Studies On The Interactions Between Ionic Liquids With Mandelic Acid And L-Proline As Anions And Small Biomolecules In Aqueous Solution

In recent years,the emergence of the third generation ionic liquid(ILs),namely pharmaceutical active ingredient ionic liquid(API-ILs),has attracted the attention of scientists.Compared with traditional solid drugs,API-ILs limit the polymorphism of drugs,improve the solubility and dissolution rate of drugs,increase the stability and permeability of drugs,and improve the drug delivery.In view of its application prospect as a drug,it is of great practical significance to explore its mechanism of action on biomolecules.Therefore,studies on the physical and chemical properties of API-ILs with small biological molecules will help to understand the fine details of the interactions between API-ILs and biological macromolecules.In this paper,we designed and synthesized four pharmaceutical active ingredient ionic liquid(API-ILs):tetradecylpyridine-mandelic acid([TetPy][MAN]),cetylpyridine-mandelic acid([CetPy][MAN]),benzalkonium-mandelic acid([BK][MAN]),and benzalkonium-proline([BK][PRO]).The thermal stability of the four API-ILs was measured by thermal analysis,and the properties of the interactions between four API-ILs and amino acids/dipeptides were studied by volume,conductivity,UV and fluorescence spectroscopy.The main conclusions are as follows:(1)The thermal stability interval and thermal decomposition rate of API-ILs were measured by a synchronous thermal analyzer.The results showed that the four API-ILs synthesized had good thermal stability.(2)The critical micelle concentrations(CMC)of four API-ILs in water and aqueous amino acid/dipeptide solution were determined by conductance method,and the thermodynamic functions such as ?Gm???Hm???Sm? during the micellar process were calculated.It was found that the CMC of[TetPy][MAN],[BK][MAN]and[BK][PRO]in water and aqueous amino acid/dipeptide solutions all showed a trend of decreasing first and then increasing with the increase of temperature,while for[CetPy][MAN],CMC increased with the increasing temperature.[TetPy][MAN],[CetPy][MAN]and[BK][MAN]have lower CMC values in the amino acid/dipeptide aqueous solution than those in water,[TetPy][MAN],[CetPy][MAN]and[BK][MAN]have lower CMC values in the amino acid/dipeptide aqueous solution than those in water,indicating that the addition of amino acid/dipeptide can promote the micellization process of three kinds of API-ILs.While the CMC value of[BK][PRO]in the aqueous amino acids/dipeptides solution is greater than that in the water,indicating that the addition of amino acids/dipeptides is not conducive to the micellization process of API-IL.Micellization of the four API-ILs in water and amino acid/dipeptide solutions was spontaneous,and there was an enthalpy-entropy compensation effect during the micellization.The CMC values of API-ILs with organic anions(mandelic acid and proline)as anions were lower than those of TetradecylPyridinium Chloride,CetylPyridinium Chloride and Benzalkonium Chloride.(3)The limiting molar conductivities of the four API-ILs in the aqueous solution of amino acids/dipeptides are all smaller than their values in water,and decrease with the increasing concentration of amino acids/dipeptides;Walden value indicates that API-ILs is preferentially solvated by amino acid/dipeptide in the ternary system.(4)The density values of "API-ILs+water" binary system and "API-ILs+amino acid/dipeptide+water" ternary system were measured by Anton Paar densitometer at different temperatures.The standard partial molar volume(V(?)0),standard partial molar transfer volume(?tV(?))theoretical hydration number(nH),partial molar expansion coeff-icient(E(?)0),thermal expansion Coefficient(?)and Hepler's constant were calculated.The effects of temperature and API-ILs concentration on the interactions of amino acids/dipeptides with API-ILs were explored.It was found that the ion/hydrophilic-hydrophobic and hydrophobic-hydrophobic interactions between amino acids/dipeptides with API-ILs with mandelic acid anions were dominant,and the ion-ion or hydrophilic-hydrophilic interactions with[BK][PRO]were dominant;The thermal expansion coefficients of amino acids/dipeptides in API-ILs aqueous solution are all positive and increase with the increase of temperature,indicating that the higher the temperature is,the greater influence on the system will be.(5)The group contribution of the standard partial molar volume of amino acid/dipeptide in API-ILs aqueous solution was analyzed.In addition,the standard partial molar volume of amino acid can be used to successfully estimate the standard partial molar volume of the corresponding glycyl dipeptide.(6)The UV spectra of four kinds of API-ILs in amino acid/dipeptide aqueous solution were measured,and the binding constants in the ternary system were calculated according to the maximum absorbance of the spectra.The binding constant increased with the increase of the length of hydrophobic alkyl chain of amino acid or dipeptide.(7)Pyrene was used as a fluorescent probe to determine the I1/I3 value of pyrene probe in water and amino acid/dipeptide solution,as well as the aggregation number of[BK][MAN].It was found that the aggregation number in the presence of amino acids/dipeptides was less than the value of[BK][MAN]in water,and the longer the alkyl chain of amino acids or dipeptides,the greater the aggregation number.