Department of Chemistry "Ugo Schiff", University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
Department of Biology, University of Florence, via Madonna del Piano 6, 50019 Sesto Fiorentino (FI), Italy.
J Inorg Biochem. 2021 Jul;220:111467. doi: 10.1016/j.jinorgbio.2021.111467. Epub 2021 Apr 22.
The antimicrobial potential of two ruthenium(II) polypyridyl complexes, [Ru(phen)L1] and [Ru(phen)L2] (phen = 1,10-phenanthroline) containing the 4,4'-(2,5,8,11,14-pentaaza[15])-2,2'-bipyridilophane (L1) and the 4,4'-bis-[methylen-(1,4,7,10-tetraazacyclododecane)]-2,2' bipyridine (L2) units, is herein investigated. These peculiar polyamine frameworks afford the formation of highly charged species in solution, influence the DNA-binding and cleavage properties of compounds, but they do not undermine their singlet oxygen sensitizing capacities, thus making these complexes attractive O generators in aqueous solution. L1 and L2 also permit to stably host Fenton -active Cu ion/s, leading to the formation of mixed Ru/Cu forms capable to further strengthen the oxidative damages to biological targets. Herein, following a characterization of the Cu binding ability by [Ru(phen)L2], the water-octanol distribution coefficients, the DNA binding, cleavage and O sensitizing properties of [Ru(phen)L2] and [CuRu(phen)L2] were analysed and compared with those of [Ru(phen)L1] and [CuRu(phen)L1]. The antimicrobial activity of all compounds was evaluated against B. subtilis, chosen as a model for gram-positive bacteria, both under dark and upon light-activation. Our results unveil a notable phototoxicity of [Ru(phen)L2] and [CuRu(phen)L2], with MIC (minimal inhibitory concentrations) values of 3.12 μM. This study highlights that the structural characteristics of polyamine ligands gathered on highly charged Ru(II)-polypyridyl complexes are versatile tools that can be exploited to achieve enhanced antibacterial strategies.
本文研究了两种钌（II）多吡啶配合物[Ru(phen)L1]和[Ru(phen)L2]（phen=1,10-菲咯啉）的抗菌潜力，它们分别含有 4,4'-(2,5,8,11,14-五氮杂[15]）-2,2'-联吡啶（L1）和 4,4'-双-[亚甲基-(1,4,7,10-四氮杂环十二烷)]-2,2'-联吡啶（L2）单元。这些特殊的多胺骨架在溶液中形成高度带电的物种，影响化合物与 DNA 的结合和切割性质，但不会破坏它们的单线态氧敏化能力，从而使这些配合物成为水溶液中很有吸引力的 O 生成剂。L1 和 L2 还可以稳定地容纳 Fenton 活性的 Cu 离子/s，形成能够进一步增强对生物靶标氧化损伤的混合 Ru/Cu 形式。在此，通过[Ru(phen)L2]对 Cu 结合能力进行了表征，分析并比较了[Ru(phen)L2]和[CuRu(phen)L2]的水-辛醇分配系数、DNA 结合、切割和 O 敏化性质，以及[Ru(phen)L1]和[CuRu(phen)L1]的性质。所有化合物的抗菌活性均针对枯草芽孢杆菌进行了评估，枯草芽孢杆菌被选为革兰氏阳性菌的模型，分别在黑暗和光照激活条件下进行。我们的研究结果揭示了[Ru(phen)L2]和[CuRu(phen)L2]具有显著的光毒性，其 MIC（最小抑菌浓度）值为 3.12 μM。这项研究强调了多胺配体在高度带电的 Ru(II)-多吡啶配合物上的结构特征是多功能工具，可以用来实现增强的抗菌策略。
