| Abstract
| - In a continuing effort to unravel mechanistic questions associated with metalloenzymes, we aredeveloping methods for rapid delivery of electrons to deeply buried active sites. Herein, we report picosecondreduction of the heme active site of inducible nitric oxide synthase bound to a series of rhenium−diimineelectron-tunneling wires, [Re(CO)3LL‘]+, where L is 4,7-dimethylphenanthroline and L‘ is a perfluorinatedbiphenyl bridge connecting a rhenium-ligated imidazole or aminopropylimidazole to a distal imidazole (F8bp-im (1) and C3-F8bp-im (2)) or F (F9bp (3) and C3-F9bp (4)). All four wires bind tightly (Kd in the micromolarto nanomolar range) to the tetrahydrobiopterin-free oxidase domain of inducible nitric oxide synthase(iNOSoxy). The two fluorine-terminated wires displace water from the active site, and the two imidazole-terminated wires ligate the heme iron. Upon 355-nm excitation of iNOSoxy conjugates with 1 and 2, theactive site Fe(III) is reduced to Fe(II) within 300 ps, almost 10 orders of magnitude faster than the naturallyoccurring reduction.
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