Picosecond Photoreduction of Inducible Nitric Oxide Synthase by Rhenium(I)−Diimine Wires

• Published in: Journal of the American Chemical Society 2005-11, Vol.127 (45), p.15907-15915
• Main Authors: Belliston-Bittner, Wendy, Dunn, Alexander R, Nguyen, Yen Hoang Le, Stuehr, Dennis J, Winkler, Jay R, Gray, Harry B
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites; Biological and medical sciences; Electron Transport; Fundamental and applied biological sciences. Psychology; Heme - chemistry; Imines - chemistry; Iron - chemistry; Luminescence; Molecular biophysics; Nitric Oxide Synthase Type II - chemistry; Nitric Oxide Synthase Type II - radiation effects; Oxidation-Reduction; Photochemistry - methods; Photochemistry. Photosynthesis. Bioluminescence; Radiation-biomolecule interaction; Rhenium - chemistry; Ultraviolet Rays
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0543088

In a continuing effort to unravel mechanistic questions associated with metalloenzymes, we are developing methods for rapid delivery of electrons to deeply buried active sites. Herein, we report picosecond reduction of the heme active site of inducible nitric oxide synthase bound to a series of rhenium−diimine electron-tunneling wires, [Re(CO)3LL‘]+, where L is 4,7-dimethylphenanthroline and L‘ is a perfluorinated biphenyl 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 (K d in the micromolar to 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, the active site Fe(III) is reduced to Fe(II) within 300 ps, almost 10 orders of magnitude faster than the naturally occurring reduction.