Issue 44, 2020

Bis[pyrrolyl Ru(ii)] triads: a new class of photosensitizers for metal–organic photodynamic therapy

Abstract

A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)2 centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (ε) ≥ 104 at 600–620 nm and longer. Phosphorescence quantum yields (Φp) were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields (ΦΔ) ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC50 values in the range of 10–100 μM and phototherapeutic indices (PIs) as large as 5400 and 260 with broadband visible (28 J cm−2, 7.8 mW cm−2) and 625 nm red (100 J cm−2, 42 mW cm−2) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC50 value of 1 nM and PI > 27 000 with visible light and subnanomolar activity with 625 nm light (100 J cm−2, 28 mW cm−2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxicity in this more resistant model (EC50 = 60 nM and PI > 1200 with 625 nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC50 values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625 nm red light, but PIs were still near 50. The ligand-localized 3ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.

Graphical abstract: Bis[pyrrolyl Ru(ii)] triads: a new class of photosensitizers for metal–organic photodynamic therapy

Supplementary files

Article information

Article type
Edge Article
Submitted
15 8 2020
Accepted
06 10 2020
First published
06 10 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2020,11, 12047-12069

Bis[pyrrolyl Ru(II)] triads: a new class of photosensitizers for metal–organic photodynamic therapy

D. A. Smithen, S. Monro, M. Pinto, J. Roque, R. M. Diaz-Rodriguez, H. Yin, C. G. Cameron, A. Thompson and S. A. McFarland, Chem. Sci., 2020, 11, 12047 DOI: 10.1039/D0SC04500D

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