抗生素抗性的日益增长的挑战在对抗医疗设备上的微生物感染和生物膜预防方面带来了巨大挑战。最近,抗菌光动力疗法(aPDT)现在正在成为克服这一问题的替代疗法。在这里,我们合成并表征了四种Ru(II)-配合物,viz.,[Ru(ph-tpy)(bpy)Cl]PF6(Ru1),[Ru(ph-tpy)(dpq)Cl]PF6(Ru2),[Ru(ph-tpy)(dppz)Cl]PF6(Ru3),和[Ru(ph-tpy)(dppn)Cl]PF6(Ru4)(其中4'-苯基-2,2':6',2″-三吡啶=ph-tpy;2,2'-联吡啶=bpy;二吡啶[3,2-f:2',3\'-h]喹喔啉=dpq;二吡啶并[3,2-a:2\',3\'-c]吩嗪=dppz;苯并[I]二吡啶并[3,2-a:2\',3\'-c]吩嗪=dppn),其中Ru2-Ru4是小说。从Ru2的晶体结构可以看出具有RuN5Cl核的配合物的八面体几何形状。Ru1-Ru4在450-600nm区域显示出MLCT吸收带,对aPDT性能有用。Further,Ru1-Ru4的最佳三重态激发态能量和优异的光稳定性使其成为aPDT的良好光敏剂。Ru1-Ru4在可见光暴露(400-700nm,10Jcm-2),使用不同的抗菌试验证实。机理研究表明,细菌生长的抑制是由于在用Ru2-Ru4处理时氧化应激的产生(通过NADH氧化和ROS产生),导致细菌壁的破坏。当暴露于光照时,Ru2对革兰氏阴性(大肠杆菌)和革兰氏阳性(枯草芽孢杆菌)细菌均表现出最佳的杀灭性能。Ru2-Ru4,当涂覆在聚二甲基硅氧烷(PDMS)圆盘上时,显示出长期的可重用性和持久的抗生物膜特性。分子对接证实了Ru2-Ru4与FabH(调节大肠杆菌的脂肪酸生物合成)和PgaB(提供结构稳定性并有助于大肠杆菌的生物膜形成)的有效相互作用,导致可能的下调。对健康Wistar大鼠的体内研究证实了Ru2的生物相容性。这项研究表明,这些铅配合物(Ru2-Ru4)可以用作低浓度的有效替代抗菌剂,以光动力疗法(PDT)根除细菌。
Growing challenges with antibiotic resistance pose immense challenges in combating microbial infections and biofilm prevention on medical devices. Lately, antibacterial photodynamic therapy (aPDT) is now emerging as an alternative therapy to overcome this problem. Herein, we synthesized and characterized four Ru(II)-complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(dpq)Cl]PF6 (Ru2), [Ru(ph-tpy)(dppz)Cl]PF6 (Ru3), and [Ru(ph-tpy)(dppn)Cl]PF6 (Ru4) (where 4\'-phenyl-2,2\':6\',2″-terpyridine = ph-tpy; 2,2\'-bipyridine = bpy; dipyrido[3,2-f:2\',3\'-h]quinoxaline = dpq; dipyrido[3,2-a:2\',3\'-c]phenazine = dppz; and Benzo[I]dipyrido[3,2-a:2\',3\'-c]phenazine = dppn), among which Ru2-Ru4 are novel. Octahedral geometry of the complexes with a RuN5Cl core was evident from the crystal structure of Ru2. Ru1-Ru4 showed an MLCT absorption band in the 450-600 nm region, useful for aPDT performances. Further, optimum triplet excited state energy and excellent photostability of Ru1-Ru4 made them good photosensitizers for aPDT. Ru1-Ru4 demonstrated enhanced antimicrobial activity on visible-light exposure (400-700 nm, 10 J cm-2), confirmed using different antibacterial assays. Mechanistic studies revealed that inhibition of bacterial growth was due to the generation of oxidative stress (via NADH oxidation and ROS generation) upon treatment with Ru2-Ru4, resulting in destruction of the bacterial wall. Ru2 performed best killing performance against both Gram-negative (Escherichia coli) and Gram-positive (Bacillus subtilis) bacteria when exposed to light. Ru2-Ru4, when coated on a polydimethylsiloxane (PDMS) disk, showed long-term reusability and durable antibiofilm properties. Molecular docking confirmed the efficient interaction of Ru2-Ru4 with FabH (regulates fatty acid biosynthesis of E. coli) and PgaB (gives structural stability and helps biofilm formation of E. coli), resulting in probable downregulation. In vivo studies with healthy Wistar rats confirmed the biocompatibility of Ru2. This study shows that these lead complexes (Ru2-Ru4) can be used as potent alternative antimicrobial agents in low concentrations toward bacterial eradication with photodynamic therapy (PDT).