Strained, Photoejecting Ru(II) Complexes That Are Cytotoxic Under Hypoxic Conditions

Overview

Journal Photochem Photobiol

Specialties Biochemistry
Biology
Chemistry

Date 2019 Nov 7

PMID 31691282

Citations 26

Authors

John Roque 3rd

Dmytro Havrylyuk

Patrick C Barrett

Tariq Sainuddin

Julia McCain

Katsuya Colon

William T Sparks

Evan Bradner

Susan Monro

David Heidary

Colin G Cameron

Edith C Glazer

Sherri A McFarland

Affiliations

Soon will be listed here.

Abstract

A series of strained Ru(II) complexes were studied for potential anticancer activity in hypoxic tissues. The complexes were constructed with methylated ligands that were photolabile and an imidizo[4,5-f][1,10]phenanthroline ligand that contained an appended aromatic group to potentially allow for contributions of ligand-centered excited states. A systematic variation of the size and energy of the aromatic group was performed using systems containing 1-4 fused rings, and the photochemical and photobiological behaviors of all complexes were assessed. The structure and nature of the aromatic group had a subtle impact on photochemistry, altering environmental sensitivity, and had a significant impact on cellular cytotoxicity and photobiology. Up to 5-fold differences in cytotoxicity were observed in the absence of light activation; this rose to 50-fold differences upon exposure to 453 nm light. Most significantly, one complex retained activity under conditions with 1% O , which is used to induce hypoxic changes. This system exhibited a photocytotoxicity index (PI) of 15, which is in marked contrast to most other Ru(II) complexes, including those designed for O -independent mechanisms of action.

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