Molecular Properties of Monoaminergic Catecholamines in Water

Three neurotransmitters belonging to catecholamines (dopamine, noradrenaline, adrenaline) and related α-amino acids (DOPA and tyrosine) were studied by quantum-chemical ab initio and DFT calculations using B3LYP and DLPNO-CCSD(T) methods in water. In addition to the three canonical forms, zwitterionic forms were also investigated, each in three oxidation states (molecular cation L⁺, electroneutral molecule L⁰, and molecular anion L^-). Each species was subjected to geometry optimization followed by vibrational analysis. Electronic properties (adiabatic ionization energy, electron affinity, chemical hardness, molecular electronegativity, electrophilicity index, dipole moment, electric polarizability, and quadrupole moment) and standard thermodynamic quantities (inner energy, entropy, enthalpy, and Gibbs energy) were evaluated, which allows the absolute oxidation and reduction potentials to be calculated. The absolute reduction potential (ARP) was found to correlate with the electrophilicity index ω along a straight line. Moreover, in addition to the standard expression for the absolute redox potential using reaction Gibbs energy, an approximation based on ionization energy and/or electron affinity was also tested. The main finding is that dopamine is a much weaker oxidizing agent with the ARP = 0.99 V relative to tyrosine with ARP = 1.38 V for canonical structures in water. This is also true for the zwitterionic structures in water: for dopamine ARP = 0.63 V is much lower relative to tyrosine with ARP = 1.31 V. The protonated form (DOPAH⁺) has the highest ARP = 2.02 V. Prediction of the redox potentials is an important factor influencing antioxidant (EC₅₀) and/or antireductant activity. Based on 16 molecular properties for 20 molecules (320 entries), advanced statistical methods (cluster analysis, principal component analysis, pair-correlation) reveal that several groups of similarity exist: {dopamine-noradrenaline}, different from {adrenaline-DOPA-(tyrosine)} and zwitterionic forms of {dopamine-noradrenaline-adrenaline}.