Targeted Antibacterial Strategy Based on Reactive Oxygen Species Generated from Dioxygen Reduction Using an Organoruthenium Complex

• Published in: JACS Au Vol. 1; no. 9; pp. 1348 - 1354
• Main Authors: Weng, Cheng, Shen, Linghui, Teo, Jin Wei, Lim, Zhi Chiaw, Loh, Boon Shing, Ang, Wee Han
• Format: Journal Article
• Language: English
• Published: American Chemical Society 27-09-2021
• Subjects: Letter
• ISSN: 2691-3704; 2691-3704
• DOI: 10.1021/jacsau.1c00262

Pathogenic microorganisms
pose a serious threat to global public
health due to their persistent adaptation and growing resistance to
antibiotics. Alternative therapeutic strategies are required to address
this growing threat. Bactericidal antibiotics that are routinely prescribed
to treat infections rely on hydroxyl radical formation for their therapeutic
efficacies. We developed a redox approach to target bacteria using
organotransition metal complexes to mediate the reduction of cellular
O
2
to H
2
O
2
, as a precursor for hydroxyl
radicals via Fenton reaction. We prepared a library of 480 unique
organoruthenium Schiff-base complexes using a coordination-driven
three-component assembly strategy and identified the lead organoruthenium
complex Ru1 capable of selectively invoking oxidative stress in Gram-positive
bacteria, in particular methicillin-resistant
Staphylococcus
aureus
, via transfer hydrogenation reaction and/or single
electron transfer on O
2
. This strategy paves the way for
a targeted antimicrobial approach leveraging on the redox chemistry
of organotransition metal complexes to combat drug resistance.