The challenge of developing organic molecules with improved antioxidant activities for a competitive marketplace requires, given the great amount of possibilities, much laboratory work. Nowadays, the ability of methodologies based on quantum chemistry to determine the influence of different modifications on a molecule core provides a powerful tool for selecting the most useful derivatives to be synthesized. Here, we report the results of the assessment of antioxidant activity for quaternary amino acids, specifically for cysteine derivatives. The effect of introducing different substituents on the cysteine core is evaluated by using DFT to obtain an adequate structure-antioxidant activity relationship. This theoretical study shows a small panel of targets among which (R)-N-acetyl-2-methylcysteine methyl ester 15 exhibits special features and relevant antioxidant activity. The conformational (1)H NMR study of this synthesized compound indicates the existence of an intramolecular C7 member ring involving S-HO[double bond, length as m-dash]C substructure, which is reported for the first time in the literature for this amino acid unit. This unusual conformation seems to be the reason for the high antioxidant capacity experimentally found for this compound.
The development of new antioxidants with enhanced activity constitutes a very active research field as it can contribute to the improvement of human health. Although the antioxidant activity occurs through different mechanisms, usually most of the antioxidant molecules present a unique active center which is able to react following a specific way. To overcome this weakness and in the belief that the coupling of different antioxidant groups is a good strategy to obtain multipotent antioxidants, the effect of introducing different N-protective groups on the cysteine core is evaluated by using DFT. As a result, in this work we present a multicenter antioxidant, N-(9-fluorenylmethyloxycarbonyl)cysteine methyl ester 8, able to fight efficiently through different mechanisms against free radicals independently of their nature. This antioxidant appears to be the first one of a promising new class of multipotent antioxidants with three operative centers: C(α) that is a good hydrogen donor, the Fmoc group that is a good electron donor and the all-around thiol group. Besides, its neutral radical shows a high stability due to the captodative effect in such a way that the subsequent toxic effects would be avoided. Then, its experimental radical-trapping antioxidant activity postulates compound 8 as a prototype of antioxidants more versatile and efficient than N-acetylcysteine, ascorbic acid or Trolox.
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