Study On The Inclusion Mechanism Of β-Cyclodextrin With C10aroma Molecules Based On Molecular Dynamics Simulation

Aromatic compounds have special odor,antibacterial and antioxidant activities,but their application is limited due to the disadvantages of volatile,oxidative and poor water solubility.Cyclodextrins（CDs）have an outer hydrophilic and inner hydrophobic cavity structure,which can encapsulate active substances to improve their solubility and stability and protect their biological activity.In this study,β-cyclodextrin（β-CD）was used to encapsulate five aromatic compounds with different structure,including menthone（Men）,thymol（Thy）,4-terpene alcohol（Ter）,γ-decalactone（Dec）and cuminaldehyde（Cum）.The structure,thermal stability and antioxidant activity of aroma molecule-β-CD inclusion complexes were analyzed.Molecular dynamics（MD）simulation was used to investigate the inclusion mechanism ofβ-CD with aroma molecules,including the formation process,conformational change,interaction energy,hydrogen bond,and binding free energy.The main conclusions are as follows:1.The encapsulation efficiency of aromatic molecules in the five inclusion complexes were Ter-β-CD（69.3%）,Men-β-CD（78.6%）,Thy-β-CD（86.6%）,Dec-β-CD（77.4%）,and Cum-β-CD（73.8%）.The XRD results showed that bothβ-CD and five inclusion complexes exhibited typical crystal properties;and some diffraction peaks ofβ-CD in the inclusion complexes disappeared and new diffraction peaks were formed.The FTIR results showed that the absorption vibration of aroma molecular functional groups weakened or disappeared in the inclusion complex,and the cavity ofβ-CD covered or inhibited the absorption vibration of aroma molecular.The ¹H NMR results showed that the chemical shifts of each proton ofβ-CD in the inclusion complex were shifted upfield,and the chemical shift differences of H3 and H5 were larger than that of H1,H2,and H4,and the chemical shift difference of H3 was larger than that of H5.2.The results of thermal stability analysis showed that the aroma molecules had a large weight loss at 60-110℃,and the weight loss of inclusion complexes mainly occurred at315-330℃,indicating that the thermal stability of aroma molecules was significantly improved after being encapsulated byβ-CD.The results of free radical scavenging experiments showed that the free radical scavenging rate of inclusion complexes was 8.45%-17.72%higher than that of aroma molecules,indicating that the antioxidant properties of aroma molecules were improved after being encapsulated byβ-CD.3.The results of molecular docking show that the binding of the host and guest must satisfy the principle of mutual matching in molecular size and the absence of spatial site resistance effects,and the dominant conformation of the inclusion complex was obtained by docking with a host-guest molar ratio of 1:1.The aroma molecules show bond rotation and molecular folding in theβ-CD cavity,with long alkyl chains and flexible backbones（Dec,Men and Ter）having more variable positions in the cavity.4.The root mean square deviation of the five inclusion complexes increased by 18.18%to 54.55%,with the increase coming from the contribution of flexible aroma molecules.The radius of gyration of the inclusion complexes were reduced by 4.92%to 6.56%,indicating that the molecular structures of the inclusion complexes were more compact compared to theβ-CD.The addition of aroma molecules reduced the interaction ofβ-CD with water molecules,resulting in a decrease in the solvent accessible surface area of the inclusion complexes by 3.07%to 5.73%.The radial distribution function shows that the water molecules distributed at r=0.18 nm and 0.93 nm form the first hydration layer ofβ-CD.The hydration property of hydroxyl oxygen atom O6 is stronger than that of O2 and O3,and the inclusion complex of Dec-β-CD and Men-β-CD showed better hydration.5.The number of intramolecular hydrogen bonds of the five inclusion complexes increased compared to the free stateβ-CD,Men-β-CD had the largest number of intramolecular hydrogen bonds（6.24）and Thy-β-CD had the largest number of intermolecular hydrogen bonds（0.91）,the number of intermolecular hydrogen bonds was much less than that of intramolecular hydrogen bonds;The-OH at C6 formed the most intermolecular hydrogen bonds,including with water molecules and aromatic molecules;The intermolecular hydrogen bonds O₁₂₄-H₁₂₅...O₁₅₈ existed for the longest time（14.15 ns）throughout the simulation,and most（85.71%）intermolecular hydrogen bonds existed for a short time during the simulation and were unstable hydrogen bonds.6.The interaction energy of the five inclusion compounds ranged from-40.82 to-26.39k J/mol.The decomposition term of the interaction energy of van der Waals interaction energy was larger than the Coulomb interaction energy,indicating that the main driving force to make the aroma molecules enter and maintain in the cavity is van der Waals interaction.The solvation free energy of the five aroma molecules is positive（ΔGsol>0）,indicating that the solvation of aroma molecules in water is not a thermodynamically spontaneous process,and the aromatic molecules tend to be insoluble and exhibit hydrophobicity.The binding free energy of the inclusion complex were Cum-β-CD（-21.35 k J/mol）,Dec-β-CD（-17.69k J/mol）,Men-β-CD（-13.96 k J/mol）,Ter-β-CD（-18.59 k J/mol）,Thy-β-CD（-24.71 k J/mol）,respectively.The binding free energy of the five inclusion complexes were negative(ΔG_Bind<0),indicating that the inclusion reaction of aroma molecules withβ-CD is a thermodynamic spontaneous process and the aroma molecules tend to be loaded into the cavity.The binding strength of the inclusion complexes evaluated by the magnitude of the binding free energy was Thy-β-CD>Cum-β-CD>Ter-β-CD>Dec-β-CD>Men-β-CD.