Glover, Caroline, Fairbanks, Simon, Robertson, Craig C., Keene, Richard, Green, Nicola H., and Thomas, Jim A. (2025) An optical ratiometric approach using enantiopure luminescent metal complexes indicates changes in the average quadruplex DNA content as primary cells undergo multiple divisions. Dalton Transactions, 54. 8241. pp. 8241-8250.

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Abstract

The three stereoisomers of a previously reported dinuclear ruthenium(II) complex have been quantitatively separated using cation-exchange chromatography and the individual crystal structures of the racemic pair are reported. Cell-based studies on the three stereoisomers disclosed differences in the rate of uptake ofbthe two chiral forms of the rac diastereoisomer with the ΛΛ-enantiomer being taken up noticeably more rapidly than the ΔΔ-form. Cell viability studies reveal that the three cations show identical cytotoxicity over 24 hours, but over more extended exposure periods, the meso-ΔΛ stereoisomer becomes slightly less active. More significantly, microscopy studies revealed that although both isomers display a near infra-red “light-switch” effect associated with binding to duplex DNA on binding to chromatin in live MCF7 and L5178-R cells, only the ΛΛ enantiomer displays a distinctive, blue-shifted component associated with binding to quadruplex DNA. An analysis of the ratio of “quadruplex emission” compared to “duplex emission” for the ΛΛ-enantiomer indicated that there was a decrease in the average quadruplex DNA content within live primary cells as they undergo multiple cell divisions.

Item ID:	85545
Item Type:	Article (Research - C1)
ISSN:	1477-9234
Keywords:	quadruplex DNA; telomere; dinuclear ruthenium complex' luminiscence; light-switch effect; enantioselectivity
Copyright Information:	© The Royal Society of Chemistry 2025. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.
Date Deposited:	20 May 2025 21:29
FoR Codes:	31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310102 Cell development, proliferation and death @ 30% 34 CHEMICAL SCIENCES > 3402 Inorganic chemistry > 340201 Bioinorganic chemistry @ 50% 34 CHEMICAL SCIENCES > 3402 Inorganic chemistry > 340211 Transition metal chemistry @ 20%
SEO Codes:	28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 40% 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280105 Expanding knowledge in the chemical sciences @ 60%
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