Study On The Interaction Between Four Drugs And Biological Small Molecules In Aqueous Solution

With the development of medicine and life science,studying the interaction mechanism between drugs and proteins or small molecules with biological activity is extremely important for understanding pharmacokinetics and developing new drugs.It is currently one of the topics of common concern and interest in medicine the life science and chemistry or clinical.Small biological molecules are the structural units of proteins,are the basis for proteins to play an active role,and are also important substances involved in various cellular functions of human body.The studing of the interaction between small biological molecules and drug molecules not only is a guiding role in studying the nature of the interaction between drug molecules and proteins,but also is important practical significance for understanding the absorption and metabolism of drugs.In this paper,the small biological molecules are four amino acids and three dipeptides,the four drugs are tetradecylpyridinium chloride?[Tet Py][Cl]?and cetylpyridinium chloride?[Cet Py][Cl]?,sodium salicylate?[Na][Sal]?,sodium sulfamidate?[Na][SA]?.The content and results of the studing are as follows:?1?The conductivity of drug molecules is measured by the conductivity method in aqueous solutions and small biological molecules aqueous solutions at different temperatures,and the surface-active drug molecules of[Tet Py][Cl]and[Cet Py][Cl]thermodynamic values were further calculated in small biological molecule aqueous solutions,such as CMC??35?G_m^???35?H_m^???35?S_m^?etc,the limits molar conductivity of[Tet Py][Cl]?[Na][Sal]and[Na][SA],and the Walden value of the three drug molecules in the aqueous solution of small biological molecules.It is found that under the same conditions,the CMC of[Tet Py][Cl]is greater than that of[Cet Py][Cl],indicating that the longer the alkyl chain of the drug molecule,the easier it is to form micelles;the CMC of both is less than its CMC that the addition of small biological molecules helps to form micelles,and the micellization process can proceed spontaneously,and there is an enthalpy entropy compensation effect in this process;the ultimate molar conductivity of[Tet Py][Cl]?[Na][Sal]and[Na][SA]decreases with the increase of the concentration aqueous solution in small biological molecules,and the solvation of drug molecules takes precedence over water in most amino acids and dipeptides.?2?The density of small biological molecules was measured by volume method in the aqueous solution of drug molecules.The relevant parameters of the volume properties were further calculated at different temperatures and different concentrations:the values of standard partial molar volumeV₂^?,_?,standard partial molar transfer volume?35?V_t^?,partial molar expansion coefficient_?E^?,theoretical hydration number N_H,thermal expansion coefficient?,Hepler's constant and other values.These results show that the standard molar volume of biological molecules is negative in the aqueous solution of drug molecules,and it gradually increases with increasing temperature and concentration.This indicates that hydrophobic group-hydrophobic group interaction and ion-hydrophobic group interaction are dominated in this ternary system,and this effect gradually increases with increasing temperature;its theoretical hydration number decreases with increasing of temperature and the concentration of the drug in aqueous solution,this indicates that the increasing of temperature and the drug concentration can produce dehydration of small biological molecules.?3?The contribution of amino acid CH₂?amphoteric groups?NH₃,COO^-?and other alkyl groups as well as glyceryl groups?CH₂CONH?of dipeptides to their standard partial molar volume was calculated by the linear relationship between the number of amino acid alkyl carbon atoms and their standard partial molar volume and the standard partial molar volume of glyceryl dipeptide in aqueous solution.The interaction between drug molecules and glycamyl?CH₂CONH?and amphoteric terminal?NH₃,COO^-?of small biomolecules is stronger than that between drug molecules and hydrophobic groups of small biomolecules?4?The absorbance of the ternary system is measured by UV spectrum method at different wavelengths and different concentrations.The absorption peak of the[Tet Py][Cl]and[Cet Py][Cl]around 210 nm is red-shifted,the absorption peak of the[Na][Sal]around 200 nm and 230 nm is red-shifted,the absorption peak of the[Na][SA]around 200 nm is red-shifted,and they have a color-increasing effect;from the calculated binding constants of drugs,it is found that the binding constants gradually increased with the growth of the alkyl chain of small biological molecules,indicats that the interaction between small biological molecules and drug molecules gradually increased.?5?The peak shape and strength change of the functional group are determined by infrared spectroscopy to determine the location of the interaction between the drug and the small biological molecules,and it is found that[Cet Py][Cl]and[Tet Py][Cl]interacting with the small biological molecules can generate micelles.When[Na][SA]interacts with small biological molecules,the amino groups of[Na][SA]with the hydroxyl groups of small biological molecules can generate hydrogen bonds.When[Na][Sal]interacts with small biological molecules,the hydroxyl groups of[Na][Sal]with the amino groups of small biological molecules can generate hydrogen bonds.?6?The hydrogen spectrum of the drug molecule aqueous solution,the small molecule aqueous solution,and the mixed aqueous solution are measured by nuclear magnetic resonance hydrogen spectroscopy.Their chemical shifts can be obtained by analyzing the nuclear magnetic resonance hydrogen spectrum.It is found that the difference of displacement after mixing is negative.It can be obtained that there is hydrogen bond formation or ion-dipole interaction when the two interact.