Microcalorimetry And Spectroscopy Study Of Temperature-sensitive Polymers And The Interaction Of Di-glypeptides With Polyphenols

Polyphenols drug has the defects such as poor solubility, side-effect, which limits the use of polyphenols drug in clinical application. So investigate on the interactions between polyphenols drug molecules and N-glycylglycine or PNIPAM and the thermodynamic properties of polyphenols drug molecules in simulated body fluid, could reveal the mechanism of drug effect in vivo and give reference for the investigation and development of drugs.On the basis of literature investigation and the device of laboratory, we measured the interactions between PNIPAM and piceatannol or oxyresveratrol in buffer solutions by the isothermal titration calorimetry, fluorescence spectroscopy and dynamic light scattering. Study on the mixing enthalpy of N-glycylglycine and protocatechuic acid and their dilution enthalpy by isothermal flow calorimetry. As a part of the project supported by National Natural Science Foundation(NO. 21103079, 21473085), the present work mainly include four parts:In the first part: In this work, poly(N-isopropylacrylamide) was prepared via reversible addition-fragmentation chain transfer polymerization and its molecular weight and hydrodynamic diameter were measured by gel permeation chromatographer and dynamic light scattering, respectively. Fluorescence spectroscopy and isothermal titration calorimetry studies indicated that there are two types of sites on poly(N-isopropylacrylamide) molecules for the binding of piceatannol, i.e., hydrophilic and hydrophobic binding sites. The number of binding site and the binding strength show pHand temperature- responsiveness. In addition, the free concentration of piceatannol calculated from thermodynamic data implies that piceatannol has maximum free concentration at 25°C and pH 6.2, which suggests that properly acidic medium and lower temperature are favorable to the release of piceatannol.In the second part: In this work, the hydrodynamic diameter of clathrate compound of PNIPAM and oxyresveratrol with various pH phosphate buffer solutions were measured by dynamic light scattering. Isothermal titration calorimetry and fluorescence spectroscopy studies disclosed that there are two types of sites on PNIPAM molecules for the binding of oxyresveratrol, i.e., hydrophilic and hydrophobic binding sites. In addition, the number of binding site, the binding strength, enthalpy change and entropy change show pH- and temperature- responsiveness.In the third part: The dilution enthalpies of N-glycylglycine in sodium phosphate and potassium phosphate buffer solutions with different pH values have been investigated by mixing-flow isothermal microcalorimetry at 298.15 K. The homotactic enthalpic interaction coefficients(h2, h3, and h4), in the pH range of phosphate buffer solution from(3.0 to 8.0), have been calculated according to the McMillan–Mayer theory. Change trends of the enthalpic pairwise interaction coefficients with increasing pH in both the phosphate buffer solutions were obtained. The trends and differences were discussed in terms of solute – solute and solute – solvent interactions.In the fourth part: The mixing enthalpies of protocatechuic acid with N-glycylglycine in sodium phosphate and potassium phosphate buffer solutions with different pH values have been investigated by mixing-flow isothermal microcalorimetry at 298.15 K. The heterotactic enthalpic interaction coefficients(hxy, hxxy, and hxyy), in the pH range of phosphate buffer solution from(3.0 to 8.0), have been calculated according to the McMillan–Mayer theory. Change trends of the enthalpic pairwise interaction coefficients with increasing pH in both the phosphate buffer solutions were obtained. The trends and differences were discussed in terms of solute – solute and solute – solvent interactions. The resulting thermodynamic parameters may be useful for the application of protocatechuic acid in pharmaceutical industries.