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

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 O-2-dependent mechanism by producing highly reactive species such as O-1(2) and/or an O-2 independent mechanism through processes such as excited state electron transfer, covalent binding to DNA or photoinduced drug delivery. Ru(II)-polypyridyl and Rh-2(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 O-1(2) production or guanine oxidation by the excited state of the chromophore. Photoinduced ligand substitution occurs through the population of triplet metal centered ((MC)-M-3) 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. (C) 2014 Elsevier B.V. All rights reserved.