Investigation On Enthalpic Pairwise Interactions Of Biological Model Molecules

Chiral discrimination and molecular interactions are of great importance in many fields such as biology, chemistry, material science, and pharmaceutics. The microcalorimetry is very useful in the study of weak nonbonding interactions and their energetic effects in solutions. In this thesis, enthalpic pairwise interactions and their solvent effects of some chiral drug molecules and crown ethers in strongly polar aqueous mixed solvents have been investigated by isothermal titration microcalorimetry. The main content consists of the following four parts:In the first part, D-penicillamine, L-penicillamine and their racemate DL-penicillamine were choosen as research objects. Dilution enthalpies of each of them in DMF+water and DMSO+water mixtures of various compositions (w0=0.30) have been determined respectively at298.15K, using an isothermal titration calorimeter (MicroCal ITC200). According to the McMillan-Mayer theory, the corresponding homochiral enthalpic pairwise interaction coefficients (hxx) of them have been calculated. It is found that the order hLL>hDD≈hm>0(“r” represents the racemate of penicillamine). The results are discussed from the point of view of competitive equilibrium between hydrophobic and hydrophilic interactions in the ternary solutions.In the second part, dilution enthalpies of two chiral diols, namely (3R,5R)-(-)-3,5-heptanediol,(3S,5S)-(+)-3,5-heptanediol, in DMF+water and DMSO+water mixtures of various compositions (w=0-0.30) have been determined respectively at298.15K, using MicroCal ITC200. According to the McMillan-Mayer theory, homochiral enthalpic pairwise interaction coefficients (hxx) of the enantiomers in each of the two mixed solvents of different mass fractions have been calculated. It is found that hxx coefficients of each enantiomer change increasingly with wDMF (or wDMSO) to the maximums at WDMF=0.20(wDMSO=0.25), and then decrease rapidly, following the order hss>hRR. Therefore, in water-rich regions, both DMF and DMSO play a role of "structure-builder", but in regions rich in DMF or DMSO, the two polar cosolvents become "structure-breaker".In the third part, dilution enthalpies of two glycidols, namely R-(-)-glycidol, S-(-)-glycidol, and their racemate RS-(±)-glycidol in DMF+water mixtures (w=0-0.25) have been determined respectively at 298.15K, using MicroCal ITC200. According to the McMillan-Mayer theory, homochiral enthalpic pairwise interaction coefficients (hxx) have been calculated. The order hRR> hn>hSS ("r" represents the racemate of glycidol) is found, indicating great effect of chirality discrimination.In the fourth part, as above, dilution enthalpies of12-crown-4,15-crown-5,18-crown-6, and4,13-diaza-18-crown-6-ether in DMF+water have been determined respectively at298.15K, and the corresponding enthalpic coefficients (hxx) have been calculated. Weak nonbonding interactions in the ternary solutions have been discussed from the point of view of solute-solute and solute-solvent interactions. It is considered that macrocyclic hydrophobic effect exist profoundly.