Intrinsic Antioxidant Potential of the Aminoindole Structure: A Computational Kinetics Study of Tryptamine

Abstract

A computational kinetics study of the antioxidant activity of tryptamine toward HO and HOO radicals in water at 298 K has been carried out. Density functional methods have been employed for the quantum chemical calculations, and the conventional transition state theory was used for rate constant evaluation. Different mechanisms have been considered: radical adduct formation (RAF), single electron transfer (SET), and hydrogen atom transfer (HAT). For the reaction of tryptamine with the hydroxyl radical, nearly all channels are diffusion-controlled, and the overall rate constant is very high, 6.29 × 10 M s. The RAF mechanism has a branching ratio of 55%, followed by the HAT mechanism (31%), whereas the SET mechanism accounts just for 13% of the products. The less hindered carbon atom neighboring to the nitrogen of the indole ring seems to be the preferred site for the RAF mechanism, with a branching ratio of 16%. The overall rate constant for the reaction of tryptamine with the HOO radical is 3.71 × 10 M s, suggesting that it could be a competitive process with other reactions of hydroperoxyl radicals in biological environments. For this reaction only the HAT mechanism seems viable. Furthermore, only two centers may contribute to the HAT mechanism, the nitrogen atom of the indole ring and a carbon atom of the aminoethyl chain, the former accounting for more than 91% of the total products. Our results suggest that tryptamine could have a noticeable scavenging activity toward radicals, and that this activity is mainly related to the nitrogen atom of the indole ring, thus showing the relevance of their behavior in the study of aminoindoles.

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“…In addition, the lowest Δ r G 0 of RAF reactions between RA − and HOO˙ is lower than those obtained by the DFT/M05-2X method for 9-amino-2-ethoxy-8-methoxy-3 H -benzo[de][1,6]naphthyridine-3-one (5.2 kcal mol −1 ) 61 and tryptamine (2.5 kcal mol −1 ). 78 In contrast to FHT and PL, the Δ r G 0 value of the RAF reaction in the PEA solvent is slightly lower than that in water. Indeed, Δ r G 0 (C20) values in PEA are equal to −3.4 and 9.0 kcal mol −1 that are lower than those in water, which are 2.4 and 9.8 kcal mol −1 for HOO˙ and CH 3 OO˙ radical, respectively ( Table 1 ).…”

“…the viscosity of water 15 is 8.91 Â 10 À4 Pa s), and a is the radius of the solute. When all rate constants of possible free radical scavenging reactions have been estimated, the total or overall rate coefficient (k tot ) 4,78 which characterizes the reaction rate of each antioxidant compound was calculated using equation (eqn ( 18)):…”

“…Besides, the lowest D r G 0 value of FHT between RA À and HOOc is very close to those obtained by the DFT/M05-2X method for piperidine [3,2-b]demethyl(oxy)aaptamine (À5.0 kcal mol À1 ), 61 pandanusin (À5.0 kcal mol À1 ), citrusinine-I (À4.9 kcal mol À1 ), 62 and 5-hydroxynoracronycin (À4.6 kcal mol À1 ) 62 and remarkably lower than those of 9amino-2-ethoxy-8-methoxy-3H-benzo[de] [1,6]naphthyridine-3one (7.1 kcal mol À1 ) 61 and tryptamine (À3.8 kcal mol À1 ). 78 In contrast, the reactions occurring at the C-H positions are all unfavorable with positive D r G 0 values ranging from 1.2 to 25.6 kcal mol À1 for the HOOc radical and from 2.2 to 26.7 kcal mol À1 for the CH 3 OOc one. Furthermore, the FHT process occurs in the PEA solvent more favorably than in the aqueous phase.…”

“…Depending on the chemical structure of the potential antioxidant, the RAF reaction may be in competition with the FHT one. 1,61,62,78 In this work, the kinetic calculations were considered for the FHT reactions at the O-H sites showing negative D r G 0 values, also for all RAF and SET reactions. Optimized structures of the transition states (TSs) for FHT and RAF reactions of RA À toward HOOc and CH 3 OOc radicals in water are presented in Fig.…”

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“…The reaction enthalpies, Δ r H 0 , of C1 , C2 , C3 , and C4 are significant compared to the referenced antioxidants such as Trolox (3.9 kcal mol –1 ), ascorbic acid (−9.7 kcal mol –1 ), and indigo (−13.5 kcal mol –1 ) calculated at the same model chemistries in the gas phase. In the water, C1 , C2 , and C3 are even more reactive via RAF process than tryptamine (Δ r H 0 , −5.9 kcal mol –1 ) . The Gibbs free energies, Δ r G 0 , of C1 (−4.4 kcal mol –1 ), C2 (−3.6 kcal mol –1 ), and C3 (−5.8 kcal mol –1 ) are all lower than the ones of Trolox (3.2 kcal mol –1 ), ascorbic acid (17.2 kcal mol –1 ), and indigo (−1.9 kcal mol –1 ) in the gas phase.…”