A DFT study on the application of fucoidan-vitamin E succinate micelle model for loading coenzyme Q10

Polymer micelles have garnered extensive research interest and found widespread applications in drug delivery, targeted modification, and intelligent controlled release in recent years. Herein, the micelle molecule (FUC-VES) is theoretically designed by embedding fucoidan (FUC) and vitamin E succinate (VES) as a carrier for loading coenzyme Q10 (CoQ10), in which FUC and VES have excellent hydrophilic and hydrophobic properties, respectively. The molecular structures, frontier molecular orbital (FMO) energies, and solvent energies of FUC, VES, and FUC-VES were optimized and calculated using density functional theory (DFT) method. The lower molecular energy of FUC-VES (-5144.176294 a.u. in gas) comparing with that of FUC (-3554.359166 a.u. in gas) and VES (-1666.241224 a.u. in gas) implies that FUC-VES has stronger stability. In addition, the binding energy and global reactivity descriptors of FUC-VES@CoQ10 were also calculated. The results indicate FUC-VES would exhibit the higher molecular reactivity and water solubility in theory due to its lower energy gap and greater solvent energy. Besides, FUC-VES can spontaneously adsorb CoQ10 due to the negative binding energy (-1.456 kcal/mol). Interestingly, from the perspective of global reactivity descriptors, FUC-VES@CoQ10 exhibits better molecular activity compared with FUC-VES and CoQ10. Through the research of this work, the theoretical reference can be provided for the design of micelle molecules based on FUC and VES.

All theoretical simulations in this work were performed using the Gaussian 16 software package. The ground-state structures of FUC, VES, FUC-VES, and CoQ10 were optimized using the DFT/B3LYP/6-31G(d) method. The molecular docking and IGMH diagram between FUC-VES and CoQ10 were carried out using AutoDock 4.2, Multiwfn 3.3.8, and VMD 1.9.4 software. The FMO energies containing the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and energy gap (∆E_H-L), and solvent energies of FUC, VES, and FUC-VES were optimized and calculated. Moreover, the binding energies and global reactivity descriptors, containing ionization potential (IP), electron affinity (EA), global hardness (η), global softness (σ), chemical potential (μ), electrophilicity (Ψ), and electronegativity (χ) of FUC-VES@CoQ10 were calculated.