Spectroelectrochemical and Computational Studies on the Mechanism of Hypoxia Selectivity of Copper Radiopharmaceuticals

摘要: Detailed chemical, spectroelectrochemical and computational studies have been used to investigate the mechanism of hypoxia selectivity a range copper radiopharmaceuticals. A revised involving delicate balance between cellular uptake, intracellular reduction, reoxidation, protonation ligand dissociation is proposed. This accounts for observed differences in reported uptake washout related bis(thiosemicarbazonato) complexes. Three zinc complexes characterised by X-ray crystallography redox chemistry series has investigated using electronic absorption EPR spectroelectrochemistry. Time-dependent density functional theory (TDDFT) calculations also probe structures intermediate species assign spectra. DFT show that one-electron oxidation ligand-based, leading formation cationic triplet species. In absence protons, metal-centred reduction gives reduced anionic copper(I) species, [Cu(I)ATSM](-), first time it shown molecular oxygen can reoxidise this anion give neutral, lipophilic parent complexes, which wash out cells. The electrochemistry pH dependent presence stronger acids both chemical electrochemical leads quantitative rapid ions from mono- or diprotonated [Cu(I)ATSMH] [Cu(I)ATSMH(2)](+). addition, protonated identified at lower acid concentrations. potential, rate reoxidation ease are on structure ligand, governs their behaviour vivo.