Synthesis, Emission Characteristics, Cellular Studies, and Bioconjugation Properties of Luminescent Rhenium(I) Polypyridine Complexes with a Fluorous Pendant

Abstract

In this article, we report the photophysical and biological properties of new luminescent rhenium(I) polypyridine fluorous complexes. The complexes [Re(N∧N)(CO)3(py-Rf-NH2)](PF6) (py-Rf-NH2 = 3-amino-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine; N∧N = 1,10-phenanthroline (phen) (1a), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen) (2a), 4,7-diphenyl-1,10-phenanthroline (Ph2-phen) (3a)) contain a fluorous pendant and a primary amine for modification. They have been converted to the isothiocyanate complexes [Re(N∧N)(CO)3(py-Rf-NCS)](PF6) (py-Rf-NCS = 3-isothiocyanato-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine; N∧N = phen (1b), Me4-phen (2b), Ph2-phen (3b)) with thiophosgene. The isothiocyanate complexes have been reacted with ethylamine, a model substrate, yielding the thiourea complexes [Re(N∧N)(CO)3(py-Rf-TU-Et)](PF6) (py-Rf-TU-Et = 3-ethylthioureidyl-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine; N∧N = phen (1c), Me4-phen (2c), Ph2-phen (3c)). Upon irradiation, all of these fluorous complexes exhibited intense and long-lived green-to-yellow triplet metal-to-ligand charge-transfer (3MLCT) (dπ(Re) → π*(N∧N)) emission in fluid solutions at 298 K and in rigid glass at 77 K. The lipophilicity, cellular uptake properties, and cytotoxicity of the amine and thiourea complexes have been studied. Results of MTT assays showed that the less lipophilic fluorous complexes displayed higher cytotoxicity. The isothiocyanate complexes 1b–3b have been used to label glutathione (GSH), bovine serum albumin (BSA), branched poly(ethyleneimine) (bPEI, average Mw = 25 kDa), and poly-l-lysine (Poly-K, Mw > 30 kDa); the photophysical properties of the resultant conjugates have been examined. Additionally, we have demonstrated that the GSH conjugates can be readily isolated and purified with fluorous solid phase extraction. The uptake of complex 3c and the conjugate BSA-3c by HeLa cells has also been studied by laser-scanning confocal microscopy. Furthermore, the DNA-binding and polyplex-formation properties of the conjugates bPEI-3c and Poly-K-3c have been investigated.