Metallacarborane Assemblies as Effective Antimicrobial Agents, Including a Highly Potent Anti-MRSA Agent

Abstract

The salts Na[ROC(O)Ph], Na[1-ROC(O)-1,12-C2B10H11], K-2[1,4-(ROC(O))(2)-C6H4], and K,[1,12-(ROC(O))(2)-1,12-C2B10H10], where R is the cobaltabis(dicarbollide)-diethylene glycol group [3,3 '-Co(8-(OCH2CH2OCH2CH2)-1,2-C2B9H10)(1',2'-C2B9H11)] , were synthesized from the corresponding carboxylate salt and the zwitterion [3,3'-Co(8-(CH2CH2O)(2)-1,2C(2)B(9)H(10))(1',2'-C2B9H11)]. The dianion in K-2[1,12-(ROC(O))(2)1,12-C2B10H10] showed at least one K+ cation to be tightly bound to the dianion via K...O and K...H-B interactions with both p-carborane and cobaltabis(dicarbollide) clusters on the basis of NMR and MS data and support of hybrid-DFT computations. An evaluation of the antimicrobial properties of these compounds revealed all of the salts to be highly effective antibacterial agents for four Gram-positive bacteria strains (standard minimum inhibitory concentration, MIC, of 1 mg/L for Na[ROC(O)Ph]; Na[3]) and antifungal agents for three Candida albicans strains (MIC 4 mg/L for the salts K-2[4] and K-2[6]). One of the four Gram-positive bacteria strains tested was a life-threatening superbug methicillin-resistant Staphylococcus aureus (MRSA) isolate, which is resistant to many commercial antimicrobial drugs. The cobaltabis(dicarbollide) derivative Na[3] has a remarkable inhibitory effect on the MRSA strain with an MIC of only 1 mg/L and a minimum bactericidal concentration (MBC) of 2 mg/L, thus suggesting its potential as an antibacterial agent against MRSA.