Core-shell octa(azidopropyl) POSS-PEO micelle via "click" chemistry

Article abstract of DOI:10.1016/j.molliq.2014.03.047

An amphiphilic OAPS-PEO was synthesized by "click" reaction between octa(azidopropyl) POSS (OAPS) and propargyl-terminated PEO. The structure of OAPS-PEO was characterized by nuclear magnetic resonance (NMR). The amphiphilic properties and aggregation process of OAPS-PEO in aqueous solution were investigated by fluorescence, dynamic and static light scattering (DLS and SLS), and transmission electron microscopy (TEM). The critical aggregates concentration was determined at ～ 0.10 mg/mL using fluorescence measurements. At this concentration, unassociated unimolecular micelles with diameter size of 40-50 nm were found by DLS, and were also studied by means of TEM. At a lower concentration, all the OAPS-PEO self-assembled into loose balls. With the increase of the OAPS-PEO polymer concentration, OAPS centralizes to be the core of the aggregates. At the concentration of 2.0 mg/mL, aggregates present to be a core-shell structure.

Full text of DOI:10.1016/j.molliq.2014.03.047

Journal of Molecular Liquids 196 (2014) 238–243
Contents lists available at ScienceDirect
Journal of Molecular Liquids
journal homepage: www.elsevier.com/locate/molliq
Core–shell octa(azidopropyl) POSS–PEO micelle via “click” chemistry
⁎
Yujing Li, Liqiang Wan, Farong Huang , Lei Du
Key Laboratory for Specially Functional Polymeric Materials and Related Technology of the Ministry of Education, School of Materials Science and Engineering,
East China University of Science and Technology, Shanghai 200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An amphiphilic OAPS–PEO was synthesized by “click” reaction between octa(azidopropyl) POSS (OAPS) and
propargyl-terminated PEO. The structure of OAPS–PEO was characterized by nuclear magnetic resonance
(NMR). The amphiphilic properties and aggregation process of OAPS–PEO in aqueous solution were investigated
by fluorescence, dynamic and static light scattering (DLS and SLS), and transmission electron microscopy (TEM).
The critical aggregates concentration was determined at ~0.10 mg/mL using fluorescence measurements. At this
concentration, unassociated unimolecular micelles with diameter size of 40–50 nm were found by DLS, and were
also studied by means of TEM. At a lower concentration, all the OAPS–PEO self-assembled into loose balls. With
the increase of the OAPS–PEO polymer concentration, OAPS centralizes to be the core of the aggregates. At the
concentration of 2.0 mg/mL, aggregates present to be a core–shell structure.
Received 27 August 2013
Received in revised form 8 February 2014
Accepted 30 March 2014
Available online 13 April 2014
Keywords:
Octa(azidopropyl) POSS
Propargyl-terminated PEO
Micelle
Core–shell
© 2014 Elsevier B.V. All rights reserved.
1. Introduction
used H2PtCl6 to catalyze the Si–H and ethylene to graft PEO onto POSS.
Aggregation of the uncondensed amphiphile leads to micelle and vesic-
Cage-like silsesquioxanes are usually called as polyhedral oligo-
meric silsesquioxanes (POSSs) which have attracted a great deal of
attention in material fields because of their unique nanoscale cage-
shaped structures and an interesting properties [1–4]. Their struc-
tures feature well-defined and highly symmetric molecules with
cubic inorganic core having the size of ~1.5 nm in diameter, while
including R groups positioned at the silicon–oxygen cage vertex
[5]. R groups (organic shell) can be varied from hydrogen to alkyl
(methyl, isobutyl, cyclopentyl or cyclohexyl, etc.), alkylene, or
arylene. The POSS molecules with the composition of R8Si8O12 or
R1R7Si8O12 are the most studied systems. Thus, POSS molecules can
be regarded as truly inorganic core/organic shell architectures,
which are compatible with polymers and natural biomaterials.
R8Si8O12 with eight reactionable R groups can be easily regarded as
a core of 3-dimension grafting polymer. As we know, poly (ethylene
oxide) (PEO) is a highly water-soluble polymer with remarkable
properties, such as biocompatibility and nontoxicity. The grafting
of PEO onto POSS could largely increase the solubility of POSS mole-
cules, and produce an amphiphile.
ular structures that can be cross-linked to liposome-like silica particles
at elevated pH. Prithwiraj Maitra et al. [7] used (HSiMe2O)8Si8O12
reacted with allyl-PEO to increase ionic conductivity of PEO. The re-
action is also between Si–H and ethylene of (HSiMe2O)8Si8O12 and
allyl-PEO. And other linkage between POSS and PEO like HN\C = O
was also reported [8]. “Click” reaction between azide and alkyne
which has advantages of high yield, mild reaction conditions, ab-
sence of by-products, excellent selectivity and tolerance to a wide
range of functionalities can smoothly form a stable 1,2,3-triazole
linkage [9,10]. Many reports have widely used this reaction for con-
structing diverse molecular structures. Zhishen Ge et al. [11] re-
ported quatrefoil-shaped star-cyclic polymer containing a POSS
core which was synthesized by “click” reaction. It was substantiat-
ed that approximately 7–8 arms of PS (polystyrene) were attached
with POSS core. It is undoubted that “click” reaction is a more effi-
cient way to graft arms onto POSS core.
To our knowledge, although the aqueous solution properties and
aggregation behavior of the amphiphilic multiarm POSS–PEO have
been previously reported [6,12], and the number of the substituent
is always less than eight. One of the reasons is the steric hindrance
of high molecular weight PEO, the other is that the reaction between
core and arms is not very efficient. Here, we apply “click” reaction in
the preparation of it.
R. Knischka et al. [6] reported the synthesis and the characterization
of monosubstituted POSS, 1-(1,ω-propylenemethoxy) oligo (ethylene
oxide)-3,4,7,9,11, 13,15-heptahydridopentacyclo octasiloxane. They
Octa (azidopropyl) POSS (OAPS) which has eight N3 groups as the
core of amphiphilic polymer can easily react with HC ≡ C\ groups.
The long chain PEO linked with POSS through triazole rings efficient-
ly. The physical properties and the aggregation behavior of amphi-
philic multiarm OAPS–PEO in aqueous solution were investigated.
⁎
Corresponding author at: Key Laboratory for Specially Functional Polymeric Materials
and Related Technology of the Ministry of Education, School of Materials Science and
Engineering, 4 East China University of Science and Technology, Shanghai 200237, PR
China. Tel.: +86 21 64251110; fax: +86 21 64251087.
E-mail address: fhuanglab@ecust.edu.cn (F. Huang).
http://dx.doi.org/10.1016/j.molliq.2014.03.047
0167-7322/© 2014 Elsevier B.V. All rights reserved.

Y. Li et al. / Journal of Molecular Liquids 196 (2014) 238–243
239
2. Experimental
2.1. Materials
Methoxypolyethylene glycols and 3-chloropropyltris(trimethylsiloxy)
silane were purchased from Aladdin Industrial Corporation and
Pansine Chemical Co., Ltd., respectively. The dialysis bag (Membra-cel,
3500 molecular weight cut-off) was provided by Serva Electrophoresis
GmbH. Analytical-grade tetrahydrofuran (THF) was refluxed with sodi-
um and distilled immediately before use. All the other regents were of
analytical grade and used as received.
2.2. Synthesis of octa(chloropropyl) POSS (OCPS)
OCPS [(C3H6Cl)8Si8O12] was synthesized by following the method
described by Jiang et al. [13] (Scheme 1). Typically, 1800 mL methanol,
79.5 g (0.4 mol) 3-chloropropyltrimethoxysilane, and 90 mL concen-
trated hydrochloric acid were mixed and the hydrolysis and rearrange-
ment reactions were allowed to carry out for at least 5 weeks and 19.3 g
(yield: 42.1%) colorless crystals were obtained after dried in vacuo at
80 °C for 24 h.
FTIR (KBr, cm−1): 2984, 2954, 2872 (ν C\H); 1109 (ν Si\O\Si), 759
(ν C\Cl).
1H NMR (CDCl3, δ, ppm, TMS): 3.54 (m, 2H, SiCH2CH2CH2Cl,); 1.88
(m, 2H, SiCH2CH2CH2Cl); 0.83 (m, 2H, SiCH2CH2CH2Cl,) (Fig. 1, A).
29Si NMR (CDCl3, δ, ppm): −67.03 (Si\CH2\) (Fig. 1, B).
2.3. Synthesis of octa(azidopropyl) POSS (OAPS)
OCPS [(C3H6Cl)8Si8O12] (1.0 g, 1.0 mmol) and 15 mL of DMF were
added into a round bottom flask. Sodium azide (0.78 g, 12.0 mmol)
was added to the solution. The reaction was kept for 60 h at 70 °C
(Scheme 1). Then deionized water was added into the reaction mixture
to wash NaN3, and ethyl acetate was added to extract the product. The
ethyl acetate solution was subjected to rotary evaporation to obtain col-
orless liquid with high viscosity and dried in a vacuum oven for 12 h at
80 °C.
Fig. 1. NMR spectrum of OAPS. A. 1H NMR spectra, B. 29Si NMR spectra.
FTIR (KBr, cm−1): 2984, 2954, 2872 (ν C\H); 1109 (ν Si\O\Si), 2100
(ν C\N3).
2.4. Synthesis of propargyl-terminated PEO
1H NMR (CDCl3, δ, ppm, TMS): 3.31 (m, 2H, SiCH2CH2CH2N3); 1.68
(m, 2H, SiCH2CH2CH2 N3); 0.72 (m, 2H, SiCH2CH2CH2 N3) (Fig. 1,A).
29Si NMR (CDCl3, δ, ppm): −68.37 (Si\CH2\) (Fig. 1,B).
Elemental analysis for (N3C3H6)8Si8O12, found (calcd) (%): N: 31.73
(32.81), C: 27.90 (28.13), H: 4.67 (4.69).
Propargyl-terminated PEO was synthesized by following the method
described by Ke Zeng et al. [14] (Scheme 1). Prior to use, the PEO sam-
ples (Mn 5000) were dried via azeotropic distillation with toluene. In a
typical experiment, to a 500 mL round bottom flask, NaH (0.96 g,
40 mmol) and anhydrous THF (50 mL), PEG (Mn 5000) (20.0 g)
dissolved in 150 mL anhydrous THF was slowly added dropwise to the
system within 30 min. The mixture was maintained at 30 °C for 3 h
and then propargyl bromide (2.38 g, 20 mmol) dissolved in 50 mL
29Si NMR and 1H NMR resonance integration shows that eight chlo-
rine groups of octa(chloropropyl) POSS (OCPS) were totally changed
into N3 groups in azido substitution step.
Scheme 1. Preparation of OAPS and propargyl-terminated PEO.

240
Y. Li et al. / Journal of Molecular Liquids 196 (2014) 238–243
Fig. 4. 1H NMR spectra of OAPS–PEG from propargyl-terminated PEO (Mn = 5000).
until the volume dropped to the 2.0 mL level, and the mass was ob-
served to decrease until it remained constant (~12 h). The drop in the
volume and mass of the solution could be mainly due to the evaporation
of THF (0.5 mL of THF was added to dissolve the polymer) as the rate of
evaporation of THF is much faster as compared with water at room tem-
perature. Before analysis, the solutions were stabilized for at least
5 days.
Fig. 2. 1H NMR spectrum of propargyl-terminated PEO (Mn = 5000).
anhydrous THF was added dropwise. The reaction was carried out for a
further 20 h with vigorous stirring to reach completion. The salt (i.e.,
NaBr) and the unreacted NaH were removed by filtration. The filtrate
was concentrated and precipitated in a large amount of petroleum
ether. The precipitates were dissolved in THF and re-precipitated with
petroleum ether. This procedure was repeated three times to purify
the products. The product was dried in vacuo at 30 °C for 24 h. The prod-
uct, propargyl-terminated PEO (19.95 g), was obtained at a yield of 93%.
FTIR (KBr, cm−1): 243 (H\C≡), 2106 (\C ≡ C\).
2.7. Characterization
2.7.1. Transmission electron microscopy (TEM)
The morphologies of the aggregates were examined by TEM
(JEM-1400, JEOL) operated at an accelerating voltage of 120 kV. Drops
of solution were placed on a copper grid coated with carbon film and
then were dried at room temperature.
1H NMR (CDCl3, δ, ppm, TMS, PEG, Mn: 5000): 2.44 (t, 1.0H, HC ≡ C),
4.23 (d, 1.6H, \C ≡ C\CH2\), 3.62 (m, 391.8H, \CH2\CH2\O), 3.41
(s, 2.8H, CH3\O\). (Fig. 2)
2.5. Synthesis of OAPS–PEO via “Click” chemistry
2.7.2. Laser light scattering (LLS) measurements
LLS was measured by an LLS spectrometer (ALV/CGS-5022F)
equipped with an ALV-High QE APD detector and an ALV-5000 digital
correlator using a He–Ne laser (the wavelength λ = 632.8 nm) as the
light source. All the samples were filtered through 0.8 μm filters, and
the measurements were carried out at 20 °C.
In static LLS, the angular dependence of the excess absolute time-
average scattered intensity, i.e. Rayleigh ratio Rvv(q) of the dilute poly-
mer solutions was measured. Rvv(q) is related to the weight-average
molar mass (Mw), polymer concentration (C), and the scattering angle
(φ) as
The OAPS–PEO was synthesized via “click” reaction as shown in
Fig. 3. OAPS (0.10 g, 0.10 mmol) and propargyl-terminated PEO (5.0 g,
1.0 mmol) were dissolved in THF (20.4 g, 20%wt), and then CuSO4
(2.6 mg, 0.016 mmol) and sodium ascorbate (6.3 mg, 0.032 mmol)
were added. The reaction was maintained at 70 °C for 24 h to reach
completion.
2.6. Preparation of micelles
OAPS–PEO was first dissolved in a small volume of THF, followed by
the slow addition (1 mL/min) of a known volume of water. An example
is given for the preparation of 1.0 mg/mL of OAPS–PEO in aqueous solu-
tion. Polymer (2.0 mg) was dissolved in THF (0.5 mL), and the solution
was diluted with deionized water (2.0 mL). To follow the THF evapora-
tion from solution, the mass of the initial polymer solution (2.5 mL) was
measured. Next, the solution was left to evaporate at room temperature
h
ꢀ
ꢁ
i
KC=Rðφ; CÞ ¼ 1=Mw 1 þ Rg2q2 =3 þ 2A2C
where K = 4π2n2(dn/dC)2/(NAλ4) and q = 4πn sin(φ/2)/λ with NA,
dn/dC, n, and λ being the Avogadro number, the specific refractive
index increment, the solvent refractive index, and the wavelength of
Fig. 3. Preparation of amphiphilic OAPS–PEO.

Y. Li et al. / Journal of Molecular Liquids 196 (2014) 238–243
241
Table 1
GPC results of OAPS, PEO and OAPS–PEO.
Mn
Mw
5728
5048
28,121
Mw/Mn
OAPS
PEO
OAPS–PEO
4802
5000
24,969
1.19
1.05
1.13
the light in vacuum, respectively; A2 is the second virial coefficient, and
Rg is the z-average radius of gyration of the aggregates in solution. By
extrapolating to zero concentration and zero angle, Rg values of the ag-
gregates can be calculated.
In dynamic LLS measurement, the Laplace inversion of each
measured intensity–intensity time correlation function G(2)(t,q) in the
self-beating mode can result in a line width distribution G(Γ). The trans-
lational diffusion coefficient D calculated from the decay time, Γ, by the
slope of the Γ versus q2 plot, can lead to hydrodynamic radius Rh by the
Stokes–Einstein equation Rh = kBT/(6πηD), where kB, T, and η are the
Boltzmann constant, the absolute temperature, and the solvent viscosi-
ty, respectively.
Fig. 6. Variation of the intensity ratio (I1/I3) as a function of OAPS–PEO concentration.
substitution of octafunctional cubic silsesquioxane in other literatures
[12], thus, the “click” reaction could probably be an efficient way to pre-
pare octasubstitution cubic silsesquioxane.
The aggregates behavior of OAPS–PEO in aqueous solution was in-
vestigated by fluorescence measurement using pyrene as a probe. This
method has been widely used to determine the aggregate process of
amphiphilic polymers in aqueous solution [14]. I1 and I3 stand for the
first and the third vibronic peak intensities (Fig. 5). The intensity ratio
of I1 to I3 of pyrene decreases with the decline of polarity of solutions.
At low concentrations, OAPS hydrophobic domains are so small that
pyrene molecules are mainly solubilized in the aqueous phase. When
aggregates occur by the addition of water, large hydrophobic domains
are formed within the aggregates, and the pyrene preferentially pene-
trates into the hydrophobic core. The critical aggregate concentration
(CAC) is identified by the inflection point in plot of I1/I3 versus concen-
tration, which is determined to be ~0.1 mg/mL (Fig. 6).
3. Results and discussion
Due to advantages of the “click” reaction with high yield, nearly
eight PEO chains linked with OAPS. Fig. 4 shows 1H NMR spectra of
the amphiphilic OAPS–PEO. The resonance at δ = 8.10 ppm is attributed
to the protons of triazole structures resulting from the click reaction.
The 1H NMR spectra indicate that amphiphilic OAPS–PEO was success-
fully obtained. Methylene protons of OAPS at δ = 3.31, 1.68, 0.72 ppm
are all shifted to δ = 4.36, 2.50, 2.27 ppm, respectively. The disappear-
ance of the peaks for the methylene groups at 0.72 ppm, 1.68 ppm
and 3.31 ppm of OAPS in 1H NMR spectra of OAPS–PEO indicates that
N3 groups were well reacted.
The GPC result of OAPS–PEO reveals the increase in molecular
weight obtained by the triazole ring of PEO with OAPS. The Mn, Mw,
and the molecular weight distribution (Mw/Mn) are listed in Table 1. It
indicates that approximately five PEO chains were attached to the
OAPS core. This result is lower than the theoretically expected value for
OAPS, with ~8 PEO chains estimated from the 1H NMR result. It is not sur-
prising that OAPS–PEO has a spherical micelle structure while the stan-
dard PEG is a linear chain, as star polymers typically possess smaller
hydrodynamic volumes. Nevertheless, a relatively narrow and unimodal
distribution (Mw/Mn = 1.13) of OAPS–PEO confirms the successful syn-
thesis of OAPS–PEO. As we know, it is difficult to obtain the complete
Fig. 7. Concentration dependence of hydrodynamic radius distribution functions of
OAPS–PEO. (Bottom to top: 0.10, 0.50, 1.0 and 2.0 mg/mL).
Fig. 5. Fluorescence spectra of OAPS–PEG. (Probe:pyrene).

242
Y. Li et al. / Journal of Molecular Liquids 196 (2014) 238–243
Fig. 8. Transmission electron micrographs of OAPS–PEO at different concentrations: (a) 0.10 mg/mL, (b) 0.50 mg/mL, and (c) 2.0 mg/mL.
Table 2
the aggregates in Fig. 8a and b. At a larger concentration higher than
1 mg/mL, the ratio of Rg/Rh has obviously ascent. It is illuminating that
the aggregates of OAPS–PEO amphiphilic are turned to be another form,
which has hard spheres surrounded by loose shell. It means OAPSs con-
centrate to be a core, and PEO arms which have greater thermodynamic
penetrability are in the outer layer of the OAPS–PEO aggregates
(Fig. 8c). K. Yi Mya and co-workers [12] described the Rg/Rh value for
core–shell structures.
Static and dynamic light scattering studies of OAPS–PEO in water at 25 °C.
Concentration
(mg/mL)
Rg
(nm)
Rh
(nm)
Rg/Rh
0.10
0.25
0.50
1.0
110
140
154
183
287
101
140
146
133
190
1.09
1.00
1.06
1.38
1.51
2.0
The conformations of the aggregates at different concentrations can
be schematically illustrated as shown in Fig. 9. At the concentration
about CAC, there exists the unassociated unimolecular micelle. By the
concentration ascending, the OAPS–PEO amphiphilics are aggregating
to be loose balls, and turning to be core–shell like micelle at the concen-
tration of 2.0 mg/mL. The micelle may have application in drug delivery
and other fields.
The hydrodynamic properties and aggregation behavior of OAPS–
PEO in aqueous solution were also investigated by dynamic and static
light scattering studies. Fig. 7 shows the size distribution of OAPS–PEO
at different concentrations measured at 90°. The peaks attributed to
the scattering from the large particles are attributable to the aggregates
of OAPS–PEO. The aggregates peak is observed, even at a concentration
of 0.1 mg/mL, which is in agreement with the fluorescence measure-
ments (CAC) ~0.1 mg/mL. Two size distribution peaks are observed at
concentrations of 0.1 mg/mL, although the scattered intensity of the
first peak is very weak about 10%. The small peak represents the unasso-
ciated unimolecular micelle with Rh = ~30 nm and the dominant peaks
attributed to the scattering from the large particles attributable to the ag-
gregation of OAPS–PEO. Fig. 8a shows the TEM micrographs of OAPS–PEO
at the concentration of 0.10 mg/mL. Unassociated unimolecular micelles
in the range of 40–50 nm can be seen in this picture. The end-to-end dis-
tance of PEO with the size of the OAPS cage was calculated according to
the literature assuming a helical configuration of PEO [15] and found to
be ~36 nm. The value of Rh for OAPS–PEO unassociated unimolecular mi-
celles is larger than the end-to-end distance of OAPS–PEO while DLS gives
the Rh in aqueous solution. Below the concentration of 0.50 mg/mL, Rg/Rh
is found to be ~1.06 (Table 2), which is reported to be the ratio of star
polymer with many arms [16]. It is also consistent with the picture of
4. Conclusions
Octa(azidopropyl) POSS was prepared and attached with propargyl-
terminated PEO to synthesize the amphiphilic OAPS–PEO. The critical
aggregation concentration was determined to be ~0.1 mg/mL by using
fluorescence measurements. At this concentration, unassociated
unimolecular micelles with a size of 30–40 nm in diameter were found
by DLS and TEM. With the increase of OAPS–PEO concentration, Rg/Rh
also ascends. At the concentration of 2.0 mg/mL, the aggregation pre-
sents to be a core–shell structure with Rg/Rh of 1.51.
Acknowledgment
The authors gratefully acknowledge the financial support of
Shanghai Leading Academic Discipline Project (B502) and Fundamental
Research Funds for the Central University (WD113006).
Fig. 9. Schematic representation of OAPS–PEO aggregates formation at different concentrations: 0.10, 0.50 and 2.0 mg/mL.

Y. Li et al. / Journal of Molecular Liquids 196 (2014) 238–243
[8] B.S. Kim, P.T. Mather, Macromolecules 35 (2002) 8378.
243
References
[9] H. Li, J. Sun, A. Qin, B.Z. Tang, Chin. J. Polym. Sci. 30 (2012) 1.
[10] H. Chow, K. Lau, M. Chan, Chem. Eur. J. 17 (2011) 8395.
[1] M.M. Sprung, F.O. Guenther, J. Am. Chem. Soc. 77 (1955) 3990.
[2] J.F. Brown, J. Am. Chem. Soc. 87 (1965) 4317.
[3] K. Pielichowski, J. Njuguna, B. Janowski, J. Adv. Polym. Sci. 201 (2006) 225.
[4] R.M. Laine, J. Mater. Chem. 15 (2005) 3725.
[5] J. Wu, P.T. Mather, Macromol. Sci. Polym. Rev. 49 (2009) 25.
[6] R. Knischka, F. Dietsche, R. Hanselmann, H. Frey, R. Mülhaupt, Langmuir 15 (1999)
4752.
[11] Z.S. Ge, D. Wang, Y.M. Zhou, H.W. Liu, S.Y. Liu, Macromolecules 42 (2009) 2903.
[12] K.Y. Mya, X. Li, L. Chen, X.P. Ni, J. Li, C.B. He, J. Phys. Chem. B 109 (2005) 9455.
[13] Z.Y. Jiang, Y. Zhou, F.R. Huang, L. Du, Chin. J. Polym. Sci. 29 (2011) 726.
[14] A.P. Narrainen, S. Pascual, D.M. Haddleton, J. Polym. Sci. A Polym. Chem. 40 (2002)
439.
[15] J.A. Johnson, M.L. Saboungi, D.L. Price, S.J. Ansell, Chem. Phys. 109 (1998) 7005.
[16] W. Burchard, M. Schmidt, W.H. Stockmayer, Macromolecules 13 (1980) 1265.
[7] P. Maitra, S.L. Wunder, Chem. Mater. 14 (2002) 4494.