Aqueous solvent effects on the conformational space of tryptamine. Structural and electronic analysis

Abstract

The TRA (3-[2-aminoethyl]indole) is an important neurotransmitter with a close structural and chemical similarity to the neurotransmitter serotonin (5-hydroxytryptamine), and to melatonin (5-methoxy-N-acetyltryptamine), which plays a key role in daily human behavior. Moreover, TRA, and other indolic compounds are very efficient antioxidants. In this work the conformational space of TRA was scanned in aqueous solution, simulating the solvent by the polarizable continuum model. Geometry optimizations were performed at B3LYP/6-31+G** level. Electronic distributions were analyzed at a better calculation level, thus improving the basis set (6-311++G**). A topological study based on Bader's theory (atoms in molecules) and natural bond orbital (NBO) framework was performed. Structural changes found in solution were related with charge delocalization mechanisms, which explained the changes in the conformational relative population in aqueous phase. Solvent effects on molecular electrostatic potential (MEPs) were also quantified and rationalized through charge delocalization mechanisms, thus connecting changes in MEPs with changes in structure, bond polarization, orbital bonding populations, natural charges, and bond topological properties. Moreover, polarizabilities and dipolar moments were calculated. All conformers were taken into account. Our results are the first prediction of TRA polarizabilities. The results reported contribute to the understanding of the structure, stability and reactivity of TRA and other indole derivatives.

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

“…In agreement with these results, when the Molecular Electrostatic Potential (MEP) was analyzed, diminished reactivity at C3 and C8 to the electrophilic attack was shown. 22 The rest of addition channels are thermodynamically favored as illustrated by their negative Gibbs free energy. The most exergonic RAF channel is addition at C1, the carbon atom belonging exclusively to the pyrrole ring and closest to N1.…”

“…This outcome is also supported by the behavior of MEPs, which showed the highest reactivity of the indole ring to electrophilic attack close to C1. 22 This addition seems to be so favorable that no transition state for this process was characterized. We found the corresponding transition state in the gas phase.…”

“…It was found a large increment in reactivity to electrophilic attack close to C1 when the system was modeled in aqueous solution by a Polarized Continuum Medium model. 22 Therefore, it seems that this process may proceed without an activation barrier in aqueous solution. Nevertheless, in Table 1 we provide the energy barrier resulting from a single-point calculation in aqueous solution at the geometry of the located TS in the gas phase.…”

“…The analysis of the conformational space of TRA were further extended by theoretical studies considering solvent effects. 22 Moreover, a recent paper showed 23 the significance of the knowledge of electronic distribution of TRA and its behavior to understand the values of thermodynamic parameters necessary for the study of the free radical scavenging capacity. More precisely, the quantification of the changes measured in serotonin (5-hydroxytryptamine, SER) regarding TRA as reference allowed concluding that the variations on the electronic population at the nitrogen belonging of the indole ring, and the electronic delocalizations from that site and those related to the π-electronic system, enabled us to explain variations associated with free radical scavenging capacity.…”

“…For that reason, we will adopt in our work the predicted conformational structure in theoretical simulations in aqueous solution. 22 Our purpose is to analyze the antioxidant properties of TRA. As model oxidant agents, we have taken into account the hydroxyl (HO • ) and hydroperoxyl (HOO • ) radicals.…”