ruthenium, copper and palladium [16,[21][22][23][24]. All of these compounds have been reported to bind DNA, either through groove binding or intercalation.…”

“…All of these compounds have been reported to bind DNA, either through groove binding or intercalation. Several compounds showed good antimicrobial activity on both Gramnegative and Gram-positive bacteria, albeit that the latter are generally more sensitive to metal complexes [16,[21][22][23][24]. These complexes have only been tested on planktonic cells, and we therefore sought to investigate the activity of a panel of copper(II) complexes against biofilms, and focussed this specifically on a clinical isolate of meticillin-resistant Staphylococcus aureus (MRSA) that is capable of forming stable 5 biofilms.…”