An Alkynyl‐Dangling Ru(II) Polypyridine Complex for Targeted Antimicrobial Photodynamic Therapy

• Published in: Chemistry : a European journal 2022-01, Vol.28 (6), p.e202103359-n/a
• Main Authors: Jian, Yao, Jin, Zhihui, Qi, Shuang, Da, Xuwen, Wang, Zhanhua, Wang, Xuesong, Zhou, Qianxiong
• Format: Article
• Language: English
• Subjects: amino-yne click reaction; Animals; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents; antibacterial photodynamic therapy; Antiinfectives and antibacterials; Antimicrobial agents; Chemical reactions; Chemistry; Cytotoxicity; Drug resistance; Irradiation; Lipids; Mammalian cells; Mammals; Methicillin; Methicillin-Resistant Staphylococcus aureus; Penicillin; Phosphatidylethanolamine; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - pharmacology; Radiation; Ruthenium; Ruthenium compounds; ruthenium(II) polypyridyl complexes; Selectivity; Singlet oxygen; Staphylococcus aureus; Staphylococcus infections; Toxicity
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202103359

To realize clinical application of antibacterial photodynamic therapy (aPDT), one of the most arduous challenges is how to render aPDT agents high selectivity against bacterial pathogens. In light of the fact that amino group‐containing lipids are rich on the outer surfaces of Gram‐positive bacteria, we herein constructed an alkynyl‐dangling ruthenium(II) polypyridine complex (Ru2) to preferentially label Staphylococcus aureus (S. aureus) and methicillin‐resistant Staphylococcus aureus (MRSA) over mammalian cells via the amino‐yne bio‐orthogonal click reaction. Thanks to the strong singlet oxygen generation ability, Ru2 could photo‐inactivate S. aureus and MRSA effectively and specifically. Phosphatidylethanolamine (PE) molecules also exist in mammalian cells but are not accessible for Ru2, leading to its poor binding/uptake and negligible cytotoxicity in the dark and upon irradiation towards mammalian cells as well as low hemolysis, all favorable for aPDT application. An alkynyl‐dangling ruthenium(II) polypyridine complex Ru2, which may rapidly conjugate to the amino groups on the unique membrane lipids of Gram‐positive bacteria through the bio‐orthogonal amino‐yne click reaction has been investigated. Such a selective labeling process in combination with its good singlet oxygen quantum yield makes Ru2 to be able to photo‐inactivate bacterial such as S. aureus and MRSA efficiently and specifically, but leaving mammalian cells undamaged under the same conditions.