Metallo-β-lactamases (MBLs) are a cause of growing concern for global health because of their role in resistance to antibiotics. For example, zinc-containing MBLs catalyze the hydrolysis of the β-lactam core present in most antibiotics. Therefore, we describe here a synthetic analogue of a zinc MBL that is derived from tris(isopropylbenzimidazolylthio)methane ([Titmi-PrBenz]H). Specifically, reaction of [Titmi-PrBenz]H with ZnMe2 affords [κ3-Titmi-PrBenz]ZnMe, which yields the ionic species {[κ4-Titmi-PrBenz]Zn}X (X = [BPh4] or [MeB(C6F5)3]) upon treatment with [PhNMe2H][BPh4] or B(C6F5)3, respectively. The non-coordinating nature of [BPh4]– and [MeB(C6F5)3]– allows for coordination of the b-lactam, 4-phenyl-2-azetidinone, to the zinc center, such that the molecular structure of {[κ4-Titmi-PrBenz]Zn(4-phenyl-2-azetidinone)}[BPh4] has been determined by X-ray diffraction, while NMR spectroscopic studies have been employed to measure the magnitude of the binding interaction of 4-phenyl-2-azetidinone Similar studies have been performed for coordination of picolinamide, piperidinone, succinamides and aminoacetamides which have potential use as inhibitors for MBLs.

Synthesis and structural characterization of a β-lactam adduct of a synthetic analogue of a metallo-β-lactamase

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.