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 M w = 25 kDa), and poly-l-lysine (Poly-K, M w > 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.

Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology

“…This is generally done by tuning the structure of the N^N ligand, since it is involved in the MLCT. Two families of ligand have been particularly explored: (i) polypyridyl ligands, mostly derived from 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) [19][20][21][23][24][25][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] and (ii) bis-quinoline and its derivatives, e.g. bis(phenanthridinylmethyl)amine (bpm) [22,[43][44][45].…”

The path for metal complexes to a DNA target

“…Due to the luminescent nature of the complexes, the authors were also able to monitor uptake in live cells via confocal microscopy, and even observe the localization of the complexes in the mitochondria of the cells. 63 …”

“…63 Using ICP-MS, the authors were able to correlate the cytotoxicities of these complexes in HeLa cells with intracellular rhenium concentrations. Using fluorescence microscopy (bottom), the authors were able to observe the localization of one such complex (structure shown in bold, fluorescence shown on bottom left in red) in HeLa cells.…”

Fluorous Organometallic Chemistry

“…The recent observation [28] of enhanced fluorophilicity of species functionalised with perfluoropolyether groups over those with perfluoroalkyl groups is a clear signpost of a direction to be followed in organometallic chemistry. Secondly, insight is provided by the recent work on the engineering of organometallic systems in which the fluorous substituent imparts specific, even unique, biological properties to the organometallic complex [79][80][81], and this is undoubtedly an area that is going to grow in the next few years. We look forward to the continued evolution of research in fluorous organometallic chemistry.…”

“…These compounds with fluorous tails show greater uptake by tumoral cells than analogues with long alkyl tails and are thermoresponsive, exerting considerable chemotoxicity on mild hyperthermia. Three luminescent rhenium(I) bipyridyl complexes [Re (CO) 3 [81], prepared by displacement of acetonitrile from the parent organometallic complexes, have been investigated as trifunctional biological probes that have luminescent properties for detection and a reactive group for bioconjugation and exploit the perfluoroalkyl functionalisation for straightforward isolation using fluorous solid-phase extraction.…”