Investigation into the role of the hydrogen bonding network in cyclodextrin-based self-assembling mesophases

Article abstract of DOI:10.1039/c4tc00448e

A series of novel amphiphilic β-CD derivatives capable of forming hydrogen bonding networks of different strengths have been synthesized to probe the role of the hydrogen bonding network in the formation of self-assembled mesophases. Using differential sc

Full text of DOI:10.1039/c4tc00448e

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Materials Chemistry C
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Investigation into the role of the hydrogen bonding
network in cyclodextrin-based self-assembling
mesophases†
Cite this: J. Mater. Chem. C, 2014, 2,
4928
Sandra Ward,a Oliver Calderon,b Ping Zhang,a Matthew Sobchuk,a
a
b
a
*
Samantha N. Keller, Vance E. Williams and Chang-Chun Ling
A series of novel amphiphilic b-CD derivatives capable of forming hydrogen bonding networks of different
strengths have been synthesized to probe the role of the hydrogen bonding network in the formation of
self-assembled mesophases. Using differential scanning calorimetry (DSC), cross-polarized optical
microscopy (POM) and X-ray diffractometry, two compounds were found to exhibit smectic
mesophases. These correlated well with their abilities to form a hydrogen bonding network with
sufficient strength to self-assemble. It was also observed that modifying the secondary face to interfere
with the hydrogen bonding network significantly affects the Tc of a CD amphiphiles while the Tm
temperature was not greatly affected.
Received 6th March 2014
Accepted 31st March 2014
DOI: 10.1039/c4tc00448e
www.rsc.org/MaterialsC
chiral centres in a carbohydrate molecule, amphiphilic carbo-
hydrate mesogens rarely form chiral mesophases.
Introduction
Cyclodextrin (CD)-based mesogens8 are of particular interest
Self-assembly of simple building blocks via non-covalent forces
into larger ordered structures has been a hot topic of research
for the last 30 years.1 Many functional systems such as liquid
crystals have been successfully designed with small molecular
building blocks (mesogens) that use intermolecular forces2–4
such as van der Waals, hydrogen bonding, p–p interaction and
ionic forces. The formation of liquid crystalline (LC) phases
relies heavily on the ability of the mesogenic molecules to self-
assemble into highly ordered structures. Carbohydrate-based
mesogens are of particular interest because of their low cost,
availability of a wide range of starting materials, and accessi-
bility of many developed chemical methods for carrying out
structure modications.5–7 Typically, monosaccharides are
transformed into mesogens by the addition of one or more
aliphatic chains, generating amphiphilic molecules that self-
assemble into periodically layered structures. The non-polar
alkyl chains of numerous molecules self-associate to form
hydrophobic regions while their polar carbohydrate head
groups form hydrophilic regions. The thermotropic liquid
crystalline phase that is created by this type of packing is known
as the smectic (Sm) phase. Despite the presence of numerous
for LC research, as the truncated cone-shaped CD cores have a
cyclic bidimensional geometry. The three common members,
a-, b- and g-CDs, form similar rigid structures with primary
hydroxyl groups (OH-6's) found at the narrow end and
secondary hydroxyl groups (OH-2's and OH-3's) at the wider
end. The difference in reactivity between the two classes of
hydroxyl groups has been exploited to regioselectively introduce
functional groups.9 In 1993, Darcy et al. synthesized10 a series of
6-thioalkylated b-CD derivatives containing different chain
lengths (Fig. 1).
They found that these CD amphiphiles exhibited thermo-
tropic LC properties – especially the n-hexadecylthio- and
n-octadecylthio-substituted derivatives (1 and 2), which dis-
played liquid crystallinity in a wide temperature range (215 ꢀC to
280 ꢀC). Upon heating, both compounds decomposed before
aDepartment of Chemistry and Alberta Glycomics Centre, University of Calgary,
Calgary, AB T2N 1N4, Canada. E-mail: ccling@ucalgary.ca; Fax: +1 403-289-9488;
Tel: +1 403-220-2768
bDepartment of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada
† Electronic supplementary information (ESI) available: Experimental details for
compounds 10–25. 1H and 13C NMR spectra of all synthesized compounds and
DSC thermograms of compounds 3, 4, 7 and 8 and TGA traces of compounds 5
and 6. See DOI: 10.1039/c4tc00448e
Fig. 1 Schematic structures of previously synthesized b-CD deriva-
tives exhibiting thermotropic LC properties.
4928 | J. Mater. Chem. C, 2014, 2, 4928–4936
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clearing into an isotropic liquid. Powder X-ray diffraction (XRD) secondary hydroxyl groups (the OH-2's) blocked with alkyl
˚
revealed that the bilayers formed by 1 had a thickness of 38 A, groups of different sizes (methyl, ethyl, allyl and benzyl). All
˚
which is shorter than twice the molecular dimension (2 ꢁ 28 A) these amphiphilic polyols should be capable of forming
of 1 in the extended conformation.
hydrogen bonds; however, in a layered LC phase, the average
Interestingly, since the rst publication, there has been only distance of adjacent layers is dened by the bulkiness of alkyl
one other publication reporting a b-CD derivative with ther- groups introduced at the O-2's; consequently, the average
motropic LC properties. Zhang et al. introduced11a seven distance between the OH-3's of adjacent layers varies, which
hydrophobic groups terminated with
a methoxy-biphenyl should result in hydrogen bonds of different strengths.
moiety to the primary face of b-CD via the Huisgen 1,3-dipolar
cycloaddition reaction, and observed that the compound
entered into LC phases starting at 115 C and cleared into an
Synthesis
ꢀ
isotropic liquid at 197 ꢀC. Using XRD, it was found that the
molecule formed Sm phases. The interesting part of
their design was the introduction of a common mesogenic
group (40-methoxybiphenyl group) which apparently enhanced
the LC properties of the synthesized b-CD derivative. In addi-
tion, Terao et al.11b also reported that an inclusion complex of
permethylated cyclodextrin with a linear polymer formed a
cholesteric phase (mesophase) in concentrated chloroform.
All of the above mentioned systems exhibited LC phases that
extended up to very high temperatures prior to clearing or
decomposition. We hypothesized that this might be due to the
strong hydrogen bonding network established between the
hydroxyl groups on the secondary face of adjacent layers. The
at secondary face of CDs allows for the proper spatial
arrangement and orientation for hydroxyl groups to interact in a
strong and cooperative manner. Herein, several novel 6-thio-
alkylated b-CD derivatives (3–8, Fig. 2) were designed and
synthesized for a systematic structure–property relationship
study of hydrogen bonding ability on LC phase formation.
The per-2,3-di-O-benzylated CD 3 was synthesized from the
previously known per-2,3,6-tri-O-benzylated b-CD (9).12 Among
the three types of benzyl groups present in 9, only those
attached to O-6's are primary and therefore experience less
steric hindrance and can be selectively modied. A procedure
was reported by Utille and co-workers in 199113 which involved
the use of acetolysis conditions on per-2,3,6-O-benzylated a-CD.
The O-6-benzyl protecting groups were regioselectively cleaved
and converted to acetate groups. Interestingly, this selective and
high yielding reaction has been largely underexploited except
for a recent report.14 We were interested in applying this reac-
tion to our synthesis (Scheme 1).
Using trimethylsilyl triuoromethanesulfonate (TMSOTf)
and acetic anhydride as reagents, it was found that the acetol-
ysis worked very well. The reaction was carried out in anhydrous
ꢀ
dichloromethane at ꢂ40 C for one hour; sodium bicarbonate
was added to quench the reaction, and the desired per-6-O-
acetate 10 was obtained in 78% by column chromatography on
silica gel. The 6-O-acetyl groups of 10 were then removed by
´
employing Zemplen transesterication conditions to provide
the polyol 11 in a quantitative yield. The 6-OH groups were then
activated with methanesulfonyl chloride in a mixture of pyri-
dine–dichloromethane to afford the desired per-6-O-mesylate
(12) in 90% yield. The mesyl groups were nally replaced aer a
nucleophilic attack by the potassium 1-octadecanethiolate
which was generated in situ by the treatment of 1-octadecane-
thiol with potassium tert-butoxide in DMF; the desired target 3
was obtained in 76% yield.
Results and discussion
The per-2,3-O-benzyl- and methyl-substituted b-CD derivatives 3
and 4 were designed because both molecules lack the ability to
form intermolecular hydrogen bonds due to the absence of
hydrogen bond donors. Direct information on whether the
presence of hydrogen bonding is necessary for self-assembly
into LC phases would be provided from these compounds.
Compounds 5–8 were designed to have seven of the fourteen
Fig. 2 Thioalkylated CD targets 3–8 designed to study the structure–
property relationship between hydrogen bonding and LC phase
formation.
Scheme 1 Synthesis of per-2,3-di-O-benzylated b-CD 3 from 9.
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The per-2,3-di-O-methylated analogue (4) was synthesized in 50% yield. Finally, the iodides in compound 18 were displaced
an analogous manner (Scheme 2) from the previously known with 1-octadecanethiolate to afford the targeted amphiphilic
compound 13 (ref. 15) via per-2,3-di-O-methyl-6-O-mesyl-b-CD compound 5 in 64% yield, using conditions described above.
(14, 95% yield) as the intermediate. The targeted nal product 4
Attempts to prepare per-2-O-benzylated compound 8 from 15
was obtained in a moderate yield (40%).
by following a similar reaction sequence as shown in Scheme 3
The preparation of per-2-O-alkylated compounds 5–8 failed to provide the per-2-O-benzylated intermediate in a
required differentiation between primary (OH-6's) and reasonableyield. Inaddition, itwas foundto bedifficultto isolate
a
secondary hydroxyl groups (OH-2's and OH-3's) and additionally the desired compound in the pure form, as the O-benzylation
between the two types of secondary hydroxyl groups. The gave a complex mixture with a close polarity which prevented an
synthesis (Scheme 3) began with the known per-2,6-di-O-tert- efficient separation of the desired product from other over- or
butyldimethylsilylated b-CD 15.9a
under-substituted by-products. To overcome this obstacle,
Under Williamson etherication conditions, the methyl another route was explored using the less sterically hindered
groups were regioselectively introduced to the O-2 positions in compound 199a,15 that contains only seven 6-O-TBS groups as a
60% yield. Consistent with a previous report,16 the 2-O-tert- starting material (Scheme 4). In fact, this compound allowed the
butyldimethylsilyl (TBS) groups underwent a migration to the synthesis of all remaining per-2-O-alkylated targets 6–8.
O-3 positions aer treating 15 with sodium hydride. Compound
Compound 19 was prepared using modied conditions.17
16 was obtained in 60% yield. A subsequent deprotection of the Thus, the polyol (19) was treated with NaH (1.5 equiv. per OH-2
TBS groups using tetra-n-butylammonium uoride (TBAF) for 20, 1.0 equiv. per OH-2 for 21 and 22) in anhydrous DMF,
afforded the 3,6-polyol 17 in an excellent yield (87%). Iodine- either ethyl iodide (2.0 equiv. per OH-2) or allyl bromide (1.0
triphenylphosphine-mediated
iodination9c
successfully equiv. per OH-2) or benzyl bromide (1.0 equiv. per OH-2) was
replaced all OH-6's with iodide leaving groups in a regiose- added and the respective mixture was stirred at room temper-
lective manner; the desired 6-heptaiodide 18 was obtained in ature overnight; the pure per-2-O-ethylated b-CD (20) was
obtained in only 30% yield, while the per-2-O-allylated and per-
2-O-benzylated b-CD derivatives 21 and 22 were obtained in
better yields (43% for 21 and 52% for 22). The unexpected low
yield for the ethylated compound 20 was probably a result of
excessive b-elimination of the electrophile (to produce ethene)
during alkylation, which consumed the reagent. However, in
each case, the purication of the reaction mixture was much
easier, as there exists larger differences in Rfs between the
desired product (20, 21 or 22) and their respective over- or
under-alkylated by-products in each reaction, because of the
differences in the number of free hydroxyl groups; this greatly
facilitated the nal separation. To introduce a leaving group at
the C-6 positions, all compounds 20–22 were directly converted
to per-6-brominated derivatives 23–25 using an elegant
Scheme 2 Synthesis of per-2,3-di-O-methylated b-CD 4 from 13.
Scheme 3 Synthesis of per-2-O-methylated b-CD derivative 5 from Scheme 4 Synthesis of per-2-O-ethylated, allylated and benzylated
15.
b-CD derivatives 6, 7 and 8 from 19.
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Table 1 Phase transition temperature (ꢀC) and DH in parenthesesa (J
approach previously reported by Darcy et al.18 Thus the tert-
butyldimethylsilyloxy groups were directly converted to
6-bromides by employing Br2/PPh3 as a reagent; the desired per-
2-O-allylated (24) and per-2-O-benzylated (25) derivatives were
isolated as precipitates by sonicating each crude reaction
mixture in ethanol (46% for 24 and 33% for 25). The per-2-O-
benzylated compound 25 was also isolated in an excellent yield
(94%) by column chromatography on silica gel using a gradient
of ethyl acetate–toluene as the eluent. However, for the per-2-O-
ethylated analog 23, although TLC revealed that bromination
worked well, it was found to be difficult to isolate the desired
product in the pure form by chromatography even by using
different eluents, as compound 23 had a similar polarity (Rf) to
triphenylphosphine oxide which was formed as a by-product
from the reaction; however, it could be precipitated out from
EtOH in the pure form as above (56% yield). All per-6-bromides
23–25 very smoothly converted to the nal targets 6, 7 and 8 in
moderate to good yields (64% for 6, 39% for 7 and 80% for 8) by
reacting with 1-octadecanethiol under argon using either
potassium tert-butoxide or cesium carbonate as a base.
gꢂ1
)
Compound Heating
Cooling
3
4
5
Crys 48.5 (15.9) Iso
Crys 53.4 (57.2) Iso
Iso 38.2 (15.0) Crys
Iso 47.5 (51.4) Crys
Iso 95 (19.4) Sm 56 (36.0)
Crys 50 (2.8) X 60 X 64.5
X 68 (31.1b) Sm 110 (20.7) X 40.5 X 37.5 (4.9c) Crys
Iso
6d
7
8
Crys 54 Sme 61 Iso
Crys 57.6 (104.9) Iso
Crys 54.0 (73.3) Iso
Iso 51.5 Sme 49 X 43.5 Crys
Iso 49.7 (66.8) Crys
Iso 46.7 (75.0) Crys
a
Crys: crystalline; Iso: isotropic liquid; Sm: smectic and X: unidentied
b
so-crystalline phase. Combined enthalpic changes of all transitions
c
at 60, 64.5 and 68 ꢀC. Combined enthalpic changes of both
d
transitions at 40.5 and 37.5 ꢀC. No enthalpic data are reported for
compound 6 due to severe overlap of peaks in DSC thermogram.
e
Based on the structural similarity and also the formed patterns
similarity (under POM) with compound 5, the mesophase was
assigned to be smectic.
The structures and purity of all target compounds 3–8 were intermolecular hydrogen bonds. In the case of compound 3, the
conrmed by high resolution mass spectrometry as well as presence of numerous benzyl groups at the secondary face
different 1D and 2D NMR experiments. For example, for the per- could have resulted in p–p interactions if the molecules self-
2-O-methylated, ethylated, allylated and benzylated compounds assembled into a smectic LC phase. However, the results clearly
5–8, high resolution MALDI mass spectrometry showed the indicated that such interactions were not strong enough to drive
expected m/z peak of the sodium adduct in each case (see the rod-like molecules to self-organize into ordered structures.
Experimental section). All 1D 1H and 13C NMR spectra of
compounds 3–8 revealed the expected C7 axial symmetry, as investigated. The DSC of per-2-O-allylated compound
only one set of H-1 and C-13 signals was observed in each case, revealed one endothermic transition at 57.6 ꢀC on heating,
Next, the thermotropic properties of compounds 5–8 were
7
which conrmed a symmetrical substitution (see ESI†).
and an exothermic transition at 49.7 ꢀC on cooling; similar
results were also observed for the per-2-O-benzylated analog
8, which showed similar phase transitions at 54.0 ꢀC (heat-
ing) and 46.7 ꢀC (cooling). Under POM it was conrmed that
Mesomorphic properties
Differential Scanning Calorimetry (DSC) was performed on neither compound formed LC phases, and the transitions
compounds 3–8 to determine possible thermotropic phase were the results of clearing from a solid to an isotropic
transitions and the associated enthalpy changes. The rst liquid.
heating cycle for all compounds was omitted because of thermal
The analogous compounds 5 and 6, which had smaller
history. The temperatures and enthalpies of transitions from groups at the O-2 position of glucopyranosyl units, exhibited
the rst cooling and second heating of compounds 3–8 are distinct thermotropic behaviour. Thermogravimetric analysis
summarized in Table 1. Subsequent heating and cooling cycles revealed the per-2-O-methylated derivative 5 to be stable up to
showed reproducible values for the phase transitions.
250 ꢀC (ꢃ95%) while the per-2-O-ethylated analog 6 to be
Dibenzylated CD 3 displayed one endothermic transition at slightly less stable – up to 200 ꢀC (ꢃ95%). Remarkably, the DSC
48.5ꢀC on heating and an exothermic transition at 38.2 C on thermogram of compound 5 (Fig. 3) displayed ve endothermic
cooling. Under the cross-polarized optical microscope (POM) on phase transitions at 50, 60, 64.5, 68 and 110 C on the heating
ꢀ
ꢀ
heating, a clear transition from the solid to isotropic liquid cycles, and four exothermic transitions at 37.5, 40.5, 56 and
ꢀ
phase was observed. The 2,3-di-O-methylated b-CD analog 4 95 C on the cooling cycles; under POM it was evident that on
exhibited similar behaviour and displayed one endothermic heating the phase transition at 110 ꢀC was the transition to the
ꢀ
transition at 53.4 C on heating and another exothermic tran- isotropic liquid. The sample was then cooled slowly at 2 ꢀC
sition at 47.5 ꢀC and a much smaller, broad transition at 36.5 ꢀC minꢂ1 from the isotropic liquid, and birefringent patterns
on cooling; like compound 3, the larger transitions at 47.5/53.4 appeared around 95 ꢀC with characteristic fan-shaped patterns
ꢀC must correspond to a phase transition between a solid and which are oen seen in Sm A packing (Fig. 3). The formed
an isotropic liquid, while the smaller one should correspond to mesophase appeared to be highly viscous and could be sheared.
a crystal (or so crystal) to another crystal phase. More impor- The fan-shaped patterns did not change on continuous cooling,
tant to note is that neither compound 3 nor 4 exhibited liquid but colours appeared gradually and aer passing the transition
crystallinity; this could be attributed to the absence of hydroxyl at 56 ꢀC, the colours became signicantly brighter and rich.
groups at the secondary face in both compounds, which elim- There was no change detected in textures under POM for the
ꢀ
ꢀ
inated their ability to self-assemble into ordered structures via transition at 40.5 C and 37.5 C on cooling.
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Fig.
4
DSC thermogram of compound
6
(top) after heating
Fig.
3 DSC thermogram of compound 5 (top) after heating
compound 6 to clearing temperature and allowing it to cool to room
temperature at 2 ꢀC minꢂ1 and snapshots taken at 57.6 and 36.8 ꢀC
under POM.
compound 5 to clearing temperature and allowing it to cool to room
temperature at 2 ꢀC minꢂ1 and snapshots taken at 77.5 and 43.9 ꢀC
under POM.
The sharp contrast in thermotropic behaviour between
On the other hand, for the per-2-O-ethylated analog 6, DSC compounds 5 and 6 compared to the analogous compounds 7
detected two very broad endothermic transitions at 54 and 61 ꢀC and 8 constitutes an interesting phenomenon. Since each of
in the heating cycle, and three closely spaced exothermic tran- them contains seven hydroxyl groups, they should be capable of
sitions peaked at 43.5, 49 (broad), 51.5 ꢀC (broad) in the cooling forming the same number of hydrogen bonds. However, as
cycle. Under POM it was clear that the transition related to the stated before, the difference resides in the nature of the alkyl
peak at 61 ꢀC on heating is the clearing temperature, and groups attached to the O-2 positions, which vary in size. The fact
compound 6 also had liquid crystalline properties, which was that molecules substituted with smaller methyl (5) or ethyl (6)
evident upon cooling from ꢃ61 ꢀC when the similar fan-shaped groups successfully self-organized into ordered smectic meso-
birefringent patterns appeared. However, the patterns and phases while the other two with larger substituents (allyl and
textures remained more or less the same on further cooling benzyl, 7 and 8) failed to do so suggests a difference in strength
(Fig. 4). Considering the structural similarity with compound 5, of intermolecular hydrogen bonds that these molecules are able
the formed mesophase was assigned to be Sm packing.
to form. The derivative 5 containing the smallest substituent
DSC also provided the enthalpy change atꢀeach phase tran- (methyl) showed the widest mesophase temperature range,
sition for compound 5. The transitions at 56 C in the cooling which correlates well to its ability to allow the strongest inter-
cycle had an enthalpy of 36 J gꢂ1. This value is larger than the molecular hydrogen bonding network to form as the small
enthalpic change (19.4 J gꢂ1) found at 95 ꢀC (isotropic liquid to methyl group creates minimal spacing between hydroxyl groups
LC phase), but smaller than those observed for the melting of the adjacent layers in the smectic packing. The allyl and
transitions of most non-liquid crystalline compounds (4, 7 and benzyl groups present in the other two compounds 7 and 8
8, 51.4–104.9 J gꢂ1). Because the liquid crystalline phase is respectively are probably just too large to permit the adjacent
structurally more similar to the isotropic liquid than to the layers to get close enough to allow an effective intermolecular
crystalline phase, there is larger enthalpic change at a phase hydrogen-bond network to establish; thus no ordered meso-
transition from LC to crystal than isotropic liquid to LC. Aer phases were observed to form for either compound. Compound
the transitions at 56 ꢀC, compound 5 had crystallized at 37.5 ꢀC. 6 bears seven ethyl groups whose size is intermediate from
The intermediate phase transition could be between different methyl to allyl; consequently, compound 6 should possess an
so crystalline phases; however, POM or XRD experiments intermediate ability to interact via intermolecular hydrogen-
could not conclusively identify them. For compound 6, unfor- bond between adjacent layers. The reduced hydrogen-bond
tunately, all phase transitions were broad thus unresolved; we network is not strong enough to stabilize the mesophase at high
did not attempt to integrate each transition peak to obtain the temperatures thus much narrower temperature range was
enthalpy change for individual transition.
observed for the mesophase formed by compound 6 (Fig. 4).
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10
˚
For comparison, the previously known compound 2 that had have a bilayer thickness of 38 A. The addition of the methyl
no substituents at the secondary face was also synthesized and group plus the two extra carbons on the chains (C16 for 1 vs. C18
examined by DSC and POM. Interestingly, the DSC did not show for 5) must account for the difference. The interlayer spacing is
evidence of the phase transition at 215 ꢀC that was reported by considerably smaller than 62.2 A (2 ꢁ 31.1 A, Fig. 5), the length
the original publication; the DSC displayed peaks at 57 and calculated for a head-to-head dimer of 5, which likely reects
61 ꢀC on heating and two corresponding peaks at 48 and 52 ꢀC substantial interdigitation of the side chains made possible by
on cooling; in addition, examination of 2 under POM also did the void associated with the CD's central cavity.
˚
˚
not reveal signicant change in birefringence patterns around
The XRD of this phase also exhibited several low intensity
ꢀ
215 C. Based on these observations, it was suggested that the peaks at wider angles that could not be indexed to an LC phase.
mesophase range of 2 could be even wider (57–280 ꢀC on These peaks suggest some degree of three dimensional ordering
heating) than previously reported. This was also in agreement within the phase, and could arise due to periodicity within the
with the behaviour of both compounds 5 and 6. The melting layer. As such, there is some ambiguity in the assignment of this
ꢀ
temperatures (Tm) of 2, 5 and 6 are similar (57, 54 and ꢃ49 C phase as a liquid crystal; although it clearly possesses lamellar
respectively), but the clearing temperatures (Tc) are signicantly ordering, the additional peaks are suggestive of a smectic so
altered (280 vs. 113 vs. 61 ꢀC) by the modication on the crystal. This assignment would also explain the relatively large
secondary face. Since the aliphatic chain length is the same for enthalpy of the mesophase-to-isotropic transition, which indi-
both CD derivatives, it can be assumed that the contribution of cates that the mesophase is highly ordered.
van der Waals interactions in the smectic mesophases was
The XRD experiments on 5 showed that at lower tempera-
ꢀ
similar for all three compounds. Therefore, the hydrogen tures (ꢃ52 C), the compound appeared to form a long-range
bonding network that each compound is capable of establish- ordered phase; however, indexing the peaks was difficult, thus
ing must account for the difference in observed Tc tempera- we were unable to identify this phase. The smectic ordering of
tures. More specically, both compounds 5 and 6 have half the the higher temperature phase was clearly disrupted, as evi-
number of secondary OH groups as compound 2, which should denced by the disappearance of the higher order (002) and (003)
correspond to much weaker abilities of the two compounds to peaks. The appearance of several low intensity peaks at wider
form a hydrogen bonding network than 2; this was in agreement angles indicates some sort of short range 3D correlation.
with the much lower Tc temperatures observed for compounds 5
and 6 compared to 2.
Packing in the LC phase
Previously, Avakyan et al. carried out ab intio and semiempirical
quantum-chemical calculations19 to look at the role of intra- and
Powder X-ray diffraction
Compound 5 was selected for analysis by powder X-ray diffrac- inter-molecular hydrogen bond networks in unmodied b-CD
tion. The phase observed between 95 and 52 ꢀC on cooling was head to head dimers. As shown in Fig. 6, the secondary hydroxyl
conrmed by (XRD) to be a smectic phase with a layer spacing of groups of two opposing CDs can establish two kinds of fairly
˚
40.7 A; this was evidenced by the consistent presence of (001), complex hydrogen bonding networks; both involve inter- and
(002), and (003) diffraction peaks whose relative intensity intramolecular hydrogen bonding. For example, the OH-2
decreased as expected. This distance correlates well with that of groups of one CD can simultaneously act as hydrogen bond
analogous compound 1, which was previously determined to donors by interacting with O-3's of another CD (red dotted
Fig. 5 Left: molecular models show compounds 1 (C16) and 5 (C18) have respectively dimensions of 27.5 and 31.1 A˚ in the most extended
conformation. Right: variable temperature XRD plots of compound 5, recorded at 81 and 52 ꢀC.
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interact with O-2's, both intermolecularly and intramolecularly
in the bilayers, via the less thermodynamically stable type II
network as shown in Fig. 6c. This model suggests a signicantly
reduced strength of the hydrogen-bonding network that both
compounds 5 and 6 could establish, which is consistent with its
observed much lower clearing temperatures, compared to
compounds 1 and 2.
We also attempted to record the FT-IR spectra of compounds
5, 7 and 8 in order to study their differences in ability to form
hydrogen-bond networks; however, due to the fact that all three
compounds are able to form a strong intramolecular hydrogen
bond network which interferes with the studies, our investiga-
tion did not provide conclusive results.
Conclusion
Through these studies, the role of hydrogen bonding in the self-
organization of amphiphilic CDs into ordered thermotropic
mesophases was claried. It was established that modifying the
secondary face to interfere with the hydrogen bonding network
signicantly affected the Tc of a CD amphiphiles while the Tm
temperature was not greatly affected. Six new CD derivatives
were designed and synthesized, and their ability to form self-
organized thermotropic mesophases correlates well with their
ability to form intermolecular hydrogen bonds. It was found
that the synthesized CD amphiphiles need to establish a
hydrogen bond network of sufficient strength to be able to drive
molecules to self-assemble. A molecular model was proposed to
help understand the probable packing in the mesophases for
the per-6-alkylthio b-CD derivatives, and such a model also
permits suggestion of a hydrogen bonding network that
explains well the nature and strength of the formed hydrogen
bond network. The results obtained from this study should help
to design future CD-based LC materials as well as understand
their thermotropic properties.
Fig. 6 Possible hydrogen-bond networks established in natural CD
dimers: (a) OH-2's as intermolecular hydrogen-bond donors while
OH-3's act as intramolecular hydrogen bond acceptors, (b) OH-3's act
as the intermolecular hydrogen-bond donors while OH-2's act as the
intramolecular hydrogen-bond acceptors, and (c) proposed
hydrogen-bond network established in the dimer formed from
compounds 5 and 6.
lines), and as hydrogen bond acceptors by accepting hydrogen
bonds (blue dotted lines) from an OH-3' of adjacent glucosyl
units of the same CD (type I, Fig. 6a). The OH-2 and OH-3
groups can also switch roles to establish a second type of
hydrogen bond network (type II) shown in Fig. 6b.
Experimental section
General methods
Analytical TLC was performed on Silica Gel 60-F254 (Merck,
Avakyan et al.'s computational studies concluded that the Darmstadt) with detection by quenching of uorescence and/or
type I hydrogen bonding network was thermodynamically more by charring with 5% sulfuric acid in water or with a ceric
stable than the type II. They reasoned that the increased ammonium molybdate dip. All commercial reagents were used
stability of the network in type I (Fig. 6a) was due to the fact that as supplied unless otherwise stated. Column chromatography
the OH-2 groups are torsionally more favoured to form stable was performed on silica gel 60 (Silicycle, Ontario). Organic
inter-CD hydrogen bonds; in addition, the more acidic nature of solutions from extractions were concentrated under vacuum at
1
ꢀ
the OH-2 groups compared to the OH-3's also makes them <40 C (bath). H NMR spectra were recorded at 400 MHz on
better hydrogen bond donors, leading to stronger intermolec- Bruker spectrometers. The rst order proton chemical shis dH
ular interactions. It can be logically assumed that the hydrogen and dC are reported in d (ppm) and referenced to either residual
bonding networks formed in the thermotropic LC phase of both CHCl3 (dH 7.24, dC 77.0, CDCl3), residual CD2HOD (dH 3.30, dC
compounds 1 and 2 resemble the network shown in Fig. 6a. 49.5, CD3OD), residual CD3SOCD2H (dH 2.50, dC 39.51,
However, for compounds 5 and 6, the hydrogens in all OH-2 CD3SOCD3) or residual C5D4HN (dH 7.22, dC 123.87, C5D5N). 1H
groups have been substituted with alkyl groups; this not only and 13C NMR spectra were assigned with the assistance of
reduces the numbers of hydrogen bonds that both compounds GCOSY, GHSQC spectra. Matrix-assisted laser desorption/ioni-
5 and 6 can form, but also completely removes their ability to zation and time-of-ight mass spectra (MALDI-TOF MS) were
form the more stable type I network. Consequently, the OH-3 recorded on a Bruker Daltonics AUTOFLEX III spectrometer
groups now must dynamically act as hydrogen bond donors to using DHP as a matrix. High resolution ESI-QTOF mass spectra
4934 | J. Mater. Chem. C, 2014, 2, 4928–4936
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Journal of Materials Chemistry C
were recorded on an Agilent 6520 Accurate Mass Quadrupole (C-4), 80.24 (C-2), 73.09 (C-3), 70.81 (C-5), 68.25 (OCHaHb),
time-of-ight LC/MS spectrometer. Polarized optical micros- 33.86 (C-6), 33.66 (S–CH2), 31.92, 29.91, 29.81, 29.80, 29.78,
copy was performed on OLYMPUS BX-41 equipped with a 29.75, 29.67, 29.48, 29.37, 29.09, 22.67, 15.26 (OCHaHbCH3),
Linkam hot stage. Thermal analyses were performed using 14.09 (CH3). m/z (HRMS MALDI-TOF) calcd for [C182H350O28S7 +
a TA-Q200 differential scanning calorimetry instrument with a Na]+ 3231.3906, found: 3231.4020.
ꢀ
heating and cooling rate of 2 C. All data were obtained by the
analytical services of the Department of Chemistry, University of
Calgary.
Powdered X-ray crystallography
Samples were heated to the isotropic liquid phase on a hot plate
and loaded by capillary action. The excess material was cleaned
off the sides with clean dry tweezers. Capillaries were then cut to
length and mounted in a capillary furnace.20 Measurements
Per-6-deoxy-2-O-methyl-6-octadecylthio-b-cyclodextrin (5)
A solution of compound 18 (0.178 g, 0.090 mmol) in a mixture of
THF (3 mL) and CH2Cl2 (1 mL) was added to a solution of KOBu-
t (0.140 g, 1.25 mmol) and thiooctadecane (0.357 g, 1.25 mmol)
in THF (3 mL) under argon and the reaction mixture was heated
at 65 ꢀC for 21 h. Aer removing the solvents under reduced
pressure, the residue was dissolved in CH2Cl2 (20 mL); the
organic solution was washed with water (1 ꢁ 30 mL) and dried
over anhydrous magnesium sulfate and evaporated. The residue
was puried by column chromatography on silica gel using 1%
MeOH–CH2Cl2 as an eluent to afford compound 5 as a white
solid (0.175 g, 64.4% yield). Rf 0.45 (MeOH–CH2Cl2, 5 : 95). [a]D
+58.6 (c 0.9, CHCl3). 1H NMR (CDCl3, 400 MHz) d 5.02 (d, J ¼ 3.4
Hz, 7H, 7 ꢁ H-1), 3.92 (dd, J ¼ 9.3, 9.3 Hz, 7H, 7 ꢁ H-3), 3.89–
3.82 (m, 7H, 7 ꢁ H-5), 3.66 (s, 21H, 7 ꢁ OCH3), 3.50 (dd, J ¼ 9.1,
9.1 Hz, 7H, 7 ꢁ H-4), 3.27 (dd, J ¼ 9.7, 3.5 Hz, 7H, 7 ꢁ H-2),
3.04–2.88 (m, 14H, 7 ꢁ H-6a + 7 ꢁ H-6b), 2.60 (t, J ¼ 7.4, 14H,
7 ꢁ S–CH2), 1.63–1.51 (m, 14H, 7 ꢁ S–CH2CH2), 1.43–1.33 (m,
14H, 7 ꢁ S–CH2CH2CH2), 1.35–1.20 (m, 196H, alkyl), 0.89 (t, J ¼
6.7 Hz, 21H, 7 ꢁ CH3). 13C NMR (CD3OD, 100 MHz) d 100.91 (C-
1), 85.80 (C-4), 82.12 (C-2), 72.98 (C-3), 70.96 (C-5), 60.35 (OCH3),
33.79 (C-6), 33.71 (S–CH2), 31.94, 29.93, 29.82, 29.76, 29.69,
29.49, 29.38, 29.10, 22.69, 14.11. m/z (HRMS MALDI-TOF) calcd
for [C1175H336O28S7 + Na]+ 3133.2805, found: 3133.2754.
were carried out on a Rigaku RAXIS rapid diffractometer using
˚
Cu Ka radiation (l ¼ 1.5418 A), a graphite monochromator and
a Fujilm Co. Ltd curved image plate (460 mm ꢁ 256 mm).
Temperature was controlled with an Omega temperature
controller connected to the capillary furnace with a K-type
thermocouple for feedback. Owing to technical issues, the
controller was set to manual mode. Due to thermal equilibra-
tion, the temperature oen dropped during the course of
acquisition. Only the nal temperature is reported. A 0.3 mm
collimator was used and all samples were irradiated for
30 minutes. Peaks and their respective angle measurements
and d-spacings were determined using the MDL JADE soware.
The peak type was analysed by taking the reciprocal d-spacings
and dividing them by the highest intensity peak, unless other-
wise noted. Only peaks with greater than 1% intensity in the low
angle region were analysed.
Acknowledgements
We thank both referees for the insightful reviews and sugges-
tions and we acknowledge stimulating discussions with Drs
Todd Sutherland and Robert Lemieux. We are grateful to Dr
Thomas Baumgartner for the use of the TA-Q200 differential
scanning calorimetry instrument. The nancial support from
Alberta Innovates – Technology Futures, the Natural Sciences
and Engineering Research Council of Canada, and the Univer-
sity of Calgary are greatly acknowledged.
Per-6-deoxy-2-O-ethyl-6-octadecylthio-b-cyclodextrin (6)
Compound 23 (50 mg, 28 mmol) was dissolved in a mixture of
anhydrous DMF (1.5 mL) and THF (1 mL) under argon; 1-octa-
decanethiol (113 mg, 0.40 mmol) and Cs2CO3 (125 mg, 0.40
ꢀ
mmol) were added and the reaction was heated to 60 C for 2
days. Then the temperature was raised to 80 ꢀC for 1 h. The
reaction mixture was diluted with EtOAc (20 mL) and washed
with H2O (1 ꢁ 40 mL), saturated brine (2 ꢁ 40 mL) and dried
over anhydrous Na2SO4. Aer concentration under reduced
pressure, the crude mixture was puried by column chroma-
tography on silica gel using EtOAc–toluene (15 : 85) as the
eluent to afford pure compound 6 as a white solid (58 mg, 64%
yield). Rf 0.24 (EtOAc–toluene, 20 : 80). 1H NMR (400 MHz,
CDCl3) d 5.08 (s, 7H, 7 ꢁ OH-3), 4.97 (d, J ¼ 3.5 Hz, 7H, 7 ꢁ H-1),
4.06 (dq, J ¼ 7.1, 9.3 Hz, 7H, 7 ꢁ OCHaHbCH3), 3.97–3.80 (m,
14H, 7 ꢁ H-3 + 7 ꢁ H-5), 3.72 (dq, J ¼ 7.1, 9.3 Hz, 7 ꢁ
OCHaHbCH3), 3.47 (dd, J ¼ 9.2, 9.2 Hz, 7H, 7 ꢁ H-4), 3.35 (dd, J
¼ 9.6, 3.4 Hz, 7H, 7 ꢁ H-2), 3.00 (dd, J ¼ 2.2, 13.8 Hz, 7 ꢁ H-6a),
2.93 (dd, J ¼ 5.3, 13.8 Hz, 7 ꢁ H-6b), 2.60 (t, J ¼ 7.4 Hz, 14H, S–
CH2), 1.63–1.53 (m, 14H, 7 ꢁ S–CH2CH2), 1.47–1.16 (m, 231H, 7
ꢁ S–CH2CH2(CH2)15 + 7 ꢁ OCHaHbCH3), 0.89 (t, J ¼ 6.7 Hz,
21H, 7 ꢁ CH3). 13C NMR (100 MHz, CDCl3) d 101.56 (C-1), 85.83
Notes and references
1 (a) C. Tschierske, Prog. Polym. Sci., 1996, 21, 775–852; (b)
J.-M. Lehn, Angew. Chem., Int. Ed., 1990, 29, 1304–1319; (c)
P. Metrangolo, F. Meyer, T. Pilati, G. Resnati and
G. Terraneo, Angew. Chem., Int. Ed., 2008, 47, 6114–6127;
(d) H. Ringsdorf, B. Schlarb and J. Venzmer, Angew. Chem.,
Int. Ed., 1988, 27, 113–158.
2 T. Kato, N. Mizoshita and K. Kishimoto, Angew. Chem., Int.
Ed., 2006, 45, 38–68.
3 S. Sergey, P. Wojciech and G. Y. Henri, Chem. Soc. Rev., 2007,
36, 1902–1929.
4 (a) C. M. Paleos and D. Tsiourvas, Liq. Cryst., 2001, 28, 1127–
1161; (b) T. Kato, N. Mizoshita and K. Kanie, Macromol. Rapid
Commun., 2001, 22, 797–814; (c) T. Kato, Struct. Bonding,
2000, 96, 95–146.
5 G. A. Jeffrey, Acc. Chem. Res., 1986, 19, 168–173.
This journal is © The Royal Society of Chemistry 2014
J. Mater. Chem. C, 2014, 2, 4928–4936 | 4935

View Article Online
Journal of Materials Chemistry C
Paper
6 J. W. Goodby, V. Goertz, S. J. Cowling, G. Mackenzie, 12 T. Sato, H. Nakamura, Y. Ohno and T. Endo, Carbohydr. Res.,
P. Martin, D. Plusquellec, T. Benvegnu, P. Boullanger, 1990, 199, 31–35.
D. Lafont, Y. Queneau, S. Chambert and J. Fitremann, 13 P. Angibeaud and J. P. Utille, Synthesis, 1991, 737–738.
Chem. Soc. Rev., 2007, 36, 1971–2032.
14 E. Zaborova, J. Deschamp, S. Guieu, Y. Bleriot, G. Poli,
M. Menand, D. Madec, G. Prestat and M. Sollogoub, Chem.
Commun., 2011, 47, 9206–9208.
15 K. Takeo, H. Mitoh and K. Uemura, Carbohydr. Res., 1989,
187, 203–221.
7 H. A. van Doren, E. Smits, J. M. Pestman, J. B. F. N. Engberts
and R. M. Kellog, Chem. Soc. Rev., 2000, 29, 183–199.
8 F. Sallas and R. Darcy, Eur. J. Org. Chem., 2008, 957–969.
9 For examples of perfunctionalization methods of
cyclodextrins, see: (a) P. Fugedi, Carbohydr. Res., 1989, 192, 16 P. R. Ashton, S. E. Boyd, G. Gattuso, E. Y. Hartwell,
366–369; (b) A. W. Coleman, P. Zhang, C.-C. Ling and
H. Parrot-Lopez, Carbohydr. Res., 1992, 224, 307–309; (c)
R. Koniger, N. Spencer and J.-F. Stoddart, J. Org. Chem.,
1995, 60, 3898–3903.
A. Gadelle and J. Defaye, Angew. Chem., Int. Ed., 1991, 30, 17 P. Zhang, C.-C. Ling, A. W. Coleman, H. Parrot-Lopez and
78–80; (d) D. A. Fulton and J. F. Stoddart, J. Org. Chem., H. Galons, Tetrahedron Lett., 1991, 32, 2769–2770.
2001, 66, 8309–8319; (e) S. Ward and C.-C. Ling, Eur. J. Org. 18 C. Byrne, F. Sallas, D. K. Rai, J. Ogier and R. Darcy, Org.
Chem., 2011, 4853–4861; (f) P. Zhang, A. Wang, L. Cui and
C.-C. Ling, Org. Lett., 2012, 14, 1612–1615.
10 C.-C. Ling, R. Darcy and W. Risse, Chem. Commun., 1993,
438–440.
Biomol. Chem., 2009, 7, 3763–3771.
19 V. G. Avakyan, V. B. Nazarov, M. V. Almov,
A. A. Bagatur'yants and N. I. Voronezheva, Russ. Chem.
Bull., 2001, 50, 206–216.
11 (a) L. Chen, T.-H. Hu, H.-L. Xie and H.-L. Zhang, J. Polym. 20 C. Lavigueur, E. J. Foster and V. E. Williams, J. Appl.
Sci., Polym. Chem. Ed., 2010, 48, 2838–2845; (b) J. Terao,
S. Tsuda, Y. Tanaka, K. Okoshi, T. Fujihara, Y. Tsuji and
N. Kambe, J. Am. Chem. Soc., 2009, 131, 16004–16005.
Crystallogr., 2008, 41, 214–216.
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This journal is © The Royal Society of Chemistry 2014