Control and utilization of ruthenium and rhodium metal complex excited states for photoactivated cancer therapy

Abstract

The use of visible light to produce highly selective and potent drugs through photodynamic therapy (PDT) holds much potential in the treatment of cancer. PDT agents can be designed to follow an O2-dependent mechanism by producing highly reactive species such as 1O2 and/or an O2 independent mechanism through processes such as excited state electron transfer, covalent binding to DNA or photoinduced drug delivery. Ru(II)-polypyridyl and Rh2(II,II) complexes represent an important class of compounds that can be tailored to exhibit desired photophysical properties and photochemical reactivity by judicious selection of the ligand set. Complexes with relatively long-lived excited states and planar, intercalating ligands localize on the DNA strand and photocleave DNA through 1O2 production or guanine oxidation by the excited state of the chromophore. Photoinduced ligand substitution occurs through the population of triplet metal centered (3MC) excited states and facilitates covalent binding of the metal complex to DNA in a mode similar to cisplatin. Ligand photodissociation also provides a route to selective drug delivery. The ability to construct metal complexes with desired light absorbing and excited state properties by ligand variation enables the design of PDT agents that can potentially provide combination therapy from a single metal complex.

Ruthenium(II) bipyridine complexes with pendant anthracenyl and naphthyl moieties: A strategy for a ROS generator with DNA binding selectivity

“…Barton and colleagues have made important contributions to this field, while a series of ruthenium-based DNA-binding compounds, including sequence selective, were developed as electrochemical sensors and tools for investigation of electron transfer process in DNA [4,5]. Turro's lab has also investigated metal-based compounds with potential therapeutic applications based on their DNA binding and photocleavage activities, including ruthenium polypyridines [6,7]. The photogeneration of reactive oxygen species (ROS) has been a valuable tool for studies on cellular biology as well as for therapy such as in chromophore-assisted laser inactivation (CALI) and photodynamic therapy (PDT).…”

Evaluation of Perylene Bisimide‐Based RuII and IrIII Complexes as Photosensitizers for Photodynamic Therapy

“…[13][14][15] In the last years, our groups focused attention in the development of new Ru II -based PSs for PDT, antibacterial PDT (aPDT) and photoactivated chemotherapy (PACT). [16][17][18][19][20][21][22][23][24][25][26] Besides ruthenium, [27][28][29][30][31][32] other metals, such as iridium(III), rhenium(I), [33][34][35][36][37][38] Fe III , [39] Co III , [40] and Gd III [41] have been investigated by us and other groups in regard to traditional chemotherapy and PDT applications. [42][43][44][45] Compared with the Ru complexes, less effective PDT agents based on Ir compounds have been reported so far, probably because of the difficulties in suppressing the competing electron-transfer processes.…”

Engineering Tunable Single and Dual Optical Emission from Ru(II)–Polypyridyl Complexes through Excited State Design

“…3 These complexes possess intriguing excited state properties and are powerful structural motifs 4 in the design of advanced optical materials for dye sensitized solar cells, [5][6][7] light-emitting electrochemical cells, 8 lightemitting diodes, 9 and non-linear optics. 10 Furthermore, Ru-polypyridyl complexes have also been used as anti-tumor agents, 11,12 in artificial photosynthesis 13 and as molecular switches and machines. [14][15][16][17] The wide range of Ru-polypyridyl complexes invokes an enormous amount of fundamental and experimental studies and the interest to the optical properties of these compounds still continues to increase.…”