The Molecular Simulation Of The Effects Of Ionic Liquids On The Structural Stability Of Biological Macromolecules

Ionic liquids(ILs)are salts that remain to be liquid at room temperature or even at 100? which are usually composed of organic cations and organic anions,or organic cations and inorganic anions.ILs have very low vapor pressure,low melting point,high thermodynamic stability,adjustable physical properties,low pollution and other well-recognized characteristics,so they are also named as "green solvents".ILs with different chemical and physical properties could be synthesized experimentally by changing the types of cations and anions,which provides great possibilities to expand their application potentialities.In recent years,ILs have been widely used in gas absorption,gas separation,bio-catalysis and material synthesis and have attracted close attention from researchers.In biological sciences,numerous theoretical and experimental works reported that ILs can be used for the separation,extraction and preservation of DNA or proteins.However,the interactions between ILs and bio-molecules and mechanism study of how ILs regulate the structure and stability of bio-molecules at atomic level are poorly documented which becomes a main hindrance for futher studies.In this thesis,taking 1-butyl-3-methyl imidazole chloride(abbreviation for[BMIM]Cl)which is used extensively in experiments as a representative IL,we studied the microstructure of the nucleotides,bases and amino acid analogues in hydrated[BMIM]Cl with different concentrations,respectively,using the molecular dynamics simulation.The solvation free energies(?G)of these molecules were calculated by thermodynamic integration method.Based on these theoretical calculations,we analyzed and discussed the dissolution of biological macromolecules(such as DNA and protein)in pure and hydrated[BMIM]Cl.The main research contents and corresponding conclusions of this thesis are as follows:(1)We calculated the solvation free energies of the basic components of DNA(four hydrogenated bases and four deoxynucleotides)in hydrated[BMIM]Cl with a range of experimental concentrations.Compared to pure water,all molecules have lower the ?G in hydrated[BMIM]Cl,suggesting that the double helix structure of DNA should tend to dissolve in hydrated[BMIM]Cl and the double helix structure would be destroyed.After further analysis of free energy decompositions,the electrostatic interaction between the solute molecules and the ionic liquid solution gradually decreased with the increase of ionic liquid concentration.In contrast,the van der Waals interaction was significantly enhanced,thus is recognized to be the driving force of DNA dissolution.We further calculated the diffusion coefficients(D)and found that D of solute molecules in hydrated[BMIM]Cl are smaller than that in pure water,and even an order of magnitude smaller in highly concentrated[BMIM]Cl.This suggests that the high viscosity of ILs could largely delay the expansion of DNA structure.Our data provides a mechanical explanation for the short term structural stability of DNA in ILs and reveal the thermodynamic nature of the final expansion of DNA structure in ILs.(2)We calculated the ?G of amino acid analogues in highly hydrated[BMIM]Cl.The free energy data suggested that,except four aliphatic amino acid analogues(including alanine,valine,leucine,and iso leucine),most analogue molecules have lower AG in ILs than in pure water,thus should be inclined to dissolve in hydrated[BMIM]Cl,which is consistent with the experimental reports of protein destruction in[BMIM]Cl solution.By calculating the contributions of electrostatic interaction and van der Waals interactions to ?G,it is found that the electrostatic interaction between amino acid analogues and ILs dominated the dissolution process.Only for tryptophan and histidine analogues,the van der Waals interactions between solute molecules and solvent support their dissolution.Most solute molecules have higher ?G in ILs than that in pure water and the van der Waals contribution was the main driving force of the higher solubility in ILs.In particular,the effect of[BMIM]Cl on neutral molecules showed a strong linear relationship between the solvation free energy changes(??G)with the number of their heavy atoms.This suggests that in[BMIM]Cl,the proteins structure may be unfolded,thus losing its vital function.From the present results,we provide a quantitative description of the solvation process in the term of solvation free energies of various molecules in ILs and pure water,providing an in-depth explanation for the experimental reports of biomolecule structure changes in ILs.