Strained ruthenium metal–organic dyads as photocisplatin agents with dual action

Strained ruthenium metal–organic dyads as photocisplatin agents with dual action Three strained Ru(II) metal–organic dyads were prepared and characterized by NMR, mass spectrometry, and analytical HPLC to probe whether these constructs could act as multifunctional photochemotherapy (PCT) agents. The compounds incorporated the crowded 6,6′-dimethyl-2,2′-bipyridine (6,6′-dmb) ligand to impart stoichiometric photocisplatin activity, and imidazo[4,5-f] [1,10]phenanthroline (IP) appended with n thiophene units (nT; n=1–3) to add capacity for singlet oxygen sensitization. With visible light activation, each complex of the series underwent rapid and selective photoejection of 6,6′-dmb in less than 10min, with half-lives (t1/2) as short as 46.3s for [Ru(6,6′-dmb)2(IP–1T)]2+. Photo-triggered ligand loss slowed with increasing n, and was slowest for [Ru(6,6′-dmb)2(IP–3T)]2+ (t1/2=273s). This trend also held for photoadduct formation with DNA; [Ru(6,6′-dmb)2(IP–1T)]2+ produced relaxed circular DNA at the lowest concentrations. Singlet oxygen yields (ΦΔ) increased with n, whereby ΦΔ for [Ru(6,6′-dmb)2(IP–1T)]2+ was only 3%, but increased to 42% on going to [Ru(6,6′-dmb)2(IP–3T)]2+. This photosensitization process was reflected by single-strand breaks in the gel-mobility shift assays of [Ru(6,6′-dmb)2(IP–3T)]2+, but was not discernible for the other compounds. Despite different photochemical and photophysical reactivities, all of the compounds were potent phototoxic agents toward cancer cells (EC50=1–2μM) with relatively short compound-to-light intervals and moderate visible light doses. [Ru(6,6′-dmb)2(IP–3T)]2+ was exceptionally photoactive toward cancer cells at longer intervals (EC50=200nM, PI=750). Phototherapeutic margins increased with n due to decreased dark cytotoxicity for the more π-expansive complexes, making metal–organic dyad [Ru(6,6′-dmb)2(IP–3T)]2+ the best multifunctional PCT agent. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Inorganic Biochemistry Elsevier

Strained ruthenium metal–organic dyads as photocisplatin agents with dual action

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Publisher
Elsevier
Copyright
Copyright © 2016 Elsevier Inc.
ISSN
0162-0134
eISSN
1873-3344
D.O.I.
10.1016/j.jinorgbio.2016.01.009
Publisher site
See Article on Publisher Site

Abstract

Three strained Ru(II) metal–organic dyads were prepared and characterized by NMR, mass spectrometry, and analytical HPLC to probe whether these constructs could act as multifunctional photochemotherapy (PCT) agents. The compounds incorporated the crowded 6,6′-dimethyl-2,2′-bipyridine (6,6′-dmb) ligand to impart stoichiometric photocisplatin activity, and imidazo[4,5-f] [1,10]phenanthroline (IP) appended with n thiophene units (nT; n=1–3) to add capacity for singlet oxygen sensitization. With visible light activation, each complex of the series underwent rapid and selective photoejection of 6,6′-dmb in less than 10min, with half-lives (t1/2) as short as 46.3s for [Ru(6,6′-dmb)2(IP–1T)]2+. Photo-triggered ligand loss slowed with increasing n, and was slowest for [Ru(6,6′-dmb)2(IP–3T)]2+ (t1/2=273s). This trend also held for photoadduct formation with DNA; [Ru(6,6′-dmb)2(IP–1T)]2+ produced relaxed circular DNA at the lowest concentrations. Singlet oxygen yields (ΦΔ) increased with n, whereby ΦΔ for [Ru(6,6′-dmb)2(IP–1T)]2+ was only 3%, but increased to 42% on going to [Ru(6,6′-dmb)2(IP–3T)]2+. This photosensitization process was reflected by single-strand breaks in the gel-mobility shift assays of [Ru(6,6′-dmb)2(IP–3T)]2+, but was not discernible for the other compounds. Despite different photochemical and photophysical reactivities, all of the compounds were potent phototoxic agents toward cancer cells (EC50=1–2μM) with relatively short compound-to-light intervals and moderate visible light doses. [Ru(6,6′-dmb)2(IP–3T)]2+ was exceptionally photoactive toward cancer cells at longer intervals (EC50=200nM, PI=750). Phototherapeutic margins increased with n due to decreased dark cytotoxicity for the more π-expansive complexes, making metal–organic dyad [Ru(6,6′-dmb)2(IP–3T)]2+ the best multifunctional PCT agent.

Journal

Journal of Inorganic BiochemistryElsevier

Published: May 1, 2016

References

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