Conformational Preferences of 2-Phenethylamines. A Computational Study of Substituent and Solvent Effects on the Intramolecular Amine−Aryl Interactions in Charged and Neutral 2-Phenethylamines

Abstract

A computational investigation of the conformational preferences of 2-phenethylamine has been carried out with a variety of techniques. To determine the intrinsic (in the absence of a solvent medium) conformational preferences of the 2-phenethylamine system, ab initio calculations at various levels of theory up to the MP2/6-311+G(d,p)//MP2/6-31G(d,p) level were carried out. This is the most sophisticated level of theory that has been applied to this biologically important system to date. In the absence of a solvent medium, phenethylamines prefer a folded gauche conformation for both the charged and neutral amines, indicating a favorable interaction between the amino group and the aromatic ring. To probe the nature of this intramolecular interaction further the effects of ring substituents on the conformational preferences were studied. The results have been compared to those obtained with semiempirical and molecular mechanics force field methods. The molecular mechanics force fields employing default parameters typically performed poorly for this system, but the results were improved significantly if the electrostatic charges were replaced. The effects of aqueous solvation have also been investigated with the GB/SA and the SM2 continuum solvation models. The best agreement with experiment is obtained when the MP2/6-311+G-(d,p)//MP2/6-31G(d,p) results are combined with the SM2-calculated solvent effect. Results of nearly the same quality can be obtained if the solvent effect is calculated with the GB/SA solvation model using AM1-CM1A charges.

Photochromism in Ruddlesden–Popper copper-based perovskites: a light-induced change of coordination number at the surface

“…It has been shown that the most stable conformer of phenethylammonium has a gauche confirmation of the NH 3 + -group with respect to the alkyl chain, in which one hydrogen atom of the NH 3 + -group is oriented towards the benzene ring. 53 In the excited state of this molecule, this hydrogen atom is situated closer to the benzene ring. 54 Therefore, UV illumination could weaken the hydrogen bonding between PEA and the chloride ions.…”

Infrared spectra of protonated neurotransmitters: dopamine

“…5 and 8 for the definition of gauche and trans). 6,9 In contrast, calculations for isolated neutral and protonated dopamine demonstrate the energetic preference for the gauche conformation. 6,8,9 In the latter case, this is largely due to the favourable interaction of the positively charged ammonium group with the p electron system of the aromatic ring (NH-p interaction).…”

“…6,9 In contrast, calculations for isolated neutral and protonated dopamine demonstrate the energetic preference for the gauche conformation. 6,8,9 In the latter case, this is largely due to the favourable interaction of the positively charged ammonium group with the p electron system of the aromatic ring (NH-p interaction). 6,9 In contrast, the analysis of the crystal structure and IR spectra of neutral dopamine in the condensed phase yields a trans conformation, which is rationalized by the stronger stabilization through solvation when compared to the gauche conformation.…”

“…6,8,9 In the latter case, this is largely due to the favourable interaction of the positively charged ammonium group with the p electron system of the aromatic ring (NH-p interaction). 6,9 In contrast, the analysis of the crystal structure and IR spectra of neutral dopamine in the condensed phase yields a trans conformation, which is rationalized by the stronger stabilization through solvation when compared to the gauche conformation. 10 These studies demonstrate that solvation has a strong influence on the preferred conformation of dopamine(H + ).…”

A new series of heteroaromatic receptors containing the 1,3-bis(6-oxopyridazin-1-yl)propane unit: their selective transport ability towards NH4+ in relation to Na+, K+ and Ca2+

“…21 All others were developed following Kollman 22 and Hopfinger 23 procedures. In order to develop suitable parameters for N -H· · ·N hydrogen bonding, ab initio calculations at STO-3G 24 level were used for calculating atomic charges compatible with the AMBER field ones, as Urban et al 25 claimed that they gave excellent results for the study of ammonium interactions. In all cases, geometries were minimized to a maximun energy gradient of 0.1 kcal/mol using the Polak -Ribiere algorithm, and simulated annealing procedure was used to cover all conformational space running molecular dynamics at 400 K. To optimize host -guests interactions the cation was moved and/or rotated and docked into the cavity of the ligand in all possible positions and then minimized the energy of the complex with no restraints.…”