Ultrafast photo-induced ligand solvolysis of cis-[Ru(bipyridine)₂(nicotinamide)₂]²⁺: experimental and theoretical insight into its photoactivation mechanism

Abstract

Mechanistic insight into the photo-induced solvent substitution reaction of cis-[Ru(bipyridine)2(nicotinamide)2](2+) (1) is presented. Complex 1 is a photoactive species, designed to display high cytotoxicity following irradiation, for potential use in photodynamic therapy (photochemotherapy). In Ru(II) complexes of this type, efficient population of a dissociative triplet metal-centred ((3)MC) state is key to generating high quantum yields of a penta-coordinate intermediate (PCI) species, which in turn may form the target species: a mono-aqua photoproduct [Ru(bipyridine)2(nicotinamide)(H2O)](2+) (2). Following irradiation of 1, a thorough kinetic picture is derived from ultrafast UV/Vis transient absorption spectroscopy measurements, using a 'target analysis' approach, and provides both timescales and quantum yields for the key processes involved. We show that photoactivation of 1 to 2 occurs with a quantum yield ≥0.36, all within a timeframe of ~400 ps. Characterization of the excited states involved, particularly the nature of the PCI and how it undergoes a geometry relaxation to accommodate the water ligand, which is a keystone in the efficiency of the photoactivation of 1, is accomplished through state-of-the-art computation including complete active space self-consistent field methods and time-dependent density functional theory. Importantly, the conclusions here provide a detailed understanding of the initial stages involved in this photoactivation and the foundation required for designing more efficacious photochemotherapy drugs of this type.

Excited‐State Dynamics of a Two‐Photon‐Activatable Ruthenium Prodrug

“…[Ru III (bpy)(bpy − )(NA) 2 ] 2+ ) 20. The broad plateau of the transient absorption signal at λ >550 nm (Figure 2, feature iii) is assigned to a pentacoordinate intermediate (PCI) complex, [Ru(bpy) 2 (NA)] 2+ , in agreement with previously calculated gas‐phase absorption profiles 12. Following these features over the first few hundred picoseconds, the GSB feature (ii) recovers back toward zero, whereas the 3 MLCT ESA feature (i) and the PCI feature (iii) concomitantly decay.…”

“…Such knowledge will provide a platform for the future design of more effective PDT agents (e.g. optimum choice of substituents) 12. To address the apparent paucity of the mechanistic insight following TPA, we studied a ruthenium(II) complex containing nicotinamide, a water soluble vitamin (part of the vitamin B group), cis ‐[Ru(bpy) 2 (NA) 2 ] 2+ ( 1 , shown in Figure 1 inset) (bpy=2,2′‐bipyridine and NA=nicotinamide, pyridine‐3‐carboxamide).…”

“…OPA), it is well established that the initial photoactivation mechanism involves the formation of the mono‐aquated species [Ru(bpy) 2 (NA)(H 2 O)] 2+ ( 2 ), as shown by the UV/Vis absorption spectra in Figure 1. This transformation occurs on a picosecond (ps) timescale, and is mediated via a pentacoordinate intermediary species 12. To allow the activation of 1 in the PDT window, we used TPA with 800 nm radiation.…”

“…For TEAS, a 650 μ m aqueous sample of 1 was probed following irradiation with an 800 nm, femtosecond (fs) pulsed laser. The TEAS setup is described elsewhere,12, 13 and briefly in the Supporting Information. The recorded transient absorption spectra (TAS) for select pump–probe time delays are shown in Figure 2.…”

“…Owing to the shrouding of early time dynamics by the glass‐only signal, a full analysis discovering ultrafast (<1 ps) processes cannot be performed. In our previous OPA study (excitation at 340 nm),12 where such time resolution was available, a detailed ′target analysis′ approach was used to extract time constants and quantum yields for the branched kinetics, as well as to formulate the general mechanism shown in Figure 3. The time constants extracted from the following analysis are used to qualitatively show that the photoactivation of 1 following TPA proceeds along the same (if not, very similar) pathway as that following OPA, that is, 1 + hν →→ 3 MLCT→ 3 MC→ PCI→ 2 .…”