computational chemistry symposium - gla carbon is a well-known ... , there are many types of...
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11thScotCHEMComputationalChemistrySymposium
UniversityofGlasgow
16June2017
http://www.chem.gla.ac.uk/compscot/
ComputationalChemistrySymposium2017
Programme
Friday,16June2017UniversityofGlasgow,SchoolofChemistry,JosephBlackBuilding,UniversityAvenue,GlasgowG128QQ9:30 Registrationopens
Coffee&pastriesintheConferenceRoom
SessionI(Chair:DrHansSenn)10:25 DrHansSenn:Welcomeandopeningremarks
10:30 K1ProfFredManby:Quantummechanicsoflight-matterandsys-tem-bathinteractionsinphotosynthesis
11:20 C1PaulMurphy:Developmentofspin-orbitcouplingforstochasticconfigurationinteractiontechniques
11:40 C2DrBenjaminD.Goddard:Photo-dissociation:Mathematicsmeetsquantumchemistry
12:00 C3DrMariaTudorovskaya:Time-resolvedphotoionizationandhigh-harmonicgenerationbycyclohexadiene
12:20 LunchintheAtrium,WolfsonMedicalSchoolBuilding
SessionII(Chair:DrAnnaStradomska)
13:30 C4DrBenHourahine:DFTB+goesopensource13:50 C5PaulRapp:Competitiveadsorptionforcleanairapplications
14:10 C6DrDavidMcKay:InvestigatingthehydrationofinnerEarthmin-eralsthroughabinitiorandomstructuresearchingandsolid-stateNMRspectroscopy
14:30 C7PattamaWapeesittipan:MillisecondproteindynamicsdoesnotcontrolcatalysisinCyclophilinA–evidencefrommoleculardynamicssimulations
14:50 C8DrZiedHosni:Developmentofanovelcomputationalmethodtoidentifykeyresiduesinproteinstructures
15:10 Coffee&teaintheConferenceRoom
ComputationalChemistrySymposium2017
SessionIII(Chair:DrTellTuttle)
15:30 C9DrFernandaDuarte:Molecularrecognitionandsolventeffectinasymmetriccounteranioncatalysis
15:50 C10RenanZorzatto:Iridium(I)complexesbearingchelatingNHC/phosphineligands:synthesisandapplicationinHIEprocesses
16:10 C11RebeccaM.Nicolson:Understandingrhodiumsolventextrac-tion:amodeofactionstudy
16:30 C12MaiconDelarmelina:Carboxylationmechanismofalkyl-boronateswithCO2catalysedby[Ni(NHC)(allyl)Cl]complexes:aDFTstudy
PosterSession
16:50 P1–P23Posters&drinksintheAtrium,WolfsonMedicalSchoolBuilding
18:00 Announcementofposterprizes
ComputationalChemistrySymposium2017
AbstractsofTalks
ComputationalChemistrySymposium2017
K1Quantummechanicsoflight-matterandsystem-bathinteractionsinpho-tosynthesis
F.ManbySchoolofChemistry,UniversityofBristol,BristolBS81TS,UKAlmostallofthebiomassintheworldderivesfromtheharvestingofsolarenergythroughphotosynthesis.Agreatdealisknownaboutthestructureanddynamicsofthemachin-eryresponsibleforthisprocess,butmysteriesremain.Photosynthesisinpurplebacteriais amazingly efficient: chemical change is induced almost every time a photon is ab-sorbed.Thisiscuriousbecauseitimpliesveryefficienttransportoftheenergythroughadisorderedsystem.Herewewillexplorethequantummechanicsofthelight-matterin-teraction,andoftheenergy-transportprocessesinvolved,totrytoarriveataclearpic-tureofhowphotosyntheticlightharvestingreallyworks.
ComputationalChemistrySymposium2017
C1Developmentofspin-orbitcouplingforstochasticconfigurationinterac-tiontechniques
P.Murphy,J.P.Coe,M.J.PatersonHeriot-WattUniversity,EdinburghEH144ASAdiscussionispresentedofthesoftwaredevelopmentoftheMonteCarloConfigurationInteraction(MCCI)techniquetoallowspinorbitcouplingcalculationstobemadeusingstochasticmethods,withtheaimofproducingacceptableresultsusinghighlycompactwavefunctions. In this first “proof of concept”work, the one-electron term from theBreit-PauliHamiltonianisused.Detailsofthedevelopmentworkalongwithresultsfromatest-bedofatomsanddiatomicmoleculesarepresented.Thesplittingofdegenerateenergylevelsofthesetest-bedspeciesandthecorrespondingspinorbitcouplingcon-stantsare comparedwithexperimentandalsowith theone-electron resultsofothermethods. A discussion of the difficulty of implementing the remaining two-electrontermsoftheBreit-PauliHamiltonianandthecurrentprogresstowardsasolutioninthisregardisalsopresented.
Splitting of Electronic States Carbon Atom (p2)
splitting caused by electrostatic
interactions and electron correlation
1S
1D
3P
splitting caused by spin orbit coupling
1S0
1D2
3P2
3P1
3P0
MJ
0
+2 +1 0
-1 -2
+2 +1 0
-1 -2
+1 0 -1
0
splitting caused by application of magnetic
field
ComputationalChemistrySymposium2017
C2Photo-dissociation:Mathematicsmeetsquantumchemistry
VolkerBetza,BenjaminD.Goddardb,UweManthec,StefanTeufeldaTUDarmstadt,SchoolofMathematicsbUniversityofEdinburgh,SchoolofMathematicscUniversityofBielefeld,FacultyofChemistrydUniversityofTübingen,SchoolofMathematics
Photo-dissociationisthebreak-downofmoleculesbylight,e.g.duringphotosynthesis.Mathematically,itsstudyinvolvestransitionsinatwo-levelpartialdifferentialequation.Givenaninitialwavepacketontheupperlevel,thechallengeistodeterminethewave-packettransmittedtothelowerlevelatlargetimes.Thisistypicallyverysmallwithrapidoscillations,prohibitingaccuratenumericalcalculations,especially inhighdimensions.Fortunately,thereexistsasmallparameterε,thesquarerootoftheratiooftheelectronand nuclearmasses. In the standard adiabatic representation, the transmittedwave-packetistypicallyoforderεgloballyintimebutexponentiallysmall(~exp(-1/ε))forlargetimes1,2.Thisstronglysuggeststhattheadiabaticrepresentationisnottherightonefortheproblem.Usingthemoregeneralsuperadiabaticrepresentations,weobtainanex-plicitformulaforthetransmittedwavepacket1,2,3.Ourresultsagreeextremelywellwithhighprecisionab-initiocalculations,inparticularforreal-worldNaI4.
[1] V.Betz,B.D.Goddard,S.Teufel,Proc.R.Soc.A2009,465,3553-3580.[2] V.Betz,B.D.Goddard,Phys.Rev.Lett.2009,103,3553-3580.[3] V.Betz,B.D.Goddard,SIAMJ.Sci.Comput.2011,33(5)2247-2276.[4] V.Betz,B.D.Goddard,U.Manthe,J.Chem.Phys.2016,144224109.
ComputationalChemistrySymposium2017
C3Time-resolvedphotoionizationandhigh-harmonicgenerationbycyclo-hexadiene
MariaTudorovskaya,AdamKirranderSchoolofChemistry,UniversityofEdinburgh,EdinburghEH93FJInourwork,wearetryingtoanswerthequestionwhetheranewspectroscopictech-nique,namely,high-harmonic(HH)spectroscopybasedonthephotoionizationinducedbyastronginfraredlasercanbeusedtoanalyseaphotochemicalreaction.Ourtheoret-icalapproachisbasedontheassumptionthatthefeaturesoftheHHspectrumarede-terminedbythephotorecombinationandthephotoionizationprobabilities.ThelatteriscalculatedwiththeuseofDysonorbitalsconstructedasanoverlapbetweenthemolec-ularandtargetwavefunctions[1,2].
WeimplementthemethodtoinvestigatetheUV-photon-inducedring-openingreactionofcyclohexodiene(CHD),whichcanbeusedaprototypeforalargeclassoforganicreac-tions.ThedynamicsfollowingthepumphasbeenrecentlydescribedbyMinnitietal.[2].WetakeintoaccounttherelevanttrajectoriesandthecorrespondingstatespopulationandshowhowthephotoionizationandHHoutputarevaryingasafunctionoftime.
[1] C.M.Oana,A.I.Krylov,J.Chem.Phys.2009,131,124114.[2] S.Gozem,A.O.Gunina,T.Ichino,D.L.Osborn,J.F.Stanton,A.I.Krylov,J.Phys.Chem.Lett.
2015,6,4532–4540.[3] M. P.Minitti,J. M.Budarz,A.Kirrander,J. S.Robinson,D.Ratner,T. J.Lane,D.Zhu,J. M.
Glownia,M.Kozina,H. T.Lemke,M.Sikorski,Y.Feng,S.Nelson,K.Saita,B.Stankus,T.Northey,J. B.Hastings,P. M.WeberPhys.Rev.Lett.2015,114,.
ComputationalChemistrySymposium2017
C4DFTB+goesopensource
BenHourahinea,BálintAradib,ThomasFrauenheimb
aSUPA,DepartmentofPhysics,UniversityofStrathclyde,GlasgowbBremenCenterforComputationalMaterialsScience,UniversityofBremen,GermanyDensity functionalbased tightbinding1 is a fast semi-empirical approximation toDFT,typicallybeingaround3ordersofmagnitudefaster,butcapableofproducingresultsthatapproachthoseofDFTtonearchemicalaccuracy.2
TheDFTB+code3isapopularimplementationoftheDFTB1,DFTB2andDFTB3modelsforgroundandexcitedstatecalculations,electronictransportandofferingbothmulti-coreandmassivedistributedparallelism.DFTB+alsocontainsfeaturesnotfoundelse-whereforDFTB(bothcrystallineandmoleculargeometries,non-collinearspin,spin-orbitcoupling,fastextendedLagrangiandynamics,interfacesforREMDandpath-integralmo-leculardynamics,…).
TheDFTBparametershaverecentlybeenreleasedunderCreativeCommonlicense[1]andtheDFTB+codeisnowmovingtotheopenLGPLlicencethisyear.
Inthiscontribution,someofthefeaturesofDFTBandDFTB+,alongwithneartermde-velopmentswillbepresentedanddiscussed.
[1] http://www.dftb.org/[2] X.Lu,M.Gaus,M.Elstner,Q.Cui,J.Phys.ChemB2015,119,1062−1082.[3] B.Aradi,B.Hourahine,T.Frauenheim,J.Phys.Chem.A2007,111,5678–5684.
ComputationalChemistrySymposium2017
C5Competitiveadsorptionforcleanairapplications
AshleighFletcher,KarenJohnston,PaulRappDepartmentofChemicalandProcessEngineering,UniversityofStrathclyde,Glasgow,UKEnvironmentalandhealthconcernsfrompollutionaresignificantsocialeconomicdriv-ers,whichpushlegislationtowardspollutionpreventionandsustainability.Inadditiontohealthconcerns,theemissionofthegreenhousegascarbondioxidemustbereducedtokeepclimatechangebelow2°C.Therefore,itisessentialtodevelopandtestenviron-mentallyfriendlymaterialsthatarehighlyoptimizedtoremovespecificpollutantspecies.Activatedcarbonisawell-knownaffordablecarbondioxideandpollutantadsorber.How-ever,therearemanytypesofactivatedcarbonsandtheseadsorbsomespeciesmoreeffectivelythanothers.Totailoractivatedcarbonsfordifferentpollutantspecies, it isnecessarytounderstandorcontroltheirchemicalandstructuralcomposition.Thispro-jectaimstoidentifywhichcharacteristicsofactivatedcarbonareoptimalforremovalofpollutants,suchascarbondioxide.
Asastartingpointwetakegraphiteasamodelsystemandstudytheadsorptionofcar-bondioxideusingacombinedcomputersimulationandexperimentalapproach.Quan-tumcalculationsfoundthatcarbondioxideadsorbsweaklyonthegraphitesurfaceviaphysisorption(vanderWaalsinteractions)withalmostnegligiblepreferenceforspecificadsorption sites. Grand canonicalMonte Carlo isotherms, with force fields based onquantumadsorptiondatawereperformedforgraphiteslitporesandamorphouscarbonstructures. Results revealedmuchhigher adsorption formicroporous structures com-paredtomesoporousslitporesatlowpressure.Experimentalresultsfoundgraphiteinpowderedformhasasignificantlylowerisostericheatofadsorptioncomparedtotheo-reticalisotherms,whichisattributedtoabroaderporesizedistributionandlargerporesizes.Futureworkisaimedtowardsa)competitiveadsorptionofseveralpollutantspe-ciesongraphiteandb)adsorptiononmodifiedgraphitetodeterminethemosteffectiveactivatedcarbons.
ComputationalChemistrySymposium2017
C6InvestigatingthehydrationofinnerEarthmineralsthroughabinitioran-domstructuresearchingandsolid-stateNMRspectroscopy
DavidMcKaya,RobertF.Moranb,DanielJ.Twista,ChrisJ.Pickardb,AndrewJ.Berryc,SharonE.AshbrookaaSchoolofChemistry,EaStCHEMCentreofMagneticResonance,UniversityofStAndrews,StAn-drewsKY169ST,UKbDepartmentofMaterialScienceandMetallurgy,UniversityofCambridge,CambridgeCB30FS,UKcAustralianNationalUniversity,ResearchSchoolofEarthSciences,ActonACT,Australia
Nominally,anhydrousminerals (NAMs),ringwooditeandwadsleyite(Fe-freeg-andb-Mg2SiO4)makeuptheEarth'stransitionzone,aregionofthemantleatdepthsof410-660km.NAMscantakeuplowlevelsofH2O(someupto~3.3wt%),leadingtotransitionzonehydration.ThestructuresofmanyhydratedNAMsarenotknown,however,duetotheinherentdifficulty in locatingHatomsanddisorderedvacanciesbydiffractionandsyntheticchallengessuchasextremesynthesisconditions(1600°C,16-20GPa),polymor-phismandsamplesizelimitations(~30mg).DiscoveryofrobuststructuralmodelswouldleadtoabetterunderstandingofthehydrationmechanismandbettermodellingoftheEarth'smantle.
Nethydrationtoisthoughttoinvolvetheadditionof2nH+,chargebalancedbylossofnMg2+or½nSi4+.Hereinwepresentmodelsofringwooditeandwadsleyiteattwohydra-tionlevels:semi-hydratedg/bMg2SiO4(~1.6wt%H2O)viaMg2+/2H+exchangeandfully-hydratedg/b-Mg2SiO4(~3.3wt%H2O)througheither2Mg2+/4H+orSi4+/4H+exchange.H+ionsdonotsitoncrystallographicsites in thehydratedstructure.Therefore,ab initiorandomstructuresearching(AIRSS)1 isusedtorandomlypositionH+ ionsneartheva-cancy,producing100-1000sofcandidatestructuresforoptimisationviaDFT.
HydrationofringwooditeproceedsviaMg2+andSi4+vacancies(inagreementwithneu-trondiffraction2a),withnewlyformedhydroxylspeciesforminghydrogenbondsalongpolyhedraledges.Thefully-hydratedgroundstateresultsfrom2×Mg2+/2H+exchange,withlowestenergySi4+/4H+structureatjust0.1eVhigher.Inwadsleyite,hydrationvia2×Mg2+/H+exchangeissubstantiallymoreaccessiblethanbySi4+/4H+exchange,discount-ingSivacancies.However,thepresenceofthreecrystallographically-uniqueMg2+sites(andfourO2–sites),complicatesthepicture.Theground-statestructureresultsfroma2×Mg3/2H+hydrationmechanism3andaccessiblehigherenergystructures(supportedbysolid-stateNMRspectroscopy4andneutrondiffractionstudies5)involveacombinationofMg1andMg3vacancies.
ComputationalChemistrySymposium2017
Figure1–Left,crystalstructuresofanhydrousringwoodite(Fd-3m,top)andwadsleyite(Imma, bottom);middle, AIRSSH placement; right, energy rankings in semi-hydratedwadsleyite.
[1] C.J.PickardandR.J.Needs,Phys.Rev.Lett.2006,97,045504.[2] N.Purevjav,etal.,Geophys.Res.Lett.2014,41,6718[3] R.F.Moran,etal.,Phys.Chem.Chem.Phys.2016,18,10173.[4] J.M.Griffinetal.,Chem.Sci.2013,4,1523.[5] A.Sano-Furukawa,etal.,Phys.EarthPlanet.Inter.2011,189,56.
ComputationalChemistrySymposium2017
C7MillisecondproteindynamicsdoesnotcontrolcatalysisinCyclophilinA–evidencefrommoleculardynamicssimulations
PattamaWapeesittipan,AntoniaS.J.S.Mey,JulienMichelEaStCHEMSchoolofChemistry,UniversityofEdinburgh,EH93FJ,UKCyclophilinA(CypA)isamemberoftheCyclophilinfamilyofpeptidyl-prolylisomeraseswhichcatalyzesthecis-transisomerizationofprolinepeptidebond.PreviousbiophysicalstudieshavesuggestedthattheCypAwildtype(WT)activesiteinterconvertsbetweena‘major’ catalytically active conformation and a ‘minor’ catalytically impaired confor-mationonmillisecondtimescales.1Aserinetothreonine(S99T)mutationdistal(ca.10Åaway)fromtheactivesitewasdevisedtostabilizethisminorconformationofCypA,lead-ing to a dramatic 70 fold drop in catalytic turnover, similar in magnitude to activitychangesuponmutationofkey residues thatmakedirect contactswith the substrate.Althoughsuchexampleisfrequentlycitedinsupportoftheimportanceofmilliseconddynamicsforenzymaticfunction,thedetailsofhowtheS99Tmutationreducescatalyticactivityarestillunclear.
Inthisresearch,moleculardynamic(MD)andbiasedMDsimulationswerecarriedouttoinvestigatethelinkbetweenconformationalchangesandcatalysisintheWTandS99Tmutant forms of CypA. In contrast to literature claims,1 we observe conformationalchangesbetweentheproposed‘major’and‘minor’activesiteconformationsonnano-secondtimescales.Yetinagreementwithpreviousexperimentaldata,freeenergypro-filesfromoursimulationsshowedthattheS99TCypA-catalyzedamideisomerizationre-actionhasalargeractivationbarrierthaninWTCypA.FurtheranalysisindicatesthatthisisaresultofweakenedhydrogenbondinginteractionsbetweenAsn102andthetransi-tionstate.Additionalsimulationsestablishedthatweakenedtransitionstatestabilisationiscausedbyanoverallincreaseinfast(nanosecond)dynamicsofactivesiteresiduesduetopoorerside-chainspackingintheS99Tmutant.
In summary,our studydisputes literature claimsof a linkbetween slow (millisecond)proteindynamicsandcatalysis,1andsuggestsinsteadthatchangesinfast(nanosecond)dynamicsaresufficienttoexplainthereducedcatalyticpoweroftheS99TCyclophilinAmutant.
[1] J.Fraser,M.W.Clarkson,S.C.Degnan,R.Erion,D.Kern,Nature2009,462,669–673.
ComputationalChemistrySymposium2017
C8Developmentofanovelcomputationalmethodtoidentifykeyresiduesinproteinstructures
ZiedHosni,SreenuVattipaliBioinformaticsHub,CentreforVirusresearch,UniversityofGlasgow,UKVirusesareinfectiousagentsthatneedhostcellstoreplicateandsurvive.Virus-infectedcellsarerecognisedbyhostimmunesystemwiththehelpoftheepitopespresentedonthecellsurfacebyMHCclass-Imolecules.MHCclass-Iepitopesareshort(generally9aalength)viralproteinfragmentsthatarerecognisedbyimmunecells(CD8T-cells).Selec-tionofaviralproteinfragmentasanepitopedependsontheindividual'sHLAsystem.RecognitionofanepitopebyCD8T-cellsisakeyineliminatingavirusfromthehost.Toescapethehostimmuneattackandsurvive,virusesoftenmutatetheirproteins.How-ever,changingthestructurallyandfunctionallyimportantresiduesinaproteinwillhaveafitnesscostonthevirus.Ifanindividual'simmunesystemdetectsanimportantregionofaproteinasanepitopethenithasahighchanceofsuccessfullyeliminatingthevirus.Herewedemonstrateanovelcomputationalapproachtoidentifystructurallyandfunc-tionallyimportantresiduesinproteinstructures.WehavedevelopedaPythonprogramthatiscapableofrankingresidues’importanceinaproteinbasedontheirnon-covalentbonds,hydrogenbonds,saltbridges,disulphidebonds,hydrophobicandVanderWaalsinteractions.Wearetestingtheprogram’sefficiencybyanalysingepitopessequencesfromHepatitisCvirus(HCV)proteins.WefoundkeyresiduesinHCVproteinsusingourprogram.HCVepitopescontainingkeyresidueswereselectedforfurtheranalysis.Spon-taneousclearanceofHCVininfectedpatientsandtheroleoftheirepitopesiscurrentlyunderinvestigationstotestourprogram.
ComputationalChemistrySymposium2017
C9Molecularrecognitionandsolventeffectinasymmetriccounteranionca-talysis
FernandaDuarteaandRobertS.PatonbaEaStCHEMSchoolofChemistry,UniversityofEdinburgh,EdinburghEH93FJ,UKbChemistryResearchLaboratory,UniversityofOxford,OxfordOX13TA,UKIon-pairingwithacharged,chiralcatalysthasemergedasaversatilestrategyinasym-metriccatalysis1.However,theoreticalworkonthestereoselectivitiesofthesetransfor-mationsremainsachallengingtask.Thisisduetothedifficultiesinidentifyingthemoststableconfigurationsinagivenenvironment,wherethepredominantlyelectrostaticna-tureoftheseinteractionsmakethenlessdirectionalandmoresolventdependentthane.g.hydrogen-bondingordispersioninteractions.
Inthisworkweinvestigatethestructures,dynamicsandstabilitiesofthechiralion-pairsinthecondensedphaseforthelandmarkanionicasymmetricPTCring-openingreactionofmeso-aziridiniumandepisulfoniumcations2.Weusebothclassicalandquantummeth-odsandexplicitlyandimplicitlysolvatedmodels.Wefindthatthestabilityofchiralion-pairs,apre-requisiteforasymmetriccatalysis,isdominatedbyelectrostaticinteractionsatlong-rangeandbyCH⋯Ointeractionsatshort-range.Thedecisiveroleofsolventuponion-pair formation and of non-bonding interactions upon enantioselectivity arequantifiedbycomplementarycomputationalapproaches.Ourcomputationalresultsra-tionalizethestereoselectivityforseveralexperimentalresultsanddemonstrateacom-binedclassical/quantumapproachtoperformrealistic-modellingofchiralcounterionca-talysisinsolution3.
[1] (a)Phipps,R.J.;Hamilton,G.L.;Toste,F.D.Nat.Chem.2012,4,603.(b)Brak,K.;Jacobsen,E.
N.Angew.Chem.Int.Ed.2013,52,534.[2] Hamilton,G.L.;Kanai,T.;Toste,F.D.J.Am.Chem.Soc.2008,130,14984.[3] F.Duarte,RS.Paton.MolecularRecognitioninAsymmetricCounteranionCatalysis:Under-
standingChiralPhosphate-MediatedDesymmetrization.UnderRevision.
ComputationalChemistrySymposium2017
C10Iridium(I)complexesbearingchelatingNHC/phosphineligands:synthe-sisandapplicationinHIEprocesses
WilliamJ.Kerr,TellTuttle,RenanZorzattoDepartmentofPureandAppliedChemistry,UniversityofStrathclyde,GlasgowG11XL,Scotland,UKTransitionmetal-catalysedC-Hactivationhasbecomeavaluabletoolforthefunctional-isationofcomplexorganicmolecules.1Inthiscontext,hydrogenisotopeexchange(HIE)allowsexpedientaccesstoisotopicallyenrichedcompounds,crucialforthetimelyexe-cution of adsorption,metabolism, excretion and toxicology (ADMET) studies,2 and inmechanisticstudiesoforganicreactions.IridiumcomplexesarecommonlyemployedinHIE3duetotheircatalyticactivityandspecificityforlabellingsitesadjacenttodirectinggroups.4 However, the poor performance of existing Ir complexeswith sterically-hin-dereddirectinggroupsconstitutesanimportantlimitation.HereinwereportanewclassofIr(I)complexes(1)bearingachelatingN-heterocycliccarbene-phosphine(NHC-P)lig-and,andtheirapplicationintheHIEofsubstratesbearingstericallydemandingcarba-mates(2–3),establishingasuccessfulstrategytoaccesstwoimportantclassesofsub-strates.
Acombinedexperimentalandtheoreticalstudywasemployedtoevaluatethemecha-nismofthisreaction.WhileDFTcalculationssuggestalowactivationbarrierof20.7kcalmol-1forthekeyC-Hbondcleavage,kineticdatarevealedthataninterestinginterplaybetweensubstratecoordinationandC-Hactivationoperatesinsolution.Throughcom-parisonofcalculatedandexperimentalprimarykineticisotopeeffects(KIE),andevalua-tionof twodirectinggroupswithmarkedlydistinct stericdemands, itwaspossible todemonstrateatemperature-dependentbalancebetweensubstratecoordinationandC-Hactivationastheratelimitingprocess.Moreover,theobservedreactivitycouldalsoberationalisedthroughevaluationoftheinteractionenergyofselectedsubstrateswiththecatalyticallyactiveiridiumdeuteride,whichalsoconstitutesanimportantstepinthecon-structionoftoolstoaidrationalcatalystdesign.
ComputationalChemistrySymposium2017
[1] K.Godula,D.Sames,Science2006,312,67-72.[2] N.Penneretal.,Chem.Res.Toxicol.2012,25,513-531.[3] J.A.Brownetal.,Adv.Synth.Catal.2014,356,3551-3562.[4] A.R.Cochraneetal.,J.LabelCompd.Radiopharm.2013,56,451-454.
ComputationalChemistrySymposium2017
C11Understandingrhodiumsolventextraction:amodeofactionstudy
RebeccaM.Nicolsona,RossJ.Gordonb,JasonB.Lovea,PeterA.Taskera,CaroleA.Mor-risonaaSchoolofChemistry,UniversityofEdinburgh,EdinburghEH93FJbJohnsonMattheyTechnologyCentre,SonningCommon,ReadingRG49NHNocommercialsolventextraction(SX)reagentcurrentlyexistsforrhodium.Recentliter-aturereportedthepromisingrecoveryofRhviaSXusinganewligandsystem.1,2How-ever,detailsconcerningthestructureoftheextractedspeciesandtheinteractionspre-sent – information key to developing a suitable commercial reagent – are not fullyknown.1,2Thisworkhasaimedtoelucidatethemodeofaction.
Initialtestextractionsusingoneofthereportedreagents,(N-n-hexyl-bis(N-methyl-N-n-octyl-ethylamide)amine(BisAA)),1,2andanalysesoftheresultingphaseswereconducted.KarlFischertitrationsshowedthat,thoughwaterappearstobeextractedinassociationwithchloride,negligiblewater isextractedwithRh,suggestingRhextractiondoesnotoccurviaareversemicellemechanism.ESI-MSsuggestedthateither[(RhCl5(H2O))(LH)2]or[(RhCl5(LH))(LH)]isthemainextractedspecies,and[(Rh2Cl9)(LH)3]iseitherextractedorformsintheorganicphase.Italsoshowed[RhCl3L]appearstoformoverlongperiodsoftime.
Figure 1. Minimum energy structures for [RhCl5(H2O)]
2- with [MonoAA(Me)H]+ or[BisAA(Me)H]+,showingdifferentbindingmodes.
Naritaetal.’sfindingssuggestthatextractionoccursviaanion-pairassociationratherthanbindingoftheligandintheinner-sphere.1,2Thefindingsofthisexperimentalworkarenotcontradictory, thereforequantummechanicalmodellingof ion-pair structureswaspursued.TruncatedR-groupversionsofBisAAandanothertwoligandsdevelopedbyNaritaetal,1,2N,N-di-n-hexyl(N-methyl-N-n-octyl-ethylamide)amine(MonoAA)andtris(Nmethyl-N-n-octyl-ethylamide)amine(TrisAA),wereused.
ComputationalChemistrySymposium2017
Figure2.Minimumenergystructuresof[MonoAA(Me)H]+and[BisAA(Me)H]+withchlo-rideand[RhCl5(H2O)]
2-,highlightingdifferentbindingsites.
Thecalculationsshowthatcomplexformationwith[RhCl5(H2O)]2-andexchangeofasso-
ciated chloride for [RhCl5(H2O)]2- ismore favourablewith protonatedBisAA(Me) than
MonoAA(Me),suggestingBisAAisastronger,moreselectiveextractant.Theminimumenergystructuresoftheassembliessuggestthat[MonoAAH]+and[BisAAH]+interactdif-ferentlywith[RhCl5(H2O)]
2-(seeFigure1).Theyalsosuggestthat[BisAAH]+offersdiffer-entbindingsitesforchlorideand[RhCl5(H2O)]
2-,butbothanionscompeteforthesamebindingsitewith [MonoAAH]+ (seeFigure2).Theseresultsare inagreementwith thefindingsreportedbyNaritaetal.2
[1] H.Narita,K.Morisaku,M.Tanaka,Chem.Commun.2008,45,5921–5923.[2] H.Narita,K.Morisaku,M.Tanaka,SolventExtr.IonExch.2015,33,407–417.
ComputationalChemistrySymposium2017
C12CarboxylationmechanismofalkylboronateswithCO2catalysedby[Ni(NHC)(allyl)Cl]complexes:ADFTstudy
MaiconDelarmelinaa,EnricoMarellib,JoséWalkimardeM.Carneiroa,MichaelBühlb aInstitutodeQuímica,UniversidadeFederalFluminense,Niterói,RiodeJaneiro,BrazilbSchoolofChemistry,UniversityofStAndrews,Fife,Scotland.Organoboronatescanbecarboxylatedundermildconditionusingtransitionmetalcom-plexesascatalysts.1Arecenthighlyefficientmethodology(Scheme1)usesNi-NHCcom-plexes(NHC=N-heterocycliccarbene)ascatalysts.2
Scheme1.Experimentalconditionforcarboxylationoforganoboronates.2
Scheme2.Proposedcatalyticcycleforcarboxylationoforganoboronates(Mec.D).
In order to rationalise these findings, we employed DFT calculations (PBE0-D3/ECP2//BP86/ECP1level),usingsmallercongenersoftheexperimentalligand(IMe),boronate(phenylboronate)andbase(methoxideanion).Wehaveinvestigatedavariety
Carboxylation mechanism of alkylboronates with CO2 catalysed by [Ni(NHC)(allyl)Cl]
complexes: A DFT study
Maicon Delarmelinaa, Enrico Marelli
b, José Walkimar de M. Carneiro
a, Michael Bühl
b
aInstituto de Química, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil. bSchool of Chemistry, University of St Andrews, Fife, Scotland.
Organoboronates can be carboxylated under mild condition using transition metal complexes as
catalysts.1 A recent highly efficient methodology (Scheme 1) uses Ni-NHC complexes (NHC = N-
heterocyclic carbene) as catalysts.2
Scheme 1. Experimental condition for carboxylation of organoboronates.2
In order to rationalise these findings, we employed DFT calculations (PBE0-D3/ECP2//BP86/ECP1 level),
using smaller congeners of the experimental ligand (IMe), boronate (phenylboronate) and base
(methoxide anion). We have investigated a variety of possible pathways for the catalytic conversion
described in Scheme 1. The most favourable pathway identified is shown in Scheme 2, in which addition
of the borate species 2-OCH3 to the catalyst 1 followed by transmetalations → oxidative addition of CO2
→ reductive elimination of the carboxylated product are the proposed sequential steps. Transmetalation is computed to be rate-determining (3 → 4 + 5, 'G‡ = 30.5 kcal mol-1).
Scheme 2. Proposed catalytic cycle for carboxylation of organoboronates (Mec. D).
Future investigations will include evaluation of the effect of bulkier ligands and base on the efficiency of
the catalysts, in order to facilitate rational catalyst design for this process.
Acknowledgments
The authors are grateful for the support given from FAPERJ.
[1] M. Brill et al, Top. Organomet. Chem. 2015, 53, 225-278.
[2] Y. Makida et al, Chem. Commun. 2014, 50, 8010-8013.
Carboxylation mechanism of alkylboronates with CO2 catalysed by [Ni(NHC)(allyl)Cl]
complexes: A DFT study
Maicon Delarmelinaa, Enrico Marelli
b, José Walkimar de M. Carneiro
a, Michael Bühl
b
aInstituto de Química, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil. bSchool of Chemistry, University of St Andrews, Fife, Scotland.
Organoboronates can be carboxylated under mild condition using transition metal complexes as
catalysts.1 A recent highly efficient methodology (Scheme 1) uses Ni-NHC complexes (NHC = N-
heterocyclic carbene) as catalysts.2
Scheme 1. Experimental condition for carboxylation of organoboronates.2
In order to rationalise these findings, we employed DFT calculations (PBE0-D3/ECP2//BP86/ECP1 level),
using smaller congeners of the experimental ligand (IMe), boronate (phenylboronate) and base
(methoxide anion). We have investigated a variety of possible pathways for the catalytic conversion
described in Scheme 1. The most favourable pathway identified is shown in Scheme 2, in which addition
of the borate species 2-OCH3 to the catalyst 1 followed by transmetalations → oxidative addition of CO2
→ reductive elimination of the carboxylated product are the proposed sequential steps. Transmetalation is computed to be rate-determining (3 → 4 + 5, 'G‡ = 30.5 kcal mol-1).
Scheme 2. Proposed catalytic cycle for carboxylation of organoboronates (Mec. D).
Future investigations will include evaluation of the effect of bulkier ligands and base on the efficiency of
the catalysts, in order to facilitate rational catalyst design for this process.
Acknowledgments
The authors are grateful for the support given from FAPERJ.
[1] M. Brill et al, Top. Organomet. Chem. 2015, 53, 225-278.
[2] Y. Makida et al, Chem. Commun. 2014, 50, 8010-8013.
ComputationalChemistrySymposium2017
ofpossiblepathwaysforthecatalyticconversiondescribedinScheme1.Themostfa-vourablepathwayidentifiedisshowninScheme2,inwhichadditionoftheboratespe-cies2-OCH3tothecatalyst1 followedbytransmetalations→oxidativeadditionofCO2→reductiveeliminationofthecarboxylatedproductaretheproposedsequentialsteps.Transmetalationiscomputedtoberate-determining(3→4+5,∆G‡=30.5kcalmol-1).
Futureinvestigationswillincludeevaluationoftheeffectofbulkierligandsandbaseontheefficiencyofthecatalysts,inordertofacilitaterationalcatalystdesignforthispro-cess. [1] M.Brilletal.,Top.Organomet.Chem.2015,53,225–278.[2] Y.Makidaetal.,Chem.Commun.2014,50,8010–8013.
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AbstractsofPosters
ComputationalChemistrySymposium2017
P1InvestigatingRu-catalysedCO2hydrogenationusingDFT
IainPrentice,AllanYounga,TellTuttlea
UniversityofStrathclyde,ThomasGrahamBuilding,Glasgow,G11XL,UKWithrecentrisingCO2concentrationsintheatmosphere,removalofCO2fromtheat-mospherehasbecomeanincreasingfieldofinterestnotjustinacademiabutalsoinin-dustry.Alongsidecarboncaptureandstoragetechnologies,acarboncaptureandrecycleapproachwhereCO2isconvertedtomoreusefulfuelsandfeedstock’sisappealing.Re-cently,Olahetal.1demonstratedacatalyticsystemforconversionCO2fromairtometh-anol. This reaction utilised a Ruthenium catalyst and polyamine, with the proposedmechanismshowninFigure1.
Here,wepresentresultsofaninvestigationintotheroleofonlytheRutheniumcatalystinthehydrogenationofCO2inordertodeterminewhetherthereactionisabletooccursolelyinthepresenceofthecatalyst.Weincludetransitionstatebarriersandrelativeenergiesforeachstepofthecatalystonlymechanismandthusareabletoprovideaninsight into themechanistic stepswhere thepolyaminemoleculemaybe required toformalternativeintermediatesinthereactionmechanism.
[1] J.Kothandaraman,A.Goeppert,M.Czaun,G.A.OlahandG.K.S.Prakash,J.Am.Chem.Soc.,
2016,138,778-781.
ComputationalChemistrySymposium2017
P2CarboxylationmechanismofalkylboronateswithCO2catalysedby[Ni(NHC)(allyl)Cl]complexes:aDFTstudy
MaiconDelarmelinaa,EnricoMarellib,JoséWalkimardeM.Carneiroa,MichaelBühlb aInstitutodeQuímica,UniversidadeFederalFluminense,Niterói,RiodeJaneiro,BrazilbSchoolofChemistry,UniversityofStAndrews,Fife,Scotland.SeeabstractC12.
P3Initiationoftransitionmetal-freecrosscouplingreactionsbybiradicalsformedunderbase-independentthermalconditions
MarkAllison,TellTuttle,JohnA.MurphyDepartmentofPureandAppliedChemistry,UniversityofStrathclyde,GlasgowG11XL,UKInrecentyearstransitionmetal-freecouplingofhaloarenestoarenes,proceedingbytheBase-promotedHomolyticAromaticSubstitution(BHAS)mechanismarewidelyreportedintheliterature.1-4Thesereactionsworkwellwhentheyareinitiatedbyorganicelectrondonorsthatareformedinsitufromorganicadditivesofvarioustypes.Intheabsenceofthe organic donor precursors, the coupling reactions can still proceed formany sub-strates,butathighertemperaturesandatamuch lowerrate.Aplausiblemechanismthathasbeenproposedfortheinitiationinthesecasesisthatbenzyne,generatedinsituthroughpotassiumtert-butoxide(KOtBu)deprotonationof thehaloarene,canactasabiradicalandstarttheBHASpathway.3
ComputationalChemistrySymposium2017
Wenowshowthatadditivesthataffordarenediylsbybase-independentroutes,provideindependentinitiationofthecouplingreactionsforthissubstrateintheabsenceofelec-trondonors,supportingasimilarcapabilityforbenzynegeneratedbybase-dependentmeans.1. Yanagisawa,S.;Ueda,K.;Taniguchi,T.;Itami,K.,Org.Lett.,2008,10,4673-6.2. Studer,A.;Curran,D.P.,Angew.Chem.Int.,2011,50,5018-22.3. Zhou,S.;Anderson,G.M.;Mondal,B.;Doni,E.;Ironmonger,V.;Kranz,M.;Tuttle,T.;Murphy,
J.A.,Chem.Sci.,2014,5,476-482.4. Shirakawa,E.;Hayashi,T.,Chem.Lett.,2012,41,130-134
P4Theisomericeffectofthecoordinationsphereonthelinearandnon-lin-earoptoelectronicpropertiesofiridium(III)complexes
ThomasMalcomson,MartinPatersonHeriot-WattUniversity,EdinburghEH144ASHerewepresentacomputationalinvestigationofthestructuralandopticalpropertiesofaseriesofIr(III)complexesofpotentialuseaphotodynamictherapyagentsusingden-sityfunctionaltheory.Detailedcomputationsofseveralaspectsofthephotochemistryhavebeenperformed:isomericeffectsviadifferentialbindingmodes,lowestspin-states,linearsingle-photonabsorption,andnon-linearexcitedstateabsorptionandtwo-photonabsorption.An increase in thenumberof transnitrogensproducesastabilisingeffectwithincreasedgeometryrelaxationintheoptimisedtripletstates,aswellasprovidingadampeningeffecttothemainOPApeakinboththesingletandtripletexcitedstates,andsignificantmodificationofthelowerenergypeaksofeachcomplex.Ared-shiftedisob-served in the lowerenergysingletpeakacrosseachcomplex,corresponding toan in-creasingnumberoftransnitrogens,whilenosuchtrendisobservedinthetripletspectra.
ComputationalChemistrySymposium2017
A)ThreeIridiumcomplexesunderinvestigation.B)Isomersinvestigatedforeachcom-plexrepresentedintheIr1complex:cc,cn,andnn,respectively,inreferencetotheat-omsinthetranspositionsrelativetothesulphuratoms.[1] Z.Liu,I.Romero-Canelon,B.Qamar,J.M.Hearn,A.Habtemariam,N.P.E.Barry,A.M.Pi-
zarro,G.J.Clarkson,P.Sadler,AngewChemIntEd,2014,53,3941.[2] V.Novohradsky,Z.Liu,M.Vojtiskova,P.J.Sadler,V.Brabec,J.Kasparkova,Metallomics,
2014,6,682.[3] S.Stolik,J.A.Delgado,A.Perez,L.Anasagasti,JPhotochPhotobioB.2000,57,90.[4] K.Hopmann,Organometallics,2016,35,3795.[5] P.Cronstrand,Y.Luo,H.Ågren,ChemPhysLet,2002,352,262.
P5Structure-basedpredictionofNMRparametersinzeolites
DanielM.Dawson,RobertF.Moran,DavidMcKay,ValerieR.Seymour,ScottSneddon,SharonE.AshbrookSchoolofChemistry,EaStCHEMandCentreofMagneticResonance,UniversityofStAndrews,NorthHaugh,StAndrews,Fife,KY169ST“NMRcrystallography”isaphilosophythatcombinesbothnuclearmagneticresonance(NMR)spectroscopicandcrystallographicexperimentswiththeuseofcomputationtoprovideadetailedpictureofboththelocalandlonger-rangestructuresofmaterials.Theapproachhasgainedpopularityinrecentyears,andhasbeenappliedparticularlysuc-cessfullytozeolitesandzeoliticmaterials.However,manyofthesematerials(particularly
A
B
Ir1 Ir2 Ir3 + + +
+ + +
ComputationalChemistrySymposium2017
intheirmostcommonandmostinterestingstates)containsomeelementofdisorder,whetherthatbecompositional(e.g.,dopinganSiO2frameworktoobtainanaluminosili-catezeolite),positional(e.g.,thepresenceofmultiplepossibleorientationsofaguestmoleculeinthepores),temporal(e.g.,motionofaguestorwatermoleculewithinthepores)oracombinationofthese(e.g.,duringacatalysedreaction).Thisdisordermaybeinherenttothechemicalandphysicalbehaviourofthematerial,andcanhavesignificanteffectsonthelocalstructure(asobservedbyNMRspectroscopy)butcangoalmostun-detectedbycrystallographicmethods,whichtypicallyprovideatime-andlength-aver-agedstructure.Insuchcases,itcanbechallengingtogenerateaseriesofstructuralmod-elscapableofadequatelydescribingthepossiblelocalstructurespresentinthematerial,butthesearearequisiteforthedensityfunctionaltheory(DFT)calculations.Here,weusecalculatedNMRparametersforaseriesoforderedmodelsystems(wheretheinputstructurecorrespondingtotheNMRparametersisknownexactly)togeneraterelativelysimplestructure-spectrumrelationships (i.e.,dependingonlyonbond lengthsandan-gles)capableofpredictingtheNMRparametersthatwouldbeobtainedbyDFTcalcula-tions.Wethendemonstrate,foraseriesofaluminophosphates1,2andsilicates,3thatthissemi-empiricalapproachopensupthepossibilityofarapidestimationoftheoutcomeofahypotheticalDFTcalculationwheretheactualcalculationwouldbeeitherprohibitivelycostlyorotherwisetoochallenging.
(a)ModelofthelocalenvironmentofaPatominanaluminophosphate,(b)comparisonoftheexperimental,calculatedandsemi-empiricallypredicted31PNMRspectraofcal-cined AlPO-14, (c) comparison of the calculated and semi-empirically predicted 29Sichemicalshiftsforaseriesofsilicatezeolites.
[1] D.M.Dawson,S.E.Ashbrook,J.Phys.Chem.C2014,118,23285–23296.[2] D.M.Dawson,D.McKay,V.R.Seymour,S.E.Ashbrook,inpreparation[3] D.M.Dawson,R.F.Moran,S.E.Ashbrook,submitted.
ComputationalChemistrySymposium2017
P6NMRcrystallography:probingcationdistributioninmixedmetaloxideceramics
ArantxaFernandes,aDaveMcKay,aScottSneddon,aDanielM.Dawson,aKarlR.Whittleb,SharonE.AshbrookaaSchoolofChemistry,EaStCHEMandCentreofMagneticResonance,UniversityofStAndrews,StAndrews,Fife,KY169ST,UKbSchoolofEngineering,CentreforMaterialsandStructures,UniversityofLiverpool,BrownlowHill,L693GH,UKTheeaseofincorporationofcationswithvariableoxidationstatesintopyrochlore-based(A2B2O7)oxidematerialsresults inarangeofapplications, includingnuclearwasteen-capsulation,1catalysis,2andenergymaterials.3Thereis,therefore,considerableinterestinunderstandingthestructure-propertyrelationshipsinthesematerials,i.e.,investigat-inghowcation/aniondisorderandlocalstructurevarywithcomposition.However,sub-stitutioncanbringaboutastructuralchange,withthepyrochlorephasepredictedtobestableonlywhentherelativeratioof thecationradii, rA/rB, isbetween1.46and1.78(e.g.,asisseenforLa2Sn2O7).Belowthis,adefectfluoritestructureisformed,exhibitingdisorderonthecationandanionlattices.WhenrA/rB>1.78,alayeredperovskite-basedstructureisobserved,asisthecaseforLa2Ti2O7).
Figure1.119SnNMRofLa2Ti1.8Sn0.2O7,showingpyrochloreandlayered-perovskitephasespresent.ThecolouredpointsrepresenttheDFT-predictedshiftsforSnsubstitutedintothefourTisitesinthetwoverysimilarstructures.
Inthiswork,weexploitthesensitivityofsolid-stateNMRspectroscopytothelocalstruc-turalenvironmenttoinvestigatethenumber,natureandcompositionofthetwodistinctphasesformedinLa2(Sn,Ti)2O7ceramics.DensityFunctionalTheory(DFT)calculations(onbothunitcellsandsupercells)areusedtoaidspectralassignmentand interpretation,andprovideinformationoncationorderinginbothpyrochloreandlayeredperovskitephases.CalculationssuggestthatthereisarandomdistributionofTicationsintheSn-
119Sn δ (ppm)
−550 −600 −650 −700
∆H / e
V
0.00
0.05
0.15
0.10
× = Structure 1
+ = Structure 2
Sn1 Sn2 Sn3 Sn4
ComputationalChemistrySymposium2017
richpyrochlorephase,althoughalimitedsolidsolutionisobserved.However,compari-sonofexperimentandcalculationsuggestapreferentialsubstitutionofSnontojust2ofthe4possibleTisitesintheTi-richlayeredperovskitephase.La2Ti2O7itselfisdifficulttostudybyNMR,owingtothepropertiesofthenuclidespresent.Oneoptionistouse17ONMRspectroscopy,afterfirstenrichingthesamplewith70%17O2gas.Thisresolves14crystallographicoxygensitesthatcanthenbeassignedusingDFTcalculations.[1] J.M.Bae,B.C.H.Steele,J.Electroceram.,1991,3:1,37-46.[2] R.C.Ewing,Ceram.Int.,1991,17,287-293.[3] S.Park,H.J.Hwang,andJ.Moon,Catal.Lett.2003,87,3-4.
P7NMRCrystallographyofaDisorderedGallophosphateFramework
JosephE.Hooper,aDanielM.Dawson,aLucyBroom,bMahrezAmri,bNathalieGuillou,cSharonE.Ashbrook,aRichardI.Walton.baSchoolofChemistry,EaStCHEMandCentreofMagneticResonance,UniversityofStAndrews,NorthHaugh,StAndrews,Fife,UK,KY169STbDepartmentofChemistry,UniversityofWarwick,Coventry,CV47ALcInstitutLavoiserVersailles,UniversitédeVersailles,UMR8180,78035Versailles,FranceGallophosphates(GaPOs)arearelativelyunderexploredfamilyofzeoliticframeworkma-terialswhosestructurescomprisealternatingcorner-sharingGaO4andPO4tetrahedra,withnetworktopologiescloselyrelatedtothebetter-knownaluminosilicatesandalumi-nophosphates. It ispossibletopreparemanysuchGaPOs,typically inthepresenceoffluorideandanorganicstructure-directingagent(SDA).Theuseofsolid-stateNMRspec-troscopy for the characterisation of GaPOs can provide much structural informationaboutthematerial, includingthenumberofcrystallographicspecies,thecoordinationnumberofGa,theprotonationstateoftheSDAandthetypesoffluoride-containingmo-tifspresent.
AnunknownGAPOhasbeenobservedasacompetingphaseinthesynthesisofGaPO-34,withboth1-methylimidazoleandpyridineasSDAs.1,2Afterthedevelopmentofase-lective synthesis, to produce thismaterial as a purephase, amultinuclear solid-stateNMRstudyhasbeenundertaken.Partialstructuralmodelshavebeenobtainedfromsin-glecrystalandpowerXRDmeasurements,butthesedonotagreewitheachother,orwiththeNMRexperiments.Inparticular,NMRhighlightsthedisorderpresentinthesys-tem,whichisnotreproducedwellintheaveragestructuralmodelsobtainedusingdif-fraction.DFTcalculationshavebeenemployedtoprovideinsightintotheF–/OH–disorder
ComputationalChemistrySymposium2017
thatNMRindicatesispresent,andtohelpassignandinterpretthemultinuclearandmul-tidimensionalNMRspectraobtained.ThecombinationofNMR,XRDandDFTcalculationsshouldprovideapowerfultoolforobtainingadetailedstructuralpictureofthisunknownmaterial.1.M.Amrietal.,J.Phys.Chem.C,2012,116,150482.C.Schott-Darieetal.,Stud.Surf.Sci.Catal.,1994,84,10
P8InvestigatingthelocalstructureofY2(Ti,Sn)2O7ceramicsusingsiteoccu-pancydisorderandNMRspectroscopy
RobertF.Morana,DavidMcKaya,ArantxaFernandesa,PaulynneC.Tornstromb,RicardoGrau-Crespob,andSharonE.AshbrookaaSchoolofChemistry,EaStCHEMandCentreofMagneticResonance,UniversityofStAndrews,NorthHaugh,StAndrews,Fife,KY169ST,UKbDepartmentofChemistry,UniversityofReading,Reading,Berkshire,RG66AH,UKPyrochlorematerials(A2B2O7)haverecentlyseensignificantinterestaspotentialcompo-nentsofceramic-basednuclearwasteforms,withtheultimateaimbeingthelong-termstorageofradioactiveactinidespeciesincludingUandPu.Asmanyceramicsarehighlyresilient tostructuraldegradationcausedbyradioactivedecayandcanaccommodatehighwaste loadings,pyrochloresarepromisingcandidatestoreplaceexistingborosili-categlasswasteforms inthefuture.The8-coordinateAsite inpyrochlorematerials isabletoaccommodatelargercations,suchasY3+orLa3+,whichareofcomparablesizetomanyactinides.Theformationofapyrochlorestructureisgovernedbytheratioofthetwocationsionicradii.IfrA/rB isbetween1.46and1.78thepyrochlorestructureisfa-voured,whereasanionicradiiratiolowerthan1.46leadstotheformationofadisor-dereddefect fluorite (A4O7) structure,whereas above1.78, a layeredperovskite-typephaseisobserved.
BuildingonpreviousstudiesoftheY2Ti2–xSnxO7pyrochloresolidsolution,where89Yand
119SnNMR,combinedwithX-raydiffractionandDFTcalculationswereused,1-3herewewillfocusonusingfirst-principlescalculationstoinvestigatelocalstructureandtheeffectofB-sitecationmixingandvariationinthenextnearestneighbor(NNN)cationarrange-mentsonthecalculated17O,89Yand119Snsolid-stateNMRparameters.WeusedifferentapproachesusedtogeneratepossiblestructuralmodelsforthedisorderedY2(Ti,Sn)2O7ceramicmaterials,fromsimplemodelswhereindividualatoms,oracombinationofat-omsweresubstitutedtomodelB-sitecationmixing,tomorecomplexapproachessuch
ComputationalChemistrySymposium2017
astheSiteOccupancyDisorder(SOD)technique.4TheuseofSODallowsforeverysym-metry-uniquearrangementofatoms foragivencomposition (valueofx) tobedeter-mined,aswellasthecorrespondingdegeneracyofeachofthesestructures,allowinganentropic,aswellasanenthalpictermtobecalculatedforeacharrangement.UsingSOD,allsymmetry-uniqueatomicarrangementsforaseriesofcompositions(x=0,0.25,0.5,0.75,1,1.25,1.5,1.75,2)weregeneratedandmodelsgeometryoptimizedbeforeNMRparameterswerecalculated,allowingadetailedinvestigationofthelocalordering,B-sitecationarrangementandstructuralvariationintheceramicmaterialstobeundertaken.ComparingtheseresultstoexperimentalNMRspectrashouldallowustodeducewhich,ifany,oftheSOD-generatedstructurescontributetotheexperimentalspectra,providingmoreinsightintotheorderingB-sitecationsintheY2(Ti,Sn)2O7pyrochloresolidsolution.[1] S.W.Reader,M.R.Mitchell,K.E.Johnston,C.J.Pickard,K.R.WhittleandS.E.Ashbrook,J.
Phys.Chem.C.,2009,113,18874-18883.[2] M.R.Mitchell,S.W.Reader,K.E.Johnston,C.J.Pickard,K.R.WhittleandS.E.Ashbrook,
Phys.Chem.Chem.Phys.,2011,13,488-497.[3] S.E.Ashbrook,M.R.Mitchell,S.Sneddon,R.F.Moran,M.delosReyes,G.R.LumpkinandK.
R.Whittle,Phys.Chem.Chem.Phys.,2015,17,9049-9059.[4] R.Grau-Crespo,S.Hamad,C.R.A.CatlowandN.H.deLeeuw,J.Phys.:Condens.Matter,
2007,19,256201-256216.
P9ExploringNMRpropertiesofparamagneticCuphenolicoximecomplexesusingDFT
ZhipengKe,DanielDawson,FreddieMack,SharonAshbrook,MichaelBühlUniversityofSt.Andrews,EaStCHEMSchoolofChemistryandCentreofMagneticResonance,NorthHaugh,StAndrews,Fife,Scotland,UKCopper(II)phenolicoximecomplexes(showninFigure1)areimportantintermediatesduringliquid-liquidextractionofcopperfromores,beinganalternativetoenergy-inten-sivetechniquesinvolvingsmelting1.InconjunctionwithDensityFunctionalTheory(DFT)calculations,solid-statenuclearmagneticresonance(NMR)canprobethelocalenviron-mentandgiveinsightsintothestructure,symmetryandbondinginthesematerials.2TheparamagnetismoftheCu(II)complexesposesabigchallengetobothexperimentandtheory.Wehavebeenusingstate-of-the-artDFTmethods(atthePBE0-⅓/IGLO-IIlevel)tosimulatethe1Hand13Cchemicalshiftsinthesecomplexes3andreportonthedetailedeffectoftemperature,intermolecularaggregationandsubstituents(R1andR2inFigure1)ontheseparameters.
ComputationalChemistrySymposium2017
Fig.1Copperphenolicoximecomplexes[1] A.M.Wilson,P.J.Bailey,P.A.Tasker,J.R.Turkington,R.aGrantandJ.B.Love,Chem.Soc.
Rev.,2014,43,123–134.[2] S.E.Ashbrook,D.M.DawsonandJ.M.Griffi,inLocalStructuralCharacterisation:Inorganic
MaterialsSeries,eds.D.W.Bruce,D.O’HareandR.I.Walton,WILEY,WestSussex,1stedn.,2013,pp.1–88.
[3] M.Bühl,S.E.Ashbrook,D.M.Dawson,R.A.Doyle,P.Hrobárik,M.KauppandI.A.Smellie,Chem.-AEur.J.,2016,22,15328-15339.
P10Dataminingsemiconductornanoclusterstructures
SusanneG.E.T.Escher,TomasLazauskas,ScottM.WoodleyDepartmentofChemistry,UniversityCollegeLondon
Nanoclustersareanavenueinmaterialsdesignwhichallowsforfine-tuningpropertiesof a variety ofmaterials, including structurally simple semiconductors (here: alkalineearthoxides).Wepreviouslyinvestigatedbariumoxideclusters1,i.e.(BaO)nwithn=4to18andn=24,usinganevolutionaryalgorithm,andfoundthattheytendtoadoptstruc-turesresemblingrocksaltcuts.Basedona largenumberof localminimafoundduringthisstudy,wehavedataminedcorrespondingstructuresforMgO,CaOandSrOclustersanddeterminedtheirrelativeenergies.Aspreviouslyreported2,3,MgOclusterstendtofavour"barrel"shapesconsistingofsix-memberedrings.WefindthatCaOandSrOclus-tersaremorelikelytoadoptstructuresthatresemblerocksaltcutslikefoundinBaO.
Basedonthisdata,wehavealsoconfirmedsmallerclusterswhereauniquestructureisfound insize-selectedexperiment3,andsuggestsynthesis targetsbasedon this samecriterionaswellaswhichsizesarerelativelymorestableforeachcompound.[1] S.G.E.T.Escher,T.Lazauskas,M.A.Zwijnenburg,S.M.Woodley,Comp.Theor.Chem.2017,
1107,74–81.[2] M.R.Farrow,Y.Chow,S.M.Woodley,Phys.Chem.Chem.Phys.,2014,39,74–81.[3] K.Kwapien,M.Sierka,J.Döbler,J.Sauer,M.Haertelt,A.Fielicke,G.Meijer,Angew.Chem.
Int.Ed.,2011,50,1716-1719
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P11PRFFECT–aversatiletoolforspectroscopists
BenjaminR.Smithab,MatthewJ.Bakerb,DavidS.PalmeraaDepartmentofPure&AppliedChemistry,UniversityofStrathclyde,ThomasGrahamBuilding,295CathedralStreet,GlasgowG11XLbBionanotechnology,TechnologyandInnovationCentre,UniversityofStrathclyde,99GeorgeStreet,GlasgowG11RDThebestchoiceofspectralpre-processingisanunresolvedprobleminthespectraldiag-nosticcommunity.Often,pre-processingisasetlocalroutineusedbyresearchgroupsacrossalldatasets.However,thechoiceoftheparticularmethodsandparametersarenot finely tuned toparticulardataset types.WithPRFFECT (Pre-processing&RandomForestFeatureExtractionCombinationTester)weprovidearobustmethodologytode-cideonoptimalchoicesforpre-processingspectraldatasets.Itisimportanttofindthesebest-possiblemethodsandparametersinordertobuildastrongroutinefortranslationintoclinicalsettings.PRFFECTaccomplishesthisthroughofferingalargearrayofuser-settablepre-processingmethodsandparameters. Aswellaspre-processing, thepro-gramcanrunaRandomForestclassifier(previouslyfoundtobeveryeffectiveforspec-traldatasets)andprovideinformationontheimportanceofvibrationalpeaksinaclassi-fication.Thisallowsthespectroscopisttoeasilyidentifyareasofthespectrumwhichareimportantindistinguishingbetweenclassesofinputdata.
The pre-processingmethods offered are in fourmain categories: Binning, smoothingmethods,normalisationmethods,andbaselinecorrection.Thereareseveralmethodsofferedineachcategory,withtheabilitytosetparametersforeach.Thesemethodscanthenbechosenandcombinedtofindthebestpossiblepre-processingregimefortheinputdata,toachievethebestclassificationandfeatureextraction.
ComputationalChemistrySymposium2017
P12X-rayscattering:fromstaticmeasurementstodynamics
AndrésMorenoCarrascosaUniversityofEdinburgh,SchoolofChemistry,EdinburghEH93FJ,UKX-rayshavebeenwidelyexploitedtounravelstructureofmattersincetheirdiscoveryin1895.Nowadays,withtheemergenceofnewX-raysourceswithhigherintensityandveryshortpulseduration,notablyXFELs(X-rayFreeElectronLasers),thenumberofexperi-mentsavailableintheX-rayregimehasincreaseddramatically,evenallowingthechar-acterizationofgasphaseatomsandmoleculesinspaceandtime.
Our aim is to characterizeultrafast X-ray scattering theoretically. Basedonelectronicstructureab-initiocalculationswehavedevelopedtoolstopredictthesignaturesofat-omsandmoleculesinbothelastic1andinelastic2scattering.Thesignalproducedbythedifferent rotational and vibrational states indiatomic4andpolyatomicmolecules3hasbeenalsocharacterizedusingthisapproach.
Ourmethodscanbeusedtoreproduceaccuratelyhowexcitedwavepacketsevolveintimeinpump-probeX-rayscatteringexperiments.5,6,7
Left:Excitationofthe(1,1,0)RotationalStateinCS2(X).Right:X-rayevolutionofa3d-4fwavepacketinAtomicHydrogen;T=6.3fs.
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WavepacketevolutionandX-raydynamicsinLiFXandBstates.[1] T.Northey,N.ZotevandA.Kirrander,J.Chem.TheoryComput.,2014,10,4911.[2] A.M.CarrascosaandA.Kirrander,submittedtoPCCP.[3] A.M.Carrascosa,T.Northey,A.Kirrander,PhysicalChemistryChemicalPhysics,2017,[4] T.Northey,A.M.Carrascosa,S.Schëffer,A.Kirrander,TheJournalofChemicalPhys-
ics,2016,145,15,154304[5] C.Vallance,Phys.Chem.Chem.Phys.,2011,13,14427.[6] A.Kirrander,K.SaitaandD.V.Shalashilin,J.Chem.TheoryComput.,2016,12,957–967.[7] UlfLorenz,KlausB.Møller,andNielsE.Henriksen,Phys.Rev.A,2010,81,023422
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P13Abinitiosurface-hoppingsimulationsofCS2photodissociationdynamics
DarrenBellshawandAdamKirranderEaStCHEM,SchoolofChemistry,UniversityofEdinburgh,DavidBrewsterRoad,EdinburghEH93FJ,UnitedKingdom.The rapid photodissociation dynamics of CS2 followingUV excitation into the
1B2(S2)stateisdictatedbythecomplexinterplaybetweenmultipleexcitedelectronicstatesinacrowdedmanifoldofpotentialenergysurfaces.ThereactionresultsintheproductionofagroundstateCS(X1Σ+)molecularfragmentalongsideatomicsulfurineitheranexcitedspin-allowedstate(1D)orthespin-forbiddengroundstate(3P).Thelatterchannelisme-diatedviathespin-orbitcouplingarisingfromthepresenceofthesulfuratoms.Althoughtheexactbranchingratiohasprovendifficulttomeasureaccurately,thespin-forbiddenproduct is seen to dominate in most experimental studies [1], highlighting the im-portanceofspin-orbitcouplinginthisphotochemicalprocess.WepresentherethefirstsimulationsofCS2photodissociationthataccountforspin-orbitcoupling.Weuse theSHARCcode (SurfaceHopping includingArbitraryCouplings) [2]interfacedwiththeMolprosuiteofelectronicstructureprograms[3].Basedonthefew-estswitchessurface-hopping(FSSH)algorithm,SHARCaccountsforspin-orbitcouplingthroughareformulationofthestandardsurface-hoppingschemeintermsofaunitarytransformationmatrixandhaspreviouslybeenused tostudy the importanceof spin-orbitcouplingandbranchingratiosinsystemssuchasIBr[2].These simulations are compared to new time-resolved photoelectron spectroscopymeasurements performedby experimental collaborators. This demonstrates that it isnowpossibletocarryouton-the-flydynamicscalculationssuchthatweareabletoex-plaintheshiftingandnarrowingofthephotoelectronspectrumintermsofthebendingmotionofthevibrationalwavepacket,andtrackpopulationchangesbetweenthesingletandtripletmanifold,withexcel-lentagreementbetweenexperimentandtheory[4].[1] D.Xu,J.Huang,W.M.Jackson,J.Chem.Phys.,120:3051–3054,2004.[2] M.Richter,P.Marquetand,J.González-Vázquez,I.Sola,L.González,J.Chem.TheoryComp.,
7:1253–1258,2011.[3] H.-J.Werner,P.J.Knowles,G.Knizia,F.R.Manby,M.Schütz,etal.Molpro,version2015.1,a
packageofabinitioprograms,2015.[4] D.Bellshaw,D.A.Horke,A.D.Smith,H.M.Watts,E.Jager,E.Springate,O.Alexander,C.Ca-
cho,R.T.Chapman,A.Kirrander,etal.Chem.Phys.Lett.,2017.
ComputationalChemistrySymposium2017
P14ImplementationandtestingoftheJEDIcollectivevariabletoexploreproteindruggability
JoanClark-Nicolas,JulienMichelEaStCHEMSchoolofChemistry,JosephBlackBuilding,EdinburghEH93FJ,UKProteindruggability(i.e.theabilityofaproteintobindadrug-likemolecule)isapropertythatoftendependsontheconformationalstateoftheproteinofinterest.Severalstudieshaveproventhatdierentconformationsofaproteinpocketareabletobinddierentligandswithbindinganitiesthatcandierfromonetoseveralordersofmagnitude.Mo-lecularDynamics(MD)simulationsallowtosampletheconformationalspaceofproteins,but very long simulation times are often required in order to detect conformationalchangesthatcaninducearelevantincreaseindruggability.Alotofeorthasbeendonetoenhancethesamplingbybiasingafewcarefullyselecteddegreesoffreedom,knownasCollectiveVariables(CV).TheJEDI(JustExploringDruggabilityatproteinInterfaces)CV1quantiesthedruggablityofproteinpocketswithagooddegreeofcorrelationwiththeexperimentaldruggabilityvaluescompiledintheDruggableCavityDirectorydataset2andallowstomonitoritduringMDsimulations.ThisCVcanalsobeconvertedtoapo-tentialandaforce,whichallowstoapplybiasingpotentialsinordertoexploreregionsofproteinconformationalspacewithadierentdruggabilityscore.ThisworkfocusesonthestabilityandperformanceofsimulationsrunusingJEDItomonitorandbiasthedrugga-bility.Directionsforfurtherimprovementarealsooutlined.[1] Cuchillo,R.etal,J.Chem.Theor.Comput.(2015),11(3),1292.[2] Schmidke,P.;Barril,X.;J.Med.Chem.(2010),53(15),5858.
P15DesignandBiophysicalCharacterizationofNovelCyclophilinInhibitors
HarrisIoannidis,AlessioDeSimone,JordiJuárez-Jiménez,CharisGeorgiou,ArunGupta,JulienMichelEaStCHEMSchoolofChemistry,JosephBlackBuilding,EdinburghEH93FJ,UKCyclophilins(Cyps)belongtoafamilyofproteinsknowntocatalyzethecis-transinter-conversionofprolinepeptidebondsandareinvolvedinvariousdiseases,suchascancer,1Alzheimer,2HIV-1,3HCV4infections.4Duetotheseveresideeffectsoftheknownimmu-nosuppressantCyclosporinA,5thereisaneedfornewdrugstargetingCyclophilinsthatcanbeselectivetowardsoneisoform.
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Atwo-prongedstrategyispursuedtodiscovernovelisoform-selectiveligands.Thefirstapproachexploitsflexibilityofthe70sloop(Fig.1)neighbouringtheknownbindingsitethatconsistsintheAbuandPropockets(Fig.1).Diversebiophysicaltechniques(NMRChemical Shift Perturbation, Saturation-Transfer Difference, and Isothermal TitrationCalorimetry)wereusedtocharacterizethebindingofligandsdesignedandsynthesizedbyco-workers.
Inparallel, the ligandabilityof thesecondary threeo’clockpocket (Fig.1) isbeingex-plored with computational and biophysical techniques. This accessory pocket showsmorestructuralvariabilitybetweendifferent isoforms, compared to themainbindingsite.TothisendmoleculardynamicssimulationsofcyclophilinisoformsA,BandDhavebeencarriedouttodetectthreeo’clockpocketconformationsthatcouldaccommodatedrug-likefragments.Furtherstepswillinvolvevirtualscreeningoffragmentlibraries,andbiophysical characterization of their binding. Ultimately we aim to incorporate threeo’clockpocketbinders into ligands that target theAbu/Propockets, leading toanewgenerationofcyclophilinligandswithenhancedisoform-selectivity.
Fig.1:Cyclophilin-compoundcomplex(4XNC.pdb)showingtheflexible70sloopandthethreedifferentbindingpockets(Abu,Proand3o’clock)presentintheCypsisoforms.[1] Q.Yao,M.Li,H.Yang,H.Chai,W.Fisher,andC.Chen,WorldJ.Surg.,2005,29(3),276–80.[2] K.R.Valasani,J.R.Vangavaragu,V.W.Day,andS.S.Yan,J.Chem.Inf.Model.,2014,54(3),
902-912.[3] J.Luban,K.L.Bossolt,E.K.Franke,G.VKalpana,andS.P.Goff,Cell,1993,73(6),1067–1078.[4] F.Yang,J.M.Robotham,H.B.Nelson,A.Irsigler,R.Kenworthy,andH.Tang,J.Virol.,2008,82
(11),5269–5278.[5] T.L.Davis,J.R.Walker,V.Campagna-Slater,P.J.Finerty,P.J.Finerty,R.Paramanathan,G.
Bernstein,F.Mackenzie,W.Tempel,H.Ouyang,W.H.Lee,E.Z.Eisenmesser,andS.Dhe-Pa-ganon,PLoSBiol.,2010,8(7),1–16.
ComputationalChemistrySymposium2017
P16ForcefieldparameterisationandmoleculardynamicssimulationstudiesofcyclosporinA(CsA)andalisporivir(DEB025)tounderstandthedifferentialdynamicsofcyclophilinA(CypA)inhibition
KanhayaLal,JordiJuárezJiménez,JulienMichelSchoolofChemistry,UniversityofEdinburgh,EdinburghEH93FJ,UKThegoalofthisresearchistocontributetowardsnewmethodologiestointegrateexper-imentalresultsofbiomolecularNMRmeasurementswithmoleculardynamics(MD)sim-ulations.Thestudyinvolvesunderstandingthedifferentialdynamicsofbindingofcyclo-sporinA(CsA)andalisporivir(DEB025)tocyclophilinA(CypA)usingMDsimulationstud-ies. Experimental studies in the literature have shown that the two cyclophilin A lig-andsCsAandDEB025havesimilarstructureanddissociationconstant(KD11nMand7nMrespectively).1However, thedissociationrate(koff)parameter isca.10foldslowerforCsAthenforDEB025(koff27+/-310
-4s-1and2.4+/-0.1x10-4s-1 respectively).2,3Therefore,tounderstandthebindingandunbindingmechanismsofboththecyclicpep-tidesMD simulation approaches involving differential dynamics of the Csa-CypA andDB025-CypAcomplexes,MarkovStateModels(MSMs)andconformationaldynamicsoffreeCsAandDEB025inaqueoussolutionswillbeused.ThestudyaimstounderstandthemajorandminorconformationalpreferencesofCsAandDEB025insolutionandchar-acterisationoftheirrateofexchange.Theinitialstudyinvolvedforcefieldparameteriza-tiontocreateanewresiduetemplatefor7non-standardaminoacidresiduesinboththepeptides.TheatomicpartialchargeswerederivedusingR.E.D.(RESPandESPchargeDe-rive)softwareandbackbonetorsionparameterswerefittedusingParamfit.Thederivedpa-rameterswereabletoreproducefreeenergyplotsforstandardaminoacidssimilartotheAM-BERforcefieldparameters.Finally,AMBER force field librariesweregenerated fornon-standardaminoacidresiduesofboththepeptides.TheresultsofMDsimulationswillbeanalysedtounderstandthebindingmechanism.[1] H.Launay,B.Parent,A.Page,X.Hanoulle,G.Lippens,AngewChemIntEdEngl.2013,52,
12587-12591.[2] D.Altschuh,W.Braun,J.Kallen,V.Mikol,C.Spitzfaden,J.C.Thierry,O.Vix,M.D.Walkishaw,
K.Wüthrich,Structure.1994,2,963–972.[3] R.Wenger,J.France,G.Bowerman,L.Walliser,A.Widmer,H.Widmer,FEBSLetter1994,
340,255–259.
ComputationalChemistrySymposium2017
P17Probingligandbindingaffinitieswithalchemicalfreeenergycalcula-tions
AntoniaSJSMey,JordiJuárezJiménez,JulienMichelEaStCHEMSchoolofChemistry,UniversityofEdinburgh,EH93FJComputeraideddrugdesignhasgainedmomentuminrecentyears,withtheaimtore-ducetheoverallcostofthedevelopmentofanewdrug.Therefore,thereliablepredic-tionofbindingposesandaffinitiesofsmall/drug-likemoleculestotargetproteins,withor without available crystal structures, is essential. However, despite the increase inavailablecomputationalpowerandvastalgorithmicimprovements,thisstillremainsachallenge. Inparticular,whilethere isavastarrayofmethodsavailableforpredictingprotein-ligandinteractions,untilrecentlytherehasnotbeenasystematicapproachtocomparedifferentmethodsandassesstheirreliabilityonasetofblindedexperimentaldata(IC50valuesfromFRETassaysorsimilar).Thedrugdesigndataresource(D3R)grandchallengetriestoaddressthisinformofacompetition.Tworoundsofthegrandchal-lengeswererunin2015and2016.Eachchallengeconsistedofablindeddatasetofsmallmolecules that serve as potential binders to a target protein. Participantswere thengivenfivemonthstopredictthebidingaffinitiesofthesmallmoleculestotheproteinasaccuratelyaspossibleusinganymethodoftheirchoice.Theaccuracyofeachofthepre-dictionswasthenassessedafterthereleaseoftheblindeddataoncethecompetitionperiodwasconcluded.
HereIwillpresentalchemicalmoleculardynamics(MD)simulation-andstate-of-the-artanalysistechniquestocomputefreeenergiesofbindingbetweenligandsandproteinsinthecontextoftheD3Rchallenges.Forthispurpose,thesemi-automatedworkflowusedforligandparameterization,simulationsetup,productionruns,andautomatedanalysiswillbeintroducedbasedonvariousfreelyavailablesoftwarepackages,suchasFESetup1andSire2.The twoD3Rgrandchallengedatasetswill serveasabasis to illustrate theworkflowandhighlightthesuccessesandfailuresinthepresentedtechniquesusedforpredictingbindingaffinities3.TheD3Rdatasetsconsistofcompoundsthatserveasinhib-itorstoheatshockprotein90(HSP90)andfarsenoidreceptorX(FSRX).Lastly,IwillshowhowwellthepresentedalchemicalMDbasedworkflowfaresincomparisontootherap-proachessuchasbiasedMDsimulationsorquantummechanicalmethodsusedbyotherparticipantsofthechallenge.[1] Löffler,H.etal,JChemInfModel.55,2485(2015)[2] Woods,C.J.,Mey,A.,Calabro,G.,Michel,J.(2016).Siremolecularsimulationsframework.[3]Mey,A.etal.Bioorg.Med.Chem.24,4890(2016)
ComputationalChemistrySymposium2017
P18Understandingproteinallostery:developinganalysismethodsformo-leculardynamics
LisaPatricka,JulienMichela,BenCossinsbaTheUniversityofEdinburgh.bUCBCelltechAlthoughallosterywasfirstdiscoveredover50yearsago,themoleculardeterminantsunderlyingsignaltransductionarenotyetcompletelyunderstood.Theabilitytopredicttheactivityofallostericsmallmoleculescouldhaveahugetherapeuticimpact,astarget-ingallostericsitesinproteinspotentiallypresentssignificantbenefitsoveractivesitein-hibitors,inbothselectivityandefficacy.Whilesomesystemsundergofairlywellunder-stoodstructuralchanges,thereisnooverallmodelthatsatisfactorilydescribeshowallo-steryworks.Moleculardynamicssimulationsprovideatooltostudyproteindynamicsattheatomisticlevel,howevertraditionallyemployedanalysismethodshavebeenprovedinadequatetodeliveramechanisticdescriptionofallostery.
Inthiswork,wepresentourapproachtotailorMDsimulationanalysismethodstoiden-tifymotionswhichmaybesignificanttosignaltransmissioninthecasestudyofPDK1(Phosphoinositide-dependentkinase-1).LongMDtrajectorieswererunforPDK1incom-plex with covalent activator and inhibitor small molecules, using the softwareSire/Somd1.AgeometricalanalysisusingtheKullback-Leiblerdivergenceallowedcom-parison of probability distributions of various descriptors. Subsequently, an energeticcomparisonwasperformedusingaper-residuedecompositionoftheinteractionenergybetweentheproteinandthesubstrate.Mutualinformationwasthenusedtodeterminewhetherparticularstructuralchangescorrelatewithchanges inenergetics, to identifymotionswhichareimportantfortheallostericsignal.[1] Woods,C.J.andMichel,J.,Sire/OpenMM,2014,(http://www.siremol.org/)
ComputationalChemistrySymposium2017
P193D-RISMforpredictingwaternetwork
LuciaFusania,bIanWall,aDavidPalmerbaComputational&ModelingSciences,GlaxoSmithKline,Stevenage,Herts.SG12NY,UKbDepartmentofPureandAppliedChemistry,UniversityofStrathclyde,Glasgow,G11XL,UKWaterplaysakeyroleintherecognitionandstabilizationoftheinteractionbetweenaligandanditsbindingsiteandasaconsequenceaccuratelymodellingithasimportantapplicationindrugdesignstrategies.
Three-DimensionalReferenceInteractionSitemodel(3D-RISM)theorycombinesarea-sonablelevelofmoleculardescriptionwithlowcomputationalcosts.ItemploysliquidsintegralequationtoproduceanapproximateaveragesolventdistributionaroundarigidsolventwithouttheneedforlongmoleculardynamicsorMonteCarlosimulationsandonlyrequiressolutestructureandsolventcomposition.1
Inthisstudy,3D-RISMdensityfunctionsareconvertedbythePlaceventalgorithm2topredictthewelldefinedwaternetworkofseveralBromodomains.3Thesensitivityofthemethodhasbeenextensivelyinvestigatedtounderstandtheapproximationsinvolvedinusingasinglecrystal structure. Initial resultsshowthatoverall themethod isgoodatpredicting thewaternetwork,but in someareas,whichmaybekey to liganddesign,importantwatermoleculescanbemissed.
Theeffectsofaveragingtheresultsovermultiplestructuresofthesameprotein,orovermultiplesnapshotsfromamoleculardynamicssimulationhavebeeninvestigated.Pre-liminaryresultssuggesttheseapproachesresultinanoverallimprovementinreproduc-ingtheBromodomains’waternetwork,althoughatanexperimentalorcomputationalcost.[1] Ratkova,E.L.;Palmer,D.S.;Fedorov,M.V.,Chem.Rev.2015,115,6312-56.[2] Sindhikara,D.J.;Yoshida,N.;Hirata,F.,J.Comput.Chem.2012,33,1536-1543.[3] Crawford,T.D.;Tsui,V.;Flynn,E.M.;etal.J.Med.Chem.2016,59,5391-402.
ComputationalChemistrySymposium2017
P20Astatisticalinvestigationofchemicalpropertiesassociatedwithconju-gatedorganicsystemsgeneratedfrommoleculardynamicssimulations
AndrewW.Prenticea,MartinJ.Patersona,JackWildmanb,IanGalbraithbaInstituteofChemicalSciences,SchoolofEngineeringandPhysicalSciences,Heriot-WattUniver-sity,EdinburghEH144AS,UnitedKingdombInstituteforPhotonicsandQuantumSciences,SchoolofEngineeringandPhysicalSciences,Her-iot-WattUniversity,EdinburghEH144AS,UnitedKingdomConjugatedmaterialsareofgreatinterestduetothepotentialapplicationinorganicop-toelectronicdevices1.Theeffectivenessofthesedevicesisgovernedbymanydifferentfactors,oneofwhichbeingageometricaldependencewhichcanbeexploredthroughmoleculardynamics(MD)simulations,ifappropriateforcefieldsdescribingthesystemsareavailable.Theoverarchingaimofthisworkistoinvestigatethesamplingstatisticsofvariouschemicalproperties,suchasionisationenergy,foroligo-fluoreneandthiopheneconformationsgeneratedbyMDsimulationsemployinganewlyparameterised force-field1.ThesamplinglandscapeforeachsystemwasexploredintermsofsamplesizeandrelativelocationintheMDsimulation,withcomparisontotheensembles.Theprelimi-naryresultsindicatethatalowerlimitsamplesizeof500and1000conformations,forthe fluoreneand thiophenedimer systems respectively isneeded togiveanaccuratecomparisontothetotalensembleionisationenergy.[1] J.Wildman,P.Repisčǎḱ,M.J.PatersonandI.Galbraith,J.Chem.TheoryComput.2016,12(8),
3813-3824.
P21InvestigatingguestuptakeinSc2BDC3metal-organicframeworkusingGCMCsimulation
JonathanRichardsona,StephenMoggacha,JorgeSoteloa,CaroleMorrisona,TinaDürenb,ClaireHobdaybaUniversityofEdinburgh,SchoolofChemistry,Edinburgh,EH93FJbUniversityofBath,DepartmentofChemicalEngineering,Bath,BA27AYMetal-organicframeworks,orMOFs,areaclassofporouscrystallinematerialsknownforthehighdegreeofstructurevariability,baseduponthemanypossiblecombinationsofmetallicclustersandorganiclinkers.Despitetheirpotential,veryfewMOFshavebeenutilisedforapplicationingasstorageandseparationbeyondtheresearchenvironment.[1]Onereasonforthisisthelackofunderstandingconcerningtheactuallocationofguest
ComputationalChemistrySymposium2017
moleculeswithintheporesuponuptakeandthenatureofspecificinteractionsbetweentheguestmoleculesandtheframework.Ifthisunderstandingwasmorethorough,theprocessdesigningMOFswithenhancedorspecificguestuptakewouldbeimprovedsig-nificantlyandaidtheresearch-to-applicationtransition.
Thekeyaspectofthisstudy,whichinvestigatestheuptakeofguestmoleculesintheMOFSc2BDC3(whereBDC=benzenedicarboxylate),isthecollaborationbetweenexperimentalmethodsandcomputation.Previousworkinthegroupspecificallyfocussedonthead-sorptionofCO2andCH4byuseofhigh-pressurecrystallography.
[2,3]UponuptakeofCO2,Sc2BDC3wasfoundtoundergoaphasetransitionatapproximately3bar,fromitsroomtemperatureorthorhombicFdddcrystal structure toamonoclinicC2/cstructure,asaresultofthesubtlerotationofapairoforganiclinkers,whichcreatestwosymmetricallyindependentchannels.Apreviouslyundiscoveredthirdadsorptionsitewasalsolocated,supportinghigh-densitygasstorage.
Thepresentedworkhasfocussedonutilisingthecrystalstructuresfromhigh-pressurecrystallographyexperimentsonSc2BDC3forcomputationalGrandCanonicalMonte-Carlo(GCMC)simulations,toverifyandbuilduponthecrystallographicresults.GCMCisspe-cificallydesignedtoallowmovementofguestmoleculesintotheporesofthematerialand to stochasticallyprobeallpossibleadsorption sites, and thereforedetermine theenergiesassociatedwith these sites.Themethodhasbeensuccessful inverifying theexperimentalCO2uptakeinSc2BDC3,aswellasdemonstratingthattheguest-frameworkinteractionsarestrongerintheC2/cstructure,whichcouldprovidereasoningforwhythephasetransitionoccursexperimentally.
[1] NatureChemistry,2016,8,987-987[2] J.Sotelo,PhDthesis,UniversityofEdinburgh,2015[3] J.Soteloetal.,Angew.Chem.Int.Ed.,2015,54,13332-13336.
ComputationalChemistrySymposium2017
P22Phasebehaviourofself-assembledmonolayerscontrolledbytuningphysisorbedandchemisorbedstates
SaraFortunaa,b,DavidL.Cheungc,andKarenJohnstondaMOlecularNAnotechnologyforLIfeScienceApplicationsTheoryGroup,DepartmentofMedicalandBiologicalSciences,UniversityofUdine,ItalybCenterforbiomedicalsciencesandengineering,UniversityofNovaGorica,SloveniacSchoolofChemistry,NationalUniversityofIreland,Galway,IrelanddDepartmentofChemicalandProcessEngineering,UniversityofStrathclyde,Glasgow,U.K.Theself-assemblyofmoleculesonsurfacesinto2Dstructuresisimportantforthebottom-upfabricationoffunctionalnanomaterials,andtheself-assembledstructuredependsontheinterplaybetweenmolecule-moleculeinteractionsandmolecule-surfaceinteractions.Halogenatedbenzenederivativesonplati-numhavebeenshowntohavetwodistinctadsorptionstates:aphysisorbedstateandachemisorbedstate,andtheinterplaybetweenthetwocanbeex-pectedtohaveaprofoundeffectontheself-assemblyandphasebehaviourofthesesystems1.Wedevelopedalatticemodelthatexplicitlyincludesbothad-sorptionstates,withrepresentativeinteractionsparameterisedusingdensityfunctionaltheorycalculations.ThismodelwasusedinMonteCarlosimulationstoinvestigatepatternformationofhexahalogenatedbenzenemoleculesontheplatinumsurface2.Moleculesthatpreferthephysisorbedstatewerefoundtoself-assemblewithease,dependingontheinteractionsbetweenphysisorbedmolecules.Incontrast,moleculesthatpreferentiallychemisorbtendtogetar-restedindisorderedphases.However,changingtheinteractionsbetweenchemisorbedandphysisorbedmoleculesaffectsthephasebehaviour.Wepro-posefunctionalisingmoleculesinordertotunetheiradsorptionstates,asanin-novativewaytocontrolmonolayerstructure,leadingtoapromisingavenuefordirectedassemblyofnovel2Dstructures.[1] R.Peköz,K.JohnstonandD.Donadio,J.Phys.Chem.C2014,1186235-6241[2] S.Fortuna,D.L.CheungandK.Johnston,J.Chem.Phys.2016,144,134707
ComputationalChemistrySymposium2017
P23ADFTstudyofpalladiumdepositionontoapyridine-terminatedself-as-sembledmonolayer
ZhenYao,ManfredBuck,MichaelBühl
EaStCHEMSchoolofChemistry,UniversityofSt.Andrews,NorthHaugh,St.Andrews,Fife,KY169ST,UKSelf-assembledmonolayers (SAMs) are attractive systems for nanotechnology. Therehavebeenmanyeffortstogenerateawell-definedmetalcontactontopofaSAM1-5asthesemetal-SAM-metalsystemsarepromisingcandidatesforapplicationsin,e.g.,mole-cule-based electronics. Recent electrochemical experiments4,5have identified a highlypracticaltwo-stepproceduretoreliablydepositmetalontopofapyridine-terminatedSAM.However,itremainsachallengetounderstandthemechanismsunderlyingmetalnucleationandgrowth.
Herewepresentadensityfunctionaltheory(DFT)studyofPd-SAMinterfaces.Theoreti-calmodelingallowsustoinvestigatestructuraldetailsofthesurfaceattheatomiclevel.This information is importantforelucidatingthenatureofPd-SAMandPd-Pdinterac-tionsinelectrochemicalenvironmentsandgaininginsightintothemechanismofmetalnucleationintheinitialstageofdeposition.BothPd(II)andPd(0)arefoundtobindtopyridine,whichillustratestheimportanceoffunctionalendgroupsinSAMs.CalculationsalsosuggestthatthereisasubstantialdrivingforcetowardstheaggregationofPdatoms.[1] H.Haick,D.Cahen,Prog.Surf.Sci.,2008,83,217-261.[2] A.Hooper,G.L.Fisher,K.Konstadinidis,D.Jung,H.Nguyen,R.Opila,R.W.Collins,N.Wino-
grad,D.L.Allara,J.Am.Chem.Soc.,1999,121,8052-8064.[3] W.J.Dressick,C.S.Dulcey,J.H.Georger,G.S.Calabrese,J.M.Calvert,J.Electrochem.Soc.,
1994,141,210-220.[4] T.Baunach,V.Ivanova,D.M.Kolb,H.-G.Boyen,P.Ziemann,M.Büttner,P.Oelhafen,Adv.
Mater.,2004,16,2024-2028.[5] C.Silien,D.Lahaye,M.Caffio,R.Schaub,N.R.Champness,M.Buck,Langmuir,2011,27,
2567-2574.
ComputationalChemistrySymposium2017
Sponsorsofthe2017Symposium
Glasgow&WestofScotlandLocalSection
TheoreticalChemistryGroup