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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
Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah B.O.208203, Saudi Arabia
2
Chemistry Department, Faculty of Science, Benisuief University, Benisuief 6251, Egypt
3
Chemistry Department, Faculty of Science, Cairo University, Cairo 12613, Egypt
*
Author to whom correspondence should be addressed.
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)
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Abstract

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 (CC BY 3.0).

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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.

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