5-单磷酸腺苷在水和乙醇-水体系中的溶解度模型

5220075生物加工过程ChineseJournalofBioprocessEngineeringMay2007615-/马骏,张磊,史隽,吴永宏,应汉杰,肖明芳*(南京工业大学制药与生命科学学院,南京210009):以固-液平衡理论溶解度模型适用于非理想体系的h方程为理论基础,结合本实验结晶条件,采用静态法测定了5-单磷酸核苷(5-AMP)在纯水以及不同配比乙醇/水体系中的溶解度,建立了5-AMP水和乙醇/水体系的结晶热力学模型显示该体系属于缔合引起的非理想溶液,并计算水及乙醇/水体系的溶解热和结晶热,为5-单磷酸腺苷的工业结晶生产提供了热力学数据:5-单磷酸腺苷;溶解度;结晶热力学:O795:A:1672-3678(2007)02-0061-06Crystallizationthermodynamicofadenosine5-monophosphateinwaterandethanolMAJun,ZHANGLe,iSHIJun,WUYong-hong,YINGHan-jie,XIAOMing-fang(CollegeofLifeScienceandPharmaceuticalEngineering,NanjingUniversityofTechnology,Nanjing210009,China)Abstract:DataofthesolubilityofAdenosine5-monophosphate(5-AMP)inwater,andinaqueousethanolisessentialforsolventing-outcrystallizationstudies.Thesolubilitiesforthebinarysystem5-AMP+H2Osolutionandternarysystem5-AMP+H2O+ethanolsolutionweredeterminedinthetemperatureranges293~323Koverthevolumefractionethanolrangesof0~20.ThesolubilitydatawereusedformodelingbasedontheApelblatequation,thesolid-liquidequilibriummodelandthehequation.TheCrystallizationthermodynamicmodelandtheexpressionoftherelationshipbetweenthemodelparametersandtheratioofsolventr,thedissolutionheatandthecrystallizationheatof5-AMPinwater/ethanolhavebeenestimatedwiththeexperimentalsolubilitydata.Thisstudyaimsatprovidingthethermodynam-icbasisinthecrystallizingprocess.Keywords:Adenosinemonophosphate;solubility;crystallizationthermodynamics5-(,5-AMP)RNA,,,,,[1-5][6],,vanlaarWilsonRedlich-Kisterh*:2006-10-18:国家十五科技攻关资助项目(2004BA71313B05-05);江苏省333新世纪科学技术带头人培养工程资助项目(20027);教育部跨世纪优秀人才培养计划基金资助项目:马骏(1981-),女,江苏常州人,硕士研究生,研究方向:生物分离工程:应汉杰,教授,博士生导师,E-mai:[e-mail]62生物加工过程52,vanlaarRaoult;,;0,Wilson;Redlich-Kister,[7-11],5-5-AMP/,h,,,,5-AMP1115-AMP/,,1,H+,:5-AMP(H2)5-AMP-(H)+H+5-AMP2-+2H+,P-O-,5-AMPH15-Fig.1Adenosine5-monophosphate12,[7]h,,,x2=c2c1+c2+c3(1),5-AMP(x2001),c1+c2+c3c1+c3(2)x2x2=c2c1+c3(3)V3=V1r,c1=1V1M1V1+V3=1V1M1V1(1+r)=1M1(1+r)c3=3V3M3=3V3M3V1+V3=3V1rM3V1(1+r)=3rM3(1+r)(4)22Fig.2Thedensityofethanolatdifferenttemperatures,3T,3=1065903-0934TT[283K,323K]R2=0998(5)(3)(4)(5)x2=c2(1+r)1M1+(1065903-0934T)rM3(6)121--,,,20075:5-/63lnr2x2=-Hm/R(1/T-1/Tm)(7)x2=1r2expHmR(1Tm-1T)(8)5-AMP,,(4)(5)(8)c2=1r2expHmR(1Tm-1T)1M1+(1065903-0934T)rM31(1+r)(9)122hh-Buckowski[12]-hln[1+(1-x2)x-12]=h(T-1-T-1m)(10)=ln(1-1)ln2(11)hR=Hm+HE/xsat2=Hsoln(12):h,,;12;Hm;HE;xsat2;Hsoln[11](3)~(5)(10)c2=1(1+)1exp[h(1T-1Tm)]-1+11M1+(1065903-0934T)rM3(13)221:():5-AMP(,99%)223,3;,42.3231,,1Superthermosfaticwaterbath;2Jacketcrystallizer;3densimeter;4Mechanicalstirring35-AMPFig.3Setupforthesolubilityof5-AMPmeasurement,288~324K5-AMP-:,(200r/min)3h,1h,,5-AMP232HPLC-:LichrospherC18(250mm46mmid,5m);A20mmol/L(NH4)H2PO4();B;10mL/min;254nm;;20L331,5-AMP(4~6),,/r,r[0,2]:/,5-AMP,(/0~1),/r,,,5-AMPr(0,1),5-AMP,5-AMP64生物加工过程5245-AMPFig.4Solubilityof5-AMPatdifferenttemperatures55-AMPFig.5Solubilityof5-AMPatdifferentsolventratior(00004mol/L),r,5-AMP65-AMPTrFig.6Solubilitysurfaceof5-AMPatdifferentsolventratiorandtemperatures325-AMP(9),,-5-AMP-R20,5-AMP-,5-AMP469~473K[13],1,h,Tm=47505K,[13]1hTable1ThecorrelationresultsindifferentsolventsofhEqr=(cexp-ccal)/cexph(106)288K294K300K306K312K318K324K000021101527-0006800054-0004300037-0003000025-00019030017102240-0002300019-000100001500005-0006100006050010003389-002590002500031000190000700034-0001508000770518800000-000610004300035-0003000026-00003100005407350-0002000030-0009700047-0001700073000431500046086480047500017000150001400012-001180000920000410975000051-00149001400002400016000230000020075:5-/65321h,h5-AMP/,h,/r5-AMP,5-AMP,,,h,787rFig.7Relationshipbetweenmodelparameterandsolventsratior8hrFig.8Relationshipbetweenmodelparameterhandsolventsratior322w()hh=125231exp(16141w)(14),w=M1rM1r+M3(1-r)(15)(12)(14)w(w[0,124])Hsoln=10412106exp(16141w)(16)[14],Hcry-Hsoln(17)Hcryw:Hcry-10412106exp(16141w)(18)h-,45-AMP/,5-AMP/,-,-h,,5-AMP,,h5-AMP/,h,/r5-AMP,5-AMP,,,h:c1c2c35-,mol/Lx1,x2,x35-13,g/LM1M3V1V3,Lr,V3/V1Hm,m,J/molTTm,,KR,83145,J/(molK)R2hh,hK-1Hsoln,Hcry,,J/mol66生物加工过程52:[1]UauyR,QuanR.RoleofNucleotidesinintestinaldevelopmentandrepair:Implicationsforinfantnutrition[J].JNutr,1994,124:1436-1441.[2]LeachJL,BaaxterJH,MolitorBE,eta.lTotalpotentialllya-vailablenucleotidesofhumanmilkbystageoflactation[J].AmJNutr,1995,61:1224-1230.[3]CarverJD.Dietarynucleotides:Effectsonimmuneandgastroin-testinalsystems[J].ActaPediatrics,1999,88:83-88.[4],,.[M].:,1991:213-219.[5],.[M].:,1985.[6]MullinJW.Crystallization[M].London:Butterworths,1992.[7],,.[M].:,1990.[8].[M].:,1991:444-450.[9].[M].:,1994:307-397.[10],,,.[M].:,1990.[11],,.[M].:,1990.[12]BuchowskiH,DsiazczakA,Pie-TrzykS.Solventactivityalongasaturationlineandsolubilityofhydrogenbondingsolids[J].JPhysChem,1980,84:975-979.[13],,,.:[J].,2002(3):13-15.[14],.[M].:,2000.,2010,20171320kg,,2007,21,,16,190kg,,2015,560kg,760kg(张春鹏)