Tumor cells are well adapted to grow in conditions of variable oxygen supply and hypoxia by switching between different metabolic pathways. However, the regulatory effect of oxygen on metabolism and its contribution to the metabolic heterogeneity of tumors have not been fully explored. In this study, we develop a methodology for the simultaneous analysis of cellular metabolic status, using the fluorescence lifetime imaging microscopy (FLIM) of metabolic cofactor NAD(P)H, and oxygen level, using the phosphorescence lifetime imaging (PLIM) of a new polymeric Ir(III)-based sensor (PIr3) in tumors in vivo. The sensor, derived from a polynorbornene and cyclometalated iridium(III) complex, exhibits the oxygen-dependent quenching of phosphorescence with a 40% longer lifetime in degassed compared to aerated solutions. In vitro, hypoxia resulted in a correlative increase in PIr3 phosphorescence lifetime and free (glycolytic) NAD(P)H fraction in cells. In vivo, mouse tumors demonstrated a high degree of cellular-level heterogeneity of both metabolic and oxygen states, and a lower dependence of metabolism on oxygen than cells in vitro. The small tumors were hypoxic, while the advanced tumors contained areas of normoxia and hypoxia, which was consistent with the pimonidazole assay and angiographic imaging. Dual FLIM/PLIM metabolic/oxygen imaging will be valuable in preclinical investigations into the effects of hypoxia on metabolic aspects of tumor progression and treatment response.
1 December 2012 in Russian Journal of General Chemistry
New carbazole- and terpyridine- containing norbornene derivatives were synthesized and structurally characterized. On the basis of these compounds by the method of metathesis polymerization copolymers were obtained with carbazole and terpyridine fragments in side chains. The synthesized copolymers react with terbium pyrazolonate complex to form the terbium-containing polymeric materials exhibiting the metalcentered photo- and electroluminescence.
The data on the synthesis and physicochemical and photo- and electroluminescent properties of carbochain linear polymers containing ions of rare-earth metals bound via chemical or coordination bonds to the polymer chain are summarized. The effects of the ligand environment at lanthanide atoms and the structures of the polymers on their luminescence activity are considered. Possible approaches to increase the efficiency of electroluminescence of polymer lanthanide emitters are discussed.
1 November 2012 in Russian Journal of Applied Chemistry
New complex of copper(I) with norbornene-substituted 1-H-2-pyridinylbenzimidazole ligand was synthesized. The compound obtained enters into a metathesis polymerization reaction to give carbochain coppercontaining copolymers exhibiting photo-and electroluminescent properties.
31 August 2013 in Russian Journal of Coordination Chemistry
New cyclometallated iridium(III) complex (NBEpz)Ir(Ppy)2 · 2CH2Cl2 (I) (NBEpzH is 1-phenyl-3-methyl-4-(5-bicyclo[2.2.1]hept-5-en-2-yl)-5-pyrazolone, PpyH is 2-phenylpyridine) is synthesized and structurally characterized. Compound I undergoes metathesis polymerization and forms new iridium-containing copolymers. The photophysical properties of complex I and related copolymers are studied.