Hydrophobic and hydrophilic balance and its effect on mesophase behaviour in hydroxyalkyl ethers of methyl glucopyranoside

Article abstract of DOI:10.1002/chem.201202933

Four series of monosubstituted methyl a-d-glucopyranoside hydroxyal- kyl ethers were prepared and their thermotropic and lyotropic self-organising properties were investigated in terms of the hydrophobic-hydrophilic balance with respect to their molecular

Full text of DOI:10.1002/chem.201202933

FULL PAPER
DOI: 10.1002/chem.201202933
Hydrophobic and Hydrophilic Balance and Its Effect on Mesophase
Behaviour in Hydroxyalkyl Ethers of Methyl Glucopyranoside
Madan K. Singh,[a, c] Rui Xu,[a, c] Sylvie Moebs,[a, c] Anil Kumar,[d] Yves Queneau,*[a, c]
Stephen J. Cowling,*[b] and John W. Goodby[b]
Abstract: Four series of monosubstituted methyl a-d-glucopyranoside hydroxyal-
A
Keywords: carbohydrates · liquid
properties were investigated in terms of the hydrophobic–hydrophilic balance with
respect to their molecular structures. The results obtained lead us to a new under-
standing of the forces that drive the formation of condensed soft-matter phases.
crystals · mesophases · self-assem-
bly · soft matter
Introduction
ances as witnessed by the development of materials for ap-
plications in displays. Conversely, lyotropic liquid crystals
are less sensitive, and are primarily affected by the polar/
non-polar balance and the curvature of packing of the am-
phiphiles in the solvent, which is a manifestation of the “hy-
drophobic effect”.[2]
Liquid crystals are classically split into two forms: lyotropic
and thermotropic. The two appear to be separate; lyotropic
phases are composed of an amphiphile and an appropriate
liquid over a defined concentration range, whereas thermo-
tropic phases are usually based on single-component systems
that form condensed phases as a function of temperature.
Lyotropic and thermotropic liquid crystals exhibit polymor-
phism as a function of concentration and temperature, re-
spectively. Amphitropic liquid crystals are materials that can
exhibit both types of phases. Glycolipids can be amphitropic
and exhibit the full range of lyotropic phases as a function
of concentration in water, but they essentially exhibit one
thermotropic phase (i.e., the lamellar/smectic A phase).[1] In
the case of both types, a balance exists with respect to the
molecular architectures of the components (e.g., flexible/
rigid, polar/non-polar, hydrogen-bonding/non-hydrogen-
bonding, aromatic/aliphatic and so on). Thermotropic liquid
crystals are very sensitive to the various intra-molecular bal-
The type of lyotropic phase formed by an amphiphile can
often be predicted by using the dimensionless packing pa-
rameter S. This simple model takes into account free ener-
gies of interaction, molecular geometry and entropy. Thus it
is useful in determining the size and shape of amphiphilic
aggregates. S is given by S=V/al, in which V is the hydrocar-
bon volume, a is the area of the head group and l is the criti-
cal length of the hydrocarbon chain.[3–6] The value of S de-
termines the aggregate formed by amphiphiles upon hydra-
tion. It has been shown that spherical micelles are formed
1
1
for S<1= , hexagonal phases for = <S<1= , lamellar for = <
3
3
2
2
S<1 and reverse micelles or hexagonal phases for S>1.
However, caution has to be taken when using this model be-
cause the limits set on the values of S predicted above are
relatively insensitive to the exact values of V and a but are
strongly dependent upon the choice of l.[7–9] For thermotrop-
ic systems, phase formation is not so predictive because the
inter-molecular interactions are usually weaker and there
are a number of structural balances in play at the same
time, as illustrated in some of our previous studies that in-
volve sucrose-based compounds.[10–12] However, one family
of substituted sugar-based polyols has been shown to exhibit
predictive properties. Figure 1 shows the transition tempera-
tures for the clearing points of dodecyl-substituted acyclic
polyols, which increase linearly with the number of hydroxyl
groups.[1,13] In addition, it was also found that there was
little or no effect of molecular chirality on the clearing
points. Thus, for this family of compounds there is one dom-
inant effect and that is the hydrophobic–hydrophilic balance,
which is typical of lyotropic systems.
[a] Dr. M. K. Singh, R. Xu, Dr. S. Moebs, Dr. Y. Queneau
INSA Lyon, ICBMS, Bꢀtiment J. Verne
20 av A. Einstein, 69621 Villeurbanne (France)
E-mail: yves.queneau@insa-lyon.fr
[b] Dr. S. J. Cowling, Prof. J. W. Goodby
Department of Chemistry, The University of York
York, YO10 5DD (UK)
E-mail: Stephen.cowling@york.ac.uk
[c] Dr. M. K. Singh, R. Xu, Dr. S. Moebs, Dr. Y. Queneau
CNRS, UMR 5246, ICBMS, Universitꢁ Lyon 1
INSA-Lyon; CPE-Lyon, Bꢀtiment CPE
43 bd du 11 novembre 1918
69622 Villeurbanne (France)
[d] Dr. A. Kumar
Physical and Materials Chemistry Division
National Chemical Laboratory
Pune - 411008 (India)
In the present study, we have examined the role of the hy-
drophobic–hydrophilic balance on the self-organising prop-
erties of the monosubstituted methyl a-d-glucopyranoside
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201202933.
Chem. Eur. J. 2013, 19, 5041 – 5049
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5041

hydroxyalkyl)-4,6-O-benzylidene-a-d-glucopyranosides (2)
or 2-O-benzyl-3-O-(2-hydroxyalkyl)-4,6-O-benzylidene-a-d-
glucopyranosides (4) in 55–70% yield. Deprotection by
acidic treatment (catalyst: p-toluenesulfonic acid in metha-
nol) followed by Pd-catalysed hydrogenation in MeOH/
EtOAc afforded methyl 2-O-(2-hydroxyalkyl)-a-d-glucopy-
AHCTUNGTREGrNNUN anosides (I) and 3-O-(2-hydroxyalkyl)-a-d-glucopyrano-
sides (II; see Scheme 1). The final hydroxyalkyl ethers are
Figure 1. Effect of the number of hydroxyl groups on clearing-point and
melting temperatures.[1]
hydroxyalkyl ethers, and we have developed a new concept
for the formation and stabilisation of thermotropic liquid-
crystal phases. The structure of the materials used in this
study is summarised in Figure 2.
Figure 2. Substitution positions around the glucose unit (left) and the hy-
droxyalkyl chain (right) of the compounds examined in this study.
Results and Discussion
Synthesis: The general methods, syntheses and analytical
data for all of the compounds in this article are given in the
Supporting Information.
Scheme 1. Synthesis of methyl 2-O-(2-hydroxyalkyl)-a-d-glucopyrano-
sides (I) and 3-O-(2-hydroxyalkyl)-a-d-glucopyranosides (II).
All hydroxyalkyl ethers were obtained by unambiguous
routes from the corresponding partially protected methyl
glucosides, which have only one available OH group ready
for etherification. For methyl 2-O-(2-hydroxylalkyl)-a-d-glu-
copyranosides (I) and methyl 3-O-(2-hydroxylalkyl)-a-d-glu-
copyranosides (II), the synthesis started from monobenzylat-
ed methyl 4,6-O-benzylidene-a-d-glucopyranoside 1 and
3,[14] which can be obtained from methyl 4,6-O-benzylidene-
a-d-glucopyranoside and benzyl bromide in the presence of
tetrabutylammonium iodide. This can be achieved by two
methods, either by means of the intermediate stannylene
formed by reaction with dibutyltin oxide[15] or under hetero-
actually mixtures of two diastereoisomers that are epimers
at the CHOH group newly formed by the opening of the ep-
oxide. The 13C NMR spectroscopic analysis reveals a very
slight differentiation in chemical shifts for both isomers of
this CHOH and some of the carbon atoms of the neighbour-
ing CH2 groups. In crude mixtures, a 1:1 mixture of both iso-
mers has been observed (within the limits of 13C NMR spec-
troscopy), which means that no diastereomeric discrimina-
tion occurred at the epoxide ring-opening reaction. Both
isomers might, however, differ slightly in their behaviour
during the purification steps by silica gel chromatography,
therefore it was carefully verified at the final purification
step of the materials that all of the samples used in our stud-
ies were consistent 1:1 mixtures.
geneous conditions using aqueous NaOH in dichloro
ACHTUNGTNERmNUNG eth-
ACHTUNGTRENNUNG
the two possible monobenzylated products at O-2 or at O-3
in slightly different ratio. Reaction of 1,2-epoxyalkanes with
methyl 2- or 3-O-benzyl-4,6-O-benzylidene-a-d-glucopy
osides was performed in dimethylsulfoxide (DMSO) in the
presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) and di-
methylaminopyridine (DMAP) as basic catalysts on the
basis of our previous studies for epoxide opening by
sugars.[17–20] The reaction yielded methyl 3-O-benzyl-2-O-(2-
ran-
To obtain methyl 4-O-(2-hydroxylalkyl)-a-d-glucopyrano-
sides (III), methyl 4,6-O-benzylidene-a-d-glucopyranoside
(5) was treated with benzyl bromide in the presence of
NaH/DMF followed by selective reductive opening of the
benzylidene ring with NaBH3CN/CH3SO3H/THF to give
methyl 2,3,6-tri-O-benzyl-a-d-glucopyranoside (6).[21] Com-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
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Hydrophobic and Hydrophilic Balance
FULL PAPER
pound 6 was treated with 1,2-epoxyalkanes in DMSO in the
presence of DABCO/DMAP to yield benzylated 4-O-(2-hy-
droxyalkyl) ethers of methyl glucoside, which was deprotect-
ed by Pd-catalysed hydrogenation in MeOH/EtOAc to
afford methyl 4-O-(2-hydroxyalkyl)-a-d-glucopyranosides
III (see Scheme 2)
For the purpose of comparison, two non-branched 6-O-
alkyl-a-d-glucopyranosides (9) were prepared by the reac-
tion of methyl 2,3,4-tri-O-benzyl-a-d-glucopyranoside (8)
with 1-bromooctane or 1-bromododecane in the presence of
NaH/DMF to give methyl 2,3,4-tri-O-benzyl-6-O-alkyl-a-d-
glucopyranoside, which was debenzylated by Pd-catalysed
hydrogenation in MeOH/EtOAc (see Scheme 4).[22–24]
Scheme 4. Synthesis of 6-O-alkyl-a-d-glucopyranosides 9.
Scheme 2. Synthesis of methyl 4-O-(2-hydroxyalkyl)-a-d-glucopyrano-
sides (III).
Thermotropic behaviour: All of the compounds were exam-
ined by polarised light microscopy and differential scanning
calorimetry (DSC). The specific methods for microscopy
and differential scanning calorimetry are given in the Sup-
porting Information. The results are given in Tables 1–5 in
which the values given represent those observed upon heat-
ing the sample except for glass transitions, which are ob-
served on cooling.
For the 6-substituted hydroxylalkyl ethers (IV), the se-
quence started with the tritylation and subsequent benzyla-
tion of methyl a-d-glucopyranoside, which afforded methyl
2,3,4-tri-O-benzyl-6-O-trityl-a-d-glucopyranoside. This was
deprotected under acidic conditions to give compound 8, in
which only OH-6 was available. The structure of this com-
pound was confirmed by comparison with an identical com-
pound obtained from an alternative reductive opening of
the benzylidene.[21] Compound 8 was reacted with 1,2-epoxy-
Table 1. Transition temperatures [8C] and enthalpy of transition (in
square brackets [kJmolÀ1]) for compounds Ia–e.[a]
ACHTUNGTRENNUNGalkanes in DMSO in the presence of DABCO and DMAP
at 1108C for 16 h, followed by catalytic hydrogenation to
give the desired methyl 6-O-(2-hydroxyalkyl)-a-d-glucopy-
ACHTUNGTRENNUNGranosides (IV; see Scheme 3).
Compound
n
K
SmA
Iso Tg
Ia
Ib
Ic
Id
Ie
6
·
·
·
·
·
49.4 [41.08]
33.0 [7.67]
59.7 [33.03]
62.8 [29.11]
–
–
–
–
·
·
·
·
·
À11.5
8
10
12
14
À11.5
(· 39.8) [0.58]
·
·
8.2
–
–
73.7 [0.72]
94.8 [0.96]
69.2/78.2 [23.76/13.53]
[a] See Figure 2 for definition of n; K=crystal; SmA=smectic A; Iso=
isotropic liquid; Tg =glass-transition temperature. A · identifies that the
phase is observed for the compound. Parentheses indicate that the phase
is monotropic (i.e., occurring only on cooling below the melting point).
For the homologous series of compounds examined, the
longer-chain homologues were found to exhibit thermotrop-
ic, lamellar (smectic A) phases, whereas the short-chain-
length members did not possess mesomorphic properties.
Those compounds, which did exhibit mesomorphism, be-
haved in a similar way; for the lower homologues, when the
Scheme 3. Synthesis of methyl 6-O-(2-hydroxyalkyl)-a-d-glucopyrano-
sides (IV).
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5043

Y. Queneau, S. J. Cowling et al.
Table 2. Transition temperatures [8C] and enthalpy of transition (in
square brackets [kJmolÀ1]) for compounds IIa–e.
contributions of the aliphatic chains to the alignment. For
the higher homologues (n=12 and 14), the defect textures,
seen through the use of transmission polarised light micro-
scopy, exhibited focal-conic defects characterised by ellipti-
cal and hyperbolic lines of optical discontinuity, accompa-
nied by regions of homeotropic alignment; see, for example,
Figure 3 for compound Ie. This combination of defect tex-
tures is diagnostic for the smectic A phase.
Compound
n
K
SmA
Iso
Tg
IIa
IIb
IIc
IId
IIe
6
–
·
·
·
·
–
–
–
·
·
·
–
–
·
·
·
·
·
À5.4
À9.8
À6.6
–
8
10
12
14
8.1 [1.22]
–
32.7 [13.95]
43.9 [31.29]
48.7[a] [1.27]
66.2 [2.17]
85.0 [1.02]
–
[a] There is a second peak at 42.08C.
Table 3. Transition temperatures [8C] and enthalpy of transition (in
square brackets [kJmolÀ1]) for compounds IIIa–e.
Figure 3. Photomicrographs (100ꢃmagnification) of the lamellar phase of
compound Ie at 908C showing focal-conic and homeotropic domains.
Compound
n
K
SmA
Iso Tg
IIIa
IIIb
IIIc
IIId
IIIe
6
8
10
12
14
·
·
·
·
·
25.2/31.3 [0.79/2.17]
64.2 [9.17]
33.7 [21.08]
34.5 [21.56]
39.7 [25.09]
–
–
–
·
–
–
–
·
·
·
·
·
À14.7
À1.3
À4.2
–
Interestingly, the homologues of all four series with rela-
tively short aliphatic chain lengths exhibited glass transitions
on cooling, but as the relative chain lengths were increased,
the glass transition temperature rose, but was then replaced
by a crystalline state. This behaviour can be rationalised by
examining the balance of the number of aliphatic methylene
groups relative to the number of hydroxyl groups free to in-
termolecular hydrogen bond. When the methylene chain is
short, the materials behave as classical sugars (i.e., they melt
from the solid and then form glassy states upon cooling).
With the increase in the aliphatic chain length, the hydrocar-
bon chain begins to dominate the melting and re-crystallisa-
tion processes. In addition, for the materials that have very
short alkyl chains (I–IVa) and are not liquid-crystalline, as
the alkyl chain is increased in length there becomes a bal-
ance in the hydrophobic and hydrophilic parts; further in-
creases in the alkyl chain length lead to domination of the
hydrophobic parts accompanied by the formation of liquid
crystallinity. The melting points were recorded by DSC and
represent the melting behaviour of the materials from their
crystalline states formed by solution crystallisation. The
DSC traces are included in the Supporting Information.
Once the crystal lattice has collapsed at the melting point,
only glassification occurs on subsequent cooling for the
short-chain homologues, whereas the long-chain homologues
re-crystallise. For the materials in which the smectic phases
are injected into the homologous series and the melting
points are close to room temperature, it should be noted
that the sample might be in a state in which there is a mix-
ture of crystal forms and glassy states due to difficulties in
crystallisation of the materials from solution; hence the en-
thalpy values can appear unusually low.
62.6 [0.11]
81.3 [0.73]
·
–
Table 4. Transition temperatures [8C] and enthalpy of transition (in
square brackets [kJmolÀ1]) for compounds IVa–IV.
Compound
n
K
SmA
Iso
Tg
IVa
IVb
IVc
IVd
IVe
6
–
·
·
·
·
–
–
–
–
–
·
·
·
·
·
–
8
10
12
14
47.9 [19.43]
64.8 [30.65]
71.3 [33.96]
72.8 [32.57]
À2.1
0.3
–
N
37.9) [0.74]
58.5) [0.89]
79.0 [0.69]
ACHTUNGTRENNUNG
·
–
Table 5. Transition temperatures [8C] and enthalpy of transition (in
square brackets [kJmolÀ1]) for compounds 9a,b.
Compound
n
K
SmA
Iso
Tg
9a
9b
8
–
·
–
·
20.1 [0.77]
33.3) [0.90]
·
·
À22.6
12
56.5 [35.83]
N
–
lamellar phase was observed, the materials tended to favour
homeotropic orientation (i.e., in which the long axes of the
molecules are oriented perpendicular to the plane of the mi-
croscope slide). This is probably due to the dominant inter-
action between the glass surface and the hydroxyl groups of
the glucoside head group. These interactions dominate the
The increase in the clearing point across each series of
compounds can be directly related to the hydrophobic–hy-
drophilic balance, which has previously been demonstrated
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Hydrophobic and Hydrophilic Balance
FULL PAPER
Figure 4. Transition temperature [8C] as a function of chain length (n) for Ia–e, IIa–e, IIIa–e and IVa–e.
in alkyl b-d-glucosides.[25–27] Figure 4 shows the transition
temperatures for the homologous series I–IV as a function
of the aliphatic chain length. In each case the clearing point
is shown to increase linearly with respect to the increase in
chain length. This behaviour indicates that the different
transition temperatures between the series of compounds
must either be related to the position of substitution of the
aliphatic chain on the sugar unit or to the extent of the in-
tramolecular hydrogen bonding that is possible between the
hydroxyl group associated with the alkyl chain and the hy-
droxyl groups in the sugar unit. In this series of compounds,
varying the substitution position of the alkyl chain around
the glucoside has little effect on the clearing point (79–
948C), relative to the melting points of the compounds.
Lower melting points are observed for the compounds sub-
stituted at O3 and O4 (II and III) and higher melting points
for the compounds substituted at O2 and O6 (I and IV).
This behaviour is similar to that observed for a series of O-
dodecyl pyranoses, whereby a change in the substitution po-
sition of the dodecyl chain has little effect on the clearing
point, but conversely the substitution at O2 and O6 results
in much lower melting points than for the O3 and O4 substi-
tution.[22]
It has been clearly demonstrated that the increase in the
mesomorphic behaviour of this series of compounds is relat-
ed to the length of the aliphatic chain attached to the gluco-
side unit, but the position of attachment also affects the sta-
bility of the mesophase formation. Figure 5 shows the iso-
tropisation temperature for the C10–14 homologues (I–IVc–
e) as a function of substitution position on the sugar unit.
The longer chain lengths (C12 and C14) exhibit consistent
behaviour whereby the isotropisation temperature decrease
O2>O3>O4>O6 and whereby the number of methylene
units in the chain is high enough to dilute the effects of the
inter- and intramolecular hydrogen bonding of the hydroxyl
groups. However, this behaviour is not observed for the C10
series. This series is on the limit at which there is a strong
dependence on the intramolecular and intermolecular hy-
drogen bonding, which is critically affected by the position
of attachment of the chain to the sugar. In this series, the
O2 (Ic) substitution has a lower clearing point than the O3
(IIc), whereas the O4 (IIIc) is no longer liquid-crystalline,
and the O6 (IVc) is similar to O2. This observation indi-
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5045

Y. Queneau, S. J. Cowling et al.
Figure 5. Smectic A to isotropic liquid transition temperature [8C] as a
function of substitution position O2 (Ic–e), O3 (IIc–e), O4 (IIIc–e) and
~
&
*
O6 (IVc–e). =c; =d; =e.
cates that there are probably some intramolecular species
that are present in the O3 or O4 materials that could either
enhance the liquid-crystalline behaviour, as in the case of
O3 (IIc), or suppress it, as in the case of O4 (IVc).
Figure 6. Energy-minimised models of Ia, IIa, IIIa and IVa.
in which the alkyl chain and glucoside unit are fixed in posi-
tion with respect to each other. In order to rationalise
whether there is intramolecular or intermolecular hydrogen
bonding, it is important to examine the enthalpies of the
smectic A to isotropic liquid transition. Table 6 shows the
In order to comprehend the effects of introducing an ad-
ditional hydroxyl group into the alkyl chains of the substi-
tuted glucosides, a comparison between the IV series and
the previously reported compound 9a was drawn. Com-
pound 9a exhibits a smectic A phase, whereas the analogue
IVa does not exhibit mesomorphism. This comparison
shows that at short alkyl chain length the hydrophobic–hy-
drophilic balance is critical to mesophase formation (i.e.,
the ratio of the number of OH groups relative to a constant
aliphatic chain length dominates). However, for longer ali-
phatic chain lengths, the relative proportion of the OH con-
tent is less, and so the comparative materials have similar
clearing points.
In order to investigate the possible intramolecular hydro-
gen-bonding interactions in the homologous series, energy-
minimised models of both enantiomers of compounds Ia,
IIa, IIIa and IVa were examined in the gas phase at abso-
lute zero (on the basis of energy minimisations in Chem-
Draw 3D using MM2 and MMFF94 force fields), as shown
in Figure 6. There was not a significant difference in the
structure or the distance of the hydrogen bonding for each
of the enantiomers and therefore the discussion can be ap-
plied to either stereoisomer. The distance between each of
the neighbouring hydroxyl groups of the glucoside to the hy-
droxyl group located in the alkyl chain was measured; the
closest interaction distances are shown in the models. Com-
pounds Ia and IVa only have the possibility of hydrogen
bonding to one neighbour, whereas compounds IIa and IIIa
have the possibility to hydrogen bond to one of two neigh-
bours (only one of the two orientations for IIa and IIIa is
shown in Figure 6, for which the effective hydrogen-bonding
distance is 3.9–4.0 ꢄ). In these configurations the structure
is more rigid through the intramolecular hydrogen bonding
Table 6. Enthalpies (DH) and entropies (DS) for smectic A to isotropic
liquid transitions for compounds showing liquid-crystalline mesophases.
Compound
DH [JmolÀ1
]
T [K]
DS [JmolÀ1 KÀ1
]
DS/R[a]
Ic
Id
Ie
618
764
312.8
346.7
367.8
321.7
339.2
358
335.6
354.3
310.9
331.5
352.0
1.98
2.20
2.75
4.18
6.77
3.00
0.35
2.17
2.54
2.84
2.08
0.24
0.27
0.33
0.50
0.81
0.36
0.04
0.26
0.31
0.34
0.25
1011
1344
2297
1075
116
768
790
940
732
IIc
IId
IIe
IIId
IIIe
IVc
IVd
IVe
[a] R is the universal gas constant (8.314472 JKÀ1 molÀ1).
relative enthalpies for all the homologues and their respec-
tive normalised entropies. In general the enthalpy of the
transition increases as the chain length increases, which indi-
cates that the mesophase is becoming more organised and
less like the liquid as the chain length is increased. Typical
values of 0.7–0.9 kJmolÀ1 are observed. Interestingly, com-
pounds in series III have lower enthalpies of transition and
very low S/R values, which means that these molecules are
more disorganised, and explains why the smectic A phase is
not observed for the C10 homologue. This result also indi-
cates that it is probable that the hydroxyl groups around the
sugar head group are intramolecularly hydrogen bonding,
which reduces the propensity of the material to organise
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Hydrophobic and Hydrophilic Balance
FULL PAPER
into a lamellar structure that is stabilised by intermolecular
hydrogen bonding. Conversely, compounds substituted in
the O3 position, series II, all exhibit large enthalpies for the
clearing-point transition, and S/R values are higher than any
of the other homologues, which suggests that the materials
self-organise more easily into lamellar structures, and this
indicates enhanced intermolecular hydrogen bonding. The
enthalpies and entropies of the clearing transitions show
that the series with O4 substitution must have a relatively
reduced hydrophobic–hydrophilic balance, which leads to a
reduction in the mesophase stability. The modelling indi-
cates that it is possible for intramolecular hydrogen bonding
to occur between the hydroxyl group of the aliphatic chain
and the O4 hydroxyl unit of the sugar head group. Such in-
teractions lead to the formation of a pseudo-six-membered
ring, thereby increasing the size of the head group relative
to the tail. This shift in the balance of the head/tail ratio
leads to a reduction in the observed mesomorphic stability.
However, as the alkyl chain is extended, its flexibility is ex-
pected to interfere in this process.
coside forms a gradient of concentration with water. The re-
sults are summarised in Table 7 and are similar to those pre-
viously reported for the alkyl b-d-glucopyranosides.[28–30]
The lyotropic behaviour clearly demonstrates that the cur-
vature in the system, due to increasing interactions between
the water and the sugar head groups, increases with increas-
ing water content, thus leading to lamellar, cubic and hexag-
onal phases being formed. At short alkyl chain length (C8–
C10) the relative cross-sectional area of the sugar head
group compared to the alkyl chain is large and this allows
the curvature of the system to be sufficient for cubic and
hexagonal phases to be formed as the sugar head group
swells. Figure 7 shows the lyotropic lamellar, cubic and hex-
The melting behaviour can also be considered as a func-
tion of intermolecular hydrogen bonding. Compounds of
series I and IV have all the hydroxyl groups on one side of
the head group plus chain, whereby the alkyl chain can be
oriented so as not to interfere with the head-group interac-
tions, and the effective number of hydroxyl groups available
for intermolecular hydrogen bonding is not significantly dif-
ferent to the previously reported alkylglucosides. However,
compounds of series II and III have the alkyl chain splitting
the hydroxyl environment whereby the chain can sterically
interfere with the head-group interactions. Additionally, one
could argue that the extent of the intermolecular hydrogen
bonding is partially decreased due to the number of free hy-
droxyl groups being reduced through two of these groups
dynamically interacting with the hydroxyl unit of the alkyl
chain. Hence the melting points for these series of com-
pounds are much lower than for compounds of series I and
IV. Compounds of series II would give a mixture of primary
and secondary alcohols either side of the molecule, whereas
compounds of series III would only leave one side with two
secondary alcohols and one side with a single primary alco-
hol.
Figure 7. The lyotropic behaviour of compound IIIc; left image is be-
tween cross polars and right image is viewed with a l waveplate (100ꢃ
magnification).
agonal phases for compound IIIc. At longer chain length
(C12), the extra number of methylene units affects the rela-
tive cross-sectional area of the sugar group with respect to
the chain, and subsequently the curvature of the system is
reduced, thus leading to the absence of the cubic phase.
Figure 8 shows the lamellar and cubic phase of compound
IIId in which the Becke line between the cubic phase and
the isotropic liquid is clearly visible. The increasing aliphatic
Lyotropic behaviour: The concentration-dependent lyotrop-
ic behaviour of the materials (Ib–e to IVb–e) was investi-
gated by examining contact preparations, whereby the glu-
Table 7. Lyotropic behaviour of compounds Ib–e to IVb–e.
I
II
III
IV
lamellar
cubic
hexagonal
lamellar
cubic
b
c
cubic
lamellar
cubic
cubic
hexagonal
hexagonal
hexagonal
lamellar
cubic
cubic
lamellar
cubic
hexagonal
hexagonal
lamellar
cubic
hexagonal
lamellar
cubic
d
e
cubic
lamellar
cubic
insoluble
Figure 8. Lamellar and cubic phase of compound IIId (100ꢃmagnifica-
tion).
insoluble
insoluble
insoluble
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ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5047

Y. Queneau, S. J. Cowling et al.
chain content leads to a reduction in solubility and this is
clearly evident in the C14 chain-length homologues, in
which the compounds are insoluble in water at room tem-
perature, and still only sparingly soluble at 708C. In this
case, the material crystallised before lyotropic behaviour
could be observed.
Interestingly, compounds in which the alkyl chain is at-
tached in the O2 position (series I) exhibited increased cur-
vature relative to the other compounds. This indicates that
the cross-sectional area of the sugar is larger for these mate-
rials than the other homologous series. Series II showed a
tendency for lower curvature than the other analogues, in
which the hexagonal phase was only observed for the short-
est chain lengths, which was lost once the chain length
reached C10.
Thus, the hydrophobic–hydrophillic balance and the “hydro-
phobic effect” are special manifestations of the molecular
dichotomy of the structure, whereas for conventional ther-
motropic liquid crystals the multiple balances will be associ-
ated with polychotomy in the structure.
Other descriptors for the formation of self-organised sys-
tems have been introduced to the field over the last ten
years. These included microphase segregation, nanosegrega-
tion, self-sorting and so on; however, these too are manifes-
tations of molecular polychotomy, which inevitably involves
complexity of structure. However, increasing complexity
does not necessarily mean complexity in topology or inter-
actions; for example, globular supermolecular systems have
lower complexities than their linear analogues. In terms of
biological systems, primary structures are more complex
than quaternary structures.[31]
Conclusion
Acknowledgements
For the four series of glucopyranosides, the clearing points
increase linearly with the number of methylene units in the
alkyl chain length. If we assume that materials have dichoto-
mous molecular structures composed of polar and non-polar
segments (hydrogen bonding to non-hydrogen-bonding),
then in comparison with the dodecyl-substituted acyclic
This work has been accomplished under IFCPAR-CEFIPRA (project no.
3805-1) with a post-doctoral grant to M.K.S and research grants and
travel grants to A.K. and Y.Q., which are gratefully acknowledged. The
authors also thank MENRES and CNRS for financial support and the
Chinese Scholarship Council for a fellowship to R.X. Dr M. K. Singhꢅs
current address is Aditya Birla Science and Technology Company Ltd,
Plot No. 1 & 1-A/1, MIDC Taloja, Tal. Panvel, Dist. Raigad 410208
(India).
polyACHTUNGTRENNUNG
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Received: August 16, 2012
Revised: January 9, 2013
Published online: February 20, 2013
Chem. Eur. J. 2013, 19, 5041 – 5049
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5049