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 310058, 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.
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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 are linked together (Figure 1).12 Because selective manipulation
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, material manufacture, and membrane protein isolation.1,2 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 monomeric ones.3 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 been designed.4−10 However, most of them are not the traditional O-glycosides but N-glycosides which lose the benefit from the richful alkyl alcohol resources. Only one type of Oglycoside gemini surfactant has been developed thus far.11 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. © XXXX American Chemical Society
Figure 1. Strategies for linkage position. (a) Known strategy, (b) new strategy.
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 Received: April 25, 2013 Revised: May 31, 2013
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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 nalkyl (C10, C12, C14, C16, C18) alcohol were employed to build the gemini surfactants (Figure 3). Fortunately, synthesis
Figure 4. γ-C curves of the mono and gemini alkyl glucosides at 293.15 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.
Figure 3. Retrosynthetic analysis of the gemini alkyl glucosides in this study.
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 (C20) (Table 1). Analysis of interfacial properties has
Scheme 1. Synthesis of the Nove Gemini Alkyl Glucosides
Table 1. Surface Activities of Mono and Gemini Alkyl Glucosides
alkyl glucosides were also prepared for systematic comparisons (Scheme 2). The stereochemical configuration of the anomeric centers of the gemini alkyl glucosides is determined as β by the 1 H NMR chemical shift of the anomeric protons, which is consistent with participation of neighboring acetyl protecting groups during glycosylation.12
surfactant
cmc (mM)
γ (mN/m)
Γ × 106 (mol/m2)
A (nm2)
ΔG (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 0.58 5.32 20.62 0.11 0.029 0.089 0.22 0.67
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 15.13 16.98 10.36 68.08 8.69 21.13 17.10 12.25
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 (Table 2).11 This observation suggests that the strategy of shifting the linkage position from sugar moieties to alkyl chains
Scheme 2. Synthesis of the Mono Alkyl Glucosides
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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 γm/γg (0.8−1.1). The Γ of the 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 issue of Gibbs analysis should be considered.14,15 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 were investigated by rheology measurements.16 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.
Table 2. Surface Activity Comparison of Mono and Gemini Alkyl Glucosides surfactant
cmcm/ cmcg
γm/γg
C-10 C-12 C-14 C-16 C-18
18.8 7.4 6.5 24.5 30.6
0.94 1.07 0.95 0.85 1.00
Γm/Γg Ag/Am 2.03 1.16 0.52 1.14 1.23
2.03 1.16 0.52 1.14 1.23
ΔGg/ ΔGm
(cmc/C20)g/ (cmc/C20)m
1.29 1.16 1.16 1.34 1.43
4.78 2.17 1.40 1.01 1.18
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.12 The relationship between log of cmc and the number of carbons in the alkyl chain is represented in Figure 5. For a given
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 in water results in this phenomenon.11,13 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 (cmcm/cmcg) with the number of carbon atoms in the alkyl chain (Table 2). Although the value of cmcm/cmcg varies with the length of the alkyl chain, they are generally significant higher than 1 (6−31). Therefore the performance of the new gemini compounds is much better than the known gemini alkyl glucosides (0.31 for C14).11 However, the same trend that the value of cmcm/cmcg 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 (self-coiling) over certain chain lengths.3,11 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 cmcm/cmcg increases. Presumably, as the number of carbon atoms increases further,
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.
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. 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 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.
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 longrange 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 aggregates.18,19 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.
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 ellipsoidal.17 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 average apparent hydrodynamic radius (Rh) of about 25−400 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 (Rh) from about 100−1000 nm are observed. Generally, 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 concentration 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.
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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 (Rh) distributions of the aggregates 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.
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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.20 The outstanding self-assembly ability of
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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(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 Reduction of 4-Nitrophenol. Langmuir 2003, 19, 5517−5521.
AUTHOR INFORMATION
Corresponding Author
*Phone: 86-571-88982186. E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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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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REFERENCES
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