Quantum-chemical investigation of the structure and the antioxidant properties of α-lipoic acid and its metabolites
Open Access
- 30 November 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Molecular Modeling
- Vol. 18 (7), 2907-2916
- https://doi.org/10.1007/s00894-011-1306-y
Abstract
Quantum-chemical computations were used to investigate the structure–antioxidant parameter relationships of α-lipoic acid and its natural metabolites bisnorlipoic acid and tetranorlipoic acid in their oxidized and reduced forms. The enantiomers of lipoic and dihydrolipoic acid were optimized using the B3LYP/6-311+G(3df,2p), B3LYP/aug-cc-pVDZ and MP2(full)/6-31+G(d,p) levels of theory as isolated molecules and in the presence of water. The geometries of the metabolites and the values of their antioxidant parameters (proton affinity, bond dissociation enthalpy, adiabatic ionization potential, spin density, and the highest occupied molecular orbital energy) were calculated at the B3LYP/6-311+G(3df,2p) level of theory. The results obtained reveal similarities between these structures: a pentatomic, nonaromatic ring is present in the oxidized forms, while an unbranched aliphatic chain (as found in saturated fatty acids) is present in both the oxidized and the reduced forms. Analysis of the spin density and the highest occupied molecular orbital energy revealed that the SH groups exhibited the greatest electron-donating activities. The values obtained for the proton affinity, bond dissociation enthalpy and adiabatic ionization potential indicate that the preferred antioxidant mechanisms for α-lipoic acid and its metabolites are sequential proton loss electron transfer in polar media and hydrogen atom transfer in vacuum.Keywords
This publication has 59 references indexed in Scilit:
- The molecular basis of working mechanism of natural polyphenolic antioxidantsFood Chemistry, 2011
- Quantum-chemical study of interactions of trans-resveratrol with guanine-thymine dinucleotide and DNA-nucleobasesJournal of Molecular Modeling, 2011
- Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parametersMultiple Sclerosis Journal, 2010
- Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potentialBiochimica et Biophysica Acta (BBA) - General Subjects, 2009
- Radical-Scavenging Activity and Mechanism of Resveratrol-Oriented Analogues: Influence of the Solvent, Radical, and SubstitutionThe Journal of Organic Chemistry, 2009
- Prevention of Hypertension, Insulin Resistance, and Oxidative Stress by α-Lipoic AcidHypertension, 2002
- Homolytic bond (H-A) dissociation free energies in solution. Applications of the standard potential of the (H+/H.bul.) coupleJournal of the American Chemical Society, 1992
- Self-Consistent Equations Including Exchange and Correlation EffectsPhysical Review B, 1965
- Inhomogeneous Electron GasPhysical Review B, 1964
- Note on an Approximation Treatment for Many-Electron SystemsPhysical Review B, 1934