Ruthenium (II) pyrene-bipyridine complexes: Synthesis, photophysics, photochemistry and in vivo oxygen sensing
Description
Specifically tailored ruthenium diimine complexes have received considerable attention as luminescent sensors for dissolved oxygen. These complexes show strong luminescence, often with long lifetimes in the range of 100 ns to 100 mus. In addition, they are both thermally and photochemically stable and their luminescence is quenched by oxygen with varying degrees of efficiency The project, which was a cooperative effort with Cornell University, was to develop a new class of bio-compatible, phosphorescent oxygen sensors for in vivo multiphoton microscopy. In 1997, a promising sensor, [Bis(2,2'-bipyridine)2 ruthenium(II) (4-(1'-pyrenyl)-2,2'-bipyridine)] 2+([(bpy)2Ru(pyr-bpy)]2+), was made in our group. Rosenzweig and co-workers illustrated that the complex [(bpy) 2Ru(pyr-bpy)]2+ was an effective oxygen indicator for intracellular oxygen measurements. However, initial multiphoton imaging studies of [(bpy)2Ru(pyr-bpy)]2+ in in vitro cell samples indicated that the complex was phototoxic and readily adsorbed into cell membranes The goal of this work is to synthesize pyr-bpy ligand derivatives, L', and their ruthenium complexes [(L)2Ru(L')]2+ additionally coupled with various spectator ligands, L, in order to obtain chromophores that exhibit a higher degree of sensitivity to oxygen in hypoxic conditions, but remain in the extracellular matrix The ligand pyr-bpy was prepared in a three-step reaction: aldol condensation reaction, hetero-Diels-Alder reaction, followed by condensation reaction converting dihydro-pyran to 2,2'-bipyridine. The ligand 4-phenyl-4'(1-pyrene)-2,2'-bipyridine) (pyr-phen-bpy) was prepared by Suzuki coupling of 4-(4-bromophenyl)-2,2'-bipyridine with 4,4,5,5-tetramethyl-2-(1-pyrenyl)-1,3,2-dioxaborolane. The ligand diethyl 6-(2,2'-bipyrid-4-yl)pyrenylphosphonate (pyr-bpy-poet) was synthesized by Hirao coupling of 4-(6-bromopryene-1-yl)-2,2'-bipyridine (Br-pyr-bpy) with diethyl phosphonate in a microwave reactor A series of Ru complexes, [(L)2Ru(L')]2+, were prepared and the mechanistic details of their oxygen-sensing abilities were investigated, along with the photochemical properties of these chromophores. These complexes exhibit emission from a triplet metal-to-ligand charge transfer state (3MLCT) that is in equilibrium with a non-emissive triplet state located on the pyrene that is readily quenched by oxygen. Photooxidation with persulfate and photolysis of pyr-Ru(II) complexes result in pyrenequinone Ru(II) complexes. The oxygen sensitivities and singlet oxygen photogeneration for these complexes were studied. The preliminary studies of intersystem crossing efficiency were performed using different methods and Ru-pyrene complexes were found to have cisc less than unity. Some tests and results of a few sensors in vitro and in vivo from Cornell University were presented and indicated the feasibility of this approach