7-Ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone (echinochrome A): A DFT study of the antioxidant mechanism. 1. Interaction of echinochrome A with hydroperoxyl radical

Abstract

The molecular geometry and electronic structure of hydroxy substituted naphthazarin (NZ) 7 ethyl 2,3,5,6,8 pentahydroxy 1,4 naphthoquinone (echinochrome A, (Et)NZ(β OH) 3 , 1) were calculated by the B3LYP/6 311G(d) method. The influence of the (i) character of the β OH groups dissociation and (ii) conformational mobility of molecule 1 and the anions, radicals, and radical anions derived from 1 on the energy of their reactions with hydroperoxyl radical was studied by the (U)B3LYP/6 31G and (U)B3LYP/6 311G(d) methods. The enol enolic tautomerism due to the transfer of hydrogen atoms of α OH groups and rotational isomerism of the β OH groups at the C(2) and C(3) atoms and of the α OH groups at the C(5) and C(8) atoms were studied. The equilibrium in the gas phase reaction 1 + • OOH (Et)(HO β) 2 NZ(β О • ) + НOOH (1) (quenching of hydroperoxyl radical) is shifted to the separated reagents. Heterolysis of the O-H bond in one of the three β hydroxy groups considerably reduces the energy of subsequent O-H bond homolysis in either of the two remaining β hydroxy groups. As a consequence, the reaction (Et)(HO β) 2 NZ(β O -) + • OOH (Et)(HO β, -О β)NZ(β О • ) + НOOH (2) (quenching of hydroperoxyl radical) becomes exothermic and the equilibrium is shifted to the formation of hydrogen peroxide. The Gibbs energy gain in reaction (2) varies from -6.4 to -10.9 kcal mol -1 depending on which β hydroxy group is involved in the O-H bond homolysis.

7-Ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone (echinochrome A): a DFT study of the antioxidant mechanism 2.* The structure of monosodium salts of echinochrome A and their reactions with the hydroperoxyl radical

“…To access the antioxidant activity of undissociated salts 7-11 in reactions with HOO • , we have preliminarily performed conformational analysis of all isomers of radicals 12-31. Isomers 12А (2) and 16А (3) correspond to the same mini mum on the ground state PES; this also holds for pairs of isomers 15С (3) and 28С (1,3) , 17C (2) and 21С (2,4) , and 22А (5) and 26А (Fig. 5).…”

“…Pairwise equivalent isomers of radicals 12А (2) and 16А (3) , 15С (3) and 28С (1,3) , 17С (2) and 21С (2,4) , 22А (5) and 26А.…”

“…Earlier, 1 we have reported a B3LYP/6 311G(d) study of the antioxidant properties of 7 ethyl 2,3,5,6,8 pen tahydroxy 1,4 naphthoquinone (echinochrome А, (Et)NZ(OH) 3 (1), where NZ is naphthazarin (5,8 di hydroxy 1,4 naphthoquinone)), the active principle of a domestic drug Histochrome ® , taking its interaction with the hydroperoxyl radical HOO • as an example. It was shown that quenching of HOO • proceeds most efficiently if compound 1 reacts in the form of a monoan ion, i.e., when the O-H bond in a β OH group undergoes heterolysis.…”

Alkaline hydrolysis of diethyl N-acetylamino(3,5-di-tert-butyl-4-hydroxybenzyl)malonate

“…The properties of the antioxidants depend on the reaction constants of the peroxide radicals with phenol and the backward reaction of the phenoxyl radical with hydroper oxide, which made it possible to use the calculation tech nologies for the prediction of the efficiency and choice of optimal structures for the synthesis. 8 For this purpose, the energies of homolysis of the Н-О bond of phenolic 2а, 2d, 3b, 3c, and 4). The results are listed in Table 1.…”

7-Ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone (echinochrome A): a DFT study of the mechanism of the antioxidant action. 4. Migration of protons and the Na+ cation in echinochrome a monosodium salts

“…The homolytic dissociation energies of the O-H bond in β OH groups of spinochrome D and echinochrome А are very close 2. …”