Metallocene QACs: The Incorporation of Ferrocene Moieties into monoQAC and bisQAC Structures

• Type of Material: Article
• Authors: Kyle J. Sommers, Villanova University; Brian S. Bentley, Villanova University; Robert G. Carden, Villanova University; Savannah J. Post, Emory University; Ryan A. Allen, Emory University; Renee C. Kontos, Villanova University; Jacob W. Black, Villanova University; William Wuest, Emory University; Kevin P. C. Minbiole, Villanova University
• Language: English
• Date: 2020-11-26
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Wiley-VCH GmbH, Weinheim
• Final Published Version (URL): http://dx.doi.org/10.1002/cmdc.202000605
• Title of Journal or Parent Work: ChemMedChem
• Volume: 16
• Issue: 3
• Start Page: 467
• End Page: 471
• Grant/Funding Information: Invasive MRSA isolates were collected by the Georgia Emerging Infections Program (EIP) as part of the Active Bacterial Core surveillance (ABCs) and Healthcare Associated Infections-Community Interface (HAIC) projects of the Centers for Disease Control and Prevention (CDC) EIP.; This work was funded by the National Institute of General Medical Sciences (R35 GM119426 to W.M.W.), a Graduate Research Fellowship from the National Science Foundation (DGE1937971 to S.J.P.) and a Major Research Instrumentation grant from the National Science Foundation (CHE-1827930 to K.P.C.M.).
• Keywords: Pharmacology & Pharmacy; Antibacterial; methicillin-resistant Staphylococcus aureus (MRSA); Science & Technology; benzalkonium chloride; Quaternary ammonium compounds; Antiseptics; antiseptics; quaternary ammonium compounds; ferrocene; Fluidity; Life Sciences & Biomedicine; Chemistry, Medicinal; bisQAC
• Research Categories: Chemistry, Biochemistry; Chemistry, Pharmaceutical; Health Sciences, Pharmacology

Abstract

Inspired by the incorporation of metallocene functionalities into a variety of bioactive structures, particularly antimicrobial peptides, we endeavored to broaden the structural variety of quaternary ammonium compounds (QACs) by the incorporation of the ferrocene moiety. Accordingly, 23 ferrocene-containing mono- and bisQACs were prepared in high yields and tested for activity against a variety of bacteria, including Gram-negative strains and a panel of clinically isolated MRSA strains. Ferrocene QACs were shown to be effective antiseptics with some displaying single-digit micromolar activity against all bacteria tested, demonstrating yet another step in the expansion of structural variety of antiseptic QACs.