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Quaternary Ammonium Compounds

As antibiotic resistance continues to rise, it is becoming increasingly important to consider how we use antibiotics in medicine and in our homes.  Common antibacterial products contain simple quaternary ammonium compounds (QACs) that are losing their effectiveness in the home and helping to strengthen resistance as they spread through groundwater and soil. 

It is our goal to design smarter QACs that do not encourage resistance mechanisms and will degrade in nature to be harmless to our environment.  This goal is reached through a collaboration with Kevin Minbiole’s group at Villanova University where talented undergraduate researchers synthesize QACs for us.  They then send their compounds to our lab where we complete the biological testing and analysis.  Together, we have synthesized and analyzed hundreds of compounds that are active against pathogens like Methicillin-resistant Staphylococcus aureus (MRSA).  We also completed a detailed investigation that suggests the commonly accepted mechanism of resistance for QACs is not the full story, which encourages us to continue questioning how resistance develops in MRSA.

Recent Publications:

Al-Khalifa, S.; Jennings, M.C.; Granata, D.; Klein, M.; Wuest, W.M.*; Minbiole, K.P.C.*; Carnevale, V.* “Analysis of the Destabilization of Bacterial Membranes by Quaternary Ammonium Compounds: A Combined Experimental and Computational Study” ChemBioChem 2020 ASAP DOI: 10.1002/cbic.201900698

Schallenhammer, S.A.; Duggan, S.M.; Morrison, K.R.; Bentley, B.S.; Wuest, W.M.*; Minbiole, K.P.C.* “Hybrid BisQACs: Potent Biscationic Quaternary Ammonium Compounds Merging the Structures of Two Commercial Antiseptics” ChemMedChem 2017 12, 1931 DOI: 10.1002/cmdc.201700597

 Jennings, M.C.; Forman, M.E.; Duggan, S.M.; Minbiole, K.P.C.*; Wuest, W.M.* “Efflux Pumps May Not Be the Major Drivers of QAC Resistance in Methicillin-Resistant Staphylococcus aureus” ChemBioChem 2017 18, 1573 DOI: 10.1002/cbic.201700233 (highlighted as a Very Important Paper, Selected as Cover Art)

Al-Khalifa, S.E.; Jennings, M.C.; Wuest, W.M.*; Minbiole, K.P.C.* “The Development of Next Generation Pyridinium-Based multiQAC Antiseptics” ChemMedChem 2017 12, 280 DOI: 10.1002/cmdc.201600546

Forman, M.E.; Jennings, M.C.; Wuest, W.M.*; Minbiole, K.P.C.* “Building a Better QAC: Branched Tetracationic Antiseptics” ChemMedChem 2016, 11, 1401 (Highlighted on the back cover!) DOI: 10.1002/cmdc.201600176