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The Application of Reversible Intramolecular Sulfonamide Ligation to Modulate Reactivity in Organometallic Ruthenium(II) Diamine Complexes

Kemp, Samuel A; Prior, Timothy J.; Savoie, Huguette; Boyle, Ross W.; Murray, Benjamin S.

Authors

Samuel A Kemp

Huguette Savoie h.savoie@hull.ac.ukh.s.



Abstract

Metallation of biomacromolecular species forms the basis for the anticancer activity of many metallodrugs. A major limitation of these compounds is that their reactivity is indiscriminate and can, in principle, occur in healthy tissue as well as cancerous tissue, potentially leading to side effects in vivo. Here we present pH-dependent intramolecular coordination of an arene-tethered sulfonamide functionality in organometallic ruthenium(II) ethylenediamine complexes as a route to controlling the coordination environment about the central metal atom. Through variation of the sulfonamide R group and the length of the tether linking it to the arene ligand the acidity of the sulfonamide NH group, and hence the pH-region over which regulation of metal coordination occurs, can be modulated. Intramolecular sulfonamide ligation controlled the reactivity of complex 4 within the physiologically relevant pH-region, rendering it more reactive towards 5ʹ-GMP in mildly acidic pH-conditions typical of tumour tissue compared to the mildly alkaline pH-conditions typical of healthy tissue. However, the activation of 4 by ring-opening of the chelate was found to be a slow process relative to the timescale of typical cell culture assays and members of this series of complexes were found not to be cytotoxic towards the HT-29 cell line. These complexes provide the basis for the development of analogues of increased potency where intramolecular sulfonamide ligation regulates reactivity and therefore cytotoxicity in a pH-dependent, and potentially, tissue-dependent manner.

Journal Article Type Article
Publication Date Jan 2, 2020
Journal Molecules
Electronic ISSN 1420-3049
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 25
Issue 2
Article Number 244
Pages 244
APA6 Citation Kemp, S. A., Kemp, S. A., Prior, T. J., Savoie, H., Boyle, R. W., & Murray, B. S. (2020). The Application of Reversible Intramolecular Sulfonamide Ligation to Modulate Reactivity in Organometallic Ruthenium(II) Diamine Complexes. Molecules, 25(2), 244. https://doi.org/10.3390/molecules25020244
DOI https://doi.org/10.3390/molecules25020244
Keywords Metallodrugs; Bioorganometallic chemistry; Ruthenium; Cancer; Sulfonamide
Publisher URL https://doi.org/10.3390/molecules25020244

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Copyright Statement
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).





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