Ru(II), Os(II), and Rh<sub>2</sub>(II,II) Complexes as Potential Photodynamic Therapy Agents

Ru(II), Os(II), and Rh<sub>2</sub>(II,II) Complexes as Potential Photodynamic Therapy Agents

Bibliographic Details
Main Author: Joyce, Lauren Elizabeth
Language:English
Published: The Ohio State University / OhioLINK 2010
Subjects:
Chemistry
Photodynamic Therapy
ruthenium
rhodium
osmium
singlet oxygen
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1291176129
id ndltd-OhioLink-oai-etd.ohiolink.edu-osu1291176129
record_format oai_dc
collection NDLTD
language English
sources NDLTD
topic Chemistry
Photodynamic Therapy
ruthenium
rhodium
osmium
singlet oxygen
spellingShingle Chemistry
Photodynamic Therapy
ruthenium
rhodium
osmium
singlet oxygen
Joyce, Lauren Elizabeth
Ru(II), Os(II), and Rh<sub>2</sub>(II,II) Complexes as Potential Photodynamic Therapy Agents
author Joyce, Lauren Elizabeth
author_facet Joyce, Lauren Elizabeth
author_sort Joyce, Lauren Elizabeth
title Ru(II), Os(II), and Rh<sub>2</sub>(II,II) Complexes as Potential Photodynamic Therapy Agents
title_short Ru(II), Os(II), and Rh<sub>2</sub>(II,II) Complexes as Potential Photodynamic Therapy Agents
title_full Ru(II), Os(II), and Rh<sub>2</sub>(II,II) Complexes as Potential Photodynamic Therapy Agents
title_fullStr Ru(II), Os(II), and Rh<sub>2</sub>(II,II) Complexes as Potential Photodynamic Therapy Agents
title_full_unstemmed Ru(II), Os(II), and Rh<sub>2</sub>(II,II) Complexes as Potential Photodynamic Therapy Agents
title_sort ru(ii), os(ii), and rh<sub>2</sub>(ii,ii) complexes as potential photodynamic therapy agents
publisher The Ohio State University / OhioLINK
publishDate 2010
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1291176129
work_keys_str_mv AT joycelaurenelizabeth ruiiosiiandrhsub2subiiiicomplexesaspotentialphotodynamictherapyagents
_version_ 1719429498575781888
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu12911761292021-08-03T06:01:01Z Ru(II), Os(II), and Rh<sub>2</sub>(II,II) Complexes as Potential Photodynamic Therapy Agents Joyce, Lauren Elizabeth Chemistry Photodynamic Therapy ruthenium rhodium osmium singlet oxygen <p>Photodynamic therapy (PDT) is a cancer therapy that operates with greater selectivity than conventional chemotherapy by the combination of a photosensitizer and visible light irradiation. Localization of irradiation allows for specificity by selectively activating the photosensitizer in the tissue of interest, while leaving healthy cells undamaged. However, PDT drawbacks remain and in this document the photophysical properties and DNA interactions of dirhodium, ruthenium, and osmium complexes are investigated for their abilities to address some of the shortcomings of current cancer photochemotherapies.</p> <p>A series of dirhodium(II,II) complexes of the type cis-[Rh<sub>2</sub>(μ-O<sub>2</sub>CCH<sub>3</sub>)<sub>2</sub>(dppn)(L)]<sup>2+</sup>, where dppn = benzo[i]dipyrido-[3,2-a:2′,3′-h]quinoxaline and L = 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-f:2′3′-h]quinoxaline (dpq), dipyrido[3,2-a:2′,3′-c]phenazine (dppz), and dppn, was synthesized and its photophysical properties investigated. The ability of the complexes to bind and photocleave DNA was also probed, along with their toxicity and photocytotoxicity toward human skin cells. Nanosecond time-resolved absorption measurements established that the lowest energy excited state in the series is dppn-localized <sup>3</sup>ππ* in DMSO. All complexes except the bis-dppn complex photocleave DNA efficiently via a mechanism that is mostly mediated by reactive oxygen species. The DNA photocleavage by the bis-dppn complex is significantly lower than that measured for the others, however, it exhibits the largest increase between toxicity and photocytotoxicity within the series.</p> <p>A discussion of three new complexes [Ru(bpy)<sub>2</sub>(dpqp)]<sup>2+</sup> (dpqp = pyrazino[2′,3′:5,6]pyrazino-[2,3-f][1,10]phenanthroline), [Ru(bpy)<sub>2</sub>(dppn)]<sup>2+</sup>, and [Os(bpy)<sub>2</sub>(dppn)]<sup>2+</sup> is also presented. These complexes provide improvement to current PDT shortcomings by utilizing longer lifetimes, dual mechanisms of reactivity, and longer wavelengths of absorption, respectively. [Ru(bpy)<sub>2</sub>(dpqp)]<sup>2+</sup> exhibits strong luminescence in water at room temperature, a striking deviation from that of the related non-emissive “DNA light-switch” prototype [Ru(bpy)<sub>2</sub>(dppz)]<sup>2+</sup> under similar conditions. The combination of its strong DNA binding affinity and relatively long-lived triplet metal-to-ligand charge-transfer (<sup>3</sup>MLCT) excited state in water results in more efficient DNA photocleavage by [Ru(bpy)<sub>2</sub>(dpqp)]<sup>2+</sup> than [Ru(bpy)<sub>2</sub>(dppz)]<sup>2+</sup>. Irradiation of [Ru(bpy)<sub>2</sub>(dppn)]<sup>2+</sup> with visible light results in nearly complete DNA cleavage within 30 s (L<sub>irr</sub> ≥ 455 nm), likely from the combination of guanine oxidation from the <sup>3</sup>MLCT state and photoproduction of <sup>1</sup>O<sub>2</sub> from population of the <sup>3</sup>ππ*. [Os(bpy)<sub>2</sub>(dppn)]<sup>2+</sup> generates <sup>1</sup>O<sub>2</sub> with a quantum yield of 0.42 upon irradiation from its low-lying <sup>3</sup>ππ* excited state, which results in efficient DNA cleavage with irradiation L<sub>irr</sub> ≥ 645 nm.</p><p>The new complexes cis-[Rh<sub>2</sub>(μ-O<sub>2</sub>CCH<sub>3</sub>)<sub>2</sub>(C<sub>6</sub>H<sub>5</sub>CN)<sub>4</sub><sup>2+</sup>] and cis-[Rh<sub>2</sub>(μ-O<sub>2</sub>CCH<sub>3</sub>)<sub>2</sub>(4F-C<sub>6</sub>H<sub>5</sub>CN)<sub>4</sub><sup>2+</sup>] were synthesized and studied as potential photo-cisplatin analogs. Theoretical calculations were performed to assist in the understanding of the electronic structures of the complexes. Both complexes were inert to ligand exchange in the dark in H<sub>2</sub>O, CH<sub>3</sub>CN, and CH<sub>2</sub>Cl<sub>2</sub>. cis-[Rh<sub>2</sub>(μ-O<sub>2</sub>CCH<sub>3</sub>)<sub>2</sub>(4F-C<sub>6</sub>H<sub>5</sub>CN)<sub>4</sub><sup>2+</sup>], however, showed photosubstitution of its four equatorial 4F-C<sub>6</sub>H<sub>5</sub>CN ligands for CH<sub>3</sub>CN with L<sub>irr</sub> ≥ 455 nm in 25 min, whereas t<sub>irr</sub> > 2 hr was required for cis-[Rh<sub>2</sub>(μ-O<sub>2</sub>CCH<sub>3</sub>)<sub>2</sub>(C<sub>6</sub>H<sub>5</sub>CN)<sub>4</sub><sup>2+</sup>]. The photosubstitution of the complexes with H<sub>2</sub>O was also investigated to assess their biological viability. Both complexes exhibit reduced ligand substitution in water due to their hydrophobicity and the π-stacking of the benzonitrile ligands. The photoinduced DNA binding of cis-[Rh<sub>2</sub>(μ-O<sub>2</sub>CCH<sub>3</sub>)<sub>2</sub>(C<sub>6</sub>H<sub>5</sub>CN)<sub>4</sub><sup>2+</sup>] was investigated by gel electrophoresis and compared to cis-[Rh<sub>2</sub>(μ-O<sub>2</sub>CCH<sub>3</sub>)<sub>2</sub>(CH<sub>3</sub>CN)<sub>6</sub><sup>2+</sup>], a complex known to covalently bind DNA upon irradiation.</p> 2010-12-17 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1291176129 http://rave.ohiolink.edu/etdc/view?acc_num=osu1291176129 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

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