English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Dinuclear metal complexes have emerged as a promising class of biologically active compounds which possess unique anticancer activity. Here, we describe a novel series of arene-linked dinuclear organometallic Ru(II) complexes, where the relative conformation of the ruthenium centres is controlled by the stereochemical configuration of 1,2-diphenylethylenediamine linker moieties, as confirmed by X-ray crystallography. The reactivity and cytotoxicity of these compounds is compared to flexible dinuclear and mononuclear analogues, demonstrating in all cases the complexes can undergo aquation, coordinate to typical biological donor ligands and importantly, in the case of dinuclear analogues, crosslink oligonucleotide and peptide sequences. Differences in the conformation of the isomeric dinuclear compounds lead to significantly different levels of cytotoxicity against A2780, A2780cisR and HEK-293 cell lines; isomers with a closed conformation are significantly more cytotoxic than isomers with a more open conformation and they are also significantly less susceptible to acquired resistance mechanisms operating in the A2780cisR cell line. These rigid dinuclear compounds possess markedly increased cytotoxicity relative to the non-cytotoxic mononuclear analogues that does not appear to be related to differences in complex lipophilicity or cellular uptake, which, in general, remain similar in magnitude across the series. Thus, the molecular conformation of such dinuclear species may be crucial in determining the nature of the adducts formed on coordination to biological targets in a cellular environment, and opens up a novel route toward the development of more active metal-based anticancer agents.

Conformational control of anticancer activity: the application of arene-linked dinuclear ruthenium(ii) organometallics