Chemistry of bifunctional photoprobes. 3. Correlation between the efficiency of CH insertion by photolabile chelating agents and lifetimes of singletnitrenes by flash photolysis: First example of photochemical attachment ofTc-99m-complex with human serum albumin

Systematic functionalization of perfluoroaryl azides with chelating agents capable of complexing transition metals produces a new class of bifunctiona l photolabile chelating agents (BFPCAs). The strategy to shield the azide f unctionality from the electronic and steric influence of the electron-rich metal Pd through ester and amide bridges raised CH insertion efficiency to unprecedented levels (>92%) in a model solvent (cyclohexane). In contrast, perfluoroaryl azides attached to chelating agents via hydrazones show no si gnificant CH insertion in cyclohexane upon photolysis. Measurements of the lifetimes of the singlet nitrenes derived from these agents by flash photol ysis techniques correlate well with the efficiency of CH insertion by demon strating longer lifetimes (10-50 times) for singlet nitrenes derived from a zidotetrafluorinated esters and amides compared with the related hydrazones , which failed to yield significant CH insertion. A representative BFPCA 12 is chelated to diagnostic radionuclide Tc-94m and covalently attached to h uman serum albumin via photochemical activation extending the favorable bim olecular insertion characteristics of BFPCA to tracer level concentrations in buffer conditions. Flash photolysis experiments correlate singlet nitren e lifetimes with the efficiency of intermolecular insertion reactions. This work provides new photo-cross-linking technology, useful in radiodiagnosti cs and radiotherapy in nuclear medicine.