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Publication Abstract from PubMed

A series of six novel metallocenyl-7-ADCA (metallocenyl = ferrocenyl or ruthenocenyl; 7-ADCA = 7-aminodesacetoxycephalosporanic acid) conjugates were synthesized and their antibacterial properties evaluated by biochemical and microbiological assays. The ruthenocene derivatives showed a higher level of inhibition of DD-carboxypeptidase 64-575, a Penicillin Binding Protein (PBP), than the ferrocene derivatives and the reference compound penicillin G. Protein X-ray crystallographic analysis revealed a covalent acyl-enzyme complex of a ruthenocenyl compound with CTX-M beta-lactamase E166A mutant, corresponding to a similar complex with PBPs responsible for the bactericidal activities of these compounds. Most interestingly, an intact compound was captured at the crystal-packing interface, elucidating for the first time the structure of a metallocenyl beta-lactam compound that previously eluded small molecule crystallography. We propose that protein crystals, even from biologically unrelated molecules, can be utilized to determine structures of small molecules.

Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M beta-Lactamase.,Lewandowski EM, Szczupak L, Wong S, Skiba J, Guspiel A, Solecka J, Vrcek V, Kowalski K, Chen Y Organometallics. 2017 May 8;36(9):1673-1676. doi: 10.1021/acs.organomet.6b00888. , Epub 2017 Feb 1. PMID:29051683^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.