Spectroscopic Signatures and the Cation-π Interaction in Conformational Preferences of the Neurotransmitter Dopamine...

The precise determination of the neurotransmitter dopamine's conformational preferences in aqueous solution is crucial for understanding its neurobiological function. The first principle Møller-Plesset perturbation theory (MP2) and dispersion corrected density functional theory (DFT-D3) methods, employing the basis set aug-cc-pVDZ(/pVTZ), are used to reinvestigate the nine lowest-energy (isolated) structures of protonated dopamine (DAH⁺) in both gas and aqueous phases. DAH⁺ trans isomer t is found higher in energy than lowest-energy gauche isomer g (g + 1) by 6.4 and 5.7 kJ mol^-1, at the MP2 and B3LYP-D3 levels of theory, respectively, in the aqueous environment within the polarizable continuum model (PCM). We found that the solvated cation, NH₃⁺, retains its attractive character, which supports the previous report that agonist DAH⁺ can be involved in cation (NH₃⁺)-π interaction in the active states of the D2 dopamine receptor. The dispersion corrected DFT evaluation of anharmonicity allows us to confirm the most experimental frequencies and suggest some new interpretations. The IR and Raman spectra's influential band for both gauche and the trans conformers observed at 1287/1288 cm^-1 were enhanced in aqueous solution. The experimental Raman spectrum for dopamine was compared with the conformer-specific computed Raman spectrum of protonated dopamine (DAH⁺). The intense Raman band at 1451 cm^-1 indicates the necessity of DAH⁺ calculated values in interpreting the Raman spectra. The most intense Raman band at 750 cm^-1 arises due to the trans DAH⁺, t, revealed by MP2/aug-cc-pVDZ Raman spectra, indicating trans DAH⁺ dominance in the bulk DAH⁺ of extracellular fluid.