J 2024

New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes

ČERVINKA, Jakub, Alba HERNÁNDEZ-GARCÍA, Delia BAUTISTA, Lenka MARKOVÁ, Hana KOSTRHUNOVÁ et. al.

Basic information

Original name

New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes

Authors

ČERVINKA, Jakub (203 Czech Republic, belonging to the institution), Alba HERNÁNDEZ-GARCÍA (724 Spain), Delia BAUTISTA (724 Spain), Lenka MARKOVÁ (203 Czech Republic, belonging to the institution), Hana KOSTRHUNOVÁ (203 Czech Republic, belonging to the institution), Jaroslav MALINA (203 Czech Republic), Jana KAŠPÁRKOVÁ (203 Czech Republic, belonging to the institution), M Dolores SANTANA (724 Spain), Viktor BRABEC (203 Czech Republic, belonging to the institution) and José RUIZ (756 Switzerland)

Edition

INORGANIC CHEMISTRY FRONTIERS, ENGLAND, ROYAL SOC CHEMISTRY, 2024, 2052-1553

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 7.000 in 2022

Organization unit

Faculty of Science

DOI

Keywords in English

metallodrugs; oncosis; anticancer therapy

Tags

International impact, Reviewed
Změněno: 27/5/2024 16:03, Mgr. Jakub Červinka

Abstract

V originále

A new generation series of cyclometalated Ru(II) polypyridyl complexes of the type [Ru(C^N)(N^N)2]+, Ru1–Ru4, were rationally designed and synthesized, where N^N = 2,2′-bipyridine (bpy) and dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq) and C^N = deprotonated methyl 1-butyl-2-aryl-benzimidazolecarboxylate with p-CF3C6H4 or p-Me2NC6H4 substituents in the R3 position of the phenyl ring. The photophysical properties of Ru1–Ru4 revealed absorption maxima around 560 nm with an absorption up to 700 nm. The new Ru complexes were able to generate singlet oxygen (1O2) upon green light irradiation in acetonitrile, with complexes containing the CF3 group, Ru1 and Ru3, being the best performers. Furthermore, Ru1 and Ru3 were also able to photogenerate hydroxyl radicals OH˙. By having PSs capable of undergoing both type I and type II mechanisms, a broader range of cytotoxic effects is achieved. Ru1–Ru4 accumulated in membrane-rich compartments, including the cytoplasmic membrane, mitochondria, and endoplasmic reticulum in HeLa cells. Upon irradiation of Ru1 with green light, all these compartments were damaged in treated cells. Based on in vitro experiments, we deduced that the compound Ru1 under irradiation has the capability to disrupt phospholipid membranes directly. Additionally, differential scanning calorimetry of living cells also indicated damage of cytoplasmic/membrane proteins, ultimately leading to cell death via oncosis.