物理有机化学-复旦大学-王全瑞4catalystbyacidandbase课件

CatalysisbyAcids,BasesandMetalIonsMechanism:1)Thediffusion-controlledformationofahydrogenbond betweenthebaseB–andtheacidHA2)Thetransferofaproton,leadingtotheformationofanew hydrogenbondedcomplex3)Thediffusion-controlleddissociationoftheproductTherateofprotontransfer1

protontransfertoN,O,Sisfast;

protontransfertocarbon(C)isslow

protontransferfromH3O+toNorOisdiffusion-controlled:k-1

1011l.mol-1.s-1Formationofthehydrogenbondbetweentheprotondonorandtheprotonacceptoristheratedeterminingstep:thisstepisslowerthantheactualprotontransfer!Typicalforcaseswhereaprotonisbothboundtoandtransferredtooxygenornitrogenatoms,wherethenegativechargeislocalizedononeatom.2Nevertheless,diffusionofH+inwaterismuchfasterthandiffusionofotherions:35Mostcarbonacidsarestabilizedbyresonance.HencesignificantstructuralreorganizationmustaccompanydeprotonationThegreaterthestructuralreorganizationduringdeprotonation,thelowerthekineticacidityInfluenceofpHonReactionRateThehydrolysisofestersiscatalysedbybothacidandbase:pHlogkobs7.06Anotherexample:themutarotationofglucosepHlogkobs7.07TwomechanismsforacidcatalysisSpecific

acidcatalysis:-Aprotonistransferredtothesubstrateinarapidpre-equilibrium;subsequently,theprotonatedsubstratereactsfurthertotheproduct(s)intheratedeterminingstep:Generalacidcatalysis:-Protontransferoccursinaslow,rate-determiningstep;subsequently,theprotonatedsubstraterapidlyreactstogivetheproduct(s):9Specificacid/basecatalysisUsuallyfoundforelectronegativeelements(O,N),whereprotontransferisfast:Thesecondstepisrate-determiningandcanbemono-orbimolecular:Reactionrate:sincewecannowwrite:SotherateisonlydependentonthepH,noton[HA]!!10Exampleofspecificacidcatalysis:hydrolysisofacetals(A1mech.)xxxxxxkobs[H+]kobsisdirectlyproportionalto[H+];additionofmoreacid(buffer)atconstantpHhasnoeffectonkobs.Protontransferisnotratelimiting,sothemechanismprobablyreads:kobs[ClCH2COOH/ClCH2COO-](2:1)xxxxxx11SpecificBaseCatalysisExample:theretro-aldolreactionofI:xxxxxxkobs[OH-]kobsisdirectlyproportionalto[OH－].Additionofmorebase(inbuffer)atconstantpHhasnoeffectonkobs;[OH-]istheonlybasethatoccursintherateequation.13Therefore,thereactionmechanismmostprobablyreads:Reactionequation:thereistheacid-baseequilibriuminwater:rewriting:soItisclearthatonly[OH-]occursintherateequation!14GeneralAcid/BaseCatalysisProtontransferistherate-determiningstep.Example:thehydrolysisoforthoesters:Thereactionisstudiedinaseriesofbuffers(m-NO2-C6H4-OH/m-NO2-C6H4-O–):reactionrateincreaseswithincreasingbufferconcentration,evenifthepHremainsconstantn={k(H2O)·[H2O]+k(H3O+)·[H3O+]+k(m-NO2-Ph-OH)·[m-NO2-Ph-OH]}·[III][buffer]n{k(H3O+)[H3O+]+k(H2O)[H2O]}[III]k(buffer)15So,thereactionmechanismismostprobably:=k(H2O)·[H2O]·[IV]+k(ClCH2COO–)·[ClCH2COO–]·[IV]+k(OH–)·[OH–]·[IV]17SummarizingSpecificacid/basecatalysis:n=k’[S][H3O+] or n=k’[S][OH–]Generalacid/basecatalysis:n={kx[H3O+]+ky[H2O]+kz[HA]+...}·[S]=S[HAi][S],orwithbases:n=S[Bi][S].Whenkx[H3O+]orkx[OH–]arelarge,thecontributionsofotheracids/basesbecomenegligibleandthekineticsresemblespecificacid/basecatalysis.Forthisreason,generalacid/basecatalysisusuallyonlyoccursaroundneutralpH.18Howeffectiveisageneralacidcatalyst:

theBrønstedrelationTheeffectivenessofageneralacidcatalystdependsonitsacidstrength(=theBrønstedrelation):logkHA=alogKHA+aconstantkHA=rateconstantofthecatalyticstepKHA=dissociationconstantoftheacidHAa=Brønstedcoefficient(normally0<a<1) indicatesthesensitivityofthecatalyticstepfor changesinacidstrengthofHA(pKa)19ThereisalsoaBrønstedrelationforgeneralbasecatalysis:

logkB=-blogKHB++aconstant Thecoefficientbhasthesamemeaningasaforgeneral acidcatalysis21TherelationbetweengeneralandspecificcatalysisWhyistheresometimesgeneralandsometimesspecificacid/basecatalysis?

pH:[H+]and[OH－]areverylowinneutralsolution,whereas

[HA]or[B－]canbehighbeneficialforgeneralcatalysis

rateofprotontransfer:HtransfertoandfromCatomsisslower

thantransfertoN,O,etc.beneficialforgeneralcatalysis

stabilityofreactionintermediatesplaysanimportantrole.

Example:comparethehydrolysisoforthoestersandacetals22Ereactionco-ordinate1a,2aEa1Ea2products1b,2b2c1c1cismorestabilisedthan2c

protonationbecomestheratelimitingstepgeneralacidcatalysis!23

PrototropicGroupsofEnzymesAminoacid AcidicgroupBasicgroup pKa N-terminus a-NH3+ a-NH2 7.8 C-terminus a-COOH a-COO– 3.8 asparticacid b-COOH b-COO– 4.4 glutamicacid g-COOH g-COO– 4.6 histidine imidazoliumion imidazole 7.0 cysteine –SH –S– 8.7 tyrosine –C6H4OH –C6H4O– 9.6 lysine e-NH3+

e-NH2 10.4 serine b-OH b-O– 13 threonine b-OH b-O– 13 arginine –NH–(C=NH2+)NH2

–NH–(C=NH)NH2

12.5 peptidebond R–CO–NH–R’ R–CO–N––R’ 14.8ThepKaisstronglyinfluencedbyitsenvironment:e.g.,inenzymesthepKaoflysinecandropto~725MetalIonCatalysisRolesofmetalsincatalysis:As“superacid”:comparabletoH+butstrongerAstemplate:metalionsareabletocoordinatetomorethan2

ligandsandcantherebybringmoleculestogetherAsredoxcatalyst:manymetalionscanacceptordonate

electronsbychangingtheirredoxstateSuperacidcatalysisFeatures:Introducespositivechargeintothesubstrate,makingitmoresusceptibletowardnucleophilicattack.Exchangeofmetalionsisfast(105-109s-1),butslowerthanexchangeofH+(1011s-1)26MetalioncatalysisinthehydrolysisofphosphateestersandanhydridesHydrolysisofphosphateesters(e.g.acetylphosphate)oranhydrides(e.g.ATP)isalwayscatalysedbymetalions,usuallyMg2+:Theroleofthemetalionistwofold:◆neutralizationofthenegativechargeinthesubstrate,toenablethetheapproachofthenucleophile;◆stabilisationoftheleavinggroup(neutralization