  Density functional theory and ab initio methods have been employed to address
the impacts of hydroxyl (OH) group substitutions on the physico-chemical
properties of levodopa (or L-dopa) against the natural amino acids,
phenylalanine and tyrosine. L-dopa, which is an important therapeutic drug for
Parkinson's disease, shares structural homology with the amino acids, whose
structures differ only by OH substitutions in their phenyl side chains. It is
revealed that the backbone geometries of the aromatic molecules do not show
apparent OH-dependent differences; however, their other molecular-level
properties, such as molecular dipole moment, electronic properties and
aromaticity, change significantly. The core binding energy spectra indicate
that the atom sites that undergo modifications exhibit large energy shifts, so
as to accommodate the changes in the intra-molecular chemical environment of
the molecules. The binding energies of the modified C 1s sites in the molecules
shift as much as 1.8 eV, whereas the electronic changes in their O 1s spectra
happen in the higher energy region (ca. 536 eV). The valence spectra provide
enhanced insights on the reactivity and chemical properties of the aromatic
molecules. The impacts of OH moieties on the valence spectra are predominantly
focussed in the energy band<16 eV, where the frontier molecular orbitals
display much reorganization and energy shifts from the amino acids to L-dopa.
Of the three molecules, L-dopa also has the least HOMO-LUMO energy gap, which
can readily explain its proactivity as a drug compound. Furthermore, the
nuclear independent chemical shift calculations suggest that L-dopa also has
more aromaticity features than those of the amino acids. The OH groups,
therefore, play a more prominent role in shaping the physico-chemical
properties of L-dopa, which significantly improve its drug potency.
