Light‐responsive and Protic Ruthenium Compounds Bearing Bathophenanthroline and Dihydroxybipyridine Ligands Achieve Nanomolar Toxicity towards Breast Cancer Cells. (13th November 2021)

• Record Type: Journal Article
• Authors: Oladipupo, Olaitan E.; Brown, Spenser R.; Lamb, Robert W.; Gray, Jessica L.; Cameron, Colin G.; DeRegnaucourt, Alexa R.; Ward, Nicholas A.; Hall, James Fletcher; Xu, Yifei; Petersen, Courtney M.; Qu, Fengrui; Shrestha, Ambar B.; Thompson, Matthew K.; Bonizzoni, Marco; Webster, Charles Edwin; McFarland, Sherri A.; Kim, Yonghyun; Papish, Elizabeth T.
• Is Part Of: Photochemistry and photobiology. Volume 98:Number 1(2022)
• Page Start: 102
• Page End: 116
• Publication Date: 2021-11-13
• Subjects: Photochemistry -- Periodicals; Light -- Physiological effect -- Periodicals; 541.35
• DOI: 10.1111/php.13508
• Languages: English
• ISSNs: 0031-8655

Abstract

ABSTRACT: We report new ruthenium complexes bearing the lipophilic bathophenanthroline (BPhen) ligand and dihydroxybipyridine (dhbp) ligands which differ in the placement of the OH groups ([(BPhen)2 Ru(n, n′‐dhbp)]Cl2 with n = 6 and 4 in 1A and 2A, respectively). Full characterization data are reported for 1A and 2A and single crystal X‐ray diffraction for 1A . Both 1A and 2A are diprotic acids. We have studied 1A, 1B, 2A, and 2B (B = deprotonated forms) by UV‐vis spectroscopy and 1 photodissociates, but 2 is light stable. Luminescence studies reveal that the basic forms have lower energy 3 MLCT states relative to the acidic forms. Complexes 1A and 2A produce singlet oxygen with quantum yields of 0.05 and 0.68, respectively, in acetonitrile. Complexes 1 and 2 are both photocytotoxic toward breast cancer cells, with complex 2 showing EC50 light values as low as 0.50 μM with PI values as high as >200 vs . MCF7. Computational studies were used to predict the energies of the 3 MLCT and 3 MC states. An inaccessible 3 MC state for 2B suggests a rationale for why photodissociation does not occur with the 4, 4′‐dhbp ligand. Low dark toxicity combined with an accessible 3 MLCT state for 1 O2 generation explains the excellent photocytotoxicity of 2. Abstract : This fundamental study explores the impact of protic OH groups on the bpy ligand in ruthenium complexes for visible light triggered toxicity towards cancerous cells. The OH groups are deprotonated under physiological conditions and allow for improved light driven toxicity when they are placed further from the metal center via the 4, 4′‐dhbp ligand (dhbp = dihydroxybipyridine). Furthermore, lipophilic bathophenanthroline ligands are critical for improving the cellular uptake and toxicity of these ruthenium complexes. Herein, spectroscopy and computational studies are used to understand how both the placement and protonation state of the OH groups influence the photochemistry and the cellular toxicity.