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2-Me hyl eso cina ene : a e y high packing coe icien in a mono-anion based
dime ic capsule and he X- ay c ys al s uc u e o he e a-anion
Pu eddy, Rakesh; Beyeh, Ngong Kodiah; Kalenius, Elina; Ras, Robin H. A.; Rissanen,
Ka i
Pu eddy, R., Beyeh, N. K., Kalenius, E., Ras, R. H. A., & Rissanen, K. (2016). 2-
Me hyl eso cina ene : a e y high packing coe icien in a mono-anion based dime ic
capsule and he X- ay c ys al s uc u e o he e a-anion. Chemical Communica ions,
52(52), 8115-8118. h ps://doi.o g/10.1039/C6CC03289C
2016
This jou nal is ©The Royal Socie y o Chemis y 2016 Chem. Commun., 2016, 52, 8115--8118 | 8115
Ci e his: Chem. Commun., 2016,
52, 8115
2-Me hyl eso cina ene: a e y high packing
coefficien in a mono-anion based dime ic
capsule and he X- ay c ys al s uc u e o he
e a-anion†
Rakesh Pu eddy,
a
Ngong Kodiah Beyeh,
b
Elina Kalenius,
a
Robin H. A. Ras
b
and
Ka i Rissanen*
a
Mono- and e a-dep o ona ed 2-me hyl eso cina ene anions
(1 and 2) as hei ans-1,4-diammoniumcyclohexane (TDAC)
2+
inclusion complexes a e epo ed. The mono-anion o ms a ully
closed dime ic capsule [1H
2
OMeOH]
22
wi h a ca i y olume o
165 Å
3
and (TDAC)
2+
as he gues wi h an ex emely high packing
coefficien , PC = 84.2%, while he e a-anion o ms a close-packed
s uc u e wi h wo s uc u ally isome ic e a-anions 2a and 2b wi h
a 50 : 50 a io in he c ys al la ice.
Reso cina enes a e s able p- ich ca i y con aining hos sys ems in he
C
4
c own con o ma ion.
1
Since he 1980’s, eso cina enes and hei
ca i and analogues ha e played a key ole in molecula ecogni ion
p ocesses in a mul i ude o hos –gues sys ems.
2
The easy syn hesis
and selec i e unc ionaliza ion ei he a he uppe im hyd oxyl
g oups o he 2-posi ion on he a oma ic ings, and he lowe ims
ha e made hem a e y use ul and accessible amily o hos com-
pounds.
2
Wi h he C
4
ase shaped ca i y, eso cina enes mani es
selec i e gues complexa ion and in some cases encapsula ion
h ough a mul i ude o weak non-co alen in e ac ions such as
ca ionp, C–Hpand ppin e ac ions.
3
In addi ion, he hyd oxyl
g oups o m s ong hyd ogen bonds wi h exo-o endo-complexed
gues s in he solid s a e.
3
The cons uc ion o hyd ogen bond based
hos –gues sys ems using eso cina enes has been well-s udied wi h
alcohols,
4
suga s,
5
s e oids,
6
as well as wi h he e ocyclic i e- and six-
membe ed ing compounds.
7
T ea ing co e eso cina enes wi h e en weak bases
8
leads o
he o ma ion o dep o ona ed species in which he inc eased
p-cha ac e o he eso cina ene ca i y can be used o mo e
efficien molecula ecogni ion p ocesses by enhancing he
weak in e ac ions.
9
In eso cina enes, he acidi y o he i s
p o on is g ea e han ha o he second and so on, and he ca i y
a ains maximum s abili y upon e a-dep o ona ion, e aining i s
c own C
4
con o ma ion, and being s abilized by s onge ci cula
in amolecula O–HO

hyd ogen bonds. The e a-dep o ona ed
eso cina enes iz. e aphenola e anions a e known o exis in
alkaline media, and a e epo ed o ha e ema kably high binding
cons an s owa ds alkyl ammonium sal s when compa ed o he
neu al non-dep o ona ed eso cina enes.
10
The s ong elec os a ic
in e ac ions be ween he p-delocalized nega i ely cha ged mac o-
cyclic ca i y and ca ionic gues s ha e been epo ed o lead o high
binding cons an s.
9
Schneide and co-wo ke s demons a ed he
hyd olysis o ace ylcholine o choline in he eso cina ene e a-
phenola e ca i y by
1
H NMR, suppo ing he hyd olysis mechanism
wi h molecula models.
11
O he biological molecules ha e also
been hos ed by he eso cina ene e aphenola e.
12
Al hough he eso cina ene e aphenola e is known in
solu ion, he c ys al s uc u e o i has emained elusi e. Along
heselines,weha ep e iously epo ed hes uc u eso mono-
and di-dep o ona ed co e eso cina enes using mono- and
diamine bases in he solid s a e.
13
In his con ibu ion, we epo
he p epa a ion, X- ay c ys al s uc u es and he elec osp ay
ioniza ion mass spec ome y (ESI-MS) cha ac e iza ion o
mono- (1) and e a-anions (2) as hei ans-1,4-diammonium-
cyclohexane, (TDAC)
2+
, complexes ob ained by eac ing 2-me hyl-
eso cina ene, 2-MeC2, and ans-1,4-diaminocyclohexane,
TDAC, as shown in Fig. 1.
Single c ys als o he complexes (TDAC)
2+
@[1H
2
OMeOH]
2
and 2(2)3(TDAC)
2+
2(TDAC)
+
15(MeOH)0.5(H
2
O) we e p e-
pa ed by mixing 1 :1 and 1 :4 mola a ios o 2-MeC2 and TDAC
in me hanol, espec i ely, ollowed by slow e apo a ion a oom
empe a u e. The eac ion o 2-MeC2 and TDAC in a 1 : 1 mola
a io o ms a igh neu al hyd ogen bonded capsule,
(TDAC)
2+
@[1H
2
OMeOH]
2
, whe e he ca i y en aps (TDAC)
2+
,
as he gues , as shown in Fig. 2. In his dime ic capsule, he
capsule hal es a e held igh ly oge he by hyd ogen bonds ia
wo me hanol [(O–H)
hos
(O)
MeOH
(H–O)
hos
] and wo wa e
molecules [(O–H)
hos
(O–H)
wa e
(O–H)
hos
]. The endo-ca i y
(TDAC)
2+
is encapsula ed e y igh ly ia addi ional N–HO
a
Uni e si y o Jy askyla, Depa men o Chemis y, Nanoscience Cen e ,
P.O. Box 35, FI-40014, Finland. E-mail: ka i. . issane[email p o ec ed]
b
Aal o Uni e si y, Depa men o Applied Physics, Puumiehenkuja 2, 02150 Espoo,
Finland
†Elec onic supplemen a y in o ma ion (ESI) a ailable: Single c ys al expe i-
men al de ails and mass spec ome y da a a e included. CCDC 1473236 and
1473237. Fo ESI and c ys allog aphic da a in CIF o o he elec onic o ma see
DOI: 10.1039/c6cc03289c
Recei ed 19 h Ap il 2016,
Accep ed 25 h May 2016
DOI: 10.1039/c6cc03289c
www. sc.o g/chemcomm
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and N–Hpin e ac ions o he hos ing capsule (see ESI,†Fig. S3a).
These conce ed gues - o-hos in e ac ions esul ed in an ex emely
highpackingcoe icien (PC)o 0.842, iz. 84.2%.The olumeo 3,
138.9 Å
3
, was ob ained using Spa an
14
a MM le el, while he ca i y
olume, 165 Å
3
, was calcula ed using MS oll
15
wi hin X-Seed
16
wi h
a 1.2 Å p obe, PC = 138.9 Å
3
/165 Å
3
=0.842.
Con a y o he mono-anion, he e a-anion 2is an open
inclusion complex, wi h o e all composi ion o 2(2)3(TDAC)
2+

2TDAC
+
15(MeOH)0.5(H
2
O), he eigh nega i e cha ges being
coun e balanced wi h wo endo-ca i y (TDAC)
2+
, one exo-ca i y
(TDAC)
2+
and wo exo-ca i y (TDAC)
+
ca ions. The dep o ona-
ion o he hyd oxyl g oups in 2-MeC2 can, om e y high
quali y single c ys al X- ay diff ac ion da a, be obse ed om
he esidual elec on densi y map [in he case o 1, all H-a oms
a e clea ly isible and his unambiguously con i ms ha one o
he hyd oxyl g oups does no ha e a H-a om in i , namely O6
(see ESI,†Fig. S1)]. Ano he way, which is mo e eliable wi h
lowe quali y da a (as in case o 2), is he ac ha a no mal OH
g oup bo h accep s and dona es H-bonds, while a dep o ona ed,
iz. phenola e, g oup accep s h ee H-bonds. In he case o 2, his
is unambiguously e i ied o he hyd oxyl O-a oms O13, O20
and O18 (see ESI,†Fig. S4). While he O-a oms O6 and O25 show
a diso de o he hyd ogen a oms wi h a diso de ed me hanol
molecule hyd ogen bonded o hese wo O-a oms. Close inspec-
ion e eals ha indeed he c ys al la ice con ains wo dis inc
s uc u al isome s o he e a-anion 2, iz. 2a and 2b,as
ep esen ed by he 2-D d awings in Fig. 3. The wo isome s
c ys allize so ha e e y second uni cell con ains 2a and 2b (see
ESI,†Fig. S4 o c ys al s uc u es), hus mani es ing posi ional
50:50 diso de wi hin he same uni cell. Howe e bo h 2a and
2b ha e he same o ien a ion in he uni cell so ha he oxygen
a oms O6 (50%) and O25 (50%) accep h ee hyd ogen bonds
13
as shown in Fig. 3.
The ollowing obse a ions we e used o asce ain he s uc-
u e o he mono-anion 1and he wo s uc u al isome s 2a and
2b o he e a-anion:
(1) The hyd ogen a om posi ions we e loca ed unambigu-
ously om he elec on densi y map o he p o ona ed –NH
3+
g oups in he (TDAC)
2+
and (TDAC)
+
ca ions o bo h 1and 2,
as well as he uppe im O–HO

hyd ogen bonds o 1(see
ESI,†Fig. S1 and S2).
(2) Dep o ona ed, iz. he phenola e, oxygen a oms ac as
iple hyd ogen bond accep o s in bo h 1and 2.
(3) The oxygen a oms, O6 and O25, in he wo s uc u al
isome s 2a and 2b we e con i med o ac as iple hyd ogen
bond accep o s a 50 :50 a ios h ough ca e ul analysis o he
simila ly diso de ed me hanol molecules hyd ogen bonded
o hem.
The effec o TDAC on he dep o ona ion o 2-MeC2 in he
gas phase was s udied h ough a se ies o ESI-MS analyses in
MeCN/MeOH. Ti a ion expe imen s showed ha he dep o o-
na ed cha ge s a es o 2-MeC2 inc eased un il ou equi alen s
o TDAC we e added (Fig. 4a). The mono- and di-dep o ona ed
ions, [2-MeC2–H]

and [2-MeC2–2H]
2
, we e clea ly obse ed
in he ESI-MS spec a (see ESI,†Fig. S5). Gas phase s abili y is
known o be low o low molecula weigh mul iply cha ged
ions in condi ions whe e s abilizing sol en in e ac ions a e
absen .
17
Highe cha ge densi y, he e o e, usually leads o
coulombic explosion o he compound. Gas phase basici ies o
he mul i-dep o ona ed ions [2-MeC2–3H]
3
and [2-MeC2–4H]
4
,
Fig. 1 Syn hesis o mono- (1) and e a-anions (2) om 2-me hyl-
eso cina ene (2-MeC2)and ans-1,4-diaminocyclohexane (TDAC).
Nomencla u e: TDAC = ans-1,4-diaminocyclohexane; (TDAC)
+
= ans-
1-ammonium-4-aminocyclohexane; (TDAC)
2+
= ans-1,4-diammonium-
cyclohexane.
Fig. 2 Dime ic capsule, (TDAC)
2+
@[1H
2
OMeOH]
2
shown in (a) as ball
and s ick wi h he calcula ed ca i y in anspa en g ey colou and he
gues (TDAC)
2+
as CPK o illus a e he e y igh encapsula ion and (b) as
he CPK model.
Fig. 3 Chemd aw ep esen a ion o e a-anions 2a and 2b. The o ien a-
ion o he eso cina ene co e and he oxygen a oms a e labelled as in he
c ys al s uc u e shown in ESI,†Fig. S4.
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a e assumed o be ela i ely high. Hence, he i- and e a-
dep o ona ed ions can easily abs ac a p o on om me hanol,
which o igina es om he MeCN: MeOH (25 :1 / ) mix u e
used in he ESI-MS expe imen s due o oo low solubili y o
TDAC in ap o ic sol en s. The s abilizing in e ac ions be ween
he dep o ona ed OH g oups o he 2-MeC2 and TDAC mole-
cules (which we e p esen in he solid s a e s uc u es) we e no
obse ed in gas phase measu emen s. Howe e , in e ac ion o
he dep o ona ed ions wi h sol en molecules was clea ly
obse ed in ime-dependen ESI-MS expe imen s, in which he
samples o 2-MeC2 and 2-MeC2 +TDAC (1:4) we e aged (Fig. 4b
and c). The in e ac ion o 2-MeC2 wi h me hanol o ace oni ile
esul ed in mono- and di-O-me hyla ion p oduc s and me hanol
adduc s (see ESI,†Scheme S1). The cha ac e iza ion o he
O-me hyla ion p oduc s was e i ied by collision induced dis-
socia ion (CID) expe imen s (see ESI,†Fig. S6).
In conclusion, we ha e u ilized a simple o ganic diamine,
ans-1,4-diaminocyclohexane, TDAC, o dep o ona e he
2-me hyl- eso cina eneandwe eable oisola e hemono-and
e a-anions. The mono-anion 1 o ms, wi h he help o wo wa e
molecules and wo me hanol molecules, an unp eceden ed ully
closed and cha ge-neu al hyd ogen bonded dime ic capsule
which has an ex emely high packing coefficien PC o 84.2%
o he ans-1,4-diammoniumcyclohexane as he gues . The X- ay
c ys al s uc u e o 2no only p o es he exis ence o he e a-
anion in solid s a e, bu e eals wo s uc u al isome s o i . The
isome s, which occu in he same c ys al la ice wi h a posi ion o
50% occupancy each, show he same dep o ona ion pa e n o
he h ee hyd oxyl g oups and he diffe ence be ween 2a and 2b
occu ing wi h he dep o ona ion o he ou h hyd oxyl g oup a
one ‘‘co ne ’’ o he eso cina ene skele on in such a way ha i
does no affec he o e all con o ma ion o he e a-anion, being
C
4
o bo h isome s.
We g a e ully acknowledge he Academy o Finland (KR:
g an no. 263256, 292746, NKB: g an no. 258653, EK: g an
no. 284562, 278743, RHAR: g an no. 272579), Uni e si y o
Jy a
¨skyla
¨and Aal o Uni e si y o inancial suppo .
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Fig. 4 (a) Rela i e in ensi ies ( .i.%) o dep o ona ed ions obse ed in
()ESI-MS spec a as a unc ion o added TDAC equi alen s. Rela i e
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