Unravelling the role of [Ru(bpy)2(OH2)2]2+ complexes in photo-activated chemotherapy.

Photoactivated chemotherapy (PACT) has emerged as a promising strategy to selectively target cancer cells by using light irradiation to generate cytotoxic complexes in situ through a mechanism involving ligand-loss. Due to their rich optical properties and excited state chemistry, Ru polypyridyl complexes have attracted significant attention for PACT. However, studying PACT is complicated by the fact that many of these Ru complexes can also undergo excited-state electron transfer to generate 1O2 species. In order to deconvolute the biological roles of possible photo-decomposition products without the added complication of excited-state electron transfer chemistry, we have developed a methodology to systematically investigate each product individually, and assess the structure-function relationship. Here, we synthesized a series of eight distinct Ru polypyridyl complexes: Ru-Xa ([Ru(NN)3]2+), Ru-Xb ([Ru(NN)2py2]2+), and Ru-Xc ([Ru(NN)(OH2)2]2+) where NN = 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, or dimethyl 2,2'-bipyridine-4,4'-dicarboxylate and py = pyridine. The cytotoxicity of these complexes was investigated in two cell lines amenable to PACT: H23 (breast cancer) and T47D (lung cancer). We confirmed that light irradiation of Ru-Xa and Ru-Xb complexes generate Ru-Xc complexes through UV-visible spectroscopy, and observed that the Ru-Xc complexes are the most toxic against the cancer cell lines. In addition, we have shown that ligand release and biological activity including bovine serum albumin (BSA) binding, lipophilicity, and DNA interaction are altered when different groups are appended to the bipyridine ligands. We believe that the methodology presented here will enhance the development of more potent and selective PACT agents moving forward.

Dispersal ability predicts spatial genetic structure in native mammals persisting across an urbanization gradient.

As the rate of urbanization continues to increase globally, a growing body of research is emerging that investigates how urbanization shapes the movement-and consequent gene flow-of species in cities. Of particular interest are native species that persist in cities, either as small relict populations or as larger populations of synanthropic species that thrive alongside humans in new urban environments. In this study, we used genomic sequence data (SNPs) and spatially explicit individual-based analyses to directly compare the genetic structure and patterns of gene flow in two small mammals with different dispersal abilities that occupy the same urbanized landscape to evaluate how mobility impacts genetic connectivity. We collected 215 white-footed mice (Peromyscus leucopus) and 380 big brown bats (Eptesicus fuscus) across an urban-to-rural gradient within the Providence, Rhode Island (U.S.A.) metropolitan area (population =1,600,000 people). We found that mice and bats exhibit clear differences in their spatial genetic structure that are consistent with their dispersal abilities, with urbanization having a stronger effect on Peromyscus mice. There were sharp breaks in the genetic structure of mice within the Providence urban core, as well as reduced rates of migration and an increase in inbreeding with more urbanization. In contrast, bats showed very weak genetic structuring across the entire study area, suggesting a near-panmictic gene pool likely due to the ability to disperse by flight. Genetic diversity remained stable for both species across the study region. Mice also exhibited a stronger reduction in gene flow between island and mainland populations than bats. This study represents one of the first to directly compare multiple species within the same urban-to-rural landscape gradient, an important gap to fill for urban ecology and evolution. Moreover, here we document the impacts of dispersal capacity on connectivity for native species that have persisted as the urban landscape matrix expands.