Next Article in Journal
Synthesis of Zinc Oxide Nanoparticles and Their Effect on the Compressive Strength and Setting Time of Self-Compacted Concrete Paste as Cementitious Composites
Next Article in Special Issue
Density Functional Theory (DFT) Study of Triphenylamine-Based Dyes for Their Use as Sensitizers in Molecular Photovoltaics
Previous Article in Journal
Salivary Defense Proteins: Their Network and Role in Innate and Acquired Oral Immunity
Int. J. Mol. Sci. 2012, 13(4), 4321-4339; doi:10.3390/ijms13044321

Toward the Understanding of the Metabolism of Levodopa I. DFT Investigation of the Equilibrium Geometries, Acid-Base Properties and Levodopa-Water Complexes

1,2,* , 1
Received: 9 January 2012 / Revised: 13 March 2012 / Accepted: 26 March 2012 / Published: 2 April 2012
(This article belongs to the Special Issue Advances in Density Functional Theory)
View Full-Text   |   Download PDF [1980 KB, uploaded 19 June 2014]   |   Browse Figures


Levodopa (LD) is used to increase dopamine level for treating Parkinson’s disease. The major metabolism of LD to produce dopamine is decarboxylation. In order to understand the metabolism of LD; the electronic structure of levodopa was investigated at the Density Functional DFT/B3LYP level of theory using the 6-311+G** basis set, in the gas phase and in solution. LD is not planar, with the amino acid side chain acting as a free rotator around several single bonds. The potential energy surface is broad and flat. Full geometry optimization enabled locating and identifying the global minimum on this Potential energy surface (PES). All possible protonation/deprotonation forms of LD were examined and analyzed. Protonation/deprotonation is local in nature, i.e., is not transmitted through the molecular framework. The isogyric protonation/deprotonation reactions seem to involve two subsequent steps: First, deprotonation, then rearrangement to form H-bonded structures, which is the origin of the extra stability of the deprotonated forms. Natural bond orbital (NBO) analysis of LD and its deprotonated forms reveals detailed information of bonding characteristics and interactions across the molecular framework. The effect of deprotonation on the donor-acceptor interaction across the molecular framework and within the two subsystems has also been examined. Attempts to mimic the complex formation of LD with water have been performed.
Keywords: levodopa; parkinson’s disease; DFT; protonation/deprotonation; NBO levodopa; parkinson’s disease; DFT; protonation/deprotonation; NBO
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
MDPI and ACS Style

Elroby, S.A.K.; Makki, M.S.I.; Sobahi, T.R.; Hilal, R.H. Toward the Understanding of the Metabolism of Levodopa I. DFT Investigation of the Equilibrium Geometries, Acid-Base Properties and Levodopa-Water Complexes. Int. J. Mol. Sci. 2012, 13, 4321-4339.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


Cited By

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert