Molecular Crosstalk Between Catecholamine Neurotransmitters and Neurologically Active Ions ( Na + $$ {Na}^{+} $$ , K + $$ {K}^{+} $$ and Cl − $$ {Cl}^{-} $$ ) and Ion-Induced Chemical Reactivity: A DFT Study

Theoretical research on the intermolecular interactions (crosstalk) between catecholamine neurotransmitters (CATs) and neurologically active ions (NAIs) such as ${\mathrm{Na}}^{+}$, $K^{+}$ and ${\mathrm{Cl}}^{-}$ has been performed using the density functional B3LYP method with 6-311++G (d, p)+SDD basis set in aqueous phase. Complexation energy analysis predicts that average interaction energy between CATs and ${\mathrm{Na}}^{+}$ ion in aqueous phase is ~−22.9 $\text{kcal}\cdot {\mathrm{mol}}^{-1}$, which is ~3 times higher (i.e., stronger) than the reported experimental interaction energy between dopamine and dopamine transporter (−7.4 $\text{kcal}\cdot {\mathrm{mol}}^{-1}$). Interaction with anion (${\mathrm{Cl}}^{-}$) is weaker than cations (${\mathrm{Na}}^{+}$/$K^{+}$). NBO charge analysis predicted that ${\mathrm{Na}}^{+}$ and $K^{+}$ interact with donor atoms (N or O) and $\pi -\text{electron}$ cloud of the benzene ring in CATs whereas ${\mathrm{Cl}}^{-}$ ion interacts with the acidic hydrogen of –OH/-CH groups by the formation of H-bonds, which is also supported with structural analysis of complexes. Fukui function analysis indicated that chemical reactivity as well as antioxidant activity of CATs is altered because of the interactions with NAIs. All these analyses suggested that molecular crosstalk between CATs and NAIs might perturb the interactions between CATs and receptors during neurotransmission as well as CATs and transporters during reuptake process.