π-Expansive Heteroleptic Ruthenium(II) Complexes as Reverse Saturable Absorbers and Photosensitizers for Photodynamic Therapy

Abstract

Five heteroleptic tris-diimine ruthenium(II) complexes [RuL(N^N)](PF) (where L is 3,8-di(benzothiazolylfluorenyl)-1,10-phenanthroline and N^N is 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), 1,4,8,9-tetraazatriphenylene (tatp) (3), dipyrido[3,2-a:2',3'-c]phenazine (dppz) (4), or benzo[i]dipyrido[3,2-a:2',3'-c]phenazine (dppn) (5), respectively) were synthesized. The influence of π-conjugation of the ancillary ligands (N^N) on the photophysical properties of the complexes was investigated by spectroscopic methods and simulated by density functional theory (DFT) and time-dependent DFT. Their ground-state absorption spectra were characterized by intense absorption bands below 350 nm (ligand L localized π,π* transitions) and a featureless band centered at ∼410 nm (intraligand charge transfer (ILCT)/π,π* transitions with minor contribution from metal-to-ligand charge transfer (MLCT) transition). For complexes 4 and 5 with dppz and dppn ligands, respectively, broad but very weak absorption (ε < 800 M cm) was present from 600 to 850 nm, likely emanating from the spin-forbidden transitions to the triplet excited states. All five complexes showed red-orange phosphorescence at room temperature in CHCl solution with decreased lifetimes and emission quantum yields, as the π-conjugation of the ancillary ligands increased. Transient absorption (TA) profiles were probed in acetonitrile solutions at room temperature for all of the complexes. Except for complex 5 (which showed dppn-localized π,π* absorption with a long lifetime of 41.2 μs), complexes 1-4 displayed similar TA spectral features but with much shorter triplet lifetimes (1-2 μs). Reverse saturable absorption (RSA) was demonstrated for the complexes at 532 nm using 4.1 ns laser pulses, and the strength of RSA decreased in the order: 2 ≥ 1 ≈ 5> 3 > 4. Complex 5 is particularly attractive as a broadband reverse saturable absorber due to its wide optical window (430-850 nm) and long-lived triplet lifetime in addition to its strong RSA at 532 nm. Complexes 1-5 were also probed as photosensitizing agents for in vitro photodynamic therapy (PDT). Most of them showed a PDT effect, and 5 emerged as the most potent complex with red light (EC = 10 μM) and was highly photoselective for melanoma cells (selectivity factor, SF = 13). Complexes 1-5 were readily taken up by cells and tracked by their intracellular luminescence before and after a light treatment. Diagnostic intracellular luminescence increased with increased π-conjugation of the ancillary N^N ligands despite diminishing cell-free phosphorescence in that order. All of the complexes penetrated the nucleus and caused DNA condensation in cell-free conditions in a concentration-dependent manner, which was not influenced by the identity of N^N ligands. Although the mechanism for photobiological activity was not established, complexes 1-5 were shown to exhibit potential as theranostic agents. Together the RSA and PDT studies indicate that developing new agents with long intrinsic triplet lifetimes, high yields for...

A Ru(II) polypyridyl complex bearing aldehyde functions as a versatile synthetic precursor for long-wavelength absorbing photodynamic therapy photosensitizers

“…[9][10][11][12][13][14] As a highly investigated class of compounds, [Ru(phen)3] 2+ derivatives have been studied as PDT PSs. [15][16][17][18] Several examples have shown that the photophysical properties, including absorption, emission as well as excited states lifetimes can be influenced by choice of the coordinated ligands. [5,9,11,13,19] Next to suitable photophysical properties, the biological abilities of a PS including, for example, cellular localisation or mechanism of cellular uptake, play a predominant role in the efficiency of the treatment.…”

Mono(2,2′‐bipyridyl)RuII Complex with Four Dimethyl Sulfoxide Ligands as Precursor for cis‐Bis‐heteroleptic RuII Complex: Syntheses, Structures, and Substitution Reactions

“…Because of their unique photophysical and photochemical properties, polypyridyl ruthenium(II) complexes have found many applications in the fields of supramolecular, bio‐inorganic, and catalytic chemistry . Although many heteroleptic polypyridyl ruthenium(II) complexes have been synthesized and investigated, most are of the [Ru(N‐N) 2 (N′‐N′)] 2+ type, in which N‐N and N′‐N′ are bidentate ligands such as 2,2′‐bipyridyl (bpy), 1,10‐phenanthroline (phen), or their analogues , . The limited range of target complexes is related to the easy synthetic access to cis ‐[RuCl 2 (bpy) 2 ] (commercially available) and its analogue complexes.…”

Recent Progress in Metal-Based Nanoparticles Mediated Photodynamic Therapy

“…The development of PDT technology can aid in the fight against a range of diseases, such as tumors of the colon and bladder, tumors of the brain and spinal cord, and to develop new methods of treatment of skin in plastic surgery and cosmetology [ 46 , 47 ]. Positive results of treatment of proinflammatory diseases by photodynamic therapy show high efficiency of this method in respect of aerobic, facultative, and obligate anaerobic bacteria, and microscopic fungi [ 48 , 49 ].…”