Ru(II) Polypyridyl Complexes Derived from Tetradentate Ancillary Ligands for Effective Photocaging

Abstract

CONSPECTUS Metal complexes have many proven applications in the caging and photochemical release of biologically active compounds. Photocaging groups derived from Ru(II) traditionally have been composed of ancillary ligands that are planar and bi- or tridentate, such as 2,2′-bipyridine (bpy), 2,2′:6′,2″-terpyridine (tpy), and 1,10-phenanthroline (phen). Complexes bearing ancillary ligands with denticities higher than three represent a new class of Ru(II)-based photocaging groups that are grossly underdeveloped. Because high-denticity ancillary ligands provide the ability to increase the structural rigidity and control the stereochemistry, our groups initiated a research program to explore the applications of such ligands in Ru(II)-based photocaging. Ru(TPA), bearing the tetradentate ancillary ligand tris(2-pyridylmethyl)amine (TPA), has been successfully utilized to effectively cage nitriles and aromatic heterocycles. Nitriles and aromatic heterocycles caged by the Ru(TPA) group show excellent stability in aqueous solutions in the dark, and the complexes can selectively release the caged molecules upon irradiation with light. Ru(TPA) is applicable as a photochemical agent to offer precise spatiotemporal control over biological activity without undesired toxicity. In addition, Ru(II) polypyridyl complexes with desired photochemical properties can be synthesized and identified by solid-phase synthesis, and the resulting complexes show properties to similar to those of complexes obtained by solution-phase synthesis. Density functional theory (DFT) calculations reveal that orbital mixing between the π* orbitals of the ancillary ligand and the Ru−N dσ* orbital is essential for ligand photodissociation in these complexes. Furthermore, the introduction of steric bulk enhances the photoliability of the caged molecules, validating that steric effects can largely influence the quantum efficiency of photoinduced ligand exchange in Ru(II) polypyridyl complexes. Recently, two new photocaging groups, Ru(cyTPA) and Ru(1-isocyTPQA), have been designed and synthesized for caging of nitriles and aromatic heterocycles, and these complexes exhibit unique photochemical properties distinct from those derived from Ru(TPA). Notably, the unusually greater quantum efficiency for the ligand exchange in [Ru(1-isocyTPQA)(MeCN)2](PF6)2, Φ400 = 0.033(3), uncovers a trans-type effect in the triplet metal-to-ligand charge transfer (3MLCT) state that enhances photoinduced ligand exchange in a new manner. DFT calculations and ultrafast transient spectroscopy reveal that the lowest-energy triplet state in [Ru(1-isocyTPQA)(MeCN)2](PF6)2 is a highly mixed 3MLCT/3ππ* excited state rather than a triplet metal-centered ligand-field (3LF) excited state; the latter is generally accepted for ligand photodissociation. In addition, Mulliken spin density calculations indicate that a majority of the spin density in [Ru(1-isocyTPQA)(MeCN)2](PF6)2 is localized on the isoquinoline arm, which is opposite to the cis MeCN, rather than on the ruthenium center. This ...

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials

“… 966 The long-lived triplet state 3 MLCT can be deactivated by radiative, non-radiative, and electron transfer pathways or be thermally activated to give a low-lying triplet ligand-field state ( 3 LF) with an Ru–ligand antibonding character that can lead to ligand release. 70 , 72 , 969 − 971 A relationship between the π-accepting ability of the ligands and the photosubstitution efficiency has been demonstrated. 972 − 975 In the triplet state, this complex is an efficient oxygen sensitizer.…”

Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy

“…To overcome these limitations, there is a need for the development of new classes of PSs. Among others, the use of transition metal complexes [6][7][8][9][10][11] and especially, Ru(II) polypyridine complexes are gaining momentum due to their attractive photophysical and chemical properties (i.e., strong luminescence, high singlet oxygen production, high chemical, and photophysical stability) [12][13][14][15][16][17][18][19][20][21][22] , with the compound TLD-1433 having just entered phase II clinical trials for the treatment of non-muscle invasive bladder cancer [23][24][25] . Despite these remarkable properties, the vast majority of Ru(II) polypyridine complexes are excited using either blue or UV-A light.…”

Ruthenium Complexes for 1- and 2-Photon Photodynamic Therapy: From In Silico Prediction to In Vivo Applications

“…[3][4][5] To overcome these limitations, there is a need for the development of new classes of PSs. Among others, the use of transition metal complexes [6][7][8][9][10][11] and especially, Ru(II) polypyridine complexes are gaining momentum due to their attractive photophysical and chemical properties (i.e., strong luminescence, high singlet oxygen production, high chemical and photophysical stability), [12][13][14][15][16][17][18][19][20][21][22] with the compound TLD-1433 having just entered phase II clinical trials for the treatment of non-muscle invasive bladder cancer. [23][24][25] Despite these remarkable properties, the vast majority of Ru(II) polypyridine complexes are excited using either blue or UV-A light.…”