Conformation and interactions of dopamine hydrochloride in solution

Abstract

The aqueous solution of dopamine hydrochloride has been investigated using neutron and X-ray total scattering data together with Monte-Carlo based modelling using Empirical Potential Structure Refinement. The conformation of the protonated dopamine molecule is presented and the results compared to the conformations found in crystal structures, dopamine-complexed protein crystal structures and predicted from theoretical calculations and pharmacophoric models. It is found that protonated dopamine adopts a range of conformations in solution, highlighting the low rotational energy barrier between different conformations, with the preferred conformation being trans-perpendicular. The interactions between each of the species present (protonated dopamine molecules, water molecules, and chloride anions) have been determined and are discussed with reference to interactions observed in similar systems both in the liquid and crystalline state, and predicted from theoretical calculations. The expected strong hydrogen bonds between the strong hydrogen bond donors and acceptors are observed, together with evidence of weaker CH hydrogen bonds and π interactions also playing a significant role in determining the arrangement of adjacent molecules.

Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin

“…In all cases, water-sites preferentially bind to the hydrogen atom. This preference for linearity in the N-H—O w binding is similar to those observed in Neutron Diffraction [ 63 , 64 ] and CSD mining studies [ 40 ]. Hence, amine hydration sites are modelled along the direction of the N-H vector with a distance of 3 Å from the nitrogen atom.…”

On the structure of an aqueous propylene glycol solution

“…EPSR has been specifically designed in order to produce a computational model constrained to fit the experimental neutron diffraction data. 34,35 The use of EPSR to analyse neutron diffraction data has been frequently exploited to study the solution properties of a range of organic liquids, 11,12,14,[36][37][38][39][40][41][42][43][44][45][46] biological and drug molecules [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] and ionic species. [63][64][65][66] A set of reference potentials are used to start the EPSR process and these potentials are subsequently modified to provide a fit to the neutron diffraction data through a reverse Monte Carlo process.…”

Spectroscopic Signatures and the Cation−π Interaction in Conformational Preferences of the Neurotransmitter Dopamine in Aqueous Solution

“…The neurotransmitter dopamine is one of the central power drivers for multiple brain functions including voluntary movement, behavior, cognition, emotion, working memory, reward, motivation, and learning, and its dysregulations cause the neuropsychiatric disorders such as Parkinson’s disease, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, and addiction. − Due to its essential role in the function of the central nervous system, there is considerable interest in understanding how dopamine interacts with a dopaminergic receptor. − The dopamine’s D2/3 receptors are hypothesized to be the major sites of action of antipsychotic drugs. − The particular conformation of a dopamine molecule at the receptor site is expected to be decisive to trigger a specific biological response. − Consequently, the more precise characterization of the flexible conformation of such ethylamino neurotransmitters contributes to comprehending these highly specific and intricate neurobiological mechanisms (of dopamine neurotransmission) at the molecular level. − In physiological media, the modification in the structure of such a flexible molecule is possible by interactions with the solvent and alternating pH values. − , A better understanding of dopamine’s conformational preferences in aqueous solutions is essential in new avenues of drug development to treat mental health problems associated with the dysfunction of the dopamine system. ,,, …”

“…It has been established by experiments that dopamine occurs in its N-protonated form {C6H3­(OH)­2–CH2–CH2–NH3 + } at physiological pH values ,− , (Figure ). Protonated dopamine (DAH + ) has been investigated theoretically and experimentally concerning its conformations and spectroscopic signatures in the gas phase and aqueous solution. ,,− DAH + may adopt many conformations, differing from each other by the arrangements of the ethylamine side chain and catechol OH groups. ,− The two functional groups are one ethylammonium and two hydroxyls, which may interact with solvents and at the receptor’s binding sites.…”