Antioxidant Properties of Kynurenines: Density Functional Theory Calculations

Abstract

Kynurenines, the main products of tryptophan catabolism, possess both prooxidant and anioxidant effects. Having multiple neuroactive properties, kynurenines are implicated in the development of neurological and cognitive disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Autoxidation of 3-hydroxykynurenine (3HOK) and its derivatives, 3-hydroxyanthranilic acid (3HAA) and xanthommatin (XAN), leads to the hyperproduction of reactive oxygen species (ROS) which damage cell structures. At the same time, 3HOK and 3HAA have been shown to be powerful ROS scavengers. Their ability to quench free radicals is believed to result from the presence of the aromatic hydroxyl group which is able to easily abstract an electron and H-atom. In this study, the redox properties for kynurenines and several natural and synthetic antioxidants have been calculated at different levels of density functional theory in the gas phase and water solution. Hydroxyl bond dissociation enthalpy (BDE) and ionization potential (IP) for 3HOK and 3HAA appear to be lower than for xanthurenic acid (XAA), several phenolic antioxidants, and ascorbic acid. BDE and IP for the compounds with aromatic hydroxyl group are lower than for their precursors without hydroxyl group. The reaction rate for H donation to *O-atom of phenoxyl radical (Ph-O*) and methyl peroxy radical (Met-OO*) decreases in the following rankings: 3HOK ~ 3HAA > XAAOXO > XAAENOL. The enthalpy absolute value for Met-OO* addition to the aromatic ring of the antioxidant radical increases in the following rankings: 3HAA* < 3HOK* < XAAOXO* < XAAENOL*. Thus, the high free radical scavenging activity of 3HAA and 3HOK can be explained by the easiness of H-atom abstraction and transfer to O-atom of the free radical, rather than by Met-OO* addition to the kynurenine radical.

Ommochromes in invertebrates: biochemistry and cell biology

“…This result is consistent with in silico measurements of hydrogen‐donor capacities of ommochromes (Fig. C) (Romero & Martínez, ; Zhuravlev et al, ). For xanthommatin, the three best H‐donor sites localise to the aspartyl chain while the two best ones of ommatin D are within the pyrido[a]phenoxazone system (Fig.…”

“…These results are in agreement with the differences in H‐donor capacities of these two ommochromes. Thus, reduced ommochromes, which also are the reddest ones, may act as better antiradical compounds in vivo than their oxidised forms (Romero & Martínez, ; Zhuravlev et al, ). To date, the ratio of these two redox forms within ommochrome‐containing organelles is not known.…”

Triplet Tuning: A Novel Family of Non-Empirical Exchange–Correlation Functionals

“…The first triplet-tuned functional, TT-ωPBEh, was constructed by an internal matching of E T from two DFT variants, ∆SCF and TDDFT. To evaluate the behavior of TT-ωPBEh, we compared its errors for Similar to conventional optimally tuned functionals, [247][248][249][250][251][252][253][254][255][256] we expected a broad application of our triplet tuning approach for π-conjugated organic molecules that were considered theoretically challenging before. Beyond the accurate predictions of spectroscopy and dynamics, the method can set the stage for the computationally aided design and screening of photoactive materials.…”

Phytochemical treatments target kynurenine pathway induced oxidative stress

“…The kynurenine pathway, which occurs in most cells of the central nervous system, catabolizes tryptophan into quinolinic acid, an N-acetyl-D-aspartate (NMDA) receptor agonist and precursor of nicotinamide adenine dinucleotide (NAD+), and picolinic acid via kynurenine [2,21]. Tryptophan is also involved in protein synthesis and is a precursor for serotonin [22]. Kynurenines, metabolites of the kynurenine pathway, often have pro and antioxidant properties with the aromatic hydroxyl acting as an electron acceptor [22].…”

“…Tryptophan is also involved in protein synthesis and is a precursor for serotonin [22]. Kynurenines, metabolites of the kynurenine pathway, often have pro and antioxidant properties with the aromatic hydroxyl acting as an electron acceptor [22].…”