Towards Water Soluble Mitochondria-Targeting Theranostic Osmium(II) Triazole-Based Complexes

Abstract

Abstract:The complex [Os(btzpy) 2 ][PF 6 ] 2 (1, btzpy = 2,6-bis(1-phenyl-1,2,3-triazol-4-yl)pyridine) has been prepared and characterised. Complex 1 exhibits phosphorescence (λ em = 595 nm, τ = 937 ns, φ em = 9.3% in degassed acetonitrile) in contrast to its known ruthenium(II) analogue, which is non-emissive at room temperature. The complex undergoes significant oxygen-dependent quenching of emission with a 43-fold reduction in luminescence intensity between degassed and aerated acetonitrile solutions, indicating its potential to act as a singlet oxygen sensitiser. Complex 1 underwent counterion metathesis to yield [Os(btzpy) 2 ]Cl 2 (1 Cl ), which shows near identical optical absorption and emission spectra to those of 1. Direct measurement of the yield of singlet oxygen sensitised by 1 Cl was carried out (φ ( 1 O 2 ) = 57%) for air equilibrated acetonitrile solutions. On the basis of these photophysical properties, preliminary cellular uptake and luminescence microscopy imaging studies were conducted. Complex 1 Cl readily entered the cancer cell lines HeLa and U2OS with mitochondrial staining seen and intense emission allowing for imaging at concentrations as low as 1 µM. Long-term toxicity results indicate low toxicity in HeLa cells with LD50 >100 µM. Osmium(II) complexes based on 1 therefore present an excellent platform for the development of novel theranostic agents for anticancer activity.

Observation of an Inversion in Photophysical Tuning in a Systematic Study of Luminescent Triazole-Based Osmium(II) Complexes

“…Indeed, we have previously found that Os1 is an efficient sensitiser of singlet oxygen (Φ 1 O2 = 57%) with the intensity of phosphorescence undergoing a 43fold reduction between degassed and oxygenated MeCN solutions. 36 Further inspection of the degassed photoluminescence lifetimes for Os1-Os6 reveal a close agreement with the energy gap law. 54,55 Complex…”

Photophysics and photochemistry of 1,2,3-triazole-based complexes

“…The bistridentate complex 89 has been reported and, unlike its iron(II) and ruthenium(II) analogues, found to be emissive at 595 nm. [123] The emission intensity is strongly affected by the presence of oxygen with a singlet oxygen quantum yield of 0.57 in acetonitrile solutions. 89 was investigated as a luminescent cellular imaging agent by confocal microscopy and is observed to enter U2OS and HeLa cancer cells with localisation in the mitochondria (Figure 12).…”

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand

“…One strategy for shifting the optical window of metal complex phototherapy agents to longer wavelengths while building on successful molecular design concepts for Ru II complexes is to utilize the Os II analogues of the Ru II complexes [26–30] . In fact, Os II complexes are becoming widely appreciated as both therapeutic compounds [31–41] and cellular imaging agents [42–47] . This approach has been explored by McFarland and co‐workers for PDT, [48] but it is has not been applied to PCT given that the Os II polypyridyl counterparts are photoinert [49, 50] .…”

“…[26][27][28][29][30] In fact, Os II complexes are becoming widely appreciateda sb oth therapeutic compounds [31][32][33][34][35][36][37][38][39][40][41] and cellular imaging agents. [42][43][44][45][46][47] This approach has been explored by McFarland and co-workers for PDT, [48] but it is has not been appliedt oP CT given that the Os II polypyridyl counterparts are photoinert. [49,50] Both in vitro and in vivo studies of the Os II photosensitizers OsH2B, OsH2IP, and OsH2dppn)( Scheme 1) publishedb yM cFarland and coworkers showedp anchromatic activation, low dark toxicity, and PDT activity.…”