Enzymatic and non-enzymatic reactions of flavonol and flavonolate ruthenium complex with small molecules: HNO and O2

Han, Xiaozhen, 1988-

Enzymatic and non-enzymatic reactions of flavonol and flavonolate ruthenium complex with small molecules: HNO and O2

dc.contributor.advisor	Farmer, Patrick Joseph, 1957-
dc.creator	Han, Xiaozhen, 1988-
dc.date.accessioned	2017-02-07T16:38:26Z
dc.date.available	2017-02-07T16:38:26Z
dc.date.created	2016-12
dc.date.issued	2016-11-17
dc.date.submitted	December 2016
dc.date.updated	2017-02-07T16:38:26Z
dc.description.abstract	Quercetin 2,3-dioxygenase (QDO) enzyme catalyzes the degradation of flavonols by incorporating both atoms of dioxygen. HNO, nitroxyl or azanone, is isoelectronic with 1O2, and acts as a reactive species for enzymatic and non-enzymatic cleavage of flavonols in the place of O2, in which N is regioselectively found in the ring-cleaved product. Kinetic and thermodynamic analysis of the nitroxygenation of a series of flavonols with HNO have been conducted to get insights of the mechanism of enzymatic and non-enzymatic nitroxygenation. It turns out that in the QDO enzyme catalyzed reaction the possible involvement of a quinone methide tautomer of the flavonol substrates rationalizes the site of nitroxyl N-atom incorporation into the product; while in the non-enzymatic reaction the determined standard state energy (ΔGo) and activation free energy, as well as the low entropic energy of reaction, are consistent with a proposed single electron transfer (SET) rate determining step. In order to mimic flavonol dioxygenase catalyzed oxygenation of flavonols, a series of Ru(II) bis-bipyridyl flavonolate complexes [RuII(bpy)2(3-hydroxyflaR)]+ (R = p-OMe, pMe, p-H, p-Cl), [RuII(bpy)2(3,7-dihydroxyfla)]+ and [RuII(bpy)2(5-hydroxyfla)]+ were designed and synthesized as functional models to investigate the oxidative cleavage of ligand flavonolate by oxygen and nitroxyl. Treatment of dry CH3CN solutions of complexes with O2 under light leads to oxidative O-heterocyclic ring opening of the coordinated substrate flavonolate, resulting in the formation of [RuII(bpy)2bpgR]+ (bpg = 2- benzoyloxyphenylglyoxylate). We have been able to rule out singlet oxygen as a possible reactive intermediate. Instead, we suggest a SET (single electron transfer) mechanism between ruthenium bis-bipyridyl flavonolate complexes and oxygen. For the formation of the oxygenation product [RuII(bpy)2bpgR]+, we were able to detect a 1,2-dioxetane intermediate by chemiluminescence spectroscopy. Both the product and the intermediate suggest that the oxygenation mechanism is through 1,2-dioxetane intermediate rather than a 1,3-endoperoxide pathway.
dc.format.mimetype	application/pdf
dc.identifier.uri	http://hdl.handle.net/2104/9924
dc.language.iso	en
dc.rights.accessrights	Worldwide access.	en
dc.rights.accessrights	Access changed 6/7/19.
dc.subject	Flavonol dioxygenase. Flavonol. Flavonolate ruthenium complex. Super oxide. Oxygenation. Nitroxygenation.
dc.title	Enzymatic and non-enzymatic reactions of flavonol and flavonolate ruthenium complex with small molecules: HNO and O2
dc.type	Thesis
dc.type.material	text
local.embargo.lift	2018-12-01
local.embargo.terms	2018-12-01
thesis.degree.department	Baylor University. Dept. of Chemistry & Biochemistry.
thesis.degree.grantor	Baylor University
thesis.degree.level	Doctoral
thesis.degree.name	Ph.D.