Ab initio study of molecular properties of l-tyrosine

Abstract

Context: l-Tyrosine is a naturally occurring agent that acts as a precursor in biosynthesis of monoaminergic neurotransmitters in brain such as dopamine, adrenaline, noradrenaline, and hormones like thyroxine and triiodothyronine. While l-tyrosine in vacuo adopts the canonical aminoacid form with -NH₂ and -COOH functional groups, from neutral solutions, is crystallizes in the zwitterionic form possessing -NH₃⁺ and -COO^- groups. As l-tyrosine is non-innocent agent with respect to redox processes, redox ability in water expressed by the absolute oxidation and reduction potentials is investigated. The cluster analysis applied to a set of nine related neurotransmitters and trace amines confirms that l-tyrosine is mostly similar to aminoacid forms of phenylalanine, octopamine, and noradrenaline.

Methods: The energetic data at the Hartree-Fock MO-LCAO-SCF method has been conducted using def2-TZVP basis set, and improved by the many-body perturbation theory using the MP2 correction to the correlation energy. For the aminoacid form and the zwitterionic form of l-tyrosine, a set of molecular descriptors has been evaluated (ionization energy, electron affinity, molecular electronegativity, chemical hardness, electrophilicity index, dipole moment, quadrupole moment, and dipole polarizability). The solvent effect (CPCM) is very expressive to the zwitterionic form and alters the sign of the electron affinity from positive to negative values. In parallel, density-functional theory with B3LYP variant in the same basis set has been employed for full geometry optimization of the neutral and ionized forms of l-tyrosine allowing assessing the adiabatic (a) ionization/affinity processes. The complete vibrational analysis enables evaluating thermodynamic functions such as the inner energy, enthalpy, entropy, Gibbs energy, and consequently the absolute oxidation and reduction potentials. Of applied methods, the most reliable are B3LYP(a) results that account to the correlation energy and the electron and nuclear relaxation during the ionization/affinity processes.

Keywords: Ab initio calculations; Electronic structure; Molecular descriptors; Molecular properties; l-Tyrosine.

Fig. 1

Structural formula of l-tyrosine in aminoacid and zwitterionic forms

Fig. 2

Structural forms of l-tyrosine. Color code: gray – C, white – H, blue – N, red – O. Notice differences in the torsion angles C–C-O–H at HO-Ph moiety

Fig. 3

Optimized geometry for the aminoacid and zwitterionic forms of l-tyrosine by DFT-B3LYP method using def2-TZVP in water. Energetic data in E_h

Fig. 4

Optimized molecular structure for amino-form of l-tyrosine in vacuo, 3D mapped isosurface of charge density; contour 0.03 ea₀⁻¹, a₀ – bohr unit. Blue – positive, red – negative

Fig. 5

Cluster analysis (Wards method) showing similarity of species in Table 5 based upon molecular electronegativity, chemical hardness, electrophilicity and polarizability calculated at MP2 level. Numbering of species according to Table 5