Oxygen containing molecules, uptake

Recent ""Tc-based imaging agents, shown in Figure 5, for hypoxic tissue are in development. These include nitroimidazole derivatives, BSM-181321 and BRU-59-2, based on the "Tc-propyleneamine oxime (PNAO) complexes. Both contain the 2-nitrounidazole functionality, that is the active component of the oxygen mimetic molecule, F-2-nitroimidazole, and have been shown in vivo to localize in ischemic tissue. The BnAO chelate also displays uptake in hypoxic tissue. The mechanism is unknown, however, electrochemical studies show an irreversible reduction at biologically accessible potentials. 

Kidney medulla From the metabolic point of view the kidney is virtually two organs, the cortex and the medulla. The cortex contains the glomeruli, through which the blood is filtered, the proximal tubules and part of the distal tubules, from which ions and molecules are reabsorbed. The cortex is well supplied with blood so that ATP is generated by the oxidation of fuels. The medulla is metabolically quite different. Here the ATP is required for the reabsorption of ions from the loop of Henle. Some ATP is generated by anaerobic glycolysis, since the supply of blood, and therefore of oxygen, to the medulla is much poorer than to the cortex. This reflects control of the uptake of water and Na+ ions into the blood by the counter current mechanism. This depends on a slow flow of the blood in the capillaries. 

Oxygen uptake studies show that the conversion of 39 to 40 requires 0.6 (1) mol of 02, indicating that four ferrous atoms are oxidized per consumed 02 (63). This stoichiometry is similar to that reported for the autoxidation of ferrous porphyrins. The proposed mechanism, shown in Scheme 5, suggests that the autoxidation is initiated by the interaction of 02 with monomeric units of 39 that are either coordinatively unsaturated or contain a labile ligand such as solvent. The reaction of a second monomeric unit with the transient superoxo ferric complex gives rise to a (fi-peroxo)diferric species similar to that reported for [Fe HB(3,5-iPr2pz)3 (OBz)(CH3CN)] (67). This species is then somehow reduced by two electrons from 39 to yield two molecules of 40. No intermediates in the autoxidation of 39 have yet been detected even at low temperatures (—80 °C), unlike the porphyrin systems in which intermediate species such as [(Por)Fe2+02], [(Por)Fe3+-00-Fe3+(Por)], and [(Por)-Fe4+ = 0] have been spectroscopically identified (68). 

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