The Molecular Simulation And Mechanism Of Me₂SO And Glycerol Based Vitrification Solution

Vitrification is assumed to be a potential method for the cryopreservation of largetissues and organs. But the thermal stress and osmotic stress may damage the cells,which limit the practical use of vitrification. The properties of vitrification solution,such as critical cooling rate, glass transition temperature, are key factors that affect itssuccessful application in cryopreservation.Differential scanning calorimetry （DSC）, dynamic mechanical analyzer （DMA） andthermal mechanical analysis （TMA） are common equipments used to determine theproperties of vitrification solution. Lots of experiments must be peformed to obtain aoptimal solution. Molecular dynamic simulation can be used to predict the properties ofvitrification solution in molecular level. It provides a shortcut for selecting suitablevitrification solutions.Applying gromacs3.3andMaterial Studio software, the propeties of severalvitrification solutions were simulated and the mechanism was analyzed in molecularlevel.The thermal and dynamic properties of the material related to its structure. As theradial distribution functions（RDFs） reflects the collective property of molecules, it isregarded as an important factor affecting the structure of vitrification solutions. Theeffect of cooling rates and pressures on the glass transition temperature and RDF wereinvestigated in this study. The results show that cooling rate affects the RDFsof vitifiedwater. Three cooling methods were used to study the structure change of Me₂SOaqueous solution. The first is cooling to final temperature via a series of temperatureswith an interval of10K at a rate of1×1012K/s and sufficient relaxation time at eachtemperature. The second is cooling to final temperature directly at1×1012K/s. The thirdis a two-step cooling method using average between the intial and final temperature asmiddle temperature. The results show that RDF, root mean squared diviation（RMSDs）and the compostion of hydrogen bond show different patterns. Meanwhile, total numberof hydrogen bond and H₂O-Me₂SO space angles are characterized by similarity,directivity and periodicity without significant change during vitrification. Threeconcentrations （70%,50%and30%, wt%） of Me₂SO solutions are investigated toobserve their effects on RDFs, RMSDs, hydrogen bond number and H₂O-Me₂SO space angles. The results show that RDFs, RMSDsand hydrogen bond numbers at threeconcentrations also show different patterns.Hydrogen bond angles, hydrogen bond distances, hydrogen bond numbers andhydrogen bond lifes under three pressures （1bar,10bar,100bar） are calculated forwater separately. Their distributions are obtained by statistical method. The results showthat:（1）hydrogen bond angles distribute in a way similar to Poisson distribution. Whentemperature drops, distributing range become narrower, peak become higher, curves ofdistribution become higher when hydrogen bond angles is in the region between0and13°, but lower when hydrogen bond angles>13°.（2） hydrogen bond distances alsodistribute in a way similar to Poisson distribution with distributing region is bwtween0.14and0.27nm.（3） both hydrogen bond angles and hydrogen bond distances underthree pressures have no significant differences.（4） both the total number of hydrogenbonds and average hydrogen bonds number of each H₂O increase as temperature drop.During vitrifying process, the portion of free water became lowerand lower. Portion ofwater molecules with four hydrogen bonds forming tetrahedron get high dramaticallyfrom290K to260K, then shows little change. Portions of those with one, two or threehydrogen bonds show a overall tendency to get higher as temperature decrease.70%Me₂SO aqueous solution was cooled at1×107K/s and1×1012K/s. Hydrogen bonddistance, angle, nⁿ+i number are calculated. The results show that （1） the distances ofsystem hydrogen bonds, Me₂SO-H₂O hydrogen bonds and H₂O-H₂O hydrogen bondsall distribute in a manner similar to Poisson distribution. With the temperaturedecreasing, the distributing range became narrower, the peak became higher. Distanceof H₂O-H₂O hydrogen bond is longer than that of Me₂SO-H₂O hydrogen bond at thesame temperature and distribution.（2） the angles of system hydrogen bonds,Me₂SO-H₂O hydrogen bonds and H₂O-H₂O hydrogen bonds all distribute in a mannersimilar to Poisson distribution. With the temperature decreasing, the distributing rangebecame narrower, the peak bacame higher. There are differences in angle distribution ofH₂O-H₂O hydrogen bond and that of Me₂SO-H₂O hydrogen bond. Cooling rate haveweak effects on angle distribution of hydrogen bonds.（3） the number of hydrogen bondrespected by n+1～n+5became stable as temperature decreases, but the higher coolingrate results in stronger ability to get stable.Hydrogen bond life distributions and their average lifes are calculated for70%Me₂SO aqueous solution at two cooling rates. The results show that with temperature dropping,（1）life distributions of system, Me₂SO-H₂O and H₂O-H₂O hydrogen bonds alloscillate by higher and higher magnitude,（2） life distributions of Me₂SO-H₂O hydrogenbonds angle are greater than those of H₂O-H₂O when time>3ps，（3） life distribute in amanner similar to power or exponential functions in which independent variable ismultiplied by a negative factor,（4） average life distributes of Me₂SO-H₂O hydrogenbonds are bigger than those of H₂O-H₂O,（5） vibrating amplitudes of life distributionsof system, Me₂SO-H₂O and H₂O-H₂O hydrogen bonds in the system cooled by highercooling rate are lower than those by lower high cooling rate, so do the changes ofamplitudes. Hydrogen bond life distributions of water are calculated under threepressures. Average lifes of water are also calculted basing on the resules of lifedistribution. Average lifes under three pressures are compared. The results show that:（1）hydrogen bond life distribute in a way similar to power or exponential functions inwhich independent variable is multiplied by a negative factor, and with temperaturesdropping, both the range and the values of life distribution show significant differences,（2） pressure has weak effects on the life distributions, but oscillations of life distributioncurves show differences when temperatures is below a temperature, leading tosignificant differences of average life at different pressures.An isothermal-isobaric molecular simulation （NPT-MD） is employed to investigatethe vitrification transition and Tgof such vitrification solution. The cohesive energydensity （CED）, solubility parameter （δ） and bulk modulus of the solution during theprocess of the glass transition are investigated as well. The results indicate that theseproperties as functions of temperature can give a definite inflexion, thus, theseproperties can be used to predict Tg more accurately than the heat capacity （Cp）, density（ρ）, volume （V） and radial distribution function （rdf）. At the same time, the predictedvalues of Tg agree well with the experimental results. Therefore, molecular dynamicsimulation is a potential method for investigating the glass transition and （Tg） of thevitrification solutions.