Fe(II)-Photoantibiotics for Potential Antibacterial, Antibiofilm, and Infective Wound Healing Applications in Rat Model

Abstract

Herein, five Fe(II) complexes, viz., [Fe(N,N,N)₂](ClO₄)₂, where N,N,N = 4′-phenyl-2,2′:6′,2″-terpyridine (Ph-tpy, Fe1), 4′-(4 aminophenyl) 2,2′:6′,2″ terpyridine (NH₂-Phtpy, Fe2), 4-([2,2′:6′,2′′-terpyridin]-4′-yl)-N,N-dimethylaniline (NMe₂-Phtpy, Fe3), 4′-(p-nitrophenyl)-2.2′:6′,2″-terpyridine (NO₂-Phtpy, Fe4), and 4′-(4-trifluoromethylphenyl)-2,2’:6′,2′′-terpyridine (CF₃-Phtpy, Fe5) were developed and screened for their visible-light-triggered antibacterial activity. Fe1–Fe5 exhibited absorption at ca. 450–600 nm, beneficial for antibacterial photodynamic therapy (aPDT) under visible light exposure. The excellent photostability and ideal energy gap between T₁ and S₀ of the complexes made them good photosensitizers for aPDT. Fe5 had the best antibacterial activity against Escherichia coli and Bacillus subtilis upon exposure to 400–700 nm (10 J cm^–2) light due to reactive oxygen species (ROS) generation. Further, Fe5 showed antibiofilm activity on different medical-grade biomaterials and devices. Biocompatibility of Fe5 was validated using in vivo and chicken embryonic models (in ovo). Moreover, in vivo studies showed that Fe5 efficiently healed infected wounds within 9 days.