A bis(triazole)benzamide receptor for the complexation of halide anions and neutral carboxylic acid guests. Guest-controlled topicity and self-assembly

Article abstract of DOI:10.1039/c2ob26797g

Bis(triazole)benzamide 1 has been readily synthesized by means of Cu-catalyzed 1,3-dipolar cycloaddition and its ability to bind halide anions and neutral gallic acid derivative 12GA has been theoretically and experimentally investigated. The cavity defined by the N-H amide group and the vicinal aromatic hydrogens is suitable to form H-bonding arrays with halide guests. The stability of complexes 1·Cl^- and 1·Br^- is very similar, as DFT calculations predict and ¹H NMR titration experiments confirm. The zigzag "anti" conformation of the molecule generates two regions with complementary positive and negative potentials that favor the statistical complexation of two molecules of the neutral carboxylic acid 12GA. This guest-controlled topicity demonstrates the versatility of this class of receptor to bind species of different nature. The amide group determines the complexation of both anionic and neutral species by primary acid-base interactions. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c2ob26797g

View Article Online / Journal Homepage
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This is an Accepted Manuscript, which has been through the RSC Publishing peer
Organic &
review process and has been accepted for publication.
Biomolecular
Accepted Manuscripts are published online shortly after acceptance, which is prior
to technical editing, formatting and proof reading. This free service from RSC
Publishing allows authors to make their results available to the community, in
citable form, before publication of the edited article. This Accepted Manuscript will
be replaced by the edited and formatted Advance Article as soon as this is available.
Chemistry
www.rsc.org/obc
Volume 8 | Number 3 | 7 February 2010 | Pages 481–716
To cite this manuscript please use its permanent Digital Object Identifier (DOI®),
which is identical for all formats of publication.
More information about Accepted Manuscripts can be found in the
Information for Authors.
Please note that technical editing may introduce minor changes to the text and/or
graphics contained in the manuscript submitted by the author(s) which may alter
content, and that the standard Terms & Conditions and the ethical guidelines
that apply to the journal are still applicable. In no event shall the RSC be held
responsible for any errors or omissions in these Accepted Manuscript manuscripts or
any consequences arising from the use of any information contained in them.
ISSN 1477-0520
PERSPECTIVE
FULL PAPER
Laurel K. Mydock and
AlexeiV. Demchenko
Shuji Ikeda et al.
Hybridization-sensitive fluorescent
DNA probe with self-avoidance ability
Mechanism of chemical O-glycosylation:
from early studies to recent discoveries
1477-0520(2010)8:3;1-H
www.rsc.org/obc
Registered Charity Number 207890

Organic & Biomolecular Chemistry
Page 1 ofJ8ournalꢀNameꢀ
Dynamic Article Links ►
Cite this: DOI: 10.1039/c0xx00000x
View Article Online
www.rsc.org/xxxxxx
ꢀ
ARTICLE TYPE
A bis(triazole)benzamide receptor for the complexation of halide anions
and neutral carboxylic acid guests. Guest-controlled topicity and self-
assembly
Fátima García,a Juan Aragó,b Rafael Viruela,b Enrique Ortí,*b Luis Sánchez*a
5ꢀ Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Bis(triazole)benzamideꢀ1 hasꢀbeenꢀreadilyꢀsynthesizedꢀbyꢀmeansꢀofꢀCuꢁcatalyzedꢀ1,3ꢁdipolarꢀ
cycloadditionꢀandꢀitsꢀabilityꢀtoꢀbindꢀhalideꢀanionsꢀandꢀneutralꢀgallicꢀacidꢀderivativeꢀ12GAꢀhasꢀbeenꢀ
theoreticallyꢀandꢀexperimentallyꢀinvestigated.ꢀTheꢀcavityꢀdefinedꢀbyꢀtheꢀN−Hꢀamideꢀgroupꢀandꢀtheꢀvicinalꢀ
10ꢀ aromaticꢀhydrogensꢀisꢀsuitableꢀtoꢀformꢀHꢁbondingꢀarraysꢀwithꢀhalideꢀguests.ꢀTheꢀstabilityꢀofꢀcomplexesꢀ
1•Cl−ꢀandꢀ1•Br−ꢀisꢀveryꢀsimilar,ꢀasꢀDFTꢀcalculationsꢀpredictꢀandꢀ1HꢀNMRꢀtitrationꢀexperimentsꢀconfirm.ꢀ
Theꢀzigꢁzagꢀ“anti”ꢀconformationꢀofꢀtheꢀmoleculeꢀgeneratesꢀtwoꢀregionsꢀwithꢀcomplementaryꢀpositiveꢀandꢀ
negativeꢀpotentialsꢀthatꢀfavorsꢀtheꢀstatisticalꢀcomplexationꢀofꢀtwoꢀmoleculesꢀofꢀtheꢀneutralꢀcarboxylicꢀacidꢀ
12GA.ꢀThisꢀguestꢁcontrolledꢀtopicityꢀdemonstratesꢀtheꢀversatilityꢀofꢀthisꢀclassꢀofꢀreceptorꢀtoꢀbindꢀspeciesꢀ
15ꢀ ofꢀdifferentꢀnature.ꢀTheꢀamideꢀgroupꢀdeterminesꢀtheꢀcomplexationꢀofꢀbothꢀanionicꢀandꢀneutralꢀspeciesꢀbyꢀ
primaryꢀacidꢁbaseꢀinteractions.
presenceꢀofꢀtheꢀamideꢀgroupꢀinꢀbis(triazole)benzamideꢀ1ꢀ(Schemeꢀ
1)ꢀrendersꢀaꢀversatileꢀreceptorꢀthatꢀbindsꢀhalideꢀanionsꢀwithꢀaꢀ1:1ꢀ
stoichiometryꢀ andꢀ theꢀ gallicꢀ carboxylicꢀ acidꢀ derivativeꢀ 12GAꢀ
withꢀ aꢀ 1:2ꢀ ratioꢀ inꢀ aꢀ nonꢁcooperativeꢀ fashion.ꢀ Additionally,ꢀ theꢀ
50ꢀ complexationꢀofꢀanionicꢀorꢀneutralꢀguestsꢀbyꢀ1ꢀisꢀaccompaniedꢀbyꢀ
noꢀremarkableꢀconformationalꢀchangeꢀofꢀtheꢀtriazoleꢀunits.ꢀ Theꢀ
neutralꢀreceptorꢀ1,ꢀtheꢀcomplexesꢀformedꢀbyꢀ1ꢀandꢀbromideꢀanionꢀ
Introduction
Enzymes,ꢀ hormones,ꢀ andꢀ proteinsꢀ areꢀ biologicalꢀ systemsꢀ thatꢀ
exertꢀaꢀspecificꢀfunctionꢀinꢀresponseꢀtoꢀcomplexationꢀofꢀspeciesꢀofꢀ
20ꢀ differentꢀnature.ꢀTheseꢀbiomoleculesꢀareꢀendowedꢀwithꢀfunctionalꢀ
groupsꢀableꢀtoꢀinteractꢀwithꢀanionsꢀandꢀcarboxylicꢀacidsꢀinꢀnaturalꢀ
processesꢀsuchꢀasꢀtheꢀcollapseꢀofꢀactinꢀfilamentsꢀbyꢀiodineꢀorꢀtheꢀ
andꢀbyꢀ 1ꢀandꢀtheꢀneutralꢀcarboxylicꢀ acid,ꢀareꢀableꢀtoꢀ aggregateꢀ
citricꢀacidꢀcycle.1ꢀToꢀemulateꢀsomeꢀofꢀtheseꢀnaturalꢀprocesses,ꢀaꢀ
intoꢀhighlyꢀorganizedꢀsupramolecularꢀstructures.ꢀ
varietyꢀofꢀneutralꢀreceptorsꢀhasꢀbeenꢀreportedꢀtoꢀbindꢀanionsꢀbyꢀ
25ꢀ theꢀ interactionꢀ withꢀ polarizedꢀ O−Hꢀ orꢀ N−Hꢀ groups.2,3ꢀ Theꢀ
55ꢀ Results and Discussion
complexationꢀ ofꢀ carboxylicꢀ acidsꢀ occursꢀ viaꢀ anꢀ acidꢁbaseꢀ
Synthesis.
equilibriumꢀ betweenꢀ theꢀ carboxylicꢀ acidꢀ groupꢀ andꢀ typicalꢀ Hꢁ
bondingꢀ donorsꢀ andꢀ acceptorsꢀ suchꢀ asꢀ amines,ꢀ carbonyls,ꢀ orꢀ
pyridines.4ꢀ Inꢀ theꢀ questꢀ ofꢀ newꢀ receptorsꢀ forꢀ anions,ꢀ 1,4ꢁ
30ꢀ substitutedꢁ1,2,3ꢁtriazoleꢁbasedꢀmacrocycles5ꢀandꢀfoldamers6ꢀareꢀ
beingꢀ investigated.ꢀ Theseꢀ triazoleꢁbasedꢀ receptorsꢀ exhibitꢀ anꢀ
arrayꢀofꢀneutralꢀbutꢀsufficientlyꢀpolarizedꢀC−Hꢀgroupsꢀcapableꢀofꢀ
interactingꢀ withꢀ differentꢀ anions.7ꢀ Inꢀ additionꢀ toꢀ theꢀ
electropositiveꢀ C−Hꢀ group,ꢀ theꢀ triazoleꢀ ringꢀ possessesꢀ twoꢀ sp2ꢀ
35ꢀ nitrogenꢀatomsꢀthatꢀcanꢀinteractꢀwithꢀtypicalꢀHꢁbondingꢀdonors.ꢀ
TheꢀHꢁbondingꢀdonorꢀandꢀacceptorꢀmoietiesꢀofꢀtheꢀtriazoleꢀringsꢀ
haveꢀbeenꢀrecentlyꢀcombinedꢀwithꢀaꢀderivativeꢀofꢀgallicꢀacidꢀtoꢀ
formꢀcolumnarꢀliquidꢁcrystallineꢀsupramolecularꢀassemblies.8ꢀ
ꢀ
Bis(triazole)benzamideꢀ 1ꢀ hasꢀ beenꢀ readilyꢀ preparedꢀ inꢀ onlyꢀ
fiveꢀ syntheticꢀ stepsꢀ fromꢀ commerciallyꢀ availableꢀ 3,5ꢁ
dibromobenzoicꢀ acidꢀ (2)ꢀ (Schemeꢀ 1).ꢀ Carboxylicꢀ acidꢀ 2ꢀ wasꢀ
60ꢀ reactedꢀ withꢀ nꢁdecylamineꢀ inꢀ theꢀ presenceꢀ ofꢀ Nꢁ(3ꢁ
dimethylaminopropyl)ꢁNꢁethylcarbodiimideꢀhydrochlorideꢀ(EDC)ꢀ
andꢀ 4ꢁ(dimethylamino)ꢁpyridineꢀ (DMAP)ꢀ toꢀ yieldꢀ amideꢀ 3ꢀ inꢀ
61%.ꢀTheꢀSonogashiraꢀcrossꢁcouplingꢀreactionꢀbetweenꢀamideꢀ3ꢀ
andꢀtrimethylsilylꢁacetyleneꢀandꢀfurtherꢀdeprotectionꢀofꢀtheꢀsilylꢀ
65ꢀ groupꢀwithꢀK2CO3ꢀaffordedꢀNꢁdecylꢁ3,5ꢁdiethynylbenzamideꢀ(5).ꢀ
Receptorꢀ1ꢀwasꢀstraightforwardlyꢀsynthesizedꢀwithꢀaꢀ78%ꢀ yieldꢀ
byꢀ followingꢀ theꢀ Cu(I)ꢁcatalyzedꢀ Huisgenꢀ 1,3ꢁdipolarꢀ
cycloaddition10ꢀbetweenꢀ 5ꢀandꢀ4ꢁbiphenylꢀazideꢀ(6),ꢀ whichꢀ wasꢀ
preparedꢀ byꢀ slightlyꢀ modifyingꢀ aꢀ previouslyꢀ reportedꢀ
70ꢀ procedure.9,11ꢀ 1Hꢀ andꢀ 13Cꢀ NMR,ꢀ FTꢁIRꢀ spectroscopy,ꢀ andꢀ massꢀ
spectrometryꢀhaveꢀbeenꢀusedꢀtoꢀconfirmꢀtheꢀchemicalꢀstructureꢀofꢀ
allꢀnewꢀreportedꢀcompounds.ꢀTheꢀ1HꢀNMRꢀspectrumꢀofꢀreceptorꢀ
1ꢀ isꢀ ratherꢀ simpleꢀ showingꢀ sevenꢀ wellꢁdefinedꢀ aromaticꢀ
resonances,ꢀ aꢀ tripletꢀ correspondingꢀ toꢀ theꢀ N−Hꢀ ofꢀ theꢀ amideꢀ
ꢀ
Weꢀhaveꢀrecentlyꢀdescribedꢀtheꢀselfꢁassemblyꢀofꢀamphiphilic,ꢀ
40ꢀ openꢀarylꢀtriazoles,ꢀwhoseꢀaggregatesꢀareꢀdisruptedꢀuponꢀbromideꢀ
complexation.ꢀ Theꢀ additionꢀ ofꢀ bromideꢀ toꢀ thoseꢀ openꢀ receptorsꢀ
provokesꢀaꢀconformationalꢀchangeꢀthatꢀimpedesꢀtheꢀformationꢀofꢀ
organizedꢀsupramolecularꢀstructures.9ꢀInꢀthisꢀcommunication,ꢀweꢀ
haveꢀ replacedꢀ theꢀ peripheralꢀ triethyleneꢀ glycolꢀ chainꢀ ofꢀ ourꢀ
45ꢀ previousꢀ reportedꢀ receptorꢀ byꢀ anꢀ amideꢀ functionalꢀ group.ꢀ Theꢀ
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

Organic & Biomolecular Chemistry
Page 2 of 8
functionalityꢀatꢀδꢀ~ꢀ6.7,ꢀandꢀallꢀtheꢀparaffinicꢀresonancesꢀ(seeꢀtheꢀ 5ꢀ moietiesꢀasꢀitꢀisꢀinferredꢀfromꢀtheꢀNOEꢀeffectsꢀobservedꢀbetweenꢀ
SupportingꢀInformation).ꢀToꢀachieveꢀanꢀantiparallelꢀalignmentꢀofꢀ
theꢀ internalꢀ electricꢀ dipolesꢀ ofꢀ theꢀ triazoleꢀ rings,ꢀ compoundꢀ 1ꢀ
adoptsꢀ aꢀ zigꢁzagꢀ ‘‘anti’’ꢀ conformationꢀ ofꢀ theseꢀ heterocyclicꢀ
theꢀ triazoleꢀ protonꢀ (Hb)ꢀ withꢀ theꢀ twoꢀ protonsꢀ ofꢀ theꢀ centralꢀ
aromaticꢀringꢀ(HaꢀandꢀHc)ꢀ(Schemeꢀ1ꢀandꢀFigureꢀS1).9ꢀ
View Article Online
Scheme 1ꢀSynthesisꢀofꢀreceptorꢀ1ꢀandꢀchemicalꢀstructureꢀofꢀtheꢀcomplexesꢀformedꢀuponꢀbindingꢀbromideꢀ(1•Br−TBA+)ꢀandꢀtheꢀgallicꢀ
acidꢀderivativeꢀ(1•(12GA)2).ꢀ
10ꢀ
ꢀ
ꢀ
thatꢀfavoursꢀtheꢀhostingꢀofꢀtheꢀanionꢀguests.ꢀ
Self-assembly and complexation in solution.
ꢀ
Priorꢀtoꢀtheꢀinvestigationꢀofꢀtheꢀcomplexationꢀofꢀanyꢀguestꢀbyꢀ
15ꢀ 1,ꢀ weꢀ haveꢀ studiedꢀ itsꢀ selfꢁassemblyꢀ inꢀ CDCl3ꢀ toꢀ discardꢀ anyꢀ
effectꢀ fromꢀtheꢀ aggregationꢀofꢀtheꢀreceptorꢀinꢀtheꢀcomplexationꢀ
processꢀ (Figureꢀ S2).ꢀ Compoundꢀ 1ꢀ selfꢁassemblesꢀ withꢀ aꢀ lowꢀ
associationꢀ constantꢀ ofꢀ ~7ꢀ M−1.ꢀ Theꢀ slightꢀ upfieldꢀ shiftꢀ ofꢀ theꢀ
aromaticꢀ resonancesꢀ andꢀ theꢀ deshieldingꢀ ofꢀ theꢀ amideꢀ protonꢀ
20ꢀ uponꢀincreasingꢀconcentrationꢀsuggestsꢀthatꢀtheꢀselfꢁassemblyꢀofꢀ
receptorꢀ 1ꢀ resultsꢀ fromꢀ aꢀ combinationꢀ ofꢀ πꢁπꢀ stackingꢀ andꢀ Hꢁ
bondingꢀinteractions.ꢀ
ꢀ
Theꢀcapabilityꢀofꢀtheꢀbis(triazole)benzamideꢀreceptorꢀ1ꢀtoꢀbindꢀ
halideꢀ guestsꢀ hasꢀ beenꢀ initiallyꢀ investigatedꢀ byꢀ performingꢀ
25ꢀ densityꢀ functionalꢀ theoryꢀ (DFT)ꢀ calculations.ꢀ Geometryꢀ
optimizationsꢀofꢀ1ꢀandꢀitsꢀrespectiveꢀcomplexesꢀ1•X−ꢀ(whereꢀX−ꢀ
isꢀF−,ꢀCl−,ꢀBr−,ꢀandꢀI−)ꢀhaveꢀbeenꢀcarriedꢀoutꢀatꢀtheꢀM06ꢁ2X/6ꢁ
311G**ꢀlevelꢀtoꢀestimateꢀtheꢀbindingꢀenergyꢀofꢀtheꢀcomplexꢀandꢀ
toꢀ analyzeꢀ theꢀ structuralꢀ changesꢀ associatedꢀ withꢀ theꢀ
30ꢀ complexationꢀprocess.ꢀInꢀcompoundꢀ1,ꢀtheꢀalkylꢀchainꢀattachedꢀtoꢀ
theꢀnitrogenꢀofꢀtheꢀamideꢀgroupꢀhasꢀbeenꢀsubstitutedꢀbyꢀaꢀmethylꢀ
groupꢀtoꢀreduceꢀtheꢀcomputationalꢀcost.ꢀ
ꢀ
Fig. 1ꢀ (a)ꢀ Minimumꢁenergyꢀ conformationsꢀ Aꢀ andꢀ Bꢀ computedꢀ forꢀ
receptorꢀ 1.ꢀ (b)ꢀ Molecularꢀ electrostaticꢀ potentialꢀ calculatedꢀ forꢀ
50ꢀ conformationꢀ Bꢀ ofꢀ receptorꢀ 1ꢀ (redꢀ andꢀ blueꢀ areꢀ negativeꢀ andꢀ positiveꢀ
potentials,ꢀ respectively).ꢀ (c)ꢀ M06ꢁ2X/6ꢁ311G**ꢀ optimizedꢀ structureꢀ ofꢀ
complexꢀ1•Br−.ꢀ
ꢀ
Theꢀoptimizedꢀstructureꢀofꢀcomplexꢀ1•Br−,ꢀwhichꢀisꢀselectedꢀasꢀ
ꢀ
Theꢀstructuralꢀandꢀelectronicꢀpropertiesꢀcalculatedꢀforꢀreceptorꢀ
aꢀrepresentativeꢀexampleꢀofꢀcomplexesꢀ1•X−,ꢀisꢀshownꢀinꢀFigureꢀ
55ꢀ 1c.ꢀInꢀallꢀoptimizedꢀcomplexes,ꢀtheꢀhalideꢀionꢀisꢀaccommodatedꢀ
inꢀ theꢀ centreꢀ ofꢀ theꢀ cavityꢀ surroundedꢀ byꢀ theꢀ fourꢀ polarizedꢀ
hydrogensꢀ(seeꢀFigureꢀ1).ꢀTableꢀ1ꢀcollectsꢀtheꢀvaluesꢀofꢀselectedꢀ
bondꢀ distancesꢀ calculatedꢀ forꢀ complexesꢀ 1•X−ꢀ atꢀ theꢀ M06ꢁ2Xꢀ
level.ꢀTheꢀHꢂꢂꢂX−ꢀdistancesꢀ(HꢀbeingꢀtheꢀamideꢀH,ꢀHb,ꢀHc,ꢀandꢀHp)ꢀ
60ꢀ areꢀ allꢀ shorterꢀ thanꢀ theꢀ sumꢀ ofꢀ theꢀ vanꢀ derꢀ Waalsꢀ radiiꢀ ofꢀ theꢀ
hydrogenꢀatomꢀandꢀtheꢀcorrespondingꢀX−ꢀionꢀ(Tableꢀ1).ꢀThisꢀisꢀ
theꢀstructuralꢀsignatureꢀthatꢀsupportsꢀtheꢀformationꢀofꢀcomplexesꢀ
1•X−.ꢀ Theꢀ Hꢁbondingꢀ interactionsꢀ betweenꢀ theꢀ halideꢀ anionꢀ X−ꢀ
andꢀ theꢀ surroundingꢀ protonsꢀ dependꢀ onꢀ theꢀ proton,ꢀ andꢀ theꢀ
65ꢀ distancesꢀ computedꢀ forꢀ theꢀ N−HꢂꢂꢂX−ꢀ andꢀ HbꢂꢂꢂX−ꢀ contactsꢀ areꢀ
1ꢀareꢀ firstꢀ discussed.ꢀ Accordingꢀtoꢀ theꢀorientationꢀofꢀ theꢀamideꢀ
35ꢀ group,ꢀtwoꢀminimumꢁenergyꢀconformationsꢀ(AꢀandꢀB,ꢀFigureꢀ1a)ꢀ
areꢀ obtainedꢀ forꢀ 1.ꢀ Conformationꢀ Aꢀ isꢀ predictedꢀ toꢀ beꢀ slightlyꢀ
moreꢀ stableꢀ thanꢀ conformationꢀ Bꢀ byꢀ 2.45ꢀ kcalꢀ mol–1.ꢀ
Nevertheless,ꢀtheꢀamideꢀfunctionalꢀgroupꢀinꢀconformationꢀAꢀcanꢀ
easilyꢀ rotateꢀ 180ºꢀ toꢀ generateꢀ conformationꢀ Bꢀ thatꢀ bindsꢀ anionꢀ
40ꢀ guestsꢀmoreꢀefficiently.ꢀConformationꢀBꢀdefinesꢀaꢀcavityꢀwithꢀtheꢀ
N−HꢀgroupꢀandꢀtheꢀthreeꢀhydrogensꢀHb,ꢀHc,ꢀandꢀHpꢀ(Schemeꢀ1ꢀ
andꢀFigureꢀ1a)ꢀthatꢀcanꢀformꢀHꢁbondingꢀarraysꢀuponꢀbindingꢀtheꢀ
halideꢀ guests.ꢀ Theꢀ molecularꢀ electrostaticꢀ potentialꢀ (MEP)ꢀ
computedꢀ forꢀ conformationꢀ Bꢀ ofꢀ receptorꢀ 1ꢀ (Figureꢀ 1b)ꢀ clearlyꢀ
45ꢀ showsꢀthatꢀtheꢀfourꢀhydrogensꢀformꢀaꢀpositivelyꢀpolarizedꢀcavityꢀ
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 8
Organic & Biomolecular Chemistry
significantlyꢀ shorterꢀ thanꢀ thoseꢀ obtainedꢀ forꢀ theꢀ HcꢂꢂꢂX−ꢀ andꢀ
theꢀ complexationꢀ processꢀ ofꢀ chlorideꢀ andꢀ bromideꢀ anionsꢀ byꢀ
receptorꢀ1ꢀwasꢀstudiedꢀinꢀfurtherꢀdetail.ꢀTheꢀ1:1ꢀstoichiometryꢀofꢀ
complexesꢀ 1•Cl−ꢀ andꢀ 1•Br−ꢀ wasꢀ confirmedꢀ byꢀ aꢀ Job’sꢀ plotꢀ
especiallyꢀtheꢀHpꢂꢂꢂX−ꢀcontact.ꢀ
ꢀ
Table 1.ꢀSelectedꢀbondꢀlengthsꢀ(inꢀÅ)ꢀcalculatedꢀforꢀreceptorꢀ1ꢀandꢀcomplexesꢀ1•X−ꢀ
50ꢀ analysisꢀ(FigureꢀS4).ꢀTheꢀcomplexationꢀofꢀtheseꢀhalideꢀanionsꢀisꢀ
View Article Online
5ꢀ atꢀtheꢀM06ꢁ2X/6ꢁ311G**ꢀlevel.ꢀ
relativelyꢀ weakꢀ sinceꢀ aꢀ poorꢀ saturationꢀ isꢀ observedꢀ uponꢀ theꢀ
Bondꢀ
1
1•F−
1•Cl−
1•Br−ꢀ
1•I−
additionꢀ ofꢀ 50ꢀ equivalentsꢀ ofꢀ theꢀ correspondingꢀ TBAXꢀ saltꢀ
(FigureꢀS5ꢀandꢀS6).ꢀToꢀdetermineꢀtheꢀbindingꢀfeaturesꢀofꢀreceptorꢀ
1,ꢀ weꢀ haveꢀ utilizedꢀ theꢀ fittingꢀ programꢀ recentlyꢀ reportedꢀ byꢀ P.ꢀ
55ꢀ Thordarsonꢀthatꢀperformsꢀaꢀglobalꢀanalysisꢀofꢀmultipleꢀdatasetsꢀtoꢀ
aꢀsingleꢀbindingꢀmodel.14aꢀThisꢀprogramꢀallowsꢀdeterminingꢀtheꢀ
bindingꢀconstantꢀKaꢀbyꢀfittingꢀtheꢀvariationꢀofꢀtheꢀchemicalꢀshiftsꢀ
(∆δ)ꢀofꢀtheꢀhostꢀ(H),ꢀdirectlyꢀrelatedꢀtoꢀtheꢀconcentrationꢀofꢀtheꢀ
freeꢀandꢀboundꢀspecies,ꢀuponꢀincreasingꢀtheꢀconcentrationꢀofꢀtheꢀ
60ꢀ guestꢀ (G).ꢀ Theꢀ Kaꢀ valueꢀ isꢀ calculatedꢀ fromꢀ Equationꢀ 1ꢀ thatꢀ
combinesꢀthisꢀbindingꢀconstantꢀandꢀtheꢀmassꢀbalanceꢀequationsꢀ
forꢀtheꢀtotalꢀconcentrationsꢀofꢀtheꢀhostꢀ[H]0,ꢀguestꢀ[G]0,ꢀandꢀtheꢀ
concentrationꢀofꢀtheꢀfinalꢀcomplexꢀHG.ꢀTheꢀcalculatedꢀvaluesꢀforꢀ
Kaꢀbyꢀusingꢀtheꢀfittingꢀprogramꢀareꢀ29.0ꢀ(±ꢀ5%)ꢀandꢀ37.4ꢀ(±ꢀ4%)ꢀ
65ꢀ Mꢁ1ꢀforꢀcomplexesꢀ1•Cl−ꢀandꢀ1•Br−,ꢀrespectivelyꢀ(Figureꢀ2).ꢀ
N−Hꢀ
HꢂꢂꢂX−ꢀ
C−Hbꢀ
1.007ꢀ
1.048ꢀ
1.645ꢀ
1.103ꢀ
1.716ꢀ
1.087ꢀ
1.911ꢀ
1.089ꢀ
2.469ꢀ
ꢀ
1.018ꢀ
2.346ꢀ
1.086ꢀ
2.357ꢀ
1.085ꢀ
2.573ꢀ
1.087ꢀ
2.885ꢀ
ꢀ
1.017ꢀ
2.508ꢀ
1.085ꢀ
2.512ꢀ
1.086ꢀ
2.778ꢀ
1.087ꢀ
2.952ꢀ
ꢀ
1.014ꢀ
2.741ꢀ
1.083ꢀ
2.787ꢀ
1.086ꢀ
3.058ꢀ
1.086ꢀ
3.136ꢀ
ꢀ
ꢁꢀ
1.076ꢀ
HbꢂꢂꢂX−ꢀ
ꢁꢀ
C−Hcꢀ
1.085ꢀ
HcꢂꢂꢂX−ꢀ
C−Hpꢀ
HpꢂꢂꢂX−ꢀ
ꢁꢀ
1.083ꢀ
ꢁꢀ
ꢀ
ꢀ
∑(vdWꢀradii)[a]ꢀ
ꢀ
2.670ꢀ
2.950ꢀ
3.050ꢀ
3.180ꢀ
[a]ꢀSumꢀofꢀtheꢀvanꢀderꢀWaalsꢀradiiꢀofꢀtheꢀhydrogenꢀatomꢀandꢀtheꢀcorrespondingꢀ
X−ꢀion.ꢀ
ꢀ
ꢀ
ꢀ
[HG] =1/ 2{([H]0 +[G]0 +1/ Ka )
Toꢀ investigateꢀ theꢀ stabilityꢀ ofꢀ complexesꢀ 1•X−,ꢀ counterpoiseꢀ
ꢀ
Eq.ꢀ1ꢀ
−
([H]0 +[G]0 +1/ Ka )2 − 4[H]0[G]0 }
10ꢀ (CP)ꢀcorrectedꢀbindingꢀenergiesꢀwereꢀcomputedꢀonꢀtheꢀpreviouslyꢀ
optimizedꢀM06ꢁ2X/6ꢁ311G**ꢀstructures.ꢀM06ꢁ2Xꢀpredictsꢀstableꢀ
molecularꢀcomplexesꢀwithꢀbindingꢀenergiesꢀofꢀ–72.03,ꢀ–43.26,ꢀ–
40.40,ꢀ andꢀ –34.73ꢀ kcalꢀ mol–1ꢀforꢀ complexesꢀ1•F–,ꢀ 1•Cl–,ꢀ 1•Br–,ꢀ
andꢀ 1•I–,ꢀ respectively.ꢀ Accordingꢀ toꢀ theꢀ computedꢀ bindingꢀ
15ꢀ energies,ꢀF–ꢀionsꢀwouldꢀinteractꢀveryꢀstronglyꢀwithꢀreceptorꢀ1,ꢀCl–ꢀ
andꢀBr–ꢀanionsꢀwouldꢀformꢀcomplexesꢀwithꢀ1ꢀofꢀsimilarꢀstabilityꢀ
(theꢀdifferenceꢀisꢀlessꢀthanꢀ3.00ꢀkcalꢀmol–1),ꢀandꢀtheꢀvoluminousꢀ
I−ꢀionsꢀwouldꢀformꢀtheꢀlessꢀstableꢀcomplexes.ꢀ
ꢀ
Theꢀ experimentalꢀ evidenceꢀ ofꢀ theꢀ complexationꢀ ofꢀ halideꢀ
20ꢀ anionsꢀ byꢀ receptorꢀ 1ꢀ wasꢀ obtainedꢀ byꢀ 1Hꢀ NMRꢀ titrationsꢀ inꢀ
CDCl3.ꢀTitrationꢀofꢀ1ꢀwithꢀtetrabutylammoniumꢀ(TBA+)ꢀsaltsꢀofꢀ
F−,ꢀCl−,ꢀBr−,ꢀandꢀI−ꢀshowsꢀtheꢀdeshieldingꢀofꢀtheꢀresonancesꢀofꢀtheꢀ
amideꢀN−HꢀprotonꢀandꢀofꢀtheꢀC−Hꢀgroupsꢀcorrespondingꢀtoꢀtheꢀ
protonꢀinꢀortoꢀtoꢀtheꢀamideꢀfunctionalityꢀ(HcꢀinꢀSchemeꢀ1)ꢀandꢀtoꢀ
25ꢀ theꢀprotonꢀofꢀtheꢀtriazoleꢀringꢀ(HbꢀinꢀSchemeꢀ1)ꢀ(FigureꢀS3).ꢀTheꢀ
variationꢀofꢀtheseꢀchemicalꢀshiftsꢀconfirmsꢀthatꢀtheꢀgeometryꢀofꢀ
receptorꢀ 1ꢀ matchesꢀconformationꢀ Bꢀpredictedꢀbyꢀtheꢀ theoreticalꢀ
calculations.ꢀTheꢀmagnitudeꢀofꢀtheꢀdeshieldingꢀisꢀdifferentꢀforꢀtheꢀ
fourꢀ halideꢀ complexes.ꢀ Titrationꢀ ofꢀ receptorꢀ 1ꢀ withꢀ TBAFꢀ
ꢀ
Fig. 2ꢀIsothermsꢀresultingꢀfromꢀtheꢀtitrationꢀofꢀreceptorꢀ1 withꢀTBAClꢀ(a)ꢀ
andꢀTBABrꢀ(b).ꢀTheꢀbindingꢀisothermsꢀcorrespondꢀtoꢀaꢀ1:1ꢀcomplexationꢀ
30ꢀ providesꢀ theꢀsmallestꢀ deshieldingꢀ shiftsꢀ forꢀ theꢀN−Hꢀ andꢀC−Hbꢀ 70ꢀ modelꢀ byꢀ usingꢀ theꢀ usingꢀ theꢀ amideꢀ N−Hꢀ (square),ꢀ Hcꢀ (diamond),ꢀ Hbꢀ
protonꢀ resonances,ꢀ whichꢀ suggestsꢀ theꢀ formationꢀ ofꢀ weakꢀ 1•F−ꢀ
(triangle)ꢀandꢀHpꢀ(circle)ꢀprotons.ꢀ
complexesꢀ (Figureꢀ S3).ꢀ Thisꢀ contrastsꢀ withꢀ theoreticalꢀ
ꢀ
TheꢀparticipationꢀofꢀtheꢀpolarizedꢀN−Hꢀprotonꢀasꢀwellꢀasꢀtheꢀ
calculations,ꢀwhichꢀpredictꢀ1•F−ꢀasꢀtheꢀmostꢀstableꢀcomplex.ꢀTheꢀ
discrepancyꢀ betweenꢀ theoreticalꢀ andꢀ experimentalꢀ resultsꢀ hasꢀ
35ꢀ beenꢀ alreadyꢀ reportedꢀ forꢀ relatedꢀ complexes,12,13ꢀ andꢀ itꢀ wasꢀ
attributedꢀ toꢀ theꢀ difficultyꢀ ofꢀ findingꢀ “free”ꢀ F−ꢀ ionsꢀ underꢀ
commonꢀexperimentalꢀconditions.ꢀTheꢀspectralꢀshiftsꢀobservedꢀinꢀ
theꢀresonancesꢀofꢀ1ꢀuponꢀaddingꢀCl−ꢀandꢀBr−ꢀanionsꢀareꢀtheꢀmostꢀ
significant,ꢀwhereasꢀtheꢀtitrationꢀofꢀreceptorꢀ1ꢀwithꢀtheꢀTBAIꢀsaltꢀ
40ꢀ causesꢀaꢀsmallerꢀdeshieldingꢀofꢀtheꢀresonancesꢀofꢀtheꢀN−H,ꢀC−Hc,ꢀ
andꢀ C−Hbꢀ protonsꢀ (Figureꢀ S3).ꢀ Thisꢀ isꢀ inꢀ concordanceꢀ withꢀ
theoreticalꢀcalculationsꢀthatꢀobtainꢀcomplexꢀ1•I−ꢀtoꢀbeꢀlessꢀstable.ꢀ
TheꢀNMRꢀexperimentalꢀfindingsꢀareꢀthereforeꢀsupported,ꢀexceptꢀ
forꢀcomplexꢀ1•F−,ꢀbyꢀDFTꢀcalculations,ꢀwhichꢀpredictꢀstableꢀ1•X−ꢀ
45ꢀ complexesꢀstabilizedꢀbyꢀstrongꢀHꢁbondingꢀinteractions.ꢀ
aromaticꢀprotonsꢀHb,ꢀHc,ꢀandꢀHpꢀinꢀtheꢀcomplexationꢀofꢀtheꢀhalideꢀ
guestsꢀisꢀconfirmedꢀbyꢀtheꢀdownfieldꢀshieldꢀexperiencedꢀbyꢀtheseꢀ
75ꢀ resonancesꢀ(Figuresꢀ2,ꢀS5ꢀandꢀS6)ꢀandꢀalsoꢀbyꢀtheꢀNOEꢀeffectsꢀ
observedꢀuponꢀirradiationꢀofꢀtheꢀtriazoleꢀprotonꢀHbꢀinꢀtheꢀcomplexꢀ
formedꢀbyꢀ 1ꢀandꢀtheꢀBr−ꢀanionꢀ(FigureꢀS7).ꢀUnlikeꢀsomeꢀ otherꢀ
triazoleꢁbasedꢀ receptors,5ꢁ7,9ꢀ compoundꢀ 1ꢀ possessesꢀ anꢀ acidicꢀ
N−Hꢀ protonꢀ thatꢀ competesꢀ withꢀ theꢀ C−Hꢀ groupsꢀ toꢀ bindꢀ theꢀ
80ꢀ halideꢀanion,ꢀandꢀnoꢀconformationalꢀchangesꢀinꢀtheꢀ1,2,3ꢁtriazoleꢀ
ringsꢀoccurꢀafterꢀhalideꢀbindingꢀ(Schemeꢀ1ꢀandꢀFigureꢀS7).ꢀ
ꢀ
Consideringꢀ theꢀ zigꢁzagꢀ “anti”ꢀ conformationꢀ ofꢀ theꢀ
bis(triazole)benzamideꢀ receptor,ꢀ weꢀ haveꢀ envisionedꢀ theꢀ
possibilityꢀofꢀformingꢀcomplexesꢀbyꢀmixingꢀ1ꢀwithꢀaꢀneutralꢀguestꢀ
85ꢀ possessingꢀ Hꢁbondingꢀ donorꢀ andꢀ acceptorꢀ moieties.ꢀ 3,4,5ꢁ
tris(dodecyloxy)gallicꢀacid15ꢀ(12GAꢀinꢀSchemeꢀ1)ꢀwasꢀselectedꢀasꢀ
ꢀ
Takingꢀintoꢀaccountꢀtheꢀtheoreticalꢀandꢀexperimentalꢀevidence,ꢀ
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Organic & Biomolecular Chemistry
Page 4 of 8
neutralꢀguestꢀbecauseꢀtheꢀcarboxylicꢀacidꢀfunctionalꢀgroupꢀmeetsꢀ
theseꢀ requirements.ꢀ Theꢀ molecularꢀ electrostaticꢀ potentialꢀ 60ꢀ complexationꢀ process,ꢀ inꢀ whichꢀ theꢀ bindingꢀ ofꢀ theꢀ firstꢀ 12GAꢀ
39.24ꢀ kcalꢀ mol–1).ꢀ Thisꢀ isꢀ indicativeꢀ ofꢀ aꢀ nonꢁcooperativeꢀ
computedꢀforꢀreceptorꢀ1ꢀinꢀconformationꢀAꢀshowsꢀtheꢀpresenceꢀofꢀ
twoꢀregionsꢀwithꢀcomplementaryꢀpositiveꢀandꢀnegativeꢀpotentialsꢀ
5ꢀ (Figureꢀ S8).ꢀ Theꢀ negativeꢀ areaꢀ isꢀ determinedꢀ byꢀ theꢀ amideꢀ
carbonylꢀgroupꢀandꢀtheꢀtwoꢀsp2ꢀnitrogensꢀofꢀoneꢀofꢀtheꢀtriazoleꢀ
rings,ꢀ whereasꢀtheꢀpositiveꢀ zoneꢀ isꢀ determinedꢀbyꢀ theꢀpolarizedꢀ
N−H,ꢀ Hb,ꢀ andꢀ Hcꢀ protons.ꢀ Thisꢀ electronicꢀ distributionꢀ suggestsꢀ
thatꢀ receptorꢀ 1ꢀ couldꢀ behaveꢀ asꢀ aꢀ ditopicꢀ hostꢀ forꢀ theꢀ
10ꢀ complexationꢀ ofꢀ upꢀ twoꢀ moleculesꢀ ofꢀ 12GAꢀ asꢀ guest.ꢀ Anꢀ
appealingꢀfeatureꢀofꢀreceptorsꢀwithꢀmoreꢀthanꢀoneꢀbindingꢀsiteꢀisꢀ
theꢀ possibleꢀ appearanceꢀ ofꢀ cooperativeꢀ effects,ꢀ whichꢀ canꢀ beꢀ
positive,ꢀ likeꢀ theꢀ bindingꢀ ofꢀ oxygenꢀ toꢀ haemoglobin,16aꢀ orꢀ
negative,ꢀ likeꢀ theꢀ bindingꢀ ofꢀ tyrosineꢀ kinaseꢀ toꢀ theꢀ EGFꢀ
15ꢀ receptor.16bꢀ Theꢀ complexationꢀ ofꢀ 12GAꢀ byꢀ receptorꢀ 1ꢀ andꢀ theꢀ
possibleꢀcooperativeꢀeffectsꢀderivedꢀfromꢀthisꢀcomplexationꢀhaveꢀ
beenꢀstudiedꢀbothꢀtheoreticallyꢀandꢀexperimentally.ꢀ
guestꢀdoesꢀnotꢀaffectꢀtheꢀcomplexationꢀofꢀtheꢀsecondꢀ12GAꢀguest.ꢀꢀ
View Article Online
ꢀ
Figureꢀ 3ꢀ displaysꢀ theꢀ minimumꢁenergyꢀ optimizedꢀ structureꢀ
calculatedꢀ forꢀ complexꢀ 1•(12GA)2ꢀ atꢀ theꢀ M06ꢁ2X/6ꢁ311G**ꢀ
20ꢀ level.ꢀTableꢀ2ꢀcomparesꢀtheꢀvaluesꢀcalculatedꢀforꢀselectedꢀbondꢀ
lengthsꢀ ofꢀ receptorꢀ 1ꢀ andꢀ complexꢀ 1•(12GA)2.ꢀ Theꢀ complexesꢀ
formedꢀbyꢀreceptorꢀ1ꢀandꢀonlyꢀoneꢀ12GAꢀmoleculeꢀplacedꢀonꢀtheꢀ
leftꢀ(1•12GA-l) andꢀ rightꢀ (1•12GA-r) sidesꢀ ofꢀ theꢀ amideꢀ groupꢀ
(Figureꢀ S10)ꢀ wereꢀ alsoꢀ computedꢀ forꢀ comparisonꢀ purposes.ꢀ Inꢀ
25ꢀ Figureꢀ3,ꢀtheꢀ12GAꢀmoleculeꢀplacedꢀonꢀtheꢀleftꢀsideꢀofꢀcomplexꢀ
1•(12GA)2 isꢀ boundꢀ toꢀ receptorꢀ 1ꢀ byꢀ theꢀ primaryꢀ acidꢁbaseꢀ
N−HꢂꢂꢂO=Cꢀ andꢀ O−HꢂꢂꢂN=Nꢀ interactionsꢀ withꢀ calculatedꢀ bondꢀ
distancesꢀ ofꢀ 1.952ꢀ andꢀ 1.783ꢀ Å,ꢀ respectivelyꢀ (bondsꢀ 7ꢀ andꢀ 9,ꢀ
Figureꢀ3bꢀandꢀTableꢀ2).ꢀCalculationsꢀalsoꢀpredictꢀshortꢀC=OꢂꢂꢂHcꢀ
30ꢀ andꢀO−HꢂꢂꢂN=Nꢀcontactsꢀofꢀ2.277ꢀÅꢀ(bondꢀ8)ꢀandꢀ2.491ꢀÅꢀ(bondꢀ
10),ꢀ respectively,ꢀ whichꢀ reinforceꢀ theꢀ interactionꢀ betweenꢀ theꢀ
12GAꢀguestꢀandꢀreceptorꢀ1.ꢀTheꢀbindingꢀofꢀtheꢀ12GAꢀmoleculeꢀ
placedꢀonꢀtheꢀrightꢀsideꢀofꢀreceptorꢀ1ꢀ(Figureꢀ3)ꢀisꢀdominatedꢀbyꢀ
theꢀ strongꢀ C=OꢂꢂꢂH−Oꢀ interactionꢀ (1.688ꢀ Å,ꢀ bondꢀ 11)ꢀ andꢀ
35ꢀ strengthenedꢀbyꢀtheꢀshortꢀC−HcꢂꢂꢂO=CꢀandꢀC−HbꢂꢂꢂO=Cꢀcontactsꢀ
(2.458ꢀ andꢀ 2.048ꢀ Å,ꢀ respectively;ꢀ bondsꢀ 12ꢀ andꢀ 13).ꢀ Theꢀ
computedꢀHꢁbondingꢀdistancesꢀareꢀinꢀgoodꢀagreementꢀwithꢀthoseꢀ
foundꢀinꢀrelatedꢀcomplexesꢀofꢀtriazoleꢀderivatesꢀwithꢀcarboxylicꢀ
acids.8ꢀ Uponꢀ binding,ꢀ theꢀ N−H,ꢀ C=O,ꢀ N=N,ꢀ andꢀ C−Hbꢀ bondsꢀ
40ꢀ undergoꢀ aꢀ significantꢀ elongationꢀ toꢀ accommodateꢀ theꢀ hydrogenꢀ
bondsꢀ (Tableꢀ 2).ꢀ Theoreticalꢀ calculationsꢀ thereforeꢀ corroborateꢀ
thatꢀtheꢀ12GAꢀguestsꢀareꢀstabilizedꢀinꢀhostꢀ1ꢀbyꢀmeansꢀofꢀanꢀarrayꢀ
ofꢀHꢁbondingꢀinteractions.ꢀ
ꢀ
Fig. 3ꢀ(a)ꢀM06ꢁ2X/6ꢁ311G**ꢀoptimizedꢀstructureꢀforꢀcomplexꢀ1•(12GA)2.ꢀ
(b)ꢀ Chemicalꢀ structureꢀ ofꢀ complexꢀ 1•(12GA)2ꢀ alongꢀ withꢀ theꢀ bondꢀ
65ꢀ numberingꢀusedꢀinꢀTableꢀ2.ꢀ
Table 2.ꢀ Selectedꢀ bondꢀ lengthsꢀ (inꢀ Å)ꢀ calculatedꢀ forꢀ receptorꢀ 1ꢀ andꢀ complexꢀ
1•(12GA)2ꢀatꢀtheꢀM06ꢁ2X/6ꢁ311G**ꢀlevel.ꢀ
Bondꢀ
1ꢀ
1
1.006ꢀ
1.216ꢀ
1.083ꢀ
1.084ꢀ
1.286ꢀ
1.076ꢀ
ꢁꢀ
1•(12GA)2ꢀ
1.012ꢀ
1.232ꢀ
1.082ꢀ
1.085ꢀ
1.292ꢀ
1.078ꢀ
1.952ꢀ
2.277ꢀ
1.783ꢀ
2.491ꢀ
1.688ꢀ
2.458ꢀ
2.048ꢀ
2ꢀ
3ꢀ
4ꢀ
5ꢀ
6ꢀ
7ꢀ
8ꢀ
ꢁꢀ
9ꢀ
ꢁꢀ
10ꢀ
11ꢀ
12ꢀ
13ꢀ
ꢁꢀ
ꢀ
Theꢀ CPꢁcorrectedꢀ bindingꢀ energiesꢀ forꢀ complexꢀ 1•(12GA)2ꢀ
ꢁꢀ
45ꢀ (Figureꢀ 3)ꢀ andꢀ forꢀ complexesꢀ 1•12GA-lꢀ andꢀ 1•12GA-rꢀ (Figureꢀ
S9)ꢀthatꢀincorporateꢀonlyꢀoneꢀ12GAꢀmoleculeꢀwereꢀcomputedꢀatꢀ
theꢀM06ꢁ2X/6ꢁ311G**ꢀlevel.ꢀTheꢀtheoreticalꢀcalculationsꢀpredictꢀ
aꢀdissimilarꢀaffinityꢀofꢀtheꢀtwoꢀpossibleꢀbindingꢀsitesꢀofꢀreceptorꢀ1ꢀ
toꢀbindꢀtheꢀ12GAꢀguest.ꢀThus,ꢀtheꢀbindingꢀenergyꢀcomputedꢀforꢀ
50ꢀ complexꢀ1•12GA-rꢀ(FigureꢀS9,ꢀright), formedꢀuponꢀbindingꢀtheꢀ
gallicꢀacidꢀguestꢀbyꢀtheꢀC=OꢀgroupꢀofꢀtheꢀamideꢀandꢀtheꢀC−Hꢀunitꢀ
ofꢀ theꢀ triazolꢀ ring,ꢀ isꢀ –20.96ꢀ kcalꢀ mol–1.ꢀ However,ꢀ theꢀ bindingꢀ
energyꢀ calculatedꢀ forꢀ complexꢀ 1•12GA-lꢀ (Figureꢀ S9,ꢀ left),ꢀ inꢀ
whichꢀtheꢀgallicꢀacidꢀisꢀboundꢀtoꢀreceptorꢀ1ꢀbyꢀtheꢀN−Hꢀunitꢀofꢀ
55ꢀ theꢀamideꢀandꢀtheꢀN=Nꢀgroupꢀofꢀtheꢀtriazoleꢀring,ꢀisꢀ–17.77ꢀkcalꢀ
mol–1.ꢀ Interestingly,ꢀ theꢀ sumꢀ ofꢀ theꢀ bindingꢀ energiesꢀ computedꢀ
forꢀtheꢀsingleꢀcomplexesꢀ1•12GA-l andꢀ1•12GA-r isꢀpracticallyꢀ
equalꢀtoꢀtheꢀbindingꢀenergyꢀcalculatedꢀforꢀcomplexꢀ1•(12GA)2ꢀ(–
ꢁꢀ
ꢁꢀ
ꢀ
ꢀ
Theꢀ formationꢀ ofꢀ theꢀ complexꢀ 1•(12GA)2ꢀ hasꢀ beenꢀ
70ꢀ experimentallyꢀdemonstratedꢀbyꢀperformingꢀaꢀJob’sꢀplotꢀanalysis.ꢀ
Inꢀ goodꢀ agreementꢀ withꢀ theoreticalꢀ calculations,ꢀ theꢀ Job’sꢀ plotꢀ
showsꢀ aꢀ maximumꢀ atꢀ 0.63ꢀ diagnosticꢀ ofꢀ aꢀ 1:2ꢀ stoichiometryꢀ
(Figureꢀ4a).ꢀTheꢀ1HꢀNMRꢀtitrationꢀofꢀreceptorꢀ1ꢀwithꢀcarboxylicꢀ
acidꢀ12GAꢀ(Figuresꢀ4bꢀandꢀS10)ꢀrevealsꢀthatꢀbothꢀtheꢀN−Hꢀdonorꢀ
75ꢀ andꢀ theꢀ C=Oꢀ acceptorꢀ Hꢁbondingꢀ unitsꢀ ofꢀ theꢀ amideꢀ groupꢀ
participateꢀinꢀtheꢀformationꢀofꢀtheꢀcomplexꢀthusꢀsupportingꢀ theꢀ
1:2ꢀ stoichiometry.ꢀ Theꢀ primaryꢀ acidꢁbaseꢀ interactionsꢀ areꢀ
reinforcedꢀbyꢀanꢀarrayꢀofꢀHꢁbondsꢀbetweenꢀtheꢀcarboxylicꢀgroupꢀ
ofꢀ 12GAꢀ withꢀ theꢀ aromaticꢀ protonsꢀ Hbꢀ andꢀ Hc.ꢀ Asꢀ theoreticalꢀ
4
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 5 of 8
Organic & Biomolecular Chemistry
calculationsꢀpredict,ꢀtheꢀtwoꢀtriazoleꢀringsꢀareꢀinvolvedꢀinꢀbindingꢀ
35ꢀ impliesꢀthatꢀtheꢀtwoꢀbindingꢀsitesꢀofꢀtheꢀreceptorꢀareꢀidenticalꢀandꢀ
independentꢀofꢀeachꢀother.19ꢀFittingꢀtheꢀvariationꢀofꢀtheꢀchemicalꢀ
shiftsꢀ involvedꢀ inꢀ theꢀ complexationꢀ processꢀ ofꢀ receptorꢀ 1ꢀ withꢀ
theꢀ12GAꢀguest:ꢀoneꢀofꢀthemꢀparticipatesꢀasꢀaꢀhydrogenꢁdonatingꢀ
unitꢀbyꢀestablishingꢀHꢁbondsꢀbetweenꢀHbꢀandꢀtheꢀcarbonylꢀgroupꢀ
ofꢀ theꢀ carboxylicꢀ acid,ꢀ whereasꢀ theꢀ otherꢀ actsꢀ asꢀ aꢀ hydrogenꢁ
5ꢀ acceptingꢀ moietyꢀ byꢀ formingꢀ Hꢁbondsꢀ betweenꢀ theꢀ twoꢀ sp2ꢀ
nitrogenꢀatomsꢀofꢀtheꢀheterocycleꢀandꢀtheꢀacidicꢀO−Hꢀgroupꢀofꢀ
theꢀcarboxylicꢀacidꢀ(seeꢀSchemeꢀ1ꢀandꢀFigureꢀ3).ꢀHowever,ꢀtheꢀ
benzeneꢀ protonꢀ Haꢀ locatedꢀ inꢀ ortoꢀ relativeꢀ toꢀ theꢀ triazoleꢀ ringsꢀ
doesꢀnotꢀdeshieldꢀinꢀtheꢀtitrationꢀexperiment,ꢀwhichꢀindicatesꢀthatꢀ
10ꢀ thisꢀ C−Hꢀ groupꢀ isꢀ notꢀ participatingꢀ inꢀ theꢀ complexationꢀ ofꢀ theꢀ
12GAꢀguestsꢀ(FigureꢀS11ꢀandꢀSchemeꢀ1).ꢀ
12GAꢀtoꢀaꢀ1:2ꢀcooperativeꢀmodelꢀshedꢀincoherentꢀvaluesꢀforꢀK
View Article On1line
and K2ꢀwithꢀerrorsꢀhigherꢀthanꢀ ±400ꢀ%.ꢀHowever,ꢀaꢀsignificantꢀ
40ꢀ improvementꢀ isꢀ achievedꢀ byꢀ performingꢀ aꢀ globalꢀ fittingꢀ ofꢀ theꢀ
experimentalꢀ dataꢀ toꢀ aꢀ statisticalꢀ bindingꢀ model.ꢀ Inꢀ thisꢀ model,ꢀ
onlyꢀ oneꢀ bindingꢀ constantꢀ (K1) andꢀ aꢀ globalꢀ ∆δꢀ forꢀ theꢀ twoꢀ
possibleꢀHGꢀandꢀHG2ꢀcomplexesꢀareꢀaveraged.ꢀTheꢀcalculatedꢀK1
and K2ꢀ valuesꢀ obtainedꢀ byꢀ performingꢀ theꢀ globalꢀ fittingꢀ areꢀ ofꢀ
45ꢀ 426.3ꢀandꢀ106.5ꢀMꢁ1,ꢀrespectively,ꢀwithꢀanꢀerrorꢀofꢀ±ꢀ22ꢀ%ꢀthatꢀ
allowsꢀ establishingꢀ thatꢀ theꢀ complexationꢀ ofꢀ theꢀ neutralꢀ
carboxylicꢀacidꢀ12GAꢀbyꢀreceptorꢀ1ꢀproceedsꢀbyꢀaꢀstatisticalꢀnonꢁ
cooperativeꢀprocess.ꢀꢀ
Self-assembly on surfaces.
50ꢀ
Theꢀupfieldꢀshiftꢀofꢀsomeꢀaromaticꢀresonancesꢀobservedꢀinꢀtheꢀ
titrationꢀ ofꢀ 1ꢀ withꢀ 12GAꢀ (Figureꢀ S10)ꢀ andꢀ withꢀ Cl−ꢀ andꢀ Br−ꢀ
anionsꢀ (Figureꢀ S5ꢀ andꢀ S6)ꢀ andꢀ alsoꢀ inꢀ theꢀ selfꢁassemblyꢀ ofꢀ 1ꢀ
(FigureꢀS2)ꢀsuggestsꢀanꢀaggregationꢀphenomenonꢀdirectedꢀbyꢀπꢁπꢀ
interactions.ꢀ Thisꢀ aggregationꢀ wasꢀ utilizedꢀ toꢀ createꢀ organizedꢀ
55ꢀ supramolecularꢀ structuresꢀ byꢀ slowꢀ diffusionꢀ ofꢀ acetonitrileꢀ
vapoursꢀintoꢀaꢀchloroformꢀsolutionꢀofꢀpristineꢀ 1ꢀandꢀalsoꢀinꢀtheꢀ
presenceꢀofꢀTBABrꢀandꢀ12GA.ꢀTheꢀaggregatesꢀformedꢀhaveꢀbeenꢀ
visualizedꢀbyꢀscanningꢀelectronꢀmicroscopyꢀ(SEM).ꢀ
Freeꢀreceptorꢀ1ꢀselfꢁassemblesꢀintoꢀstarꢁlikeꢀobjectsꢀcomposedꢀ
60ꢀ ofꢀwellꢁdefinedꢀneedleꢁlikeꢀstructuresꢀwithꢀanꢀaverageꢀthicknessꢀ
ofꢀ ~1ꢀ µmꢀ (Figureꢀ 5a,ꢀ 5b,ꢀ andꢀ S11).ꢀ Theꢀ presenceꢀ ofꢀ bromideꢀ
anionsꢀalsoꢀgivesꢀriseꢀtoꢀpseudoꢁmonodimensionalꢀstructuresꢀthatꢀ
resembleꢀcactusꢀpricklesꢀ(Figuresꢀ5c,ꢀandꢀS12).ꢀTheꢀanisotropicꢀ
growthꢀofꢀtheꢀmicrocrystalsꢀformedꢀfromꢀ1ꢀinꢀtheꢀabsenceꢀorꢀinꢀ
65ꢀ theꢀ presenceꢀ ofꢀ bromideꢀ anionsꢀ couldꢀ beꢀ accountedꢀ forꢀ byꢀ theꢀ
generationꢀofꢀanꢀactiveꢀplaneꢀofꢀseveralꢀmoleculesꢀinteractingꢀbyꢀ
theꢀparaffinicꢀchainsꢀwithꢀaꢀhighꢀsurfaceꢀfreeꢀenergy.ꢀTheseꢀactiveꢀ
plainsꢀ growꢀ fastꢀ inꢀ theꢀ directionꢀ perpendicularꢀ toꢀ theꢀ planeꢀ byꢀ
meansꢀofꢀπꢁstackingꢀaromaticꢀinteractions.ꢀ
ꢀ
Fig. 4ꢀ(a)ꢀJobꢀplotꢀshowingꢀtheꢀ1:2ꢀstoichiometryꢀofꢀcomplexꢀ1•(12GA)2.ꢀ
(b)ꢀHyperbolicꢀbindingꢀisothermsꢀforꢀtheꢀbindingꢀofꢀ12GAꢀtoꢀreceptorꢀ1
15ꢀ fitted toꢀaꢀ1:2ꢀstatisticalꢀassociationꢀprocess.ꢀꢀ
Theꢀ titrationꢀ experimentꢀ ofꢀ 1ꢀ withꢀ 12GAꢀ didꢀ notꢀ shedꢀ
sigmoidalꢀ curvesꢀ butꢀ hyperbolicꢀ bindingꢀ isothermsꢀ (Figureꢀ 4b),ꢀ
whichꢀsuggestsꢀthatꢀtheꢀcomplexationꢀofꢀ12GAꢀbyꢀreceptorꢀ1ꢀisꢀ
nonꢁcooperative.17ꢀ Asꢀ inꢀ theꢀ caseꢀ ofꢀ theꢀ complexesꢀ formedꢀ byꢀ
20ꢀ receptorꢀ1ꢀandꢀhalideꢀanions,ꢀweꢀhaveꢀfittedꢀtheꢀexperimentalꢀdataꢀ
byꢀusingꢀtheꢀfittingꢀprogramꢀreportedꢀbyꢀP.ꢀThodarsonꢀbutꢀusingꢀaꢀ
1:2ꢀ modelꢀbasedꢀonꢀ cubicꢀ equationꢀ2.14a,ꢀ 18ꢀ Inꢀ thisꢀ equation,ꢀ K1
andꢀ K2ꢀ areꢀ theꢀ firstꢀ andꢀ secondꢀ stepwiseꢀ associationꢀ constants,ꢀ
respectivelyꢀandꢀ[G]ꢀisꢀtheꢀconcentrationꢀofꢀtheꢀunboundꢀguest.ꢀꢀ
[G]3 (K K ) +[G]2{(K (2K [H] − K [G] ) +1}+
25ꢀ
ꢀ
Eq.ꢀ2ꢀ
1
2
1
2
0
2
0
[G]{K1([H]0 −[G]0 ) +1}−[G]0 = 0
Inꢀ1:2ꢀcomplexes,ꢀitꢀisꢀnecessaryꢀtoꢀconsiderꢀtwoꢀpossibilities:ꢀ
i)ꢀaꢀcooperativeꢀscenarioꢀinꢀwhichꢀtheꢀcomplexationꢀofꢀtheꢀfirstꢀ
guestꢀ influencesꢀ theꢀ complexationꢀ ofꢀ theꢀ secondꢀ one,ꢀ andꢀ ii)ꢀ aꢀ
nonꢁcooperativeꢀscenarioꢀinꢀwhichꢀtheꢀcomplexationꢀofꢀtheꢀfirstꢀ
70ꢀ
ꢀ
Fig. 5ꢀSEMꢀimagesꢀofꢀtheꢀaggregatesꢀformedꢀbyꢀtheꢀselfꢁassemblyꢀofꢀ1ꢀ(aꢀ
andꢀb).ꢀTheꢀaggregationꢀofꢀreceptorꢀ1ꢀinꢀtheꢀpresenceꢀofꢀbromideꢀanionsꢀ
(c)ꢀorꢀꢀinꢀtheꢀpresenceꢀofꢀtheꢀgallicꢀacidꢀderivativeꢀ12GAꢀ(d)ꢀresultsꢀinꢀtheꢀ
formationꢀofꢀaggregatesꢀofꢀdifferentꢀmorphology.ꢀ
30ꢀ guestꢀdoesꢀnotꢀinfluenceꢀtheꢀcomplexationꢀofꢀtheꢀsecondꢀone.14b
ꢀ
Inꢀ theꢀ firstꢀ case,ꢀ thereꢀ mustꢀ beꢀ twoꢀ differentꢀ valuesꢀ forꢀ theꢀ
bindingꢀ constantsꢀ K1 and K2ꢀ butꢀ theꢀ equalityꢀ K1 = 4K2ꢀ isꢀ notꢀ
fulfilled.ꢀ Inꢀ theꢀ secondꢀ case,ꢀ K1 and K2ꢀ areꢀ differentꢀ butꢀ thisꢀ
equalityꢀ K1 = 4K2ꢀ mustꢀ beꢀ fulfilled.ꢀ Thisꢀ sequentialꢀ bindingꢀ
75ꢀ Theꢀ selfꢁassemblyꢀ ofꢀ 1ꢀ inꢀ theꢀ presenceꢀ ofꢀ theꢀ gallicꢀ acidꢀ
derivativeꢀ 12GA producesꢀ flowerꢁlikeꢀ structuresꢀ byꢀ theꢀ
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

Organic & Biomolecular Chemistry
Page 6 of 8
interactionꢀofꢀflatꢀribbonsꢀ(Figureꢀ5dꢀandꢀS13).ꢀTheꢀcomplexationꢀ
potassiumꢀ carbonateꢀ wasꢀ addedꢀ (3.11ꢀ g,ꢀ 22.50ꢀ mmol).ꢀ Theꢀ
ofꢀ12GAꢀbyꢀreceptorꢀ1ꢀobservedꢀinꢀsolutionꢀcouldꢀgivesꢀriseꢀtoꢀ
supramolecularꢀplatformsꢀ withꢀ aꢀ largerꢀ πꢁsurfaceꢀ endowedꢀwithꢀ
manyꢀparaffinicꢀchains.ꢀTheꢀinterdigitationꢀofꢀtheꢀchainsꢀandꢀtheꢀ
5ꢀ πꢁπꢀstackingꢀbetweenꢀtheꢀaromaticꢀcagesꢀwouldꢀformꢀtheꢀlamellaeꢀ
constitutiveꢀofꢀtheꢀflatꢀribbons.ꢀ
reactionꢀmixtureꢀwasꢀstirredꢀforꢀthreeꢀhours.ꢀAfterꢀevaporationꢀofꢀ
theꢀsolventꢀunderꢀreducedꢀpressure,ꢀtheꢀresidueꢀwasꢀwashedꢀwithꢀ
water,ꢀextractedꢀwithꢀmethyleneꢀchloride,ꢀdriedꢀoverꢀMgSO4,ꢀandꢀ
View Article Online
60ꢀ theꢀsolventꢀevaporatedꢀtoꢀyieldꢀcompoundꢀ5ꢀthatꢀwasꢀusedꢀwithoutꢀ
1
furtherꢀ purificationꢀ (310ꢀ mg,ꢀ 73%).ꢀ Mp:ꢀ 114.5ꢁ115.6ꢀ ºC;ꢀ Hꢀ
NMRꢀ(CDCl3,ꢀ300ꢀMHz):ꢀδꢀppmꢀ7.83ꢀ(d,ꢀJꢀ=ꢀ1.4ꢀHz;ꢀ2H,ꢀHb),ꢀ
7.70ꢀ(t,ꢀJꢀ=ꢀ1.4ꢀHz,ꢀ1H,ꢀHa),ꢀ6.12ꢀ(br,ꢀ1H,ꢀHd),ꢀ3.45ꢀ(m,ꢀ2H,ꢀHe),ꢀ
3.14ꢀ (s,ꢀ 2H,ꢀ Hc),ꢀ 1.60ꢀ (m,ꢀ 2H,ꢀ Hf),ꢀ 1.34ꢁ1.27ꢀ (br,ꢀ 14H,ꢀ
65ꢀ Hg+h+i+j+k+l+m),ꢀ 0.89ꢀ (t,ꢀ Jꢀ =ꢀ6.8ꢀHz;ꢀ 3H,ꢀ Hn);ꢀ 13Cꢀ NMRꢀ (CDCl3,ꢀ
75Mz):ꢀδꢀppmꢀ165.7,ꢀ137.8,ꢀ135.6,ꢀ130.7,ꢀ123.1,ꢀ81.8,ꢀ78.9;ꢀFTIRꢀ
(neat):ꢀνꢀ653,ꢀ692,ꢀ759,ꢀ845,ꢀ891,ꢀ982,ꢀ1075,ꢀ1167,ꢀ1251,ꢀ1329,ꢀ
1425,ꢀ 1461,ꢀ 1545,ꢀ 1585,ꢀ 1640,ꢀ 1814,ꢀ 2159,ꢀ 2856,ꢀ 2926,ꢀ 3073,ꢀ
3310ꢀ cm–1.ꢀ HRMSꢀ (ESIꢁFT)ꢀ m/zꢀ calcd.ꢀ forꢀ C21H28NOꢀ [M+H]+,ꢀ
70ꢀ 310.217089;ꢀfound,ꢀ310.21654.ꢀ
Experimental
3,5-dibromo-N-decylbenzamide (3).ꢀ 3,5ꢁdibromobenzoicꢀ acidꢀ
(1.78ꢀ g,ꢀ 6.36ꢀ mmol),ꢀ 1ꢁethylꢁ3ꢁ(3ꢁdimethylaminopropyl)ꢁ
10ꢀ carbodiimideꢀ hydrochlorideꢀ (1.34ꢀ g,ꢀ 6.99ꢀ mmol)ꢀ andꢀ 4ꢁ
dimethylaminopyridineꢀ (0.85ꢀ g,ꢀ 6.99ꢀ mmol)ꢀ wereꢀ dissolvedꢀ inꢀ
dryꢀ dichloromethaneꢀ (80ꢀ mL)ꢀ underꢀ argonꢀ atmosphereꢀ atꢀ 0ꢀ ºC.ꢀ
Theꢀ mixtureꢀ wasꢀ stirredꢀ forꢀ 15ꢀ minutesꢀ andꢀ thenꢀ 1ꢁdecylamineꢀ
(1.3ꢀmL,ꢀ6.36ꢀmmol)ꢀwasꢀaddedꢀdropwise.ꢀTheꢀreactionꢀmixtureꢀ
15ꢀ wasꢀallowedꢀtoꢀwarmꢀupꢀtoꢀroomꢀtemperatureꢀandꢀwasꢀstirredꢀforꢀ
3ꢀhours.ꢀTheꢀorganicꢀlayerꢀwasꢀwashedꢀwithꢀHClꢀ1Mꢀandꢀwater,ꢀ
driedꢀwithꢀMgSO4,ꢀfiltered,ꢀandꢀtheꢀsolventꢀwasꢀremovedꢀunderꢀ
reducedꢀ pressure.ꢀ Theꢀ residueꢀ wasꢀ purifiedꢀ byꢀ columnꢀ
chromatographyꢀ(silicaꢀgel,ꢀhexane:ethylꢀacetateꢀ5:1)ꢀaffordingꢀ3ꢀ
20ꢀ asꢀ aꢀ whiteꢀ solidꢀ (1.63ꢀ g,ꢀ 61%).ꢀ Mp:ꢀ 82.4ꢁ84.3ꢀ ºC;ꢀ 1Hꢀ NMRꢀ
(CDCl3,ꢀ300ꢀMHz):ꢀδꢀppmꢀ7.74ꢀ(d,ꢀJꢀ=ꢀ1.7ꢀHz,ꢀ2H,ꢀHb),ꢀ7.71ꢀ(t,ꢀJꢀ
=ꢀ1.7ꢀHz;ꢀ1H,ꢀHa),ꢀ5.91ꢀ(br,ꢀ1H,ꢀHc),ꢀ3.36ꢀ(m,ꢀ2H,ꢀHd),ꢀ1.54ꢀ(m,ꢀ
2H,ꢀHe),ꢀ1.27ꢁ1.20ꢀ(br,ꢀ14H,ꢀHf+g+h+i+j+k+l),ꢀ0.81ꢀ(t,ꢀJꢀ=ꢀ6.5ꢀHz,ꢀ3H,ꢀ
Hm);ꢀ13CꢀNMRꢀ(CDCl3,ꢀ75Mz):ꢀδꢀppmꢀ165.2,ꢀ138.4,ꢀ136.9,ꢀ129.2,ꢀ
25ꢀ 123.5,ꢀ40.8,ꢀ32.2,ꢀ29.8,ꢀ29.6,ꢀ27.3,ꢀ23.0,ꢀ14.4;ꢀFTIRꢀ(neat):ꢀνꢀ674,ꢀ
717,ꢀ 739,ꢀ 767,ꢀ 866,ꢀ 899,ꢀ 1107,ꢀ 1158,ꢀ 1284,ꢀ 1310,ꢀ 1371,ꢀ 1411,ꢀ
1462,ꢀ1550,ꢀ1590,ꢀ1639,ꢀ2854,ꢀ2925,ꢀ3286ꢀcm–1.ꢀHRMSꢀ(ESIꢁFT)ꢀ
m/z:ꢀ calcd.ꢀ forꢀ C17H24Br2NOꢀ [MꢁH]+,ꢀ 416.022461;ꢀ found,ꢀ
416.02301.ꢀ
30ꢀ N-decyl-3,5-bis(2-(trimethylsilyl)ethynyl)benzamide (4).ꢀ 3,5ꢁ
dibromoꢁNꢁdecylꢁbenzamideꢀ (3)ꢀ (770ꢀ mg,ꢀ 1.93ꢀ mmol),ꢀ bisꢁ
(triphenylphosphine)ꢁpalladium(II)ꢁchlorideꢀ (133ꢀ mg,ꢀ 0.19ꢀ
mmol),ꢀcopperꢀ(I)ꢀiodideꢀ(19ꢀmg,ꢀ0.10ꢀmmol)ꢀandꢀtriethylamineꢀ
(1.1ꢀ mL,ꢀ 7.72ꢀ mmol)ꢀ wereꢀ dissolvedꢀ inꢀ dryꢀ THFꢀ (4ꢀ mL).ꢀ Theꢀ
35ꢀ mixtureꢀ wasꢀ subjectedꢀ toꢀ severalꢀ vacuum/argonꢀ cyclesꢀ andꢀ
trimethylsilylacetyleneꢀ (0.8ꢀ mL,ꢀ 5.80ꢀ mmol)ꢀ wasꢀ added.ꢀ Theꢀ
mixtureꢀ wasꢀ heatedꢀ atꢀ 70ꢀ ºCꢀ andꢀ stirredꢀ overnight.ꢀ Afterꢀ
evaporationꢀofꢀtheꢀsolventꢀunderꢀreducedꢀpressure,ꢀtheꢀcrudeꢀwasꢀ
washedꢀwithꢀHClꢀ1M,ꢀNH4Clꢀsaturatedꢀsolution,ꢀwater,ꢀextractedꢀ
40ꢀ withꢀmethylenechloride,ꢀandꢀfilteredꢀwithꢀcelite.ꢀTheꢀresidueꢀwasꢀ
purifiedꢀ byꢀ columnꢀ chromatographyꢀ (silicaꢀ gel,ꢀ hexane:ethylꢀ
acetateꢀ 20:1)ꢀ affordingꢀ 4ꢀ asꢀ aꢀbrownishꢀ oilꢀ (490ꢀ mg,ꢀ 56%).ꢀ 1Hꢀ
NMRꢀ(CDCl3,ꢀ300ꢀMHz):ꢀδꢀppmꢀ7.79ꢀ(d,ꢀJꢀ=ꢀ1.5ꢀHz,ꢀ2H,ꢀHb),ꢀ
6.69ꢀ(t,ꢀJꢀ=ꢀ1.5ꢀHz;ꢀ1H,ꢀHa),ꢀ6.17ꢀ(br,ꢀ1H,ꢀHd),ꢀ3.45ꢀ(m,ꢀ2H,ꢀHe),ꢀ
45ꢀ 1.61ꢀ(q,ꢀJꢀ=ꢀ6.8ꢀHz,ꢀ2H,ꢀHf),ꢀ1.36ꢁ1.30ꢀ(br,ꢀ14H,ꢀHg+h+i+j+k+l+m),ꢀ
0.91ꢀ(t,ꢀJꢀ=ꢀ6.5ꢀHz,ꢀ3H,ꢀHn),ꢀ0.27ꢀ(s,ꢀ18H,ꢀHc);ꢀ13CꢀNMRꢀ(CDCl3,ꢀ
75Mz):ꢀ δꢀ ppmꢀ 166.1,ꢀ 137.7,ꢀ 135.4,ꢀ 130.2,ꢀ 124.1,ꢀ 103.3,ꢀ 96.4,ꢀ
40.4,ꢀ32.1,ꢀ29.8,ꢀ29.7,ꢀ29.5,ꢀ27.2,ꢀ22.9;ꢀFTIRꢀ(neat):ꢀνꢀ640,ꢀ674,ꢀ
712,ꢀ 767,ꢀ 891,ꢀ 936,ꢀ 989,ꢀ 1067,ꢀ 1155,ꢀ 1247,ꢀ 1326,ꢀ 1373,ꢀ 1466,ꢀ
50ꢀ 1538,ꢀ 1586,ꢀ 1634,ꢀ 1817,ꢀ 2853,ꢀ 2921,ꢀ 2955,ꢀ 3067,ꢀ 3288ꢀ cm–1.ꢀ
HRMSꢀ (ESIꢁFT)ꢀ m/zꢀ calcd.ꢀ forꢀ C27H42NOSi2ꢀ [MꢁH]+,ꢀ
452.280495;ꢀfound,ꢀ452.28079.ꢀ
N-decyl-3,5-bis(1-biphenyl-1H-1,2,3-triazol-4-yl)benzamide (1).ꢀ
Compoundꢀ5ꢀ(126ꢀmg,ꢀ0.41ꢀmmol),ꢀ4ꢁbiphenylꢀazideꢀ(4)ꢀ(228ꢀmg,ꢀ
1.22ꢀ mmol),ꢀ copperꢀ sulphateꢀ pentahydrateꢀ (2ꢀ mg,ꢀ 0.008ꢀ mmol)ꢀ
andꢀsodiumꢀascorbateꢀ(4ꢀmg,ꢀ0.02ꢀmmol)ꢀwereꢀdissolvedꢀinꢀ4ꢀmLꢀ
75ꢀ ofꢀ aꢀ dichloromethane:waterꢀ mixtureꢀ (1:1)ꢀ andꢀ metallicꢀ copperꢀ
wasꢀaddedꢀtoꢀtheꢀmixtureꢀunderꢀArgonꢀatmosphere.ꢀTheꢀreactionꢀ
mixtureꢀwasꢀstirredꢀforꢀ72ꢀhoursꢀandꢀthen,ꢀtheꢀorganicꢀlayerꢀwasꢀ
separate,ꢀdriedꢀoverꢀMgSO4,ꢀandꢀfiltered.ꢀAfterꢀevaporationꢀofꢀtheꢀ
solventꢀ underꢀ reducedꢀ pressure,ꢀ theꢀ residueꢀ wasꢀ purifiedꢀ byꢀ
80ꢀ columnꢀchromatographyꢀ(silicaꢀgel,ꢀchloroform:methanolꢀ100:1)ꢀ
affordingꢀ 1ꢀasꢀaꢀlightꢀ yellowꢀsolidꢀ(223ꢀmg,ꢀ78%).ꢀMp:ꢀ 201.7ꢁ
202.7ꢀºC;ꢀ1HꢀNMRꢀ(CDCl3,ꢀ300ꢀMHz):ꢀδꢀppmꢀ8.58ꢀ(br,ꢀ1H,ꢀHa),ꢀ
8.38ꢀ(s,ꢀ2H,ꢀHc),ꢀ8.31ꢀ(d,ꢀJꢀ=1.3ꢀHz,ꢀ2H,ꢀHb),ꢀ7.85ꢀ(d,ꢀJꢀ=ꢀ8.6Hz,ꢀ
4H,ꢀHd),ꢀ7.75ꢀ(d,ꢀJꢀ=ꢀ8.6ꢀHzꢀ4H,ꢀHe),ꢀ7.63ꢀ(m,ꢀ4H,ꢀHf),ꢀ7.51ꢁ7.38ꢀ
85ꢀ (m,ꢀ6H,ꢀHg+h),ꢀ6.71ꢀ(t,ꢀJꢀ=ꢀ5.7ꢀHzꢀ1H,ꢀHi),ꢀ3.53ꢀ(m,ꢀ2H,ꢀHj),ꢀ1.70ꢀ
(q,ꢀJꢀ=ꢀ6.8ꢀHz,ꢀ2H,ꢀHk),ꢀ1.46ꢁ1.28ꢀ(br,ꢀ14H,ꢀHl+m+n+o+p+q+r),ꢀ0.89ꢀ
(t,ꢀJꢀ=ꢀ6.7ꢀHz,ꢀ3H,ꢀHs);ꢀ13CꢀNMRꢀ(CDCl3,ꢀ75Mz):ꢀδꢀppmꢀ166.7,ꢀ
147.2,ꢀ 141.9,ꢀ 139.5,ꢀ 136.2,ꢀ 135.9,ꢀ 131.3,ꢀ 129.0,ꢀ 128.4,ꢀ 128.0,ꢀ
127.1,ꢀ 125.3,ꢀ 123.9,ꢀ 120.7,ꢀ 118.3,ꢀ 40.4,ꢀ 31.9,ꢀ 29.7,ꢀ 29.6,ꢀ 29.4,ꢀ
90ꢀ 29.3,ꢀ27.1,ꢀ22.7,ꢀ14.1;ꢀFTIRꢀ(neat):ꢀ νꢀ626,ꢀ647,ꢀ658,ꢀ695,ꢀ 722,ꢀ
763,ꢀ841,ꢀ892,ꢀ991,ꢀ1042,ꢀ1117,ꢀ1234,ꢀ1296,ꢀ1402,ꢀ1459,ꢀ1491,ꢀ
1527,ꢀ 1610,ꢀ 1643,ꢀ 2363,ꢀ 2854,ꢀ 2924,ꢀ 3062,ꢀ 3138,ꢀ 3291ꢀ cm–1;ꢀ
HRMSꢀ(ESIꢁFT)ꢀm/zꢀcalcd.ꢀforꢀ[C45H46N7O]+:ꢀ700.37584;ꢀfound,ꢀ
700.37608.ꢀ
95ꢀ Computational details.
Allꢀ theoreticalꢀ calculationsꢀ wereꢀ carriedꢀ outꢀ withinꢀ theꢀ densityꢀ
functionalꢀtheoryꢀ(DFT)ꢀapproachꢀbyꢀusingꢀtheꢀC.01ꢀrevisionꢀofꢀ
theꢀ Gaussianꢀ 09ꢀ programꢀ package.20ꢀ DFTꢀ calculationsꢀ wereꢀ
performedꢀ usingꢀ theꢀ hybridꢀ metaꢀ exchangeꢁcorrelationꢀ M06ꢁ2Xꢀ
100ꢀ functional,ꢀ whichꢀ hasꢀ beenꢀ speciallyꢀ designedꢀ toꢀ accountꢀ forꢀ
noncovalentꢀinteractions.21ꢀGeometryꢀoptimizationsꢀwereꢀcarriedꢀ
outꢀwithꢀtheꢀM06ꢁ2Xꢀfunctionalꢀinꢀcombinationꢀwithꢀtheꢀstandardꢀ
6ꢁ311G**ꢀbasisꢀset.22ꢀTheꢀalkylꢀchainsꢀattachedꢀtoꢀtheꢀnitrogenꢀofꢀ
theꢀamideꢀgroupꢀinꢀreceptorꢀ1ꢀandꢀformingꢀtheꢀalkoxyꢀgroupsꢀofꢀ
105ꢀ 12GAꢀ wereꢀ substitutedꢀ byꢀ methylꢀ groupsꢀ toꢀ reduceꢀ theꢀ
computationalꢀ cost.ꢀ Onꢀ theꢀ previouslyꢀ optimizedꢀ structures,ꢀ
singleꢁenergyꢀ calculationsꢀ atꢀ theꢀ M06ꢁ2X/6ꢁ311G**ꢀ levelꢀ wereꢀ
performedꢀ toꢀ computeꢀ theꢀ bindingꢀ energies.ꢀ Theꢀ basisꢀ setꢀ
superpositionꢀ errorꢀ (BSSE)ꢀ affectingꢀ theꢀ bindingꢀ energiesꢀ wasꢀ
110ꢀ correctedꢀ byꢀ usingꢀ theꢀ standardꢀ counterpoiseꢀ method.23ꢀ Theꢀ
BSSEꢀisꢀestimatedꢀtoꢀbeꢀalmostꢀnegliglibleꢀforꢀ1•X−ꢀcomplexesꢀ
N-decyl-3,5-diethynylbenzamide
(trimethylsilyl)ethynyl)ꢁbenzamideꢀ(4)ꢀ(639ꢀmg,ꢀ1.39ꢀmmol)ꢀwasꢀ
55ꢀ dissolvedꢀ inꢀ 20ꢀ mLꢀ ofꢀ aꢀ THF:methanolꢀ mixtureꢀ (1:1)ꢀ andꢀ
(5).ꢀ
Nꢁdecylꢁ3,5ꢁbis(2ꢁ
6
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 7 of 8
Organic & Biomolecular Chemistry
(1−2ꢀkcalꢀmol–1ꢀforꢀCl−,ꢀBr−,ꢀandꢀI−).ꢀForꢀcomplexꢀ1•(12GA)2,ꢀtheꢀ
BSSEꢀincreasesꢀtoꢀ6.4ꢀkcalꢀmol–1ꢀthatꢀonlyꢀrepresentsꢀaꢀ15ꢀ%ꢀofꢀ
theꢀtotalꢀbindingꢀenergy.ꢀTheseꢀresultsꢀsuggestꢀthatꢀtheꢀcalculationꢀ
ofꢀ bindingꢀ energiesꢀ forꢀ thisꢀ kindꢀ ofꢀ supramolecularꢀ complexes,ꢀ
5ꢀ forꢀ whichꢀ theꢀ associationꢀ isꢀ determinedꢀ byꢀ strongꢀ electrostaticꢀ
andꢀ Hꢁbondingꢀ interactions,ꢀ canꢀ beꢀ quiteꢀ accuratelyꢀ estimatedꢀ
withoutꢀtakenꢀintoꢀaccountꢀtheꢀBSSEꢀcorrection.24ꢀ
(b)ꢀ C.ꢀ H.ꢀ Lee,ꢀ H.ꢀ Miyaji,ꢀ D.ꢀ W.ꢀ Yoonꢀ andꢀ J.ꢀ L.ꢀ Sessler,ꢀ Chem.
Commun.ꢀ2008,ꢀ24.ꢀ
4ꢀ (a)ꢀ Y.ꢀ Furusho,ꢀ T.ꢀ Kimura,ꢀ T.ꢀMizunoꢀ andꢀ T.ꢀ Aida,ꢀ J. Am. Chem.
Soc.ꢀ1997,ꢀ119,ꢀ5267;ꢀ(b)ꢀE.ꢀYashima,ꢀK.ꢀMaedaꢀandꢀY.ꢀOkamoto,ꢀ
60ꢀ
65ꢀ
Natureꢀ 1999,ꢀ 399,ꢀ 449;ꢀ (c)ꢀ T.ꢀ Ishiꢁi,ꢀ M.ꢀ CregoꢁCalama,ꢀ P.ꢀ
View Article Online
Timmerman,ꢀD.ꢀN.ꢀReinhoudtꢀandꢀS.ꢀShinkai,ꢀAngew. Chem. Int. Ed.ꢀ
2002,ꢀ41,ꢀ1924.ꢀ
5ꢀ (a)ꢀY.ꢀLiꢀandꢀA.ꢀH.ꢀFlood,ꢀAngew. Chem. Int. Ed.ꢀ2008,ꢀ47,ꢀ2649;ꢀ(b)ꢀ
Y.ꢀLiꢀandꢀA.ꢀH.ꢀFlood,ꢀJ. Am. Chem. Soc.ꢀ2008,ꢀ130,ꢀ12111;ꢀ(c)ꢀY.ꢀ
Li,ꢀM.ꢀPink,ꢀJ.ꢀA.ꢀKartyꢀandꢀA.ꢀH.ꢀFlood,ꢀJ. Am. Chem. Soc.ꢀ2008,ꢀ
130,ꢀ17293.ꢀ
Conclusions
6ꢀ (a)ꢀR.ꢀM.ꢀMeudtner,ꢀM.ꢀOstermeier,ꢀR.ꢀGoddard,ꢀC.ꢀLimbergꢀandꢀS.ꢀ
Hecht,ꢀ Chem. Eur. J.ꢀ 2007,ꢀ 13,ꢀ 9834;ꢀ (b)ꢀ H.ꢀ Juwarker,ꢀ J.ꢀ M.ꢀ
Lenhardt,ꢀD.ꢀM.ꢀPhamꢀandꢀS.ꢀL.ꢀCraig,ꢀAngew. Chem. Int. Ed.ꢀ2008,ꢀ
47,ꢀ3740;ꢀ(c)ꢀH.ꢀJuwarker,ꢀJ.ꢀM.ꢀLenhardt,ꢀJ.ꢀC.ꢀCastillo,ꢀE.ꢀZhao,ꢀS.ꢀ
Krishnamurthy,ꢀR.ꢀM.ꢀJamiolkowski,ꢀK.ꢁH.ꢀKimꢀandꢀS.ꢀL.ꢀCraig,ꢀJ.
Org. Chem.ꢀ 2009,ꢀ 74,ꢀ 8924;ꢀ (d)ꢀ Y.ꢀ Huaꢀ andꢀ A.ꢀ H.ꢀ Flood,ꢀ J. Am.
Chem. Soc.ꢀ2010,ꢀ132,ꢀ12838.ꢀ
75ꢀ 7ꢀ Y.ꢀHuaꢀandꢀA.ꢀH.ꢀFlood,ꢀChem. Soc. Rev.ꢀ2010,ꢀ39,ꢀ1262.ꢀ
8ꢀ M.ꢁH.ꢀRyu,ꢀJ.ꢁW.ꢀChoi,ꢀH.ꢁJ.ꢀKim,ꢀN.ꢀParkꢀandꢀB.ꢀK.ꢀCho,ꢀAngew.
Chem. Int. Ed.ꢀ2011,ꢀ50,ꢀ5737.ꢀ
9ꢀ F.ꢀ García,ꢀ M.ꢀ R.ꢀ Torres,ꢀ E.ꢀ Matesanzꢀ andꢀ L.ꢀ Sánchez,ꢀ Chem.
Commun.ꢀ2011,ꢀ47,ꢀ5016.ꢀ
80ꢀ 10ꢀ V.ꢀ V.ꢀ Rostovtsev,ꢀ L.ꢀ G.ꢀ Green,ꢀ V.ꢀ V.ꢀ Fokinꢀ andꢀ K.ꢀ B.ꢀ Sharpless,ꢀ
Angew. Chem. Int. Ed.ꢀ2002,ꢀ41,ꢀ2596.ꢀ
11ꢀ M.ꢀHu,ꢀJ.ꢀLiꢀandꢀS.ꢀQ.ꢀYao,ꢀOrg. Lett.ꢀ2008,ꢀ10,ꢀ5529.ꢀ
12ꢀ I.ꢀ Bandyopadhyay,ꢀ K.ꢀ Raghavachariꢀ andꢀ A.ꢀ H.ꢀ Flood,ꢀ
ChemPhysChemꢀ2009,ꢀ10,ꢀ2535.ꢀ
85ꢀ 13ꢀ R.ꢀ Schwesinger,ꢀ R.ꢀ Link,ꢀ P.ꢀ Wenzlꢀ andꢀ S.ꢀ Kossek,ꢀ Chem. Eur. J.ꢀ
2006,ꢀ12,ꢀ438.ꢀ
14ꢀ (a)ꢀ P.ꢀ Thordarson,ꢀ Chem. Soc. Rev.,ꢀ 2011,ꢀ 40,ꢀ 1305;ꢀ (b)ꢀ Bindingꢀ
Constants:ꢀTheꢀMeasurementsꢀofꢀMolecularꢀComplexꢀStability,ꢀ(ed.ꢀ
K.ꢀA.ꢀConnors)ꢀWiley,ꢀNewꢀYork,ꢀ1987;ꢀ
90ꢀ 15ꢀ M.ꢀShirakawa,ꢀN.ꢀFujita,ꢀT.ꢀTani,ꢀK.ꢀKanekoꢀandꢀS.ꢀShinkai,ꢀChem.
Commun.ꢀ2005,ꢀ4149.ꢀ
16ꢀ (a)ꢀ M.ꢀ F.ꢀ Perutz,ꢀ Annu. Rev. Biochem.ꢀ 1979,ꢀ 48,ꢀ 327;ꢀ (b)ꢀ J.ꢀ L.ꢀ
MacdonaldꢀandꢀL.ꢀJ.ꢀPike,ꢀProc. Natl. Acad. Sci. U.S.A.ꢀ2008,ꢀ105,ꢀ
112.ꢀ
95ꢀ 17ꢀ (a)ꢀA.ꢀV.ꢀHill,ꢀBiochem. J.ꢀ1913,ꢀ7,ꢀ471;ꢀ(b)ꢀS.ꢀShinkai,ꢀM.ꢀIkeda,ꢀA.ꢀ
SugasakiꢀandꢀM.ꢀTakeuchi,ꢀAcc. Chem. Res.ꢀ2001,ꢀ34,ꢀ494;ꢀ(c)ꢀC.ꢀA.ꢀ
HunterꢀandꢀH.ꢀL.ꢀAnderson,ꢀAngew. Chem. Int. Ed.ꢀ2009,ꢀ48,ꢀ7488.ꢀ
18ꢀ H.ꢀTsukube,ꢀH.ꢀFuruta,ꢀA.ꢀOdani,ꢀY.ꢀTakeda,ꢀY.ꢀKudo,ꢀY.ꢀInoue,ꢀY.ꢀ
Liu,ꢀH.ꢀSakamotoꢀandꢀK.ꢀKimura,ꢀinꢀComprehensive Supramolecular
Chemistry,ꢀed.ꢀJ.ꢀL.ꢀAtwood,ꢀJ.ꢀE.ꢀD.ꢀDavies,ꢀD.ꢀD.ꢀMacNicolꢀandꢀF.ꢀ
Vögtle,ꢀPergamon,ꢀOxford,ꢀ1996,ꢀvol.ꢀ8,ꢀch.ꢀ10,ꢀpp.ꢀ425–482.ꢀ
19ꢀ (a)ꢀB.ꢀPerlmutterꢁHayman,ꢀAcc. Chem. Res.,ꢀ1986,ꢀ19,ꢀ90;ꢀ(b)ꢀA.ꢀJ.ꢀ
Lowe,ꢀF.ꢀM.ꢀPfefferꢀandꢀP.ꢀThordarson,ꢀSupramolec. Chem. 2012,ꢀ24,ꢀ
585.ꢀ
Theꢀ synergyꢀ betweenꢀ experimentalꢀ evidencesꢀ andꢀ theoreticalꢀ
10ꢀ calculationsꢀ hasꢀ demonstratedꢀ theꢀ versatilityꢀ ofꢀ theꢀ 70ꢀ
bis(triazole)benzamideꢀ receptorꢀ 1ꢀ toꢀ bindꢀ speciesꢀ ofꢀ differentꢀ
natureꢀ and,ꢀ hence,ꢀ anꢀ interestingꢀ guestꢁcontrolledꢀ topicity.ꢀ
Compoundꢀ1ꢀbindsꢀhalideꢀanionsꢀformingꢀcomplexesꢀwithꢀaꢀ1:1ꢀ
stoichiometryꢀwithꢀsimilarꢀbindingꢀconstantsꢀofꢀ29.0ꢀ(±ꢀ5%)ꢀandꢀ
15ꢀ 37.4ꢀ (±ꢀ4%)ꢀMꢁ1ꢀforꢀ chlorideꢀandꢀbromideꢀ anions,ꢀ respectively.ꢀ
However,ꢀ receptorꢀ 1ꢀ isꢀ ableꢀ toꢀ bindꢀ aꢀ neutralꢀ carboxylicꢀ acidꢀ
formingꢀ theꢀ correspondingꢀ 1:2ꢀ complexesꢀ inꢀ aꢀ nonꢁcooperativeꢀ
statisticalꢀfashion,ꢀthatꢀis,ꢀtheꢀbindingꢀofꢀtheꢀfirstꢀguestꢀdoesꢀnotꢀ
influenceꢀ theꢀ interactionꢀ withꢀ theꢀ secondꢀ guest.ꢀ Theꢀ calculatedꢀ
20ꢀ bindingꢀconstantsꢀforꢀtheꢀformationꢀofꢀtheꢀcomplexꢀ1·[12GA]2ꢀareꢀ
K1ꢀ =ꢀ 426ꢀ Mꢁ1ꢀ andꢀ K2ꢀ =ꢀ 106ꢀ Mꢁ1.ꢀ Theꢀ presenceꢀ ofꢀ theꢀ amideꢀ
functionalityꢀ playsꢀ aꢀ pivotalꢀ roleꢀ inꢀ theꢀ complexationꢀ ofꢀ bothꢀ
anionicꢀ andꢀ neutralꢀ species,ꢀ whichꢀ areꢀ boundꢀ byꢀ meansꢀ ofꢀ Hꢁ
bondingꢀ arraysꢀ involvingꢀ N−H,ꢀ O−H,ꢀ andꢀ C−Hꢀ groups.ꢀ Theꢀ
25ꢀ initialꢀzigꢁzagꢀ“anti”ꢀconformationꢀofꢀtheꢀreceptorꢀisꢀnotꢀalteredꢀ
uponꢀtheꢀcomplexation.ꢀTheꢀaromaticꢀsurfaceꢀofꢀtheꢀfreeꢀreceptor,ꢀ
ofꢀ complexꢀ 1•BrꢁTBA+,ꢀ andꢀ ofꢀ complexꢀ 1•(12GA)2ꢀ allowsꢀ theꢀ
generationꢀofꢀorganizedꢀsupramolecularꢀstructures.ꢀ
Acknowledgements
30ꢀ Financialꢀ supportꢀ byꢀ theꢀ MICINNꢀ ofꢀ Spainꢀ (CTQ2011ꢁ22581,ꢀ
CTQ2009ꢁ08970,ꢀ CTQ2008ꢁ00795,ꢀ andꢀ ConsoliderꢁIngenioꢀ
CSD2007ꢁ00010ꢀ inꢀ Molecularꢀ Nanoscience),ꢀ theꢀ Generalitatꢀ
Valencianaꢀ (PROMETEO/2012/053),ꢀ andꢀ UCMꢀ (GR42/10ꢁ
962027)ꢀisꢀacknowledged.ꢀF.ꢀG.ꢀisꢀindebtedꢀtoꢀMECꢀforꢀaꢀFPUꢀ
35ꢀ studentship.ꢀ
100ꢀ
105ꢀ 20ꢀ Gaussianꢀ 09,ꢀ Revisionꢀ C.01,ꢀ M.ꢀ J.ꢀ Frisch,ꢀ G.ꢀ W.ꢀ Trucks,ꢀ H.ꢀ B.ꢀ
Schlegel,ꢀG.ꢀE.ꢀScuseria,ꢀM.ꢀA.ꢀRobb,ꢀJ.ꢀR.ꢀCheeseman,ꢀG.ꢀScalmani,ꢀ
V.ꢀBarone,ꢀB.ꢀMennucci,ꢀG.ꢀA.ꢀPetersson,ꢀH.ꢀNakatsuji,ꢀM.ꢀCaricato,ꢀ
X.ꢀ Li,ꢀ H.ꢀ P.ꢀ Hratchian,ꢀ A.ꢀ F.ꢀ Izmaylov,ꢀ J.ꢀ Bloino,ꢀ G.ꢀ Zheng,ꢀ J.ꢀ L.ꢀ
Sonnenberg,ꢀM.ꢀHada,ꢀM.ꢀEhara,ꢀK.ꢀToyota,ꢀR.ꢀFukuda,ꢀJ.ꢀHasegawa,ꢀ
Notes and references
a Departamento de Química Orgánica, Facultad de Ciencias Químicas,
Ciudad Universitaria s/n. 28040 Madrid (Spain), e-mail:
lusamar@quim.ucm.es
110ꢀ
M.ꢀIshida,ꢀT.ꢀNakajima,ꢀY.ꢀHonda,ꢀO.ꢀKitao,ꢀH.ꢀNakai,ꢀT.ꢀVreven,ꢀJ.ꢀ
A.ꢀMontgomery,ꢀJ.ꢀE.ꢀPeralta,ꢀF.ꢀOgliaro,ꢀM.ꢀBearpark,ꢀJ.ꢀJ.ꢀHeyd,ꢀE.ꢀ
Brothers,ꢀK.ꢀN.ꢀKudin,ꢀV.ꢀN.ꢀStaroverov,ꢀR.ꢀKobayashi,ꢀJ.ꢀNormand,ꢀ
K.ꢀRaghavachari,ꢀA.ꢀRendell,ꢀJ.ꢀC.ꢀBurant,ꢀS.ꢀS.ꢀIyengar,ꢀJ.ꢀTomasi,ꢀ
M.ꢀCossi,ꢀN.ꢀRega,ꢀJ.ꢀM.ꢀMillam,ꢀM.ꢀKlene,ꢀJ.ꢀE.ꢀKnox,ꢀJ.ꢀB.ꢀCross,ꢀ
V.ꢀBakken,ꢀC.ꢀAdamo,ꢀJ.ꢀJaramillo,ꢀR.ꢀGomperts,ꢀR.ꢀE.ꢀStratmann,ꢀO.ꢀ
Yazyev,ꢀA.ꢀJ.ꢀAustin,ꢀR.ꢀCammi,ꢀC.ꢀPomelli,ꢀJ.ꢀW.ꢀOchterski,ꢀR.ꢀL.ꢀ
Martin,ꢀK.ꢀMorokuma,ꢀV.ꢀG.ꢀZakrzewski,ꢀG.ꢀA.ꢀVoth,ꢀP.ꢀSalvador,ꢀJ.ꢀ
J.ꢀDannenberg,ꢀS.ꢀDapprich,ꢀA.ꢀD.ꢀDaniels,ꢀFarkas,ꢀJ.ꢀB.ꢀForesman,ꢀJ.ꢀ
V.ꢀOrtiz,ꢀJ.ꢀCioslowski,ꢀD.ꢀJ.ꢀFox,ꢀGaussian, Inc., Wallingford CT,ꢀ
2009.ꢀ
40ꢀ b Instituto de Ciencia Molecular, Universidad de Valencia, 46980
Valencia (Spain), e-mail: enrique.orti@uv.es
†ꢀElectronicꢀ Supplementaryꢀ Informationꢀ (ESI)ꢀ available:ꢀ NOEꢀ
experiments,ꢀconcentrationꢀdependentꢀ1HꢀNMRꢀexperiments,ꢀMEPꢀforꢀ1ꢀ
inꢀitsꢀconformationꢀA,ꢀoptimizedꢀstructuresꢀofꢀ1·(12GA-l) andꢀ1·(12GA-r)ꢀ
45ꢀ complexes;ꢀ SEMꢀ images,ꢀ experimentalꢀ details,ꢀ andꢀ atomicꢀ coordinatesꢀ
andꢀtotalꢀenergyꢀforꢀallꢀoptimizedꢀmolecularꢀstructuresꢀatꢀtheꢀM06ꢁ2X/6ꢁ
311G**ꢀlevel.ꢀSeeꢀDOI:ꢀ10.1039/b000000x/ꢀ
115ꢀ
120ꢀ
1ꢀ (a)ꢀ F.ꢀ Guba,ꢀ Natureꢀ 1950,ꢀ 165,ꢀ 439;ꢀ (b)ꢀ H.ꢀ A.ꢀ Krebsꢀ andꢀ W.ꢀ A.ꢀ
Johnson,ꢀFEBS Lettersꢀ1980,ꢀ117,ꢀ148.ꢀ
50ꢀ 2ꢀ (a)ꢀ M.ꢀ Boiocchi,ꢀ L.ꢀ Delꢀ Boca,ꢀ D.ꢀ E.ꢀ Gomez,ꢀ L.ꢀ Fabbrizzi,ꢀ M.ꢀ
Licchelliꢀ andꢀ E.ꢀ J.ꢀ M.;ꢀ Monzani,ꢀ J. Am. Chem. Soc. 2004,ꢀ 126,ꢀ
16507;ꢀ(b)ꢀS.ꢀJ.ꢀBrooks,ꢀP.ꢀA.ꢀGaleꢀandꢀM.ꢀE.ꢀLight,ꢀChem. Commun
2005,ꢀ4696;ꢀ(c)ꢀX.ꢀHe,ꢀF.ꢀHerranz,ꢀE.ꢀChungꢁChinꢀCheng,ꢀR.ꢀVilarꢀ
andꢀV.ꢀWingꢁWahꢀYam,ꢀChem. Eur. J. 2010, 16,ꢀ9123.ꢀ
21ꢀ Y.ꢀZhaoꢀandꢀD.ꢀG.ꢀTruhlar,ꢀTheor. Chem. Acc. 2008,ꢀ120,ꢀ215.ꢀ
22ꢀ (a)ꢀR.ꢀKrishnan,ꢀJ.ꢀS.ꢀBinkley,ꢀR.ꢀSeegerꢀandꢀJ.ꢀA.ꢀPople,ꢀJ. Chem.
Phys.ꢀ 1980,ꢀ 72,ꢀ 650;ꢀ (b)ꢀ M.ꢀ N.ꢀ Glukhovstev,ꢀ A.ꢀ Pross,ꢀ M.ꢀ P.ꢀ
McGrathꢀandꢀL.ꢀRadom,ꢀJ. Chem. Phys. 1995,ꢀ103,ꢀ1878.ꢀ
125ꢀ 23ꢀ S.ꢀF.ꢀBoysꢀandꢀF.ꢀBernardi,ꢀMol. Phys. 1970,ꢀ19,ꢀ553.ꢀ
24ꢀ F.ꢀGarcía,ꢀP.ꢀM.ꢀViruela,ꢀE.ꢀMatesanz,ꢀE.ꢀOrtíꢀandꢀL.ꢀSánchez,ꢀChem.
Eur. J.ꢀ2011,ꢀ17,ꢀ7755.ꢀ
55ꢀ 3ꢀ (a)ꢀK.ꢀA.ꢀNielsen,ꢀW.ꢀS.ꢀCho,ꢀJ.ꢀLyskawa,ꢀE.ꢀLevillain,ꢀV.ꢀM.ꢀLynch,ꢀ
J.ꢀL.ꢀSesslerꢀandꢀJ.ꢀO.ꢀJeppesen,ꢀJ. Am. Chem. Soc.ꢀ2006,ꢀ128,ꢀ2444;ꢀ
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 7

Organic & Biomolecular Chemistry
Page 8 of 8
Dynamic Article Links ►
JournalꢀNameꢀ
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
View Article Online
ARTICLE TYPE
5ꢀ
Table of contents
10ꢀ
Theꢀ cavityꢀ definedꢀ byꢀ theꢀ N−Hꢀ amideꢀ groupꢀ andꢀ theꢀ vicinalꢀ aromaticꢀ hydrogensꢀ ofꢀ
bis(triazole)benzamideꢀ 1ꢀ isꢀ suitableꢀ toꢀ formꢀ Hꢁbondingꢀ arraysꢀ withꢀ halideꢀ guestsꢀ andꢀ
neutralꢀgallicꢀacidꢀderivativeꢀ12GAꢀwithꢀ1:1ꢀandꢀ1:2ꢀstoichiometries,ꢀrespectively.ꢀ
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 8