Hydrogen-bond-assistedsymmetrybreakinginanetworkofchiralmetal-organicassemblies

FelixJ.Rizzuto‡,PatrickPröhm‡,AlexJ.Plajer,JakeL.Greenfield,JonathanR.Nitschke*

DepartmentofChemistry,UniversityofCambridge,LensfieldRdCB21EW,UKKEYWORDS:chirality,hydrogenbonding,metal-organiccages,heteroleptic

ABSTRACT:Hereinweelucidatetheinterplayofchiral,chelate,solventandhydrogen-bondinginformationintheself-assem-blyofaseriesofnewthree-dimensionalmetal-organicarchitectures.Enantiopureligands,eachcontainingH-bonddonorsandacceptors,formdifferentstructuresdependingontheratioinwhichtheyarecombined:enantiopurecomponentsformM4L4assemblies,whereasracemicmixturesformM3L3stacks.ChiralamplificationwithinM3L3enantiomerswasobservedwhena2:1ratioofRandSsubcomponentenantiomerswasemployed.Simplyswitchingthesolvent(fromMeCNtoMeOH)orchelatingunit(frombidentatetotridentate)increasedthediversityofstructuresthatcanbegeneratedfromthesebuildingblocks,leadingtotheselectiveformationofnovelM2L2andM3L2assemblies.Theadditionofachiralligandbuildingblocksresultedintheformationoffurtherstructures:WhenanachiralsubcomponentwascombinedwithitsR-andS-chiralconge-ners,athree-layerheterolepticarchitecturewasgenerated,withtheachiralunitsittingatthetopofthestack.WhencombinedwiththeSenantiomeronly,however,theachiralunitassembledinthecenterofthestructure,thusdemonstratingtheselec-tiveplacementofachiralunitswithinchiralsystems.FurthersortingexperimentsrevealedthatcombiningRandSstereo-centerswithinasingleligandledtodiastereoselectiveproductgeneration.Theseresultsshowhowgeometriccomplementa-ritybetweendifferentligandsimpactsuponthedegreeofhydrogenbondingwithintheassembly,stabilizingspecificlow-symmetryarchitecturesfromamongmanypossiblestructuraloutcomes.

INTRODUCTIONMany discrete structures have been successfully pre-

paredusingmetal-organic self-assembly, includingplanarpolygons,1Platonic2andArchimedean3solids,4prisms,5el-lipsoidal hosts6 and spherical frameworks.7 These struc-tures typically display high symmetry, as symmetry ele-mentsaredefinedduring the formationof thedirectionalbondsbetweenpolydentateligandsandmetalcenters.8Forhosts,functionfollowsform:9efficientguestbinding,10reac-tivityenhancement11andcatalysis12relyonboundspeciesfittingsnuglywithin thecavities framedbyspecificarchi-tecturalscaffolds.13Byunderstandinghowthegeometriesandconnectionpropertiesofthecomponentsofanassem-blywork together, high-symmetry structures can thus besynthesizedwithspecificgeometries.14In contrast, the generation of low-symmetry architec-

tureshasprovedmorechallenging:15 ligandstendtohaverigidtwo-dimensionalshapes,whichgiverisetorigidthree-dimensionalstructures.16Low-symmetry ligandsmightbeemployedtogeneratedesymmetrisedstructures;however,this method often generates polymers17 or complex mix-turesofproducts18owingtogeometrymismatches.Ifflexi-ble components are used, entropy often drives the for-mation of low-nuclearity products,19 or high-symmetryproductsforminunexpectedways.20Secondary interactions have been shown to lower the

symmetry during self-assembly:21 guest binding,22 stericcrowding,23 aromatic interactions,24 and radical pairing25haveallbeenobservedtocontributetotheself-assemblyof

low-symmetryproducts.Wehypothesized thathydrogen-bonding siteswithin subcomponentsmight also favor theformationoflower-symmetrycomplexes.Hydrogenbondsare directional and complementary, and the strength oftheir interactioncanbe tunedbychanging solvents.26Wethussetouttoinvestigatetheeffectsofinstallinghydrogen-bonding motifs on enantiopure C3-symmetric subcompo-nentsuponthesymmetriesoftheproductsformedfollow-ingself-assembly.Ourresultsshowthattheinterplaybetweenchiralrecog-

nition and hydrogen-bonding density dictate the stereo-chemistry of a new series of heteroleptic metal-organiccomplexes.Factorsthatincludethepresenceofstereocen-ters,thesolvent,andthedegreeofchelation(denticity)canstabilize one structurewith respect to another. Transfor-mationscanthusbeeffectedbetweenfourdistinctassem-blies,severalofwhichcanbegeneratedinenantiopureform(Figure1a).Ourmethodthusallowsthediastereoselectivesynthesis of a varietyof asymmetrical and low-symmetryarchitectures by subcomponent self-assembly. We alsodemonstrate stereochemical amplification from sub-stoi-chiometricadditionsofenantiopurebuildingblocks,andameansofusingchiralityandhydrogen-bondinginformationtodictatethenumberofbuildingblocks incorporatedpercomplex,andtheirconnectivity.

RESULTSANDDISCUSSION

Enantiopuretetrahedra.Tetrahedron(S)-1assembledfrom(S)-A(4equiv),Zn(OTf)2(4equiv)and2-formylpyri-dine(P1,12equiv)ineitherMeOHorCH3CN(Supplemen-tary Information Section 3.1). An ESImass spectrum dis-playedpeaksconsistentwithZnII4L4stoichiometry.The1HNMRspectrumwascomplex,displayingfourtimesthenum-berofsignalsexpectedforaT-symmetrictetrahedron(Fig-ure1b).This spectrumwas consistentwith twopotentialconfigurations,bothhavingC3symmetry:eitherastructureinwhichallmetalcenterspossessfacstereochemistry,butonehasoppositehandednesstotheotherthree,orastruc-turecomposedofonefacandthreemervertices.MM3mo-lecularmodellingofbothconfigurationsdidnotrevealanobviousenergeticdifferentiationbetweentheseconfigura-tions(FigureS29).Amideprotonswereobservedintheregion7.5-8.3ppm

inthe1HNMRspectrumoftheassembly,suggestingthatlig-andswerenotparticipatinginhydrogenbondingwitheachother. This precluded the possibility of a ligand arrange-mentinwhichligandsstackedontopofoneanother,asisobserved in polymeric assemblies incorporating 1,3,5-tri-carboxamidecomponents.27MultinuclearNMRstudiesprovidedevidencesuggesting

that1 exists ina3:1mer:fac configuration, ina structuretype first reportedbyHooley.23aNOEcorrelations (FigureS28)wereconsistentwith thepresenceofmer configura-tions for threeof the fourZnII centers,wherepyridylandphenyleneringsstackinclosecontact.NosuchNOEcorre-lationswereobservedbetweentheseenvironmentsinthe

fourthsignalset,suggestingthatthiscornermaintainedfacgeometry.1H-13CHMBCcorrelations(FigureS16)betweenthe central phenyl protons and carbonyl 13C signalswerealso consistent with this ligand configuration. The dis-persed13Csignals(FigureS12)alsosuggestedmixturesoffacial and meridional corners in the complex: diastere-omers containing only fac metal centers typically showmoretightlyclustered13Csignals.28Thisstructuralconfigurationisenabledbytheflexibility

ofthe(S)-Asubcomponentswithin(S)-1.Weproposethat(S)-1existsina3:1mer:facconformationbecausethebasalligand partially fills the cavity volume, as compared to alargercavityinanall-facisomer.(S)-1wouldthusbemorefavoredentropically,asitwouldcontainfewerhigh-energysolventmoleculestrappedwithinitscavity.(R)-1wasalsogeneratedbyemploying(R)-Ainplaceof

(S)-A during the assembly process. The 1H NMR and ESImass spectra of (R)-1 and (S)-1 were identical, as antici-pated.Theenantiopurityoftheassemblieswasestablishedby1HNMRtitrationofLacour’snBu4NΔ-TRISPHATintoaCD3CNsolutionof(R)-1or(S)-1.Thisanionresolvesenan-tiomericcationsbyformingdiastereotopicionpairs.29Weobservedshifting,butnotsplitting,oftheprotonsignalsofboth(R)-1and(S)-1duringtitrationwithΔ-TRISPHAT,sug-gestingthat(R)-1and(S)-1wereenantiopure(FiguresS30andS31).Mirror-imageCottoneffectswerealsoobservedby CircularDichroism (CD) spectroscopy, consistentwith(R)-1beingtheenantiomerof(S)-1(FiguresS17andS27).

Figure1.(a)Transformationpathwaysemployingcombinationsof(S)-A,(R)-A,P1,P2andZnII.AllreactionsoccurredinMeCNunlessotherwiseindicated.(b)1HNMRspectra(500MHz,298K,MeODfor1&3,CD3CNfor2&4)showingthesymmetriesofproducts1-4,withiminesignalsofthemajorandminorspeciesmarkedwithreddotsandpinkstars,respectively.Compound1 transformedsequentiallyinto3,2and4 followingthepathwaydefinedbyredarrowsin(a),aftertheapplicationoftheindicatedstimuli.FullNMRassignmentsareavailableintheSupportingInformation.

Generation of 2 by chiral recognition. NOESY NMRspectroscopy revealed the ligands of (R)-1 to be labile inMeCN,exchangingbetweenfouruniquechemicalenviron-ments slowly on the NMR timescale (Figure S21). When(S)-1wasaddedtoanacetonitrilesolutionof(R)-1(1:1ra-tio),followedbystirringatroomtemperaturefor12h,weobserveda simplificationof the 1HNMRspectrum,whichnowdisplayedonlythreeuniquesetsofligandprotonsig-nals (Figure 1b, Supplementary Information Section 3.2).Low- andhigh-resolutionESI-MS spectra indicated that1had transformed into 2, with a ZnII3L3 composition. Thesame 1H NMR spectrum resulted when (S)-A, (R)-A,Zn(OTf)2 andP1 were combined in CD3CN and heated to70°Cfor12h.Acrystalof2wasgrownthroughdiffusionofiPr2Ointoa

solutionof2containingCsCB11H12(3equiv)inCD3CN.X-raydiffractionrevealedthestructuretobecomposedofastackof three ligands inwhich theenantiomersofLA alternate.Oneequivalentof2 thuscontains twoL(R)-A ligands sand-wichingoneL(S)-Aligand,withallthreemetalcentershavingfac stereochemistry and Δ handedness; its enantiomer isalsopresentinthecrystal(Figure2).Themetalcentersof2describe an approximately equilateral triangle,with ZnII–ZnIIdistancesof17-18Å.Thestructurethuspossesseside-alized C3 symmetry, consistent with its NMR spectrum,whereineachofthethreearmsoneachligandareinidenti-cal environments. Both the crystal structure and solutionNMR spectra provide evidence for hydrogen bonding be-tween amide groups on adjacent ligands,which reinforcetheconfigurationofthestack(Figure2c).

Figure2.(a)Schematicrepresentationof2,showingthestereochem-icalconfigurationofasingleenantiomer,whereligandarmscontainingSstereocentersareblue,RligandarmsareredandΔmetalcentersareblack.(b)X-raycrystalstructureof2,vieweddowntheC3axis(anions

anddisorderremovedforclarity;ZnII=yellow,C=gray,N=blue,O=red,H=white).(c)Hydrogen-bondingthroughthecentralcolumnishighlightedwithdashedblacklines.(d)Viewofthestructureperpen-diculartoitsC3axis,color-codedasin(a).

Stereochemicalamplificationof2.Theprogressivead-

ditionof (R)-1 to (S)-1 indicatedcomplete formationof2following the addition of 0.5 equivalents of (R)-1 (FigureS41).Thisobservationindicatedthat2couldbeobtainedinenantiopure form froma1:2 ratio ofR:S subcomponents.TheΔ-TRISPHATanionwasagainemployedtodifferentiatetheenantiomersof2(FigureS42).Whentitratedwith2thathadbeenpreparedusinga1:1ratioofthetwoenantiomersofA,signalsplittingandshiftingwasobserved,consistentwith the presence of the two enantiomers that were ob-servedinthesolidstate.Whentitratedwith2synthesizedfroma1-to-2ratioof(S)-Ato(R)-A,however,nopeaksplit-tingwasobserved, consistentwith thepresenceofonlyasingleenantiomer.Cottoneffectsoppositeinsignwereob-servedinCDspectraforthetwoenantiomerspreparedinthismanner(FigureS43).Theadditionof3equivalentsofenantiopure(S)-1toara-

cemicmixtureof4equivalentsof(SRS)-2and4equivalentsof(RSR)-2generated12equivalentsofenantiopure(SRS)-2astheexclusiveproduct(Figure3).Theadditionofsub-stoi-chiometricamountsofenantiopureligandtoaracemicmix-turethusproducedanexclusivelyenantiopureproduct,inastereochemicalamplificationevent.30Thisbehaviorstandsincontrasttothenormalcase,wherein1:2mixturesofen-antiomers generate a system of enantiomeric bias, corre-sponding to33%ee.31Here,100%ee isobservedwhena1:2ratioofRandSligandsisemployed.Thisreactionisthusbothdiastereo-andenantio-selective.

Figure 3. Stereochemical amplification of 2 from the sub-stoichio-metricadditionof1.Initially,combiningequimolarquantitiesof(R)-1and(S)-1generatedequimolarquantitiesof(SRS)-2and(RSR)-2.Thesubsequentadditionof3/8ofanequivalentof (R)-1 to thismixtureproduced(RSR)-2exclusively.Theracemicmixtureof2 couldbere-generatedbyadding(S)-1.

Solvent-induced reorganization. When a 1:1 ratio of

(R)-A:(S)-AwascombinedwithZn(OTf)2andP1inMeOHin-steadofMeCN,acombinationof2andnewstructure3wereformed.ESI-MSanalysisindicatedaZnII2L2compositionfor3 (Supplementary Information Section 3.3). The 1H NMRspectrumofthemixtureof2and3displayedsixsetsofNMRsignals(Figure1b),correspondingtothreedistinct ligand

environmentsineachof2and3.Upondilutionfrom3.5mMto0.35mM,thesignalsattributedto2decreasedininten-sity,leaving3asthedominantproduct,asconfirmedbyESI-MS.Thus,upondilution,theequilibriumbetween2and3shiftstowardentropically-favorable3.DiffusionofEt2Ointoadilutemethanolsolutionof3pro-

ducedacrystalsuitableforX-raydiffraction(Figure4).Inthismesostructure,twoarmsofoneligandandonearmofanothermeetateachmetalcenter.Thestructurepossessesaninversioncenter, lending3Cisymmetry,withbothZnIIcenters having fac stereochemistry but opposite handed-ness. Both enantiomers ofA are thus incorporated into asingleachiralstructure.Twohydrogenbondsbetweenen-antiomericpairsofligandsflanktheinversioncenter(Fig-ure4c).

Figure4.(a)X-raycrystalstructureof3,withhydrogenbondinghigh-lightedwithdashedblacklines(anionsandsolventremovedforclarity;ZnII=yellow,C=gray,N=blue,O=red,H=white).(b)Schematicrep-resentationof3 (S ligandarms=blue,R ligandarms=red,Δ-ZnII =black,Λ-ZnII=white).(c)Hydrogen-bondingbetweenligandsisshownwithdashedblacklines.(d)Viewperpendicularto(a),withcolorsin-dicatingstereochemistryasin(b).

Product 2 transformed into 3 when the MeOH solvent

was removed and the residue was redissolved in MeCN.Thisprocesswasreversible:redissolutionof isolated2 inMeOHgenerated3.Introductionofchelateinformation.ZnII3L3structure2

transformedintoZnII3L2analog4followingtheintroductionof2-formylphenanthrolineP2andadditionalZnII(Figure1a,Supplementary Information Section 3.4). This subcompo-nentsubstitutionprocessthusresultedinthereplacement

ofthebidentateligandterminiof2withtridentatecoordi-natinggroups.Weinferthedrivingforceforthissubstitu-tiontoderivefromtheprincipleofcoordinativesaturation,whereby the thermodynamically most favorable set ofproducts contains the largest number of metal-ligandbonds.32AlthoughtheESImassspectrumof4(FigureS62)displayedonlysignalsattributabletoaZnII3L2productcom-position,the1HNMRspectrum(FigureS64)wascomplex,suggestingtheformationofmultiplediastereomers.When enantiopure (S)-A was combined with P2 and

Zn(OTf)2, a better-defined 1H NMR spectrum, with fewersignals,wasobserved(Figure1b).Ahigh-symmetryspecieswithonesetof1Hsignals,andasecondaryspecies,havingthreetimesasmanysignals,wereidentified.Weattributethehigher-symmetryspeciestoaΔΔΔ/ΛΛΛD3-symmetricZnII3L2 architecture, and the lower-symmetry one to itsΔΔΛ/ΛΛΔ C2-symmetric diastereomer (Figure S55). Thepresenceoftwodiastereomersissupportedbytheobserva-tionsthatthe13Csignalsforeachprotonenvironmentareclustered in the 1H–13CHSQC spectrum (Figure S58), andthatallprotonsignalsdiffusedatthesamerateby1HDOSYNMRspectroscopy(FigureS61).Integrationofthe1HNMRspectrumoftheassemblyindi-

cateda1:1ratioofD3-4:C2-4insolution.Astatisticaldistri-bution ofΛ- and Δ-ZnII stereocenterswithin the productmixturewouldcorrespondtoa1:3ratioofD3-4:C2-4,sug-gestingthattheD3-symmetricisomerisfavoredduringas-sembly. The presence of diastereomers also explains thecomplexityoftheNMRspectraoftheassemblyformedfroma racemicmixture of (S)-A and (R)-A,wherein additionalsignalscorrespondingtotheintegrationofbothSandRlig-andsintoanMII3L2frameworkwereobserved.The observation of all amide signals of both diastere-

omersaroundδ=7.5ppm(FigureS55)suggestedthatnohydrogenbondingoccurredbetweenligandsinthisassem-bly.33Wethusinferthepresenceofligandconfigurationsinwhich NH and CO moieties on different ligands are notwithinhydrogen-bondingdistancewithintheseassemblies.Self-assembly from achiral building blocks.WhenB

(anachiralderivativeofA),Zn(OTf)2andP1wereheatedat70°Cfor12hinMeCN,product5,havingaZnII3L3composi-tion,was identified by ESI-MS (Figure 5a, SupplementaryInformationSection3.5).Ninesetsofsignalswereobservedinthe1HNMRspectrumof5,havingequalintensities.1H–13CHSQCandHMBCspectrafurthermoreindicatedthatthecentralphenylprotonsoneachligandwerechemicallyin-equivalent (each ligand displayed 4J coupling to nearest-neighbor protons on the same ring), suggesting threefolddesymmetrization of each ligandwithin5. These spectrasuggest thateach ligandarmwithin theassembly ismag-neticallyunique,andthat thestructure isdesymmetrised,ascomparedtoC3-symmetric2.Eachof thebenzylicprotonsof theBresidueswithin5

wasrendereddiastereotopic,consistentwithastackedcon-figurationsimilartotheoneobservedin2.Allamideprotonsignals assigned to the central ligandwere shifted down-field, suggesting participation in hydrogen bonding. Thecentral-phenyl-ring proton signals were shifted upfield,whichweinfertobeaconsequenceofshieldingbythelig-andsoneitherside.NOESYcross-peaksattributedtochem-icalexchangewereobservedbetweenthesixenvironments

assigned to the top and bottom ligands, suggesting thatthesecomponentsareexchangingpositionsslowlyon theNMRtimescale.The lackof symmetryof5 suggesteda configuration in

which theΛΛΔ/ΔΔΛ diastereomer was generated exclu-sively,incontrastto2,whichcontainsallmetalcentersofthesamehandedness.Thestructure-directingeffectsofhy-drogen-bonding between amide groups, as evidenced bythepresenceof signalsatδ>10ppm(FigureS66), alongwith removal of the steric bulk of the methyl groups at-tached to the stereogenic centers in A, thus led to sym-metry-breakingwithinthisM3L3assembly.

Figure5.Sortingexperiments togenerateheterolepticarchitectures(whereSligandarms=blue,Rligandarms=red,ligandarmscontain-ingno stereocenters=green,Δ-ZnII = blackandΛ-ZnII =white).(a)GenerationofaΛΛΔ/ΔΔΛM3L3diastereomer5fromanachiralligand.(b)Onlythreespecieswereobservedfromthereactionoffourdiffer-ent ligandswith different stereochemical configurations, ofwhich2and6werestructurallycharacterized.(c)Aheteroleptic,homochiralcomplex7incorporatingeachof(S)-A,(R)-AandBself-assembledse-lectively.

Sortingexperimentswitha racemic ligand. Subcom-

ponent A contains three stereocenters with either the(R,R,R)or(S,S,S)configuration.Weenvisionedthataligandwith mixed stereocenters might diversify the number ofproduct structures obtained (Supplementary InformationSection5.1).Wethussynthesizedadiastereomericmixtureofderiva-

tivesofA,containingamixtureofboth(R)-Aand(S)-A,aswellasthenewsubcomponents(R,R,S)-Cand(S,S,R)-C.CisadiastereomerofA,whereinthearmsofChaveeithertwo

RandoneS,ortwoSandoneR,stereocenters.Thedistribu-tionofdiastereomerswithinthismixturethusreflectedsta-tisticalincorporationof(R)and(S)stereocenters.Thereac-tionofthismixtureofsubcomponentswithZn(OTf)2andP1providedaproductmixturewithasharp1HNMRspectrum;itsESImassspectrumwasconsistentwiththeexclusivefor-mationofZnII3L3products(Figure5b).Of the23possibleZnII3L3productdiastereomers (Table

S1),onlythreecouldbeobservedbyNMRspectroscopy;a1H–13CHSQCspectrumrevealed21uniqueligandenviron-ments (FigureS84).This corresponds to the formationofthreeproducts:onewithC3symmetry(2,threesetsofsig-nals)andtwohavingC1symmetry(eachwith9setsofsig-nals=18signalsets)(FigureS83).SlowdiffusionofEt2Ointothismixtureofproductscon-

tainingnBu4NBF4(10equiv)producedacrystalofproduct6suitableforX-raydiffractionanalysis(Figure6).Thiscom-plexissimilarto2,butiscomposedexclusivelyofthehet-erochiralsubcomponents(R,R,S)-Cand(S,S,R)-C.Thetrian-gleformedbyitsthreeZnIIcentersisscalene,ascomparedtoequilateral2.Itscoreisreinforcedbythreeintramolecu-larhydrogenbondsbetweenadjacentamides(Figure6c).Onemetalcenterhastheoppositehandednesstotheothertwo,andbothenantiomersarepresentinthecrystal.

Figure6.(a)X-raycrystalstructureof6,withcolorshighlightingthestereochemistryofeachligandarmandmetalcenter(Sligandarms=blue,Rligandarms=red,Δ-ZnII =black,Λ-ZnII=white;anions,solventanddisorderremovedforclarity).(b)Cartoonrepresentationof(a).(c)Threeintramolecular,andtwointermolecular(withabridgingH2Omolecule),hydrogenbondsreinforcethecoreof6(dashedblacklines).

(d)Thecrystalpackingof6showsstackingofoppositeenantiomersof6,promotedbythreeintermolecularhydrogenbonds.

In the solid state, three intermolecularhydrogenbonds

reinforcecolumnaraggregationsofenantiomersof6alongthec-axis(Figure6d).Thesestacksarereminiscentofthepolymeric architectures described byMeijer and cowork-ers.34Optimization of heteroleptic product formation.

Structurally complex heteroleptic assemblies reminiscentof2resultedfromthecombinationenantiopureandachiralligands during self-assembly (Supplementary InformationSection5.2).A1:1:1ratioof(S)-A:(R)-A:Bgenerated7asthemajorproduct(in79%yieldbyNMRintegration,rel-ativetominoramountsofhomoleptic2and5).Assembly7incorporatesresiduesof(S)-A,(R)-AandBtogetherintoaheterolepticM3L3assembly(Figure5c).The1HNMRspec-trumof7 (FigureS85)wassharp,withonly threesetsofsignals,suggestingthateachligandmaintaineditsthreefoldsymmetryuponintegrationintoheteroleptic7.NMRexper-iments(FiguresS85-S91)verifiedthattheBresiduesoccu-piedanoutward-facingpositionwithin7,withtheirNHdo-norsnotparticipatinginintramolecularH-bonding.Theproposedsolutionstateconfigurationwasreflected

inthecrystalstructureof7:athree-tierheterolepticcom-plexcontainingeachofthedistinctsubcomponentresidues(Figure7).Both2and7co-crystallizedinadisorderedcon-figuration,reflectingtheirsimilarmorphologies.Indeed,7showed the same hydrogen bonding configuration as ob-servedin2(Figure2).Bothenantiomersof7wereobservedinthecrystal.

Figure7.(a)Schematicrepresentationof7,showingasingleenantio-mer,whereligandsderivedfromS-Aareblue,ligandsderivedfromR-

Aarered,ligandsderivedfromachiralBaregreen,andΔ-ZnIIcentersareblack.(b)X-raycrystalstructureof7,viewedoffsetfromthetopofthestructure.(c)Hydrogenbondsthroughthecentralcore,highlightedwithdashedblacklines.(d)ViewofthestructureperpendiculartotheC3axis.Anions,solventanddisorderhavebeenremovedforclarity.

Tofurtherverifythat7incorporatedboth(R)-Aand(S)-A

insolution,asopposedtoasingleenantiomer,controlsort-ingexperiments,whereinonly(S)-AandBwerecombinedindifferentratios (1:3,1:2,1:1and2:1)duringassembly,wereconducted(SupplementaryInformationSection5.2).AmixtureofheterolepticM4L4andM3L3specieswereob-servedbyESI-MSineachcase.Importantly,no1HNMRsig-nalsattributedto7wereobservedduringthesesortingex-periments, confirming that 7 incorporates equimolaramountsof(R)-A,(S)-AandBinsolution.FurtherNMRandESI-MSexaminationofthesortedout-

putfroma2:1reactionof(S)-AandBrevealedthatdifferentligandscouldbeaccommodatedintodifferentmetal:ligandconfigurations:oneheteroleptictetrahedron(ZnII4L(S)-A3LB)andtwoheterolepticstacks(ZnII3L(S)-A2LBandZnII3L(S)-ALB2)wereobserved(FigureS94).Thepresenceofanamidetri-pletatδ=9.7ppminthe1HNMRspectrumofthisreactionoutputsuggestedthattheZnII3L(S)-A2LBassemblycontainedLB, which contains no stereocenters, as its central ligand(FigureS95).Thisconfigurationcontrastswith7,whereLBsits at an externally-facing site.This ability to control thepositionofachiralcomponentswithinchiralself-assembledstructurescouldleadtopreferentialandsite-specificinter-actionswithenantiopureorasymmetriccompounds.

CONCLUSIONSDifferentinputsofchiral,chelateandsolventinformation

ledtotheexpressionofdifferentstructuraloutputs(Table1).Distinctligandenantiomersformeddifferentsupramo-leculargeometriesthantheirracemicmixtures,andachiralsubcomponentsdisplayeddifferentstereochemicaloutputsthantheirchiralcongeners.Bymodulatingthedegreeandnatureofthechiralinformationpresentineachassembly,distinct product outputs resulted, leading to the selectivegenerationofspecificdiastereomersfromamonglargecol-lectionsofpossibleproductstructures,includingtheselec-tiveformationofheterolepticassemblies.Ofparticularin-terest is the distinctly different assembly behavior dis-playedby enantiopure ligands,which contrasted stronglywith their racemic counterparts: for instance, employingonly(S)-Aproduced1,whereascombining(S)-Awith(R)-Aproduced 2 or 3. Furthermore, the formation of enanti-opurestructureswasobservedfrom1:2mixturesofR:Siso-mers,indicativeofchiralamplificationuponself-assembly.Theseresultsthusreflecttheincreaseddiversityinproductstructuresthataccompaniestheuseofanexpandedchiralpool.35

Table1.Summaryofthestructuresobservedfromcombinationsoflig-ands,whereenantiopurestructuresarecoloredblue.

a=mixtureofproducts,wherea’istheenantiomersetofa.

Ourcrystallographic investigationssuggestthatthechi-

rality(RorS)oftheligandimpactsdirectlyuponthehand-edness of the coordinated metal center (Λ or Δ). For in-stance,ametalcenterchelatedbytwoRandoneS ligandarmgeneratedonlyΔcornersinallof2,3and6;likewise,twoSandoneR ligandarmsresultedinaΛcorner.WhenachiralBwas introducedinto7, thestereochemical infor-mationfromtheoneSandtheoneR ligandbalancedout,resultinginnostereochemicalinfluenceuponthemetalcor-ners.Thedegreeofhydrogenbondingobservedwithin these

structures results from geometric complementarity be-tweensubcomponentsheld inspecificstereochemicalori-entations bymetal coordination. Intra-complex hydrogenbonding favored the formation of specific isomers.Whenhydrogen-bondingwasabsent(asin4,forinstance),multi-ple diastereomerswere evident;when hydrogen-bondingwaspromoted(asin2,5,6and7),strongdiastereomericselectivitywasobserved.Withinthesetofcomplexesstud-ied,metalcoordinationthusservedtodictatetheshapeoftheoverallframework,followingtheprincipleofcoordina-tive saturation,32 and hydrogen-bonding served to fix thestereochemistrywherepossible.Ourresultschart,forthefirsttime,theprocessingofste-

reochemical information within mixtures of enantiopure,racemicandachiralbuildingblockssimultaneously in thegenerationofmetal-organicarchitectures.Thisstudypro-videsnewmeanstotransformspeciesselectively,generateheterolepticstructures,andimprovethespecificityofsort-ingreactions,andprovides insight into the importanceofligand symmetry, stereochemistry and intramolecularhy-drogenbondingasdrivingforcesindeterminingstructure.

ASSOCIATEDCONTENTSupporting Information: synthetic details, characterizationdata, sorting experiments and crystallographic details. Thismaterial is available free of charge via the Internet athttp://pubs.acs.org.X-raydatafor2(CCDC1877024)X-raydatafor3(CCDC1877023)X-raydatafor6(CCDC1877025)X-raydatafor7/2co-crystal(CCDC1877026)

AUTHORINFORMATION

CorrespondingAuthor

*jrn34@cam.ac.uk

ORCID

Felix J. Rizzuto 0000-0003-2799-903X Patrick Pröhm 0000-0002-3318-9941

Jake L. Greenfield 0000-0002-7650-5414 Jonathan R. Nitschke 0000-0002-4060-5122

AuthorContributions

‡These authors contributed equally.

FundingSources

This work was supported by the European Research Council (695009) and the UK Engineering and Physical Sciences Research Council (EPSRC, EP/P027067/1 and EP/M506242/1).

ACKNOWLEDGMENTS

WethankCambridgeAustraliaScholarships(FJR),theEras-mus+ Programme (PP), the Cambridge Trust (FJR& AJP)andthePPF(AJP)forPhDfunding.WethankDiamondLightSource for synchrotron time atBeamline I19 (MT15768),andtheEPSRCUKNationalMassSpectrometryFacilityatSwanseaformassspectrometricanalyses.

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