Nitric oxide synthase (NOS) is a heme-containing monoxygenase that catalyzes the oxidation of l-arginine to l-citrulline and NO in two steps. In the second step of the NOS reaction, citrulline and NO are generated from the heme-catalyzed 3-electron oxidation of l-N-hydroxyarginine. To model this unusual reaction, iron porphyrin-catalyzed oxygenations of oximes with O2 were investigated. The oxidation of fluorenone oxime and a stoichiometric amount of hydroxoiron(III) porphyrin (Fe(OH)P, P = TMP and TPFPP) with O2 in benzene generated Fe(NO)P, fluorenone, and O-(9-nitro-9-fluorenyl)fluorenone oxime. The X-ray crystal structure of the oxime ether product suggests that it originated from the dimerization of the fluorenyl iminoxy radicals. Detailed analysis of this reaction showed that the oxime reacted first with Fe(OH)P to generate a 5-coordinate, high-spin oximatoiron(III) porphyrin species [Fe(oximate)P]. The X-ray crystal structure of oximatoiron(III) tetrakis(2,6-dichlorophenyl)porphyrin [Fe(oximate)TDCPP] showed that the oximate ligand was monodentate, O-bound to Fe(III)P. The aerobic oxidation of Fe(oximate)P followed the characteristic kinetics of a metalloporphyrin-catalyzed radical-type autoxidation. O2 surrogates, the π-acids NO and CO, induced the homolysis of Fe(oximate)P to generate Fe(NO)P or Fe(CO)P and the iminoxy radical, implicating a similar reaction mode for O2 with Fe(oximate)P. Fe(oximate)TMP reacted with 18O2 to generate predominantly 18O-labeled fluorenone (75% yield), while the reaction conducted under 16O2 and H2 18O generated only 16O-labeled fluorenone. This reaction is proposed to proceed via an Fe−O bond homolysis of Fe(oximate)TMP followed by O2 insertion to generate 9-nitroso-9-fluorenylperoxyFe(III)TMP, which decomposes via an O−O bond homolysis to generate NO, fluorenone, and oxoFe(IV)P. The implications of this system for the NOS reaction mechanism are discussed.

Computational studies at the HF/3-21G and B3LYP/6-31G(d) levels suggest that 5,6,8-tri(tert-butyl)-1,2,3,4-tetraphenylnaphthalene (2) is perhaps the most crowded naphthalene derivative that will show normal stability; more highly congested naphthalenes will prefer to exist as the corresponding Dewar isomers. Initial attempts to prepare 2 by reacting 3,4,5,6-tetraphenylbenzyne with 2,3,5-tri(tert-butyl)cyclopentadienone at 83 degrees C gave instead a stable norbornadienone, 1,2,4-tri(tert-butyl)-5,6,7,8-tetraphenyl-9-oxo-1,4-dihydro-1,4-methanonaphthalene (3), which was characterized by X-ray crystallography. The experimental and calculated (HF/3-21G) activation energies (E(a)) for the decarbonylation of 3 were quite high: 39 and 46 kcal/mol, respectively, a manifestation of the substantially increased strain in the transition state as the tert-butyl groups are forced together. The naphthalene 2 was obtained in good yield by heating 3 in refluxing toluene, and its X-ray structure showed exceptional distortions from a normal naphthalene geometry. However, 2 is not completely stable, and it decomposes upon prolonged heating in xylenes.