Wang et al.
Article
hybridspacer, therigid aromatic rings were placedclose to both of
the hydrophilic headgroups with a flexible hydrocarbon chain
between them and the terminal groups were blocked byusing ester
derivatives. It has been found that with the introduction of the
hybrid spacer the bolaamphiphiles showed interesting self-assem-
bly properties in organic solvents.10,14,21,22
was obtained as a white solid (93% yield). HRMS (FAB): m/z
699.3134 (m/z calcd for [C36H48N2O12-H]þ, 699.3129). 1H NMR
(400 MHz, DMSO-d6): δ 1.23 (m, 12H), 1.37 (t, 4H), 1.69 (t, 4H),
1.92 (m, 2H), 2.04 (m, 2H), 2.32 (t, 4H), 3.99 (t, 4H), 4.35 (m, 2H),
6.96 (d, 4H), 7.82 (d, 4H), 8.4 (d, 2H), 12.33 (s, 4H). Elemental
analysis calcd for C36H48N2O12: C 61.70%, H 6.90%, N 4.00%.
Found: C 61.79%, H 7.08%, N 3.87%.
In this article, we changed the terminal groups of the bolaam-
phiphiles into active carboxylic acids while keeping the hybrid
spacer. The -COOH group can be either protonated or depro-
tonated at certain pH values, which will largely change the hydro-
gen bonding and ionic interactions.23 With such a simple molec-
ular design, we have easily regulated the interactions between the
bolaamphiphiles and realized diverse morphologies from vesicles
to nanofibers and nanotubes in water. Moreover, these morpho-
logical changes are controlled or modulated by the integrated
effect of several influencing factors. These influencing factors include
the length of alkyl linkers, the pH value, and the solid substrate
used for the measurements. In the case of bolaamphiphiles, man-
agement of multiple influencing factors rather than one to mod-
ulate the self-assembled nanostructures is very important but is
still rarely studied.
Compounds BECA4 and BECA12 were prepared in similar
manners.
1,4-Butyloxy-bis(4-benzoyl-L-glutamic acid) (BECA4). Yield
60%. HRMS (FAB): m/z 587.1882 (m/z calcd for [C28H32N2O12-
1
H]þ, 587.1877). H NMR (400 MHz, DMSO-d6): δ 1.88-1.96
(m, 6H), 2.05 (m, 2H), 2.32 (t, 4H), 4.09 (t, 4H), 4.36 (m, 2H), 6.98
(d, 4H), 7.83 (d, 4H), 8.41 (d, 2H), 12.34 (s, 4H). Elemental
analysis calcd for C28H32N2O12: C 57.14%, H 5.48%, N 4.76%.
Found: C 56.84%, H 5.46%, N 4.80%.
Instruments for Measurement. High-resolution mass spectra
(HRMS) were recorded on a Bruker Daltonics Apex-II spectro-
meter. Elemental analysis was carried out with a Flash EA Carlo-
Erba-1106 Thermo-Quest. Jasco UV-550 and J-810 CD spectro-
meters were used for the UV-vis and CD spectral measurements,
respectively. FTIR spectra were obtained with a Jasco FT/IR-660
plus spectrophotometer with a wavenumber resolution of 4 cm-1
.
However, because the solid/liquid interface is different from the
bulk solution, solid surfaces can also be used as an important
means to control supramolecular assemblies.24-26 From different
kinds of solid substrates, mica is relatively special because freshly
cleaved mica surfaces covered with aqueous solution are nega-
tively charged.27 At higher pH values, because the headgroups of
the bolaamphiphiles are also charged, they interacted strongly
with solid surfaces, especially with mica. Therefore, with these
bolaamphiphiles, higher-order nano/micro structures were ob-
served through further hierarchical self-assembly on solid sur-
faces. The present work shows that by using cooperative inter-
actions between the headgroups and the surface and by using rigid
necks as well as different lengths of flexible linkers, various mor-
phologies can be obtained and their changes can be regulated in a
controlled manner.
Atomic Force Microscopy (AFM) was performed in tapping mode
(Nanoscope IIIa, Digital Instruments, Inc.) with silicon cantilever
probes. The scanning rate was usually 1 Hz. Cryo-TEM was per-
formed on a JEOL JEM-2200FS TEM operating at 200 kV and
equipped with a Gatan cryoholder. For standard TEM measure-
ments, a JEOL 1011 system operating at 200 kV was used.
Procedures. The bolas (BECA4 and BECA12, 1 ꢀ 10-3 mmol)
were dispersed in 10 mL of 0.02 M NaOH, and the corresponding
mixture was treated with ultrasound and stirred for 1 h at 80 °C.
The resulting solution was titrated very slowly with 1 M HCl under
stirring to obtain an aqueous solution with a certain pH; the sample
was again heated to 80 °C for 1 h and slowly cooled to room tem-
perature. The hydrophilic silicon wafers were prepared as follows:
(1) The wafers were kept in acetone under ultrasound for 15 min
and rinsed with distilled water. (2) The wafers were then cleaned
byimmersing theminpiranhasolution(a mixtureof7:3 (v/v) 98%
H2SO4 /30% H2O2) at 90 °C for 30 min and washing them with
distilledwater. (3)Theobtainedclean waferswereagain immersed
in a mixture of 1:1:5 (v/v/v) 25% ammonia/30% H2O2/distilled
water at 70 °C for 20 min and washed with distilled water. (4) Finally,
the silicon wafers were immersed in 1:1:5 (v/v/v) 37% hydro-
chloric acid/30% H2O2/distilled water at room temperature for
30 min, washed thoroughly with distilled water, and dried in a
stream of clean nitrogen. For the AFM measurement, freshly
cleaved mica or hydrophilic silicon wafers were first deposited
with 20 μL of the corresponding samples with certain pH values.
This piece of substrate was kept at room temperature for 30 min
and then stored under vacuum for 3 days to remove additional
solvent. For the cryo-TEM measurements, a small droplet of
solution was placed on a holey carbon film, which was further
supported on a TEM copper grid. The sample-loaded grid was
then plunged into liquid nitrogen, transported under liquid nitro-
gen, and mounted onto the cryoholder of the TEM. The tempera-
ture of the sample was maintained at -178 °C. During the entire
measurement, the sample was under vacuum. For the standard
TEM measurements, a drop of samples was cast on a copper grid,
which was again dried under vacuum. The samples for standard TEM
measurements at room temperature were stained with 2% uranyl
acetate solution. In the case of FT-IR measurement, the bola samples
with different pH value were cast onto a freshly cleaned silicon wafer
and dried under vacuum. In the process of obtaining the UV and CD
spectra, a quartz cuvette with a 10 mm width was used.
Experimental Section
Synthesis. Solid reagents were used as obtained from com-
mercial suppliers without further purification, and solvents were
freshly distilled before use. Milli-Q water (18.2 MΩ cm) was used
in all cases. Bolaamphiphiles with esterified L-glutamic acid head-
groups (BEC4 and BEC12) were prepared according to the meth-
ods described previously,20 and the target molecules (BECA4 and
BECA12) were obtained from the hydrolysis of corresponding
esterified derivatives.
1,12-Dodecyloxy-bis(4-benzoyl-L-glutamic acid) (BECA12).
1,12-Dodecyloxy-bis(4-diethyl benzoyl-L-glutamate) (BEC12,
500 mg) was suspended in 30 mL of ethanol, and 15 mL of an
aqueous solution of sodium hydroxide (2 M) was slowly added to
the mixture at 0 °C, which was again stirred overnight at room
temperature. The reaction mixture was acidified to pH 3 with
dilute HCl, and the precipitate was filtered off. BECA12 (400 mg)
(20) Wang, T.; Li, Y.; Liu, M. Soft Matter 2009, 5, 1066–1073.
(21) Song, B.; Wang, Z.; Chen, S.; Zhang, X.; Fu, Y.; Smet, M.; Dehaen, W.
Angew. Chem., Int. Ed. 2005, 44, 4731–4735.
(22) Yin, S.; Song, B.; Liu, G.; Wang, Z.; Zhang, X. Langmuir 2007, 23, 5936–
5941.
(23) Imae, T.; Takahashi, Y.; Muramatsu, H. J. Am. Chem. Soc. 1992, 114,
3414–3419.
(24) Marchin, K. L.; Berrie, C. L. Langmuir 2003, 19, 9883–9888.
(25) Sakai, K.; Smith, E. G.; Webber, G. B.; Schatz, C.; Wanless, E. J.; Butun,
€ €
V.; Armes, S. P.; Biggs, S. Langmuir 2006, 22, 5328–5333.
(26) van Hameren, R.; Schon, P.; van Buul, A. M.; Hoogboom, J.; Lazarenko,
S. V.; Gerritsen, J. W.; Engelkamp, H.; Christianen, P. C.; Heus, H. A.; Maan,
J. C.; Rasing, T.; Speller, S.; Rowan, A. E.; Elemans, J. A.; Nolte, R. J. Science
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Results
Self-Assembly in Aqueous Solutions. The two designed
bolaamphiphiles are shown in Scheme 1. These bolaamphiphiles
(27) Helt, J. M.; Batteas, J. D. Langmuir 2005, 21, 633–639.
Langmuir 2010, 26(24), 18694–18700
DOI: 10.1021/la103435t 18695