Use of Computational Methods to Determine the Relative Thermodynamic Stability of Myricetin, and 4-Methylesculetin for Use as Spin Traps
Location
D.P. Culp Center Room 303
Start Date
4-5-2024 1:30 PM
End Date
4-5-2024 2:30 PM
Name of Project's Faculty Sponsor
Scott Kirkby
Faculty Sponsor's Department
Chemistry
Competition Type
Competitive
Type
Oral Presentation
Presentation Category
Science, Technology and Engineering
Abstract or Artist's Statement
A radical is an atom or molecule with one or more unpaired electrons. Radicals are often highly reactive and are responsible for several deleterious processes in biological systems including oxidative stress. Because most radicals have very short lifetimes making detection difficult, indirect methods are often needed to study them. One such method is spin trapping, which was developed in the late 1960’s to detect radicals using Electron Paramagnetic Resonance (EPR) spectroscopy. Currently, nitrones, such as 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and N-tert.-butyl-α-phenylnitrone (PBN) are widely used as spin traps and are the only types that distinguish between hydroxyl (OH•) and superoxide (O2·-) radicals via EPR. However, they have low water solubility and adduct stability, and hence, are of limited value when investigating biological systems. Another problem is that many of the reaction pathways and mechanisms for spin trapping are still not fully understood. Thankfully, with the advancement of technology, computational chemistry has made a major impact on how research is conducted. With computational chemistry, molecular properties can be modelled to determine if the candidate has the desired properties. This type of chemical research has been used effectively in the chemical industry and academia. The goal of this research was to observe the potential of myricetin, and 4-methylesculetin to determine if they would form stable radical addition products with hydroxyl radical. Standard ab initio computational methods (HF/6-31G*, cc-pVXZ,; DFT/B3LYP/6-31G*, cc-pVXZ,; X = D, T, ) were used to calculate the optimized geometry and energy for each potential spin trap, the hydroxyl radical, and the spin adducts. The calculations were performed using NWChem 7.0.2, originally developed at the Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory. The results found during this research indicate that myricetin, and 4-methlesculetin form stable spin adducts with OH•, and may be of use as spin traps. The most stable addition sites for Myricetin were found to be carbons 10 and 16 located on the B and C rings respectively. For 4-methlesculetin, the most stable sites are carbons 6 and 8. The work presented here is part of ongoing research into using natural product antioxidants and selected synthetic derivatives as potential spin traps.
Use of Computational Methods to Determine the Relative Thermodynamic Stability of Myricetin, and 4-Methylesculetin for Use as Spin Traps
D.P. Culp Center Room 303
A radical is an atom or molecule with one or more unpaired electrons. Radicals are often highly reactive and are responsible for several deleterious processes in biological systems including oxidative stress. Because most radicals have very short lifetimes making detection difficult, indirect methods are often needed to study them. One such method is spin trapping, which was developed in the late 1960’s to detect radicals using Electron Paramagnetic Resonance (EPR) spectroscopy. Currently, nitrones, such as 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and N-tert.-butyl-α-phenylnitrone (PBN) are widely used as spin traps and are the only types that distinguish between hydroxyl (OH•) and superoxide (O2·-) radicals via EPR. However, they have low water solubility and adduct stability, and hence, are of limited value when investigating biological systems. Another problem is that many of the reaction pathways and mechanisms for spin trapping are still not fully understood. Thankfully, with the advancement of technology, computational chemistry has made a major impact on how research is conducted. With computational chemistry, molecular properties can be modelled to determine if the candidate has the desired properties. This type of chemical research has been used effectively in the chemical industry and academia. The goal of this research was to observe the potential of myricetin, and 4-methylesculetin to determine if they would form stable radical addition products with hydroxyl radical. Standard ab initio computational methods (HF/6-31G*, cc-pVXZ,; DFT/B3LYP/6-31G*, cc-pVXZ,; X = D, T, ) were used to calculate the optimized geometry and energy for each potential spin trap, the hydroxyl radical, and the spin adducts. The calculations were performed using NWChem 7.0.2, originally developed at the Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory. The results found during this research indicate that myricetin, and 4-methlesculetin form stable spin adducts with OH•, and may be of use as spin traps. The most stable addition sites for Myricetin were found to be carbons 10 and 16 located on the B and C rings respectively. For 4-methlesculetin, the most stable sites are carbons 6 and 8. The work presented here is part of ongoing research into using natural product antioxidants and selected synthetic derivatives as potential spin traps.