Title | Targeted live-cell nuclear delivery of the DNA 'light-switching' Ru(II) complex via ion-pairing with chlorophenolate counter-anions: the critical role of binding stability and lipophilicity of the ion-pairing complexes. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Chao X-J, Tang M, Huang R, Huang C-H, Shao J, Yan Z-Y, Zhu B-Z |
Journal | Nucleic Acids Res |
Volume | 47 |
Issue | 20 |
Pagination | 10520-10528 |
Date Published | 2019 11 18 |
ISSN | 1362-4962 |
Keywords | Cell Nucleus, Chlorophenols, DNA, Gene Transfer Techniques, HeLa Cells, Humans, Hydrophobic and Hydrophilic Interactions, Ruthenium |
Abstract | We have found recently that nuclear uptake of the cell-impermeable DNA light-switching Ru(II)-polypyridyl cationic complexes such as [Ru(bpy)2(dppz)]Cl2 was remarkably enhanced by pentachlorophenol (PCP), by forming ion-pairing complexes via a passive diffusion mechanism. However, it is not clear whether the enhanced nuclear uptake of [Ru(bpy)2(dppz)]2+ is only limited to PCP, or it is a general phenomenon for other highly chlorinated phenols (HCPs); and if so, what are the major physicochemical factors in determining nuclear uptake? Here, we found that the nuclear uptake of [Ru(bpy)2(dppz)]2+ can also be facilitated by other two groups of HCPs including three tetrachlorophenol (TeCP) and six trichlorophenol (TCP) isomers. Interestingly and unexpectedly, 2,3,4,5-TeCP was found to be the most effective one for nuclear delivery of [Ru(bpy)2(dppz)]2+, which is even better than the most-highly chlorinated PCP, and much better than its two other TeCP isomers. Further studies showed that the nuclear uptake of [Ru(bpy)2(dppz)]2+ was positively correlated with the binding stability, but to our surprise, inversely correlated with the lipophilicity of the ion-pairing complexes formed between [Ru(bpy)2(dppz)]Cl2 and HCPs. These findings should provide new perspectives for future investigations on using ion-pairing as an effective method for delivering other bio-active metal complexes into their intended cellular targets. |
DOI | 10.1093/nar/gkz152 |
PubMed ID | 31584083 |
PubMed Central ID | PMC6847114 |