A novel type of highly effective nonionic gemini Alkyl O-glucoside surfactants: A nersatile strategy of design

Article abstract of DOI:10.1021/la401569n

A novel type of highly effective gemini alkyl glucosides has been rationally designed and synthesized. The gemini surfactants have been readily prepared by glycosylation of the gemini alkyl chains that are synthesized with regioselective ring-opening of ethylene glycol epoxides by the alkyl alcohols. The new gemini alkyl glucosides exhibit significantly better surface activity than the known results. Then rheological, DLS, and TEM studies have revealed the intriguing self-assembly behavior of the novel gemini surfactants. This study has proved the effectiveness of the design of gemini alkyl glucosides which is modular, extendable, and synthetically simple. The new gemini surfactants have great potential as nano carriers in drug and gene delivery.

Full text of DOI:10.1021/la401569n

Article
pubs.acs.org/Langmuir
A Novel Type of Highly Effective Nonionic Gemini Alkyl O‑Glucoside
Surfactants: A Versatile Strategy of Design
Songbai Liu,* Ruocheng Sang, Shan Hong, Yujing Cai, and Hua Wang
,†
†
†
†
‡
†Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou
3
10058, China
‡
Center of Analysis and Measurement, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China
S Supporting Information
*
ABSTRACT: A novel type of highly effective gemini alkyl glucosides has been rationally
designed and synthesized. The gemini surfactants have been readily prepared by glycosylation
of the gemini alkyl chains that are synthesized with regioselective ring-opening of ethylene
glycol epoxides by the alkyl alcohols. The new gemini alkyl glucosides exhibit significantly
better surface activity than the known results. Then rheological, DLS, and TEM studies have
revealed the intriguing self-assembly behavior of the novel gemini surfactants. This study has
proved the effectiveness of the design of gemini alkyl glucosides which is modular,
extendable, and synthetically simple. The new gemini surfactants have great potential as nano
carriers in drug and gene delivery.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
To realize a class of highly effective gemini alkyl glycosides,
several requirements should be satisfied. First, the linkage
position of the gemini molecules is optimized to produce
greatest organizing effect. Second, the gemini molecules are
synthetically accessible. Third, the gemini molecules are
extendable and of modular architecture. We think placement
of the linkage position at the alkyl chain instead of the sugar
group will be a good choice because a tighter connection can be
easily achieved owing to elimination of the steric interaction
between bulky sugar moieties which exists if two sugar moieties
Alkyl O-glycosides (AGs) are nonionic surfactants prepared
from long-chain alcohols and carbohydrates. Their excellent
biodegradability, nontoxicity, and availability from renewable
resources render them more attractive than other nonionic
surfactants for industrial applications including pharmaceuticals,
1
,2
material manufacture, and membrane protein isolation.
Gemini surfactants containing two surfactant chains connected
by a spacer adjacent to the hydrophilic groups are known to be
orders of magnitude more surface active than conventional
12
3
are linked together (Figure 1). Because selective manipulation
monomeric ones. Although a great number of anionic and
cationic gemini surfactants have been developed, the studies on
nonionic gemini surfactants are relatively scarce. However,
development of sugar-based nonionic gemini alkyl glycoside
surfactants is more fascinating in terms of sustainability and
environmental safety.
Recently, a few sugar-based nonionic gemini surfactants have
4
−10
been designed.
However, most of them are not the
Figure 1. Strategies for linkage position. (a) Known strategy, (b) new
traditional O-glycosides but N-glycosides which lose the benefit
from the richful alkyl alcohol resources. Only one type of O-
glycoside gemini surfactant has been developed thus far.
strategy.
11
of sugars is always challenging, it would be beneficial to
construct the gemini alkyl chain first followed by introduction
of sugar moieties at the final stage. Ethylene glycol is chosen as
the spacer because it is hydrophilic, nontoxic, and has readily
available polymeric forms of variable length. The gemini alkyl
chain can be readily prepared from regioselective ring-opening
of an ethylene glycol epoxide by the alkyl alcohols. Eventually, a
double glycosylation of the gemini alkyl chain will finalize
Unfortunately, the surface activity of that type of gemini
surfactant is not generally good and sometimes even lower than
that of the monomeric counterparts. Therefore, a highly
effective gemini mimic of alkyl O-glycosides is still unavailable.
In this work, a highly efficient gemini alkyl O-glucoside has
been developed based on a novel linkage strategy, modular
molecular construction, and concise synthesis. Surface activity
studies have revealed that this novel nonionic gemini alkyl
glucosides are generally significantly more surface active than
the monomeric counterparts.
Received: April 25, 2013
Revised: May 31, 2013
©
XXXX American Chemical Society
A
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synthesis of the gemini alkyl glycoside. Hence the gemini alkyl
glycoside of this design is modular, extendable, synthetically
simple, and expected to be highly surface active (Figure 2).
To evaluate the performance and structural implication of
this new gemini surfactants, several interfacial properties have
been analyzed via the surface tension curves (Figure 4), which
Figure 2. Modular design of the novel gemini alkyl glycosides.
In this study, glucose, ethylene glycol diglycidyl ether, and n-
alkyl (C10, C12, C14, C16, C18) alcohol were employed to
build the gemini surfactants (Figure 3). Fortunately, synthesis
Figure 3. Retrosynthetic analysis of the gemini alkyl glucosides in this
study.
Figure 4. γ-C curves of the mono and gemini alkyl glucosides at
2
93.15 K. (a) The mono alkyl glucosides M-10, M-12, M-14, M-16,
and M-18 and (b) the gemini alkyl glucosides G-10, G-12, G-14, G-16,
and G-18 corresponding to C10, C12, C14, C16, and C18 alkyl chains,
respectively.
of the designed gemini alkyl glucosides proceeded smoothly as
the shown route (Scheme 1). The corresponding monomeric
include critical micellar concentration (cmc), surface excess
concentration (Γ), area per molecule (A), Gibbs free energy of
adsorption (ΔG), and the concentration of surfactant to
produce a 20 mN/m reduction in the surface tension of the
solvent (C ) (Table 1). Analysis of interfacial properties has
Scheme 1. Synthesis of the Nove Gemini Alkyl Glucosides
20
Table 1. Surface Activities of Mono and Gemini Alkyl
Glucosides
6
cmc
(mM)
γ
Γ × 102
A
ΔG
2
surfactant
(mN/m) (mol/m ) (nm ) (kJ/mol) cmc/C20
M-10
M-12
M-14
M-16
M-18
G-10
G-12
G-14
G-16
G-18
2.04
0.21
28.74
38.62
28.82
29.94
31.88
30.45
36.09
30.31
35.24
31.85
0.74
0.76
0.36
0.86
0.94
0.36
0.65
0.69
0.75
0.76
2.24
2.20
4.57
1.94
1.77
4.55
2.56
2.40
2.22
2.18
−24.88
−30.39
−27.95
−22.54
−19.24
−32.03
−35.26
−32.50
−30.34
−27.57
14.24
4.01
0.58
15.13
16.98
10.36
68.08
8.69
5.32
20.62
0.11
alkyl glucosides were also prepared for systematic comparisons
0.029
0.089
0.22
(
Scheme 2). The stereochemical configuration of the anomeric
21.13
17.10
12.25
centers of the gemini alkyl glucosides is determined as β by the
1
H NMR chemical shift of the anomeric protons, which is
0.67
consistent with participation of neighboring acetyl protecting
12
groups during glycosylation.
revealed that cmc values of the gemini surfactants are roughly 1
order of magnitude (6−31 times) smaller than those of the
monomeric counterparts and 2 orders of magnitude (118 times
for C12) lower than those of the reported gemini alkyl
glucosides in which the linkage was placed at the sugar moieties
Scheme 2. Synthesis of the Mono Alkyl Glucosides
11
(
Table 2). This observation suggests that the strategy of
shifting the linkage position from sugar moieties to alkyl chains
B
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Table 2. Surface Activity Comparison of Mono and Gemini
Alkyl Glucosides
the greater hydrophobic packing effect forces the gemini
molecules to take a more organized alignment.
The great capacity to reduce surface tension has been
maintained after dimerization as indicated by the surface
tension at cmc (γ, 29−32 mN/m for monomers, 30−36 mN/m
for dimers) and the ratio of γ /γ (0.8−1.1). The Γ of the
cmcm/
cmcg
ΔG /
(cmc/C ) /
20 g
g
surfactant
γ /γ Γm/Γg Ag/Am
ΔG
(cmc/C20)m
m
g
m
C-10
C-12
C-14
C-16
C-18
18.8
7.4
0.94
1.07
0.95
0.85
1.00
2.03
1.16
0.52
1.14
1.23
2.03
1.16
0.52
1.14
1.23
1.29
1.16
1.16
1.34
1.43
4.78
2.17
1.40
1.01
1.18
m
g
gemini compounds except for C14 decreases slightly (1.1−2.0
times smaller) compared with the monomers (Table 2). The A
of the gemini molecules is 1.1−2.0 times larger than that of the
monomeric surfactants except for C14. The unusual properties
of C14 surfactants presumably result from the notable
aggregation effect of the C14 chain. The large interfacial area
difference between C10 and C12 reflects complicated
molecular behavior of this gemini surfactants, and the recent
6.5
24.5
30.6
has taken effect and a tighter connection between the
monomers has been realized. The downward slope of the
post-CMC plots presumably results from incomplete saturation
of Gibbs monolayer at CMC.
The relationship between log of cmc and the number of
carbons in the alkyl chain is represented in Figure 5. For a given
12
1
4,15
issue of Gibbs analysis should be considered.
The data of γ
and A suggests highly organized orientation of the gemini
molecules at the air/water interface (Table 2). The cmc/C20
ratio of the gemini surfactants is 1.0−4.8 times larger than that
of the corresponding monomers, which reveals that adsorption
at the interface is promoted over micellization in solution for
the gemini molecules due to the large molecule size.
The self-assembly behavior of the geimini alkyl glucosides
16
were investigated by rheology measurements. The relative
viscosity of gemini alkyl glucosides in aqueous media was
measured at the shear rate of 100/s in two concentrations (5
and 25 times of cmc). The relative viscosity corresponding to
the length of the alkyl chains is represented in Figure 6.
Figure 5. Relationship between log of cmc and the length of the alkyl
chain in the mono and gemini alkyl glucosides.
alkyl chain, the cmc values of gemini alkyl glucosides are
generally significantly lower than those of the mono alkyl
glucosides. Mono and gemini alkyl glucosides have the similar
trend for the relationship to the length of the alkyl chain, both
with the lowest cmc at the dodecyl alkyl chain. It is interesting
that for mono and geimini alkyl glucosides with longer alkyl
chains (14−18), the cmc increases almost linearly. A possible
explanation is that increased self-coiling of these longer chains
Figure 6. Relative viscosity versus number of carbons in the alkyl
chains of gemini alkyl glucosides at two concentrations (5 cmc and 25
cmc) with the shear rate (100/s) at 298.15 K.
1
1,13
in water results in this phenomenon.
The general superiority of this new gemini alkyl glucosides
has further been demonstrated by examining the relationship of
the ratio of cmc value of monomeric alkyl glucoside to that of
the corresponding gemini form (cmc /cmc ) with the number
Although the value of viscosity varies with the length of the
alkyl chains, it is interesting to observe a similar trend for these
two concentrations in this study. With the length of the alkyl
chain increasing, the value of relative viscosity increases and
reaches the peak at C14, and then the value decreases. This
phenomenon exhibits greatest self-assembly ability of the C14
gemini glucoside, which is consistent with the interfacial results.
The relative viscosities of these gemini surfactant solutions at
25 times of cmc are higher than those at 5 times of cmc,
especially for C14, suggesting formation of much more
organized self-assembly structures.
m
g
of carbon atoms in the alkyl chain (Table 2). Although the
value of cmc /cmc varies with the length of the alkyl chain,
m
g
they are generally significant higher than 1 (6−31). Therefore
the performance of the new gemini compounds is much better
11
than the known gemini alkyl glucosides (0.31 for C14).
However, the same trend that the value of cmc /cmcg
m
decreases (19−6) as the length of the gemini alkyl chain
increases (C10−C14) has been observed in this study. This
phenomenon can be rationalized by transition to a coiled state
3
,11
(
self-coiling) over certain chain lengths.
Our results exhibit
that the new linkage strategy has greatly neutralized the adverse
effect of self-coiling. Interestingly, a new trend has been
observed in this study. As the length of the alkyl chain grows
beyond C14, the value of the ratio of cmc /cmc increases.
We also investigated the viscosity of these gemini surfactant
solutions and obtained the results of the relationships between
the shearing rate versus shearing stress for gemini alkyl
glucosides at two concentrations (5 and 25 times of cmc)
(Figure 7). It is revealed that the viscosities of these gemini
m
g
Presumably, as the number of carbon atoms increases further,
C
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Figure 7. Shearing rate versus shearing stress for gemini alkyl glucoside surfactants at two concentrations (5 cmc and 25 cmc) at 298.15 K: (A) G-10,
B) G-12, (C) G-14, (D) G-16, (E) G-18.
(
surfactant solutions basically remain unchanged at high
shearing rate and the shearing stress versus the shearing rate
curve is linear. The shearing rate dependence of shearing stress
is similar to that of water. This suggests the aggregation does
not affect solution viscosity greatly at high shearing rate.
Therefore, these results demonstrate the gemini alkyl glucoside
surfactant solutions have the rheological properties of the
Newtonian fluid. According to the previous publications, the
shape of the aggregates is mostly likely to be spherical or
much arger than other surfactants at 25 cmc, whereas the
viscosity of G-14 was much higher than other surfactants at the
same concentration. The reason for the differences between
DLS and viscosity data are that the viscosity from rheological
measurement is a macroscopic property which reflects a long-
range of molecular organization behavior and is influenced by
many factors such as interactions between aggregates and shape
of aggregates except for the size of aggregates, whereas the size
of aggregates from DLS measurement is a microscopic property
which only reflects the apparent hydrodynamic radius of
1
7
ellipsoidal.
18,19
The size distributions of the organized assemblies of the
geimini alkyl glucosides were investigated by dynamic light
scattering (DLS) as shown in Figure 8. The peaks with an
aggregates.
Hence these data further demonstrate the
extraordinary aggregation behavior of G-14.
Then transmission electron microscopy (TEM) was applied
to directly observe the self-assembly aggregates of the new
gemini surfactants. As shown in Figure 9, vesicles are observed
in aqueous solutions of these novel gemini surfactants
corresponding to the large aggregates in the DLS measurement.
Spherical and ellipsoidal vesicles are generally formed, which is
consistent with the rheological investigation. It is well-known
that the TEM measurement is sensitive to the electron dense
portion of the aggregates, whereas the DLS measurement is
sensitive to the whole aggregates including the hydrated layers.
average apparent hydrodynamic radius (R ) of about 25−400
h
nm at 5 times of the cmc reflect the typical size of a large
aggregate. Upon increasing the concentrations of the geimini
alkyl glucoside surfactant to 25 times the cmc, new size
distributions with a wide range of the apparent hydrodynamic
radius (R ) from about 100−1000 nm are observed. Generally,
h
the size of aggregates increases with the concentration and the
length of the alkyl chains of gemini alkyl glucosides. According
to the DLS data, the size of formed aggregates of G-18 was
D
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C14 gemini glucoside suggested in the interfacial and
rheological studies is further confirmed by its pretty spherical
to ellipsoidal vesicles. More interestingly, when the concen-
tration of C14 gemini glucoside is increased to 25 times of cmc,
wormlike aggregates with large size are clearly observed,
demonstrating its intriguing self-assembly behavior with great
potential as a nano carrier in drug and gene delivery.
CONCLUSIONS
■
A novel type of gemini alkyl glucosides has been developed.
The gemini glucosides have been readily prepared by
glycosylation of the gemini alkyl chains that are synthesized
from regioselective ring-opening of ethylene glycol epoxides by
the alkyl alcohols. The new gemini alkyl glucosides exhibit
significantly better surface activity than the known class of alkyl
glucosides and intriguing self-assembly behavior. This study has
proved the effectiveness of the design of gemini alkyl
glucosides, particularly the linkage strategy of shifting the
linkage position from sugar moieties to alkyl chains. The new
molecules have great potential as nano carriers in drug and gene
delivery. Extension of this novel type of gemini surfactants is
undergoing.
Figure 8. Hydrodynamic radius (R ) distributions of the aggregates
h
formed in aqueous solutions of gemini surfactants at concentrations of
5
and 25 times of the cmc at 298.15 K: (a) 5 cmc, (b) 25 cmc.
ASSOCIATED CONTENT
■
*
S
Supporting Information
Experimental details, 1H NMR, 13C NMR, IR, and mass
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
Therefore, the sizes of the formed aggregates obtained in the
TEM measurement are significantly smaller than those from
DLS measurement. The outstanding self-assembly ability of
20
Figure 9. TEM micrographs of the aqueous solutions of the gemini alkyl glucosides at concentrations of 5 and 25 times of the cmc: C10 (a1, 5 cmc;
a2, 25 cmc), C12 (b1, 5 cmc; b2, 25 cmc), C14 (c1, 5 cmc; c2, 25 cmc), C16 (d1, 5 cmc; d2, 25 cmc), and C18 (e, cmc).
E
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AUTHOR INFORMATION
Article
(
18) Larson, R. G. The Structure and Rheology of Complex Fluids;
■
Oxford University Press: New York, 1999.
19) Brown, W. Dynamic Light Scattering: The Methods and Some
Applications; Clarendon Press: Oxford, 1993.
20) Hayakawa, K.; Yoshimura, T.; Esumi, K. Preparation of Gold−
Dendrimer Nanocomposites by Laser Irradiation and Their Catalytic
Corresponding Author
Phone: 86-571-88982186. E-mail: songbailiu@zju.edu.cn.
(
*
(
Notes
The authors declare no competing financial interest.
Reduction of 4-Nitrophenol. Langmuir 2003, 19, 5517−5521.
ACKNOWLEDGMENTS
■
This work was supported by Public Welfare Technology
Research Program of Department of Scientific and Technology
of Zhejiang Province (grant no. 2011C22080), Zijin Plan of
Zhejiang University, and “The Fundamental Research Funds
for the Central Universities”.
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