S1

SUPPORTING INFORMATION

Ordered co-encapsulation of chloride with polar neutral guests in a tetraurea calix[4]pyrrole dimeric capsule

Albano Galán‡, Virginia Valderrey‡ and Pablo Ballester*‡§

‡ Institute of Chemical Research of Catalonia (ICIQ), Avgda. Països Catalans, 16, 43007, Tarragona, Spain. § Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys, 23, 08018, Barcelona, Spain. pballester@iciq.es

Table of Contents

Experimental details ............................................................................................................. S2 

NMR experiments of tetraurea 1, pyridine N-oxide 5 and ion-pairs. ................................... S3 1H NMR titrations and ITC experiments with the model systems ..................................... S15 

NMR experiments of tetraurea 1, trimethylamine N-oxide 3 and ion-pairs. ...................... S27 

NMR experiments of tetraurea 1, betaines and ion-pairs. .................................................. S39 

DOSY NMR experiments ................................................................................................... S52 

Energy minimized structures and packing coefficients ...................................................... S64 

Electronic Supplementary Material (ESI) for Chemical Science.This journal is © The Royal Society of Chemistry 2015

S2

Experimental details Tetraurea calixpyrrole 11, calixpyrrole model 102 , urea model 93 and betaine 124 were prepared according to known procedures. Other chemicals and solvents were purchased from Aldrich and used without further purification.

1H NMR spectra were recorded on a Bruker Avance 400 (400.1 MHz for 1H-NMR) and Bruker Avance 500 (500.1 MHz for 1H-NMR) ultrashield spectrometer. The deuterated solvents (Aldrich) used are indicated in the experimental part; chemical shifts are given in ppm, relative to residual solvent. DOSY NMR experiments were performed using precision Micro NMR tubes from New Era Enterprises (Ref NE-H5/2.5) for the solutions containing the supramolecular assemblies. Regular 5 mm NMR tubes were used for the DOSY experiments of the free guests. In all cases, the spectra were acquired at 298K using a big delta (d20) = 150 ms and a little delta (p30) = 1000 µs on a Bruker Avance 500 MHz equipped with a cryoprobe. The fit of the decay data was achieved using the Dynamics Center software, version 2.3, provided by Bruker BioSpin GmbH.

1 P. Ballester and G. Gil-Ramirez, Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 10455-10459. 2 G. Gil-Ramirez, E. C. Escudero-Adan, J. Benet-Buchholz and P. Ballester, Angew. Chem., Int. Ed., 2008, 47, 4114-4118. 3 W. Zhang, C. H. T. Chen and T. Nagashima, Tetrahedron Lett., 2003, 44, 2065-2068. 4 Y. Chevalier and P. Leperchec, J. Phys. Chem., 1990, 94, 1768-1774.

NMR

Figursoluti

R experime

re S1. 1H Nion of tetrau

ents of tetra

NMR spectrurea 1 and 1

aurea 1, pyr

CH3f

a of a) d-ch1.2 equivalen

ridine N-ox

1

N

NO

NHi

Hi

Hd

H

Hm

Ho

Hc

hloroform sunts of MTO

xide 5 and i

N

CH3e

Ha

Hb

Hg

Hh

uspension oOACl c) d6-D

ion-pairs.

of tetraurea DMSO solut

1 b) d-chlotion of tetra

S3

oroform aurea 1.

S4

In non-polar solvents the tetraurea derivative aggregates and produces ill-defined spectra (Figure S1a). However in polar solvents, like dimethylsulphoxide, the 1H NMR of 1 shows sharp and well-defined signals (Figure S1c). The tetraurea derivative 1 does not produce a single and well-defined species upon the addition of 1.2 equivalents of methyltrioctylammonium chloride (Figure S1b).

The addition of 1 equivalent of pyridine N-oxide 5 to a d-chloroform solution of 1 produces the precipitation of the urea and the NMR spectrum shows no proton signals for 1 or 5 (See spectrum in Figure S9).

Figure S2. 1H NMR spectrum in d-chloroform of an equimolar mixture of tetraurea 1, pyridine N-oxide 5 and MTOACl 6. *Residual water.

Figurpyridproto

The mare bmethyevide

The uMTObrom

The aform rema

The 1

(Figudifferwitho

re S3. 1H Ndine N-oxideon assignme

methylene parely shiftedylene proto

ences the be

urea NH prOABr. The hmide is the an

addition of athe 1:1:1

ins insolubl

1H NMR of ure S2 andrences. We out the inter

NMR spectrae 5 and a) Mnt.

protons alphd when com

ons of the Metter fit of th

rotons are dhydrogen bonion resultin

a non-coordcomplex a

le. Only pro

f the 1:1:1 cd Figure S3used d2-dich

rference of t

a in d2-dichMTOACl b)

ha to the nitmpared to thMTOA cati

he MTOA ca

downfield sonding betwng in an incr

dinating aniand the comoton signals

omplex is f3a respectivhloromethanthe residual

hloromethan) TBACl c)

trogen of thhe chemical ion (H7) reation in the

shifted folloween chlorid

reased down

on (PF6TBAmplex pyridof the TBA

formed bothvely). Bothne when posolvent pea

ne of an equMTOABr d

he TBA catishift of free

esonate upfishallow cav

owing the tde and the urnfield shifti

A) does not dine N-oxid

A cation are o

h in d-chloroh NMR spessible to sho

ak.

uimolar mixd) PF6TBA.

ion (δ = 3.0e TBACl. Oield shifted vity of the c

trend TBACrea NHs is sing when ch

break the ude and tetrobservable.

oform and dectra displaow the arom

ture of tetra. See Figure

0 ppm, FiguOn the contra

at 2.3 ppmalixpyrrole.

Cl >> MTOstronger thahloride is inv

urea aggregaraurea calix

d2-dichloromay no apprmatic proton

S5

aurea 1, e S2 for

re S3b) ary, the m. This .

OACl > an when volved.

ation to xpyrrole

methane reciable n region

Figurdichl6. Se

re S4. Seloromethanee Figure S2

lected regioe of an equi2 for proton

on of the imolar mixtuassignment

aromatic reure of tetrau.

egion of aurea 1, pyri

a 1H NMRidine N-oxid

R spectrum de 5 and MT

S6

in d2-TOACl

Figurdichl6. Se

re S5. Seloromethanee Figure S2

lected regioe of an equi2 for proton

on of the imolar mixtuassignment

upfield reure of tetrau. *Residual

egion of a urea 1, pyriwater.

1H NMR idine N-oxid

spectrum de 5 and MT

S7

in d2-TOACl

Figurpyridinclu

re S6. ROEdine N-oxideded pyridin

ESY experime 5 and MTO

ne protons an

ment of a d2OACl shownd the arom

2-dichloromwing cross-pmatic walls o

methane equieaks indicat

of 1. Mixing

imolar solutting close-c

g time (d8 =

tion of tetraontact betw300 ms).

S8

aurea 1, ween the

S9

Figure S7. ROESY experiment of a d2-dichloromethane equimolar solution of tetraurea 1, pyridine N-oxide 5 and MTOACl showing cross-peaks indicating close-contact between the beta-pyrrolic protons of 1 and the cation protons evidencing the location of the cation in the shallow cavity of the calixpyrrole. Mixing time (d8 = 300 ms).

S10

Figure S8. 1H NMR titration of a d-chloroform solution of tetraurea 1 with increasing amounts of MTOACl. The number of equivalents of salt added is at the right margin.

The ion-pair does not break the aggregation between the urea groups to form discrete species even with an excess of salt.

FigurcalixpSee F

The 1is comthe mcompscale chlor

re S9. 1H Npyrrole 1 aFigure S2 fo

1:1 equimolmpletely inmixture alloplex. The ex when mor

ride, the pro

NMR titratiand pyridineor proton ass

lar mixture soluble. Thowing the xchange betre than one ton signals

ion of a 1.5e N-oxide wsignment.

of tetraureahen, the add

observationtween free equivalent for the urea

5 mM d-chlwith methyl

a aryl-extenddition of men of the fand bound of MTOA

as NHs (Hg a

loroform eqltrioctylamm

ded calix[4]thyltrioctyla

four particleMTOA catis present.

and Hh) shif

quimolar somonium chl

]pyrrole andammonium e assemblytion is fast Upon incre

ft downfield

olution of teloride (MT

d pyridine Nchloride di

y 5⊂1·MTOon the NMeasing amod progressiv

S11

etraurea OACl).

N-oxide issolves OA·Cl¯

MR time ounts of vely.

Figurmixtumolar

The atetrau5⊂1·

re S10. 1H ure of tetraur ratio. See

addition of urea solutioMTOA·Cl¯

NMR specurea 1, pyriFigure S2 f

0.5 equivalon (Figure ¯ (Figure S1

ctra of a d2-idine N-oxifor proton as

lents of pyrS10b) pro

10c) and ill-

-dichloromeide and MTssignment. *

ridine N-oxioduces a mdefined agg

ethane solutTOACl in a *Residual w

ide and 0.5mixture of

gregates.

tion of a) frb) 2:1:1 m

water.

equivalentsf the four

ree tetraureamolar ratio c

s of MTOAparticle co

S12

a and a c) 1:1:1

ACl to a omplex

S13

Figure S11. a) 1H NMR spectrum of a d-chloroform solution of an equimolar mixture of 1,3,5-trimethoxybenzene (internal standard) and MTOACl b) addition of 1 equivalent of pyridine N-oxide to the previous mixture and c) addition of 0.5 equivalent of tetraurea 1 to the previous mixture. Integrals of selected peaks are displayed below the proton peak. See Figure S2 for proton assignment.

Figurpyridand t

re S12. 1H dine N-oxideetraurea 1. S

NMR spece to a tetrauSee Figure S

ctrum in d6-urea 1 chloroS2 for proto

-DMSO of oform suspeon assignme

the precipiension. We ent.

itate formedobserve fre

d upon addie pyridine N

S14

ition of N-oxide

1H N

Figurtetrab

NMR titratio

re S13. 1H butylammon

ons and IT

NMR titranium chlorid

C experime

ation of an de (TBACl)

ents with th

8 mM d-ch).

he model sy

hloroform so

ystems

olution of uurea model

S15

9 with

S16

Figure S14. Fit of the chemical shift changes, experienced by the signals of NH protons of 9 during the titration with TBACl, using a 1:1 binding model (line) implemented in the HypNMR2008 software.

The association constant obtained by the fit of the chemical shift changes was:

K9•7 = 797 ± 131 M-1

0 0.010 0.020 0.030concentration of G

6.5

7.5

8.5ch

emic

al s

hifts

for n

ucle

us H

2

Figurmethy

re S15. 1H yltrioctylam

NMR titrammonium ch

ation of a 9hloride (MT

9 mM d-chlTOACl).

loroform soolution of uurea model

S17

9 with

S18

Figure S16. Fit of the chemical shift changes, experienced by the signals of NH protons of 9 during the titration with MTOACl, using a simple 1:1 binding model (line) and the HypNMR2008 software.

The association constant obtained by the fit of the chemical shift changes was:

K9•6 = 710 ± 128 M-1

A CDCl3 solution of urea 9 was titrated with increasing amounts of a stock solution of MTOACl (Figure S15) or TBACl (Figure S13). In both cases the urea NHs are gradually downfield shifted, as a result of the hydrogen-bonding. The formation of the complex presents fast exchange kinetics on the NMR time scale. The mathematical analysis of the NMR data fitted to a 1:1 binding model with association constant of ca. K = 800 M-1 for the formation of both complexes 9·7 and 9·6. These data reveals that the interaction between a urea group and an ion-pair is practically not cation-dependent.

0 0.004 0.008 0.012 0.016concentration of G

5.5

6.0

6.5

7.0

chem

ical

shi

fts fo

r nuc

leus

H2

Figurcalixp

re S17. 1Hpyrrole mod

H NMR titdel 10 with

tration of tetrabutylam

a 2.5 mMmmonium ch

M d-chlorofhloride (TB

form solutioBACl).

on of tetra

S19

aphenyl

S20

Figure S18. Fit of the chemical shift changes, experienced by the signals of NH protons of 10 during the titration with TBACl, using a 1:1 binding model (line) implemented in the HypNMR2008 software.

The association constant obtained by the fit of the chemical shift changes was:

K10•7 = 17.0 ± 1.4 M-1

0 0.04 0.08 0.12 0.16concentration of G

7.65

7.70

7.75

7.80ch

emic

al s

hifts

for n

ucle

us H

2

Figurmodesigna

A (Figuevideof salan asestimtitrati10 wassocshiftsimpostudie

re S19. 1H Nel 10 with als of proton

CDCl3 soluure S19). Wencing a binlt to the calissociation c

mate the assion calorime

with TBACl ciation conss (Figure Sortance of thes showed t

NMR titratimethyltrioc

ns bound.

ution of caliWe observe nding procesixpyrrole soconstant lowsociation coetry (ITC) e(Figure S17

stant of only18). This dhe cation ithat unlike t

ion of a 2 mctylammoniu

ixpyrrole 10different sess that is sloolution doeswer than 1onstant provexperiments7) shows a fy ca. K = 2drop on thein the ion-pthe TBA ca

mM d-chloroum chlorid

0 was titratet of protonow on the N not result i04 M-1. Dirves to be ds (vide infrafast exchang

20 M-1 as ese magnitudepair recogniation, MTOA

oform solutide (MTOAC

ed with incn signals forNMR time sn full comprect integra

difficult. Tha). The analoge regime ostimated by e of the binition by theA cation nic

ion of tetrapCl). Primed

creasing amor the free ancale. Additi

plexation of ation of thehus, we perogous titrat

on the NMRthe fit of th

nding conste calixpyrrocely fits in t

phenyl calixnumbers i

ounts of MTnd the bounion of 1 equthe host ind

e NMR speformed isotion of calix

R time scale he NMR chtant highligole core. Pthe shallow

S21

xpyrrole indicate

TOACl nd host uivalent dicating ectra to thermal

xpyrrole and an hemical ghts the revious

w cup of

S22

the calixpyrrole.5 This translates into higher association constants in the recognition of ion-pairs by calixpyrroles when MTOA is used as countercation instead of TBA.

Figure S20. Normalized integration heat vs molar ratio obtained in the ITC experiment of a chloroform solution of tetraphenyl calixpyrrole 10 with MTOACl. The continuous red line represents the least-squares-fit of the data to a one set of sites binding model.

The ITC data fitted to a theoretical isotherm considering a 1:1 binding model by using Microcal ITC data analysis software. The calculated thermodynamic variables derived from the fit were: K6⊂10 = 2.8 x 103 ± 1.2 x 103 M1, n = 0.93, ΔH = -2 kcal/mol.

5 V. Valderrey, E. C. Escudero-Adan and P. Ballester, Angew. Chem., Int. Ed., 2013, 52, 6898-6902.

Figurpyrid

re S21. 1H dine N-oxide

NMR titrae.

ation of a 10 mM d-ch

hloroform soolution of mmodel urea

S23

9 with

S24

Figure S22. Fit of the chemical shift changes, experienced by the signals of NH protons of 9 during the titration with pyridine N-oxide, using a 1:1 binding model (line) implemented in the HypNMR2008 software.

The association constant obtained by the fit of the chemical shift changes was:

K9•5 = 28.6 ± 9.0 M-1

A CDCl3 solution of urea 9 was titrated with increasing amounts of a stock solution of pyridine N-oxide 3 (Figure S21). The urea NHs are gradually downfield shifted but large amounts of guest needs to be added to appreciate the shifting, revealing a low binding constant. The binding process shows fast kinetics in the NMR time scale and the data fitted to a 1:1 binding model with an association constant for the formation of the complex 9·5 of ca. 30 M-1.

0 0.04 0.08 0.12concentration of G

5.1

5.3

5.5

5.7

5.9ch

emic

al s

hifts

for n

ucle

us H

2

Figurtetrap

ThmeasInstea(Figuseparregim11 tothe aaccur

re S23. 1

phenylcalixp

he binding sured using ad, we deci

ure S23). Arated set of me for this bo a CDCl3 soassociation rately measu

1H NMR pyrrole 10 w

constant fo10 and 3 duided to use

Addition of proton sign

binding procolution of caconstant foured by 1H N

titration owith 4-meth

or the calixue to the po

the 4-methN-oxide 11

nals for the bcess is slow alixpyrrole

or the bindiNMR.

of a 3 mhylpyridine N

xpyrrole-pyror solubility

hyl substitut1 to a CDCbound and on the NM10 produceing process

mM d-chloN-oxide.

ridine N-oxy of the resuted pyridineCl3 solutionfree guest. I

MR time scals the full co

s is higher

oroform so

xide interaculting compe N-oxide 1n of calixpyIn consequele. Additionomplexation

than 104 M

olution of

ction could plex in chlor11 for this pyrrole 10 prence, the ex

n of 1 equivan of the hostM-1 and can

S25

model

not be roform. purpose roduces xchange alent of t. Thus, nnot be

S26

Figure S24. Normalized integration heat vs molar ratio obtained in the ITC experiment of a chloroform solution of tetraphenyl calixpyrrole 10 with 4-methylpyridine N-oxide. Fit to the theoretical binding isotherm (red line) using a 1:1 binding model. The mathematical analysis of the titration data was performed using the Origin software.

The ITC data fitted to a theoretical isotherm considering a 1:1 binding model by using Microcal ITC data analysis software. The calculated thermodynamic variables derived from the fit were: K = 1.0 x 106 ± 0.2 x 106 M1, n = 0.80, ΔH = -14 kcal/mol.

NMR

Figurtrimeequivhemi

R experime

re S25. 1H ethylamine Nvalent protospheres. *R

ents of tetra

NMR specN-oxide andons. Letter

Residual wat

aurea 1, trim

ctrum of a d MTOAClrs marked ter.

methylamin

d-chloroforl in a 2:1:1

with aste

ne N-oxide

rm solutionmolar ratio

erisk indica

3 and ion-p

n of a mixtuo. Primed leated proton

pairs.

ure of tetraetters indicans from d

S27

aurea 1, ate non

different

Figurof tet

re S26. Seletraurea 1, tri

ected regionimethylamin

n of 1H NMne N-oxide

MR spectrumand MTOA

m of a d-chlACl in a 2:1:

oroform sol1 molar rati

lution of a mio.

S28

mixture

Figurof tewater

re S27. Seletraurea 1, tr.

ected regiontrimethylam

n of 1H NMmine N-oxid

MR spectrumde and MTO

m of a d-chlOACl in a

oroform sol2:1:1 mola

lution of a mar ratio. *R

S29

mixture Residual

Figurtrimein an

An ecapsuadditheterco-enencapwhenthe di

re S28. 1Hethylamine N

equimolar r

equimolar aular assembions of trim

ro-pair capsuncapsulated,psulated trimn co-encapsuimeric capsu

H NMR sN-oxide andratio. See F

amount of tbly with tmethylamineular assemb, both hemimethylaminulated withule.

spectra of d MTOACl igure S25 fo

trimethylamthe tetrauree N-oxide ably (Figure ispheres of e N-oxide r

h a chloride

a d-chloroin a 2:1:1 m

for proton as

mine N-oxidea calixpyrrand MTOAS28a). Mosthe capsule

esonate at 0anion evid

oform solutmolar ratio assignment.

de templatesrole, 32⊂12

ACl to a tetst notably, we are dissym0.54 ppm in dencing the

tion of tetand b) trime

s the forma2 (Figure traurea soluwhen two dmmetric. Th the 32⊂12 cdifferent en

traurea 1 thylamine N

ation of a dS28b). Equution produdifferent guehe protons capsule and nvironment

S30

and a) N-oxide

dimeric uimolar

uces the ests are for the at 0.90

t within

Figurtrimein an

The 3(Figuformedefinmolebelt imoleaccom

re S29. 1Hethylamine N

equimolar r

32⊂12 assemure S29b). ed in both s

ned in d-chlocule of solvis more stacule and thmmodate th

H NMR speN-oxide andratio. See F

mbly was foIdentically

solvents (Figoroform soluvent. Chloroable than inhe packing

he solvent.

ectra of a dd MTOACl igure S25 fo

formed bothy, the hetergure S28a anution. This ioform provin the case

is not so

d2-dichloromin a 2:1:1 m

for proton as

h in chloroforo-encapsulnd Figure Sis due to theides a tighteof dichlorotight so the

methane somolar ratio assignment.

form (Figureation comp

S29a) but thee co-encapsuer packing womethane. De urea belt

olution of tand b) trime

e S28b) andplex capsule ureas NHsulation withwithin the cDichloromet

has to dis

tetraurea 1 thylamine N

d dichloromlar assembs protons arhin the capsucapsule so ththane is a stort a little

S31

and a) N-oxide

methane ly was e better ule of a he urea smaller

e bit to

Figurtetrauproto

PyrrohintinpeaksAromthe uassign

re S30. Seurea 1, trimeon assignme

olic protonsng to the fors with arom

matic protonurea belt in nment of th

elected regiethylamine nt. Mixing t

Hd show crmation of a

matic protonns Ha appear

a capsular he non equiv

ion of a RN-oxide antime (d8 = 3

close-contaca capsular ans Ha and ur as non equassembly. C

valent Ha pro

ROESY expnd MTOACl300 ms).

ct cross-peaassembly. Uurea protonuivalent dueChemical eotons.

periment ofl in 2:1:1 m

ks with theUrea protonsns Hh, helpie to the unidexchange be

f a d-chloromolar ratio. S

e aromatic ps Hg show cing in the pdirectional setween Ha p

oform soluSee Figure

protons Ho alose-contac

proton assigsense of rotaprotons allo

S32

ution of S25 for

and Hm t cross-

gnment. ation of ows the

FigurN-oxtime

The cpyrroprotoencap

re S31. ROide and MT(d8 = 300 m

close-contacolic NHs reons appearinpsulated chl

OESY experiTOACl in 2ms).

ct cross-peaesonating atng at δ = loride.

iment of a d:1:1 molar r

ak between t δ = 10.85

11.96 ppm

d-chloroformratio. See F

included pr5 ppm allom to the o

m solution oigure S25 f

rotons of triwed the as

ones formin

of tetraureafor proton a

methylaminssignment ong hydrogen

a 1, trimethyssignment.

ne N-oxide of the pyrron bonds w

S33

ylamine Mixing

and the ole NH

with the

Figurtetrausignacapsuprocereson

re S32. GOurea 1, trimals was thatular assembess on the Nnating at δ =

OESY 1H Nmethylaminet of the bul

bly (3•CHClNMR timesc= 6.60 ppm.

NMR spectrue N-oxide alk solvent (l3•Cl¯)⊂12•ale with the

um performand MTOA(δ = 7.27 pp•MTOA+ ise bulk solve

med at 253 ACl in 2:1:1

pm). The cs experiencinnt and it’s o

K using a 1 molar ratco-included ng a slow c

observed as

CHCl3 solutio: The irrchloroform

chemical exa separated

S34

ution of radiated

m in the xchange d singlet

Figurtrimeassign

Figur1, trimfrom black

In anproduC4v sprotodimerS29a

re S33. 1H ethylamine Nnment.

re S34. 1H methylaminthe hetero

k circle. See

n equimolaruces the forsymmetry bons for the ric capsule ).

NMR specN-oxide and

NMR spectne N-oxide encapsulati Figure S25

r ratio, the rmation of aboth in dichincluded N co-encapsu

ctrum of a d MTOACl

trum of a d2and MTOAon complex

5 for proton

mixture oa four partihloromethan

N-oxide resoulating a m

d-chloroforl in a 1:1:1

2-dichloromACl in a 1:1x dimeric caassignment

f tetraurea,icle complexne (Figure onate at 0.75molecule of

rm solution molar rati

methane solu1:1 molar raapsule (3·Clt.

trimethylax 3⊂1·MTOS34) and c5 ppm. As f N-oxide a

n of a mixtuo. See Figu

ution of a matio. *Residl¯)⊂12·MTO

amine N-oxOA·Cl¯ (1:chloroform

a minor spand a chlor

ure of tetraure S25 for

mixture of tedual water. POA marked

ide and MT1:1 complex(Figure S33

pecies, thereride anion

S35

aurea 1, proton

etraurea Protons

d with a

TOACl x) with 3). The e is the (Figure

Figurtrimeassign

The m(FiguS33).

Figurtrimeassign

The oS25),(mark

re S35. 1H ethylamine Nnment.

major specieure S25) an.

re S36. 1H ethylamine Nnment.

observed sp, the 1:1:1 ked with a r

NMR specN-oxide and

es is the hetnd the 1:1:1

NMR specN-oxide and

ecies are thcomplex (m

red square, F

ctrum of a d MTOACl

tero-encapsu complex 3

ctrum of a d MTOACl

e hetero-encmarked withFigure S28b

d-chloroforl in a 2:1:2

ulation com3⊂1·MTOA

d-chloroforl in a 2:2:1

capsulation h a black cib).

rm solution2 molar rati

mplex dimeriA·Cl¯ (mark

rm solution molar rati

complex inircle, Figure

n of a mixtuo. See Figu

ic capsule (3ked with a

n of a mixtuo. See Figu

n the dimerice S33) and

ure of tetraure S25 for

3 ·Cl¯)⊂12·black spot,

ure of tetraure S25 for

c assembly the 32⊂12 c

S36

aurea 1, proton

MTOA Figure

aurea 1, proton

(Figure capsule

Figurtrimemark

TBAassem

Figurtrimemark

re S37. 1H ethylamine Nked with a bl

Cl does nombly 32⊂12

re S38. 1H ethylamine Nked with a bl

NMR specN-oxide andlack spot.

ot produce (Figure S28

NMR specN-oxide andlack spot. S

ctrum of a d TBACl in

the hetero-8b) and ill-d

ctrum of a d TBACl inee Figure S

d-chloroforn a 2:1:1 mo

-encapsulatidefined aggr

d-chloroforn an equimo25 for proto

rm solutionolar ratio. Pr

ion assembregates.

rm solutionolar ratio. Pron assignme

n of a mixturotons from

bly but the

n of a mixturotons froment.

ure of tetram the 32⊂12

pairwise c

ure of tetram the 32⊂12

S37

aurea 1, capsule

capsular

aurea 1, capsule

Figurtrimefrom

In anspecicalixpwith and il

re S39. 1H ethylamine N

the 32⊂12 c

n equimolaries in solutipyrrole, thethe ureas. Inll-defined a

NMR specN-oxide andcapsule mark

r mixture oion is the 1e cation at tn a 2:1:1 mggregates.

ctrum of a d MTOABr ked with a b

of tetraurea1:1:1 complthe shallow

molar ratio w

d-chloroforin a a) 2:1:

black spot.

a, trimethylalex, with thcup of the

we observe b

rm solution1 molar rati

amine N-oxhe N-oxide calixpyrrol

both the 1:1

n of a mixtuio b)1:1:1 m

xide and Mincluded ine and the b:1 complex,

ure of tetramolar ratio. P

MTOABr, thn the cavitybromide inte, the 32⊂12 c

S38

aurea 1, Protons

he only y of the eracting capsule

NMR

FigurMTOdiffer

Figurbetain

R experime

re S40. 1H OACl in a rent hemisp

re S41. Selene 12 and M

ents of tetra

NMR spec2:1:1 molaheres.

ected regionMTOACl in

aurea 1, bet

ctrum of a dar ratio. Let

n of 1H NMRa 2:1:1 mol

taines and i

d-chloroformtters marke

R spectrum lar ratio. See

ion-pairs.

m solution oed with ast

of a d-chlore Figure S4

of tetraureaterisk indica

roform solu0 for proton

a 1, betaine ated proton

ution of tetran assignmen

S39

12 and ns from

aurea 1, nt.

Figurbetain*Res

Figurand M

The fchlorident

re S42. Selene 12 and idual water.

re S43. 1H MTOACl in

formation ofroform (Figical evidenc

ected regionMTOACl i.

NMR spectn a 2:1:1 mo

f the hetero-gure S40) cing the no c

n of 1H NMRin a 2:1:1 m

trum of a d2lar ratio. Se

-encapsulatiand dichloco-encapsul

R spectrum molar ratio.

2-dichloromee Figure S4

ion complexromethane lation of a m

of a d-chlor See Figure

methane solu40 for proton

x (12·Cl¯)⊂(Figure S4

molecule of

roform solue S40 for p

ution of tetran assignmen

⊂12·MTOA 43). Both Nsolvent.

ution of tetraproton assig

aurea 1, betnt.

takes place NMR spec

S40

aurea 1, gnment.

taine 12

both in ctra are

S41

Figure S44. 1H NMR titration of a d2-dichloromethane suspension of tetraurea 1 with betaine 12 a) 0 eq. b) 0.5 eq. c) 1 eq. d) 1.5 eq.

The addition of betaine 12 to a suspension of tetraurea 1 did not break the aggregation between urea groups to form well-defined species.

Figurand Mthe ar= 300

re S45. ROMTOACl inromatic pro0 ms).

ESY experin 2:1:1 molatons of the c

iment of a dar ratio showcapsule. See

d2-dichloromwing close-ce Figure S4

methane solucontact betw0 for proton

ution of tetraween the incn assignmen

aurea 1, betcluded beta

nt. Mixing ti

S42

taine 12 aine and ime (d8

S43

Figure S46. COSY experiment of a d2-dichloromethane solution of tetraurea 1, betaine 12 and MTOACl in 2:1:1 molar ratio. See Figure S40 for proton assignment.

COSY NMR reveals the location of the bound methylene protons H27 of betaine 12, hidden under the cation protons.

S44

Figure S47. 1H NMR spectrum of a d-chloroform solution of tetraurea 1, betaine 12 and MTOACl in a 1:1:1 molar ratio. See Figure S40 for proton assignment.

Figure S48. 1H NMR spectrum of a d2-dichloromethane solution of tetraurea 1, betaine 12 and MTOACl in a 1:1:1 molar ratio. See Figure S40 for proton assignment.

In an equimolar stoichiometry of urea, betaine and salt, a 1:1:1 complex (four particle assembly, C4v symmetry) is formed both in chloroform (Figure S47) and dichloromethane (Figure S48). The betaine is included in the calixpyrrole cavity, the cation is located at the shallow cup of the calixpyrrole and the chloride interacts with the urea groups at the upper rim.

FigurBrMT

In anspecicalixpheterwithisituatspeci

re S49. 1H TOA in a a)

n equimolaries is the 1:pyrrole, and

ro-encapsulain the dimetion is obseries the 1:1:1

NMR spec) 2:1:1 mola

r mixture of1:1 compled the bromidation compleric tetraurerved. The m complex.

ctra of a d-ar ratio b) 1:

f tetraurea, x, where a de is interaclex where aea capsule. major specie

-chloroform:1:1 molar r

betaine 12molecule octing with ta betaine anIn a 2:1:1

es is the hete

m solution oratio.

and MTOAof betaine isthe urea grond a bromimolar ratio

ero-encapsu

of tetraurea

ABr (Figures included inoups. The mde anion ar

o (Figure Sulation comp

1, betaine

e S49b) then the cavity

minor speciere co-encap49a), the oplex and the

S45

12 and

e major y of the es is the psulated opposite e minor

Figurand T

The produfit foassem

re S50. 1H TBACl in a

addition of uces a heteror the calixmbly quantit

NMR spect2:1:1 molar

f betaine 12ro-encapsulaxpyrrole shtatively (Fig

trum of a d2r ratio. See F

2 and MTOation complhallow cavigure S50).

2-dichloromFigure S40

OACl to a tlex (Figure ity and TB

methane soluand Figure

tetraurea soS43). Howe

BACl does

ution of tetraS13 for pro

olution in a ever, TBA cnot produc

aurea 1, betton assignm

1:1:2 molacation is notce the hete

S46

taine 12 ment.

ar ratio t a well ero-pair

Figur13 an

re S51. 1H Nnd MTOAC

NMR spectrl in a 2:1:1

ra of a d-chmolar ratio

loroform soolution of a mmixture of ttetraurea 1,

S47

betaine

S48

Figure S52. 1H NMR spectra of a d-chloroform solution of a mixture of tetraurea 1, betaine 13 and MTOACl in a 1:1:1 molar ratio

Figurbetainproto

The eparticcalixpintera(Figuin sochlorare co

re S53. 1H ne 13 and M

on assignme

equimolar mcle assemblpyrrole caviacting with ure S53b). Wlution a mi

roform (Figuo-encapsula

NMR spectMTOACl innt.

mixture of tely 1:1:1 comity, the catiothe urea g

When the urixture of theure S51) andated within d

tra of a d2-dn a) 2:1:1 m

etraurea, betmplex 13⊂1on is at the groups bothrea, betaine e 1:1:1 comd dichloromdimeric tetra

dichloromethmolar ratio

taine 13 and1·MTOA·Cshallow cav

h in chlorof13 and MTO

mplex and thmethane (Figaurea capsu

hane solutiob) 1:1:1 mo

d MTOACl Cl¯, where tvity of the cform (FigurOACl are a he hetero-engure S53a) wule 12.

on of a mixtolar ratio. S

produces exthe betaine alixpyrrole re S52) and2:1:1 mola

ncapsulationwhere the be

ture of tetraSee Figure S

xclusively tis includedand the chl

d dichloromar ratio, we on complex etaine and c

S49

aurea 1, S51 for

the four d in the oride is

methane observe both in

chloride

Figurbetaintwo s(heter

re S54. Selne 13 and Mspecies in soroencapsula

ected regionMTOACl in olution: the ation compl

n of a 2D Ea 2:1:1 mofour particlex) in the E

EXSY NMRlar ratio shole assembly

EXSY time s

R of a d-chlowing no ch

y (1:1:1 comscale. Mixin

loroform solhemical exc

mplex) and thng time (d8

lution of tethange betwhe dimeric c= 300 ms).

S50

traurea, ween the

capsule

S51

Figure S55. 1H NMR spectra of a d-chloroform solution of tetraurea 1, betaine 13 and BrMTOA in a a) 2:1:1 molar ratio b) 1:1:1 molar ratio

In an equimolar mixture of tetraurea, betaine 13 and MTOABr (Figure S55b) the observed species is the four particle 1:1:1 complex, where a molecule of betaine is included in the cavity of the calixpyrrole, and the bromide is interacting with the urea groups. In a 2:1:1 molar ratio (Figure S55a), we observe a mixture of hetero-encapsulation complex and 1:1:1 complex.

DOS

Figurfitted

SY NMR ex

re S56. 1Hd to a monoe

xperiments

H pseudo-2Dexponential

D DOSY plfunction. S

lot of 5⊂1·ee Figure S

·MTOA·Cl¯2 for proton

¯four-particn assignmen

cle assemblynt.

S52

y. Data

FigurData

re S57. 1H fitted to a m

pseudo-2Dmonoexpone

D DOSY ploential functi

ot of (3·CHion. See Fig

HCl3·Cl¯)⊂1gure S25 for

12·MTOA cr proton assi

capsular assignment.

S53

sembly.

Figurfitted

re S58. 1Hd to a monoe

H pseudo-2Dexponential

D DOSY plfunction. S

lot of 3⊂1·ee Figure S

·MTOA·Cl¯25 for proto

¯four-particon assignme

cle assemblyent.

S54

y. Data

Figurmono

re S59. 1H oexponentia

pseudo-2Dal function. S

D DOSY ploSee Figure S

ot of (12·ClS40 for prot

l¯)⊂12·MTOton assignm

OA complement.

ex. Data fitt

S55

ted to a

Figurmono

re S60. 1Hoexponentia

H pseudo-2Dal function.

D DOSY pplot of 12⊂⊂1·MTOA·CCl¯complexx. Data fitte

S56

ed to a

Figurmono

re S61. 1Hoexponentia

H pseudo-2Dal function. S

D DOSY pSee Figure S

plot of 13⊂S51 for prot

⊂1·MTOA·Cton assignm

Cl¯complexment.

x. Data fitte

S57

ed to a

Figurand MFigur

re S62. 1H pMTOACl inre S51 for p

pseudo-2D n a 2:1:1 ratiroton assign

DOSY plotio and expanment.

t of a d-chloansion. Data

oroform mixa fitted to mo

xture of tetraonoexponen

aurea 1, betntial functio

S58

taine 13 ons. See

Figurfitted

re S63. 1H d to a monoe

pseudo-2Dexponential

D DOSY plofunction. S

ot of a CDCee Figure S

Cl3 solution2 for proton

n of pyridinn assignmen

ne N-oxide 5nt.

S59

5. Data

FigurData

re S64. 1H fitted to a m

pseudo-2D monoexpone

DOSY ploential functi

ot of a CDCion. See Fig

Cl3 solution gure S25 for

of trimethyr proton assi

ylamine N-oignment.

S60

oxide 3.

Figurmono

re S65. 1H oexponentia

pseudo-2D al function. S

DOSY ploSee Figure S

ot of a CDCS2 for proto

Cl3 solution on assignme

of MTOACent.

Cl. Data fitt

S61

ted to a

Figurmono

re S66. 1H oexponentia

pseudo-2D al function. S

DOSY ploSee Figure S

t of a CDCS40 for prot

Cl3 solution oton assignm

of betaine 1ment.

12. Data fitt

S62

ted to a

Figurmono

re S67. 1H oexponentia

pseudo-2D al function. S

DOSY ploSee Figure S

t of a CDCS51 for prot

Cl3 solution oton assignm

of betaine 1ment.

13. Data fitt

S63

ted to a

S64

Energy minimized structures and packing coefficients

Energy minimized (MM3) structures of dimeric capsular assemblies. Cavity volumes and guest volumes calculated with the software SwissPDB. A volume of 39.35 Å3 was estimated for the chloride anion.6

52⊂12 5·Cl-⊂12 3·Cl-⊂12 3·CHCl3·Cl-⊂12

Cavity volume (Å3)

338 289 314 327

Guest volume (Å3)

170 124 122 191

PC 0.50 0.43 0.39 0.58

6 C. Estarellas, A. Bauza, A. Frontera, D. Quinonero and P. M. Deya, Phys. Chem. Chem. Phys., 2011, 13, 5696-5702.

S65

3·CH2Cl2·Cl-⊂12 12·Cl-⊂12 13·Cl-⊂12

Cavity volume (Å3)

321 309 296

Guest volume (Å3)

179 172 158

PC 0.55 0.55 0.53

3·Br-⊂12 3·CHCl3·Br-⊂12 3·CH2Cl2·Br-⊂12

12·Br-⊂12

Cavity volume

(Å3)

299 327 328 318

Guest volume

(Å3)

137 206 191 187

PC 0.45 0.63 0.58 0.58