Date of Award

2008

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Environmental Science

First Advisor

D r. Ihsan Ahmed Sheadi

Second Advisor

D r. Lucia Pappalardo

Third Advisor

D r. Sayed Saman Ashraf

Abstract

Flavonoids are phenolic compounds with significant antioxidant properties. The propensity of a flavonoid to inhibit free-radical mediated events is governed by its chemical structure. Since these compounds are based on the flavan nucleus, the number, positions, and types of substitutions influence radical scavenging and chelating activity. The main objective of this thesis was to establish structure-activity relationships of flavonoids by means of experimental and computational techniques.

Initially, a series of dietary flavonoids belonging to the most representative families (flavonols; myricetin, quercetin, morin, kaempferol, and 3-hydrxoyflavone, flavones; flavone and flavanones; naringenin) were studied during the reaction with DPPH radical following addition of the flavonoid by UV -Vis spectrophotometry; they revealed two distinctive steps of reaction, a first rapid and a second slower. DPPH scavenging followed a second order kinetics during the rapid step; stoichiometric factors, rate constants as well as antiradical activities were determined. The DPPH radical allowed good discrimination between the flavonoids, as demonstrated by the relatively large ranges of rate constants (k = 10-10,000 M-1S-1), total stoichiometric factors (2-5) and antiradical activities (1-84%).

Since the oxidizabi1ity of flavonoids reflects their ability to scavenge free radicals, the electrochemical oxidations of the 8 flavonoids were measured in different pH solutions using cyclic voltammetry. Flavone with no hydroxyl groups showed no oxidation potentials. Myricetin, quercetin, morin and kaempferol had the lowest oxidation potentials. This is in good agreement with the DPPH radical scavenging activities. Oxidation of flavonoids appeared to be pH dependent.

Experimental studies revealed that the catechol structure in quercetin scavenged the highest number of DPPH radicals (4.44 ± 0.24) and exhibited the highest antiradical activity (84%). On the other hand, pyrogallol structure in myricetin had the lowest oxidation potential.

A series of density functional theory calculations using Gaussian program for 28 flavonoids belonging to the major flavonoids' families were carried out to establish the structural requirements of flavonoids for appreciable radical-scavenging activity. Energy of the same number and type of nuclei were compared. On the other hand, the dipole moments were compared for flavonoids of similar structures but different substituents i.e OCH3 and/or OH. Methoxy groups introduced unfavorable steric effects and therefore decreased the dipole moments of the studied flavonoids. Calculations of HOMO-LUMO gaps were performed to give insights of flavonoids' reactivity. Flavonols exhibited the lowest HOMO-LUMO gap among all other classes in this study.

Since chemical potential properties of flavonoids measure their tendency to give or capture electrons and therefore their antioxidant potential, these properties which include: electronic affinity (EA), ionization potential (IP), chemical potential (µ), electronegativity (χ), hardness (η) and electrophilicity (ω) were computed for all flavonoids in each class. Again, flavonols showed the lowest values among all classes which is another proof of their antioxidant ability.

Structure-activity relationships are well established from density functional calculations. Multiple hydroxyl groups confer upon the molecule substantial antioxidant activity. Methoxy groups introduce unfavorable steric effects. A double bond and carbonyl function in the heterocycle of the nuclear structure increases activity by affording a more stable flavonoid radical through electron delocalization.

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