Synthesis, DFT Calculations, and In Vitro Antioxidant Study on Novel Carba-Analogs of Vitamin E.

Aneta Baj,Artur Ratkiewicz,Ewa Olchowik-Grabarek,Stanislaw Witkowski,Jakub Cedrowski

doi:10.3390/antiox8120589

Aneta Baj, Artur Ratkiewicz + Show 3 more

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https://doi.org/10.3390/antiox8120589

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Journal: Antioxidants	Publication Date: Nov 26, 2019
Citations: 23	License type: CC BY 4.0

Affiliation: University of Białystok, University of Warsaw

Abstract

Vitamin E is the most active natural lipophilic antioxidant with a broad spectrum of biological activity. α-Tocopherol (α-T), the main representative of the vitamin E family, is a strong inhibitor of lipid peroxidation as a chain-breaking antioxidant. Antioxidant and antiradical properties of vitamin E result from the presence of a phenolic hydroxyl group at the C-6 position. Due to stereoelectronic effects in the dihydropyranyl ring, the dissociation enthalpy for phenolic O–H bond (BDEOH) is reduced. The high chain-breaking reactivity of α-T is mainly attributed to orbital overlapping of the 2p-type lone pair on the oxygen atom (O1) in para position to the phenolic group, and the aromatic π-electron system. The influence of the O1 atom on the antioxidant activity of vitamin E was estimated quantitatively. The all-rac-1-carba-α-tocopherol was synthesized for the first time. Along with model compounds, 1-carba-analog of Trolox and its methyl ester were screened for their in vitro antioxidant activity by inhibition of styrene oxidation, and for the radical-reducing properties by means of 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) scavenging assay. To study the antioxidant activity, density functional theory (DFT) was also applied. Reaction enthalpies related to HAT (hydrogen atom transfer), SET–PT (sequential electron transfer—proton transfer), and SPLET (sequential proton loss—electron transfer) mechanisms were calculated.

Highlights

Vitamin E is one of the most effective natural lipophilic chain-breaking antioxidants, which exhibits a broad spectrum of other biological functions
Due to lipophilic properties vitamin E incorporates into biological membranes and protects them from oxidative damage
The main goal of the synthetic work was to obtain vitamin E analogs in which the heterocyclic oxygen atom O1 would be substituted by CH2 group

Summary

Introduction

Vitamin E is one of the most effective natural lipophilic chain-breaking antioxidants, which exhibits a broad spectrum of other biological functions. Due to lipophilic properties vitamin E incorporates into biological membranes and protects them from oxidative damage. It regulates the structural and functional properties of cell membranes, giving them adequate fluidity, stability, and permeability. The vitamin E family includes four tocopherols with a saturated phytyl side-chain and four tocotrienols with a side-chain with three double bonds at the 3’, 7’, and 11’ positions (farnesyl chain). Both groups consist of four forms: α-, β-, γ-, and δ-, differing in location and number of methyl groups on the aromatic ring (Figure 1). Both groups consist of four forms: α-, β-, γ-, and δ-, differing in location and number of methyl groups on the aromatic ring (Figure 1). α-Tocopherol (α-T) shows the highest antioxidant activity [1,2,3]

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