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

Abstract

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.

Metals to combat antimicrobial resistance

“…Extensive reviews have been published elsewhere on this class of metal complexes [225][226][227] . Probably inspired by their success in anticancer PDT, ruthenium complexes have been among the most explored for this application [228][229][230][231][232][233] . In 2014, one of the first ruthenium photosensitizer agents was reported to show in vitro activity against S. aureus and E. coli, with a large reduction in colony-forming units upon light irradiation, but low activity in the dark 234 .…”

Ru(II) Complexes with Enaminone Structures for Rapid Sterilization of Staphylococcus aureus and MRSA with Little Accumulation of Drug Resistance

“…Synthesis of Ru1 . Ru0 was synthesized according to our previous work [29] . 40 mg Ru0 (0.04 mmol) and 20 μL propylamine (0.24 mmol) were dissolved in CH 2 Cl 2 (2 mL).…”

“…Ru0 was synthesized according to our previous work. [29] 40 mg Ru0 (0.04 mmol) and 20 μL propylamine (0.24 mmol) were dissolved in CH 2 Cl 2 (2 mL). The reaction mixture was stirred for 12 h at room temperature.…”

“…RuÀ OH was synthesized according to our previous work. [29] 200 mg RuÀ OH (0.22 mmol) and 138.4 mg hept-2enoic acid (1.08 mmol) were dissolved in CH 2 Cl 2 (50 mL) at 0 °C under an argon atmosphere, then DCC (223.3 mg, 1.08 mmol) and DMAP (30 mg) were added. The reaction mixture was stirred at 0 °C for 1 h and a further 16 h at room temperature.…”

Recent Advances in Metal Complexes for Antimicrobial Photodynamic Therapy

“…were also interested in targeting bacteria by binding to their surface. The group developed a [Ru(bpy) 3 ] 2+ complex with pendent alkyne moieties ( Ru‐19 , Figure 18), able to selectively and covalently bind to the surface of Gram‐positive bacteria on blue light irradiation (470 nm) in an amino‐yne click reaction [89] . The complex can also generate 1 O 2 and thus induce bacterial cell death.…”