Fluorinated Rh(I)-NHC Compounds as Potential Antibacterials Against Multidrug-Resistant Klebsiella pneumoniae...

Background/objectives: The increasing prevalence of multidrug-resistant (MDR) bacteria, particularly Klebsiella pneumoniae, calls for the development of new antimicrobial agents. This study investigates a series of fluorinated azolium salts and their rhodium(I) complexes for antibacterial activity against clinical and reference strains of K. pneumoniae. Methods: Eleven fluorinated azolium salts and their corresponding Rh(I) complexes (22 compounds total) were synthesized and tested against several K. pneumoniae strains, including three MDR clinical isolates (U-13685, H-9871, U-13815) and ATCC reference strains. Minimum inhibitory concentrations (MICs) were determined. In silico ADMET analyses were conducted to evaluate intestinal absorption, oral bioavailability, Caco-2 permeability, carcinogenicity, solubility, and synthetic accessibility. Results: Among the Rh(I) complexes, Rh-1, Rh-3, and Rh-11 showed activity against the three MDR isolates (MIC = 62.5-250 µg/mL), while Rh-1, Rh-4, Rh-6, and Rh-11 were active against all ATCC strains (MIC = 3.9-250 µg/mL). The corresponding azolium salts displayed weak or no activity, highlighting the critical role of the metal center. ADMET predictions indicated that most Rh complexes had good intestinal absorption, and all except Rh-3, Rh-4, and Rh-9 were predicted to be orally bioavailable. Compounds Rh-1 to Rh-7 showed Caco-2 permeability, and all were classified as non-carcinogenic. Rh-8 to Rh-11 exhibited lower solubility and synthetic accessibility. Conclusions: The results underscore the potential of fluorinated Rh(I) complexes as antibacterial agents against MDR K. pneumoniae, with Rh-1 and Rh-11 emerging as promising leads based on activity and favorable predicted pharmacokinetics.