Author : Tsun-Tung Chu
Release : 2017-01-27
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Book Synopsis Biomimetic Reactions of Nitric Oxide Synthase by : Tsun-Tung Chu

Download or read book Biomimetic Reactions of Nitric Oxide Synthase written by Tsun-Tung Chu. This book was released on 2017-01-27. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Biomimetic Reactions of Nitric Oxide Synthase: Study of the Reactions of N-substituted-N'-hydroxyguanidines With Metalloporphyrin and Non-heme Complexes" by Tsun-tung, Chu, 朱俊東, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled BIOMIMETIC REACTIONS OF NITRIC OXIDE SYNTHASE - STUDY OF THE REACTIONS OF N-SUBSTITUTED-N-HYDROXYGUANIDINES WITH METALLOPORPHYRIN AND NON-HEME COMPLEXES Submitted by Chu Tsun Tung For the Degree of Doctor of Philosophy at The University of Hong Kong in April 2007 Nitric oxide (NO) is one of the most important biological messengers. The generation of NO in animals is carried out by nitric oxide synthase (NOS), an enzyme which catalyzes the two-step. The first step is a 2-electron oxidation of L- Arg to N-hydroxyarginine (NHA), which similar to cytochrome P450 monoxidase type reaction. The second step is a three 3-electron oxidation of N-hydroxyarginine to NO and citrulline. Continuous studies of unusual aerobic oxidation of NHA catalyzed by NOS lead to several proposed mechanisms for the reaction. One of the proposed mechanisms features the ligation of NHA to Fe(III)-heme followed by Fe- O bond homolysis to generate Fe(II)-heme and iminoxy radical. This mechanism was supported by a chemical model system that employs fluorenone oxime and [Fe(OH)(Por)]. Inspired by this model, some N-hydroxyguanidines (NHGs), instead of an oxime, were used as substrate in our studies because N-hydroxyguanidine is the characteristic function group of NHA. All these NHGs were found ligating to [Fe(TMP)], and an X-ray crystal structure of NHG ligated [Fe(TMP)] has been determined, which supports that NHGs can ligate to iron via oxygen. Mechanistic studies of the aerobic oxidation of NHGs support that the NHG oxidation is initiated by O -assisted Fe-O bond homolysis. Guanidine and urea were thought to be the reaction products of iminoxy radical with other iminoxy radical or NHGs. HNO was thought to be one of the nitrogen oxide products, which was supported by the detection of N O in the reaction headspace gas. A modified mechanism of NOS catalyzed oxidation of NHA to citrulline and NO was proposed according to the findings of our studies and other new mechanistic findings about NOS reaction. The aerobic oxidations of some trisubstituted NHGs catalyzed by [Fe(OH)(TMP)] generated 3-amino-1,2,4-oxadiazoles as products. Some non-heme iron complexes and metalloporphyrins were tested for the catalytic properties towards the oxidative cyclization of NHGs. Complexes [nBu N][Fe(L)(Cl) ] (L = 4 2 bispyridylamide type ligands) were found to be good catalysts, which gave the corresponding oxadiazole in 80% yield within 1.5 hours from N, N-dimethyl-N'- benzyl-N"-hydroxyguanidine (DMBH). Mechanistic studies for the oxidative cyclization of NHGs catalyzed by the [nBu N][Fe(L)(Cl)] complexes were 4 2 performed and a mechanism for the reaction was proposed. DOI: 10.5353/th_b3963409 Subjects: Nitric-oxide synthase Chemical reactions Biomimetics Bioactive compounds