Synthesis and assembly of novel poly(organophosphazene) structures based on noncovalent "host-guest" inclusion complexation

Article abstract of DOI:10.1021/ma500020p

The design and assembly of new organophosphazene polymeric materials based on supramolecular "host-guest" interactions was accomplished by linkage of supramolecular coupling units to either the main-chain terminus or the side-chains of the parent phosphazene polymer. Noncovalent interactions at the main chain terminus were used to produce amphiphilic palm-Tree like pseudoblock copolymers via host-guest interactions between an adamantane end-functionalized polyphosphazene and a 4-armed β-cyclodextrin (β-CD) initiated poly[poly(ethylene glycol) methyl ether methacylate] branched-star type polymer. Moreover, noncovalent interactions involving polymer side-chains were achieved between polyphosphazenes with β-CD pendant units and other polyphosphazene molecules with adamantyl moieties on the side-chains. These new organo-phosphazene structures based on noncovalent "host-guest" interactions generate new opportunities for the macromolecular modification of polyphosphazenes. The resultant materials demonstrated useful properties including self-aggregation, supramolecular gelation, and stimulus-responsive behavior.

Full text of DOI:10.1021/ma500020p

Article
pubs.acs.org/Macromolecules
Synthesis and Assembly of Novel Poly(organophosphazene)
Structures Based on Noncovalent “Host−Guest” Inclusion
Complexation
Zhicheng Tian, Chen Chen, and Harry R. Allcock*
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States
S
* Supporting Information
ABSTRACT: The design and assembly of new organophosphazene
polymeric materials based on supramolecular “host−guest” interactions
was accomplished by linkage of supramolecular coupling units to either
the main-chain terminus or the side-chains of the parent phosphazene
polymer. Noncovalent interactions at the main chain terminus were used
to produce amphiphilic palm-tree like pseudoblock copolymers via host−
guest interactions between an adamantane end-functionalized polyphos-
phazene and a 4-armed β-cyclodextrin (β-CD) initiated poly[poly-
(ethylene glycol) methyl ether methacylate] branched-star type polymer.
Moreover, noncovalent interactions involving polymer side-chains were
achieved between polyphosphazenes with β-CD pendant units and other polyphosphazene molecules with adamantyl moieties
on the side-chains. These new organo−phosphazene structures based on noncovalent “host−guest” interactions generate new
opportunities for the macromolecular modification of polyphosphazenes. The resultant materials demonstrated useful properties
including self-aggregation, supramolecular gelation, and stimulus-responsive behavior.
Polyphosphazenes possess a backbone of alternating
phosphorus and nitrogen atoms with two (usually organic)
side groups attached to each phosphorus. Several hundred
poly(organophosphazenes) with different side groups and
architectures have been reported in the past several decades.15
Most of the syntheses of these polymers utilize the replacement
of the chlorine atoms in poly(dichlorophosphazene) by
alkoxides,16 aryloxides,17 or amines.18 As a unique class of
organic−inorganic hybrid polymers, polyphosphazenes possess
numerous properties including facile and tunable side group
substitution, biocompatibility, and in some cases controllable
biodegradability.15 Construction of β-CD containing poly-
phosphazenes could expand the category of useful polymers,
enable the study of structure−property relationships of novel
species and, most important, endow the polymer with new
properties which would be of benefit in challenging
applications.
In this work, palm tree-like pseudoblock organophosphazene
copolymers were prepared by “host−guest” inclusion complex-
ation between a phosphazene polymer chain with a terminal
adamantyl group and a tetra-branched β-CD functionalized
organic polymeric block. The micellization of the prepared
amphiphiles was also studied. In a related system, poly-
(organophosphazenes) with 10% of the side groups in the form
of β-CD pendent units and 10% of adamantane guest units on
the side-chains of a second polyphosphazene were synthesized.
INTRODUCTION
■
The assembly of new polymeric structures by noncovalent
connections such as hydrogen bonding, ligand−metal coordi-
nation, or “host−guest” inclusion complexation has attracted
considerable recent interest.1−4 Such connections at polymer
chain-ends or through units on the side chains may respond to
various stimuli including changes in temperature, pH, or
irradiation and allow the separation and recombination of each
connection.5,6 β-Cyclodextrin (β-CD), a macrocycle with seven
glucose units, has long been recognized as a natural host for
various small molecules.7 Chemical attachment of β-CD to
polymers has generated considerable interest due to the unique
properties of these macromolecules in supramolecular chem-
istry, analytical studies, separation technology, and pharma-
ceutical applications.8,9 Adamantane is one of the most
important guests for β-CD due to its effective inclusion
entrapment and high binding affinity.10,11 Several possibilities
have been reported using the above “host−guest” inclusion
complexation to construct noncovalent polymeric structures.
For example, host−guest interactions have been used as a
bridge to construct amphiphilic pseudoblock copolymers.3
Main-chain supramolecular polymers have been obtained by
alternating host and guest moieties along the backbone.12 Self-
healing materials have been prepared by mixing β-CD modified
polymers with guest molecule modified polymers.13 However,
polymers that contain β-CD present many synthetic challenges
including the chemical complexity associated with the seven
glucose units, the substantial size of the cyclic molecule, and the
potential insolubility of the resultant polymers.14
Received: January 3, 2014
Revised: January 28, 2014
Published: February 3, 2014
© 2014 American Chemical Society
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δ (ppm) 4.36−4.81 (br, 120H, −OCH2CF3), 1.97−1.68 (br, 15H,
adamantane). 31P NMR (acetone-d6): δ (ppm) −2.71 (s, 1P), −3.75
(s, 1P), −7.01 to −8.12 (br, 25P). 19F NMR (acetone-d6): δ (ppm)
−75.22 (s, −OCH2CF3).
The capability of this configuration to participate in supra-
molecular gelation of the mixed polymer solutions was
investigated (Figure 1).
Synthesis of β-CD End-Functionalized Poly[poly(ethylene
glycol) methyl ether methacylate] by ATRP (7) (β-CD-
PmPEGMA). 4-Bromo-β-cyclodextrin (0.20 g, 0.12 mmol) was
dissolved in 20 mL of anhydrous DMF, followed by addition of
mPEGMA (33.6 g, 96 mmol) and PMDETA (80 mg, 0.46 mmol).
Argon gas was bubbled through the solution for 20 min to remove any
dissolved oxygen. Meanwhile, CuBr (34 mg, 0.24 mmol) was weighed
in a small vial and air in the vial was removed by three 10 min purge/
backfill cycles of vacuum and argon. The degassed CuBr was added to
the solution, and the mixture was stirred for 2, 4, or 6 h under argon at
room temperature to give polymers with various molecular weights.
To terminate the polymerization, air was bubbled into the reaction
medium for 10 min, and the copper catalyst was removed by passing
the sample through a flash alumina column. Products in the collected
clear solution were then precipitated into diethyl ether (200 mL). The
precipitates were isolated by centrifugation as colorless adhesives. Each
sample was then redissolved in 50 mL of methanol, and the solution
was dialyzed versus methanol for 3 d (Spectra/Por dialysis membrane,
MWCO: 6,000−8,000). Solvent was removed under reduced pressure
to give colorless adhesive polymers (convn % = 6.5%, 12%, and 17%).
1H NMR (CDCl3): δ (ppm) 6.06 (s, β-CD), 5.51 (s, β-CD), 4.24 (s,
Figure 1. Construction of new organophosphazene structures by
host−guest interactions using polymers 5 and 7 or using polymers 15
and 16. The solid circles represent adamantyl units, and the cap-
shaped motifs are cyclodextrin hosts.
β-CD), 4.02 (s, PmPEGMA), 3.78 (s, β-CD), 3.74−3.48 (br,
PmPEGMA and β-CD), 3.31 (s, PmPEGMA and β-CD), 1.89 (s, β-
CD), 1.74 (s, PmPEGMA), 0.96 (br, PmPEGMA).
Synthesis of 2-[2-(Tetrahydropyranyloxy)ethoxy]ethanol
(8). 3,4-Dihydro-2H-pyran (21.27 g, 0.25 mol) was added over a
period of 30 min to a mixture of p-toluenesulfonic acid (0.05 g, 0.267
mmol) in diethylene glycol (201.24 g, 1.89 mol) at 0 °C. The reaction
mixture was stirred for 2 h at 0 °C. It was then allowed to warm to
room temperature, and was stirred for 1 d. After that, the mixture was
poured into 500 mL of 1 M NaOH(aq) and was extracted with DCM
(5 × 200 mL). The collected organic layers were dried over MgSO4
overnight. The solvent was removed and the crude product was
distilled at 40−50 °C under reduced pressure (4−5 × 10−1 mbar) to
collect the colorless liquid product, 8 (yield: 69%). 1H NMR (CDCl3):
δ 4.55 (t, 1H), 3.80−3.43 (m, 10H), 1.72−1.44 (m, 6H).
Synthesis of Poly[bis[2-[2-(tetrahydropyranyloxy)ethoxy]-
ethoxy]phosphazene] (12). To a THF solution of poly-
(dichlorophosphazene) (3 g, 25.89 mmol) was added the sodium
salt of 10 prepared by the reaction of (tetrahydropyranyloxy)ethoxy]-
ethanol (12.3 g, 64.7 mmol) with NaH (2.90 g, 72.5 mmol, 60% in
mineral oil). The mixture was stirred under reflux for 2 d. After that,
the reaction medium was concentrated, and dialyzed against methanol
for 2 d, and then against methanol/acetone/hexanes 50/20/30 for 2 d
(Spectra/Por dialysis membrane; MWCO = 12 000−14 000). Solvent
was removed by rotary evaporation at 40 °C, and a pale yellow
adhesive product was obtained after drying under vacuum (yield:
71%). 31P NMR (CDCl3): δ −8.12 (s). 1H NMR (CDCl3): δ 4.59 (s,
1H), 4.07 (s, 2H), 3.90−3.24 (bm, 8H), 1.92−1.47 (bm, 6H).
Synthesis of Poly[bis[2-(2-hydroxyethoxy)ethoxy]-
phosphazene] (13). Compound 12 (2 g, 5.96 mmol) was dissolved
in 40 mL of trifluoroacetic acid in 40 mL of water. The solution was
stirred at room temperature for 3 h, followed by neutralization of the
solution with 5 M aqueous NaOH. The solution was then dialyzed
against water for 2 d, then against methanol for 2 d (Spectra/Por
dialysis membrane; MWCO = 12 000−14 000). The solution was
dried, and a brownish adhesive product was obtained (yield: 62%). 31P
NMR (D2O): δ −8.03 (s). 1H NMR (D2O): δ 4.11 (s, 2H), 3.72−3.48
(bm, 6H).
EXPERIMENTAL SECTION
Materials and Equipment. See Supporting Information.
Synthesis of 1-Aminoadamantane-Functionalized Fluoroe-
thoxyphosphoranimine (2) (AdamantaneNH(CF3CH2O)2P
NSiMe3). To a tetrahydrofuran (THF) solution of 1-amino-
adamantane (0.06 g, 0.38 mmol) and triethylamine (TEA) (0.04 g,
■
0.38 mmol) was added bromophosphoranimine
1 (Br-
(CF3CH2O)2PNSiMe3) (0.10 g, 0.25 mmol). The reaction mixture
was then stirred at room temperature overnight. The white precipitate
was filtered off, and all volatiles were removed under reduced pressure
to yield a colorless liquid (2). 31P NMR (CDCl3): δ (ppm) −4.43. 19
NMR (CDCl3): δ (ppm) −75.67 (s, −OCH2CF3).
F
Synthesis of Adamantyl End-Functionalized Poly[bis-
(trifluoroethoxy)phosphazene] (5) (Ad-PTFE). Phosphorus penta-
chloride (0.10 g, 0.50 mmol) was dissolved in 20 mL of DCM, and
trifluoroethoxyphosphoranimine 3 ((CF3CH2O)3PNSiMe3) (0.10
g, 0.25 mmol) was added to the solution. The initiation reaction
mixture was stirred at room temperature for 1 h, and the
chlorophosphoranimine (Cl3PNSiMe3) (2.24 g, 10.00 mol) was
added rapidly to the reaction medium. This mixture was stirred at
room temperature for 4 h to give living poly(dichlorophosphazene).
The 1-aminoadamantane functionalized fluoroethoxyphosphoranimine
2 (0.25 mmol) was redissolved in 10 mL of dichloromethane (DCM)
in a separate vial, and was added rapidly to the living polymer solution.
The reaction mixture was then stirred at room temperature overnight.
Solvent was removed under reduced pressure to yield 4 as a colorless
viscous liquid. The freshly prepared polymer 4 was then redissolved in
30 mL of anhydrous THF. The solution was treated with an excess of
NaOCH2CF3, prepared by the reaction of HOCH2CF3 (2.20 g, 22.00
mmol) with NaH (0.88 g, 22.00 mmol) in 50 mL of THF, and the
reaction mixture was stirred at room temperature for 12 h to complete
the chlorine replacement reaction (monitored by 31P NMR spectros-
copy). The medium was concentrated to about 20 mL, and the solid
product was precipitated from THF into water (3 × 500 mL), then
from THF into hexanes (1 × 500 mL). This product was isolated by
centrifugation as a white powder. The product was further purified by
redissolving in 50 mL acetone, and dialyzing the solution versus
acetone/methanol 80/20 for 3 d (Spectra/Por dialysis membrane;
MWCO = 1000). The solvent was removed and the resultant white
powder was dried under vacuum (yield: 59%). 1H NMR (acetone-d6):
Synthesis of Partially Alkyne-Functionalized Poly-
(organophosphazene) (14). Compound 13 (0.50 g, 1.96 mmol)
was dissolved in 20 mL of anhydrous DMF. A suspension of NaH
(0.118g, 2.94 mmol, 60% in mineral oil) in 10 mL of anhydrous DMF
was added to the polymer solution. The mixture was stirred for 30 min
at room temperature. Then, propargyl bromide (0.17 g, 0.78 mmol,
80% in toluene) in 10 mL of anhydrous DMF was added dropwise to
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the reaction mixture. The mixture was stirred at 80 °C for 1 d, and was
then dialyzed against methanol/acetone/hexanes 50/20/30 for 2 d
(Spectra/Por dialysis membrane; MWCO = 12 000−14 000). The
solvent was removed to give pale brown adhesive product (yield:
74%). 31P NMR (D2O): δ −5.92 (s). 1H NMR (D2O): δ 4.23 (s, 2H),
4.16 (s, 2H), 3.74−4.58 (br, 6H), 2.86 (s, 1H).
ization of a phosphoranimine for preparing poly-
(dichlorophosphazene) allows the generation of polymers
with controllable molecular weights and narrow polydisper-
sity.19,20 More important, the modifiable chain-ends provide
accessibility to various polyphosphazene-containing polymeric
structures including di- or triblock copolymers,21,22 den-
drimers,23 and graft copolymers.24 As shown in Scheme 1,
Synthesis of β-CD Containing Poly(organophosphazene)
(15) (PPhos-β-CD). Polymer 14 (0.36 g, 1.33 mmol) was dissolved in
10 mL of DMF. To this solution was added β-CD-N3 (0.47 g, 0.40
mmol) in a mixture of 10 mL of DMF and 4 mL of DMSO, sodium
ascorbate (8 mg, 0.04 mmol), and copper sulfate pentahydrate (10 mg,
0.04 mmol). The mixture was stirred at 100 °C under an argon
atmosphere for 3 d. The copper catalyst was removed by means of a
short neutral alumina column. The collected solution was precipitated
into acetone (500 mL), and the suspension was stirred overnight. The
pale brown precipitate was isolated by centrifugation, redissolved in 50
mL water, and dialyzed versus H2O for 3 d (Spectra/Por dialysis
membrane; MWCO = 12 000−14 000). Solvent was removed under
reduced pressure at 50 °C, and the remaining pale brown solid was
Scheme 1. Synthesis Chart of Ad-PTFE (5)
1
freeze-dried (yield: 40%). 31P NMR (DMSO-d6): δ −8.01 (s). H
NMR (DMSO-d6): δ 8.26 (s, 1H, triazole), 5.92−5.68 (s, 14H, β-CD),
4.89−4.76 (s, 7H, β-CD), 4.48−4.36 (s, 6H, β-CD), 4.23 (s, 2H,
diethylene glycol), 4.18 (s, 2H, diethylene glycol), 3.89−3.17 (br, 42H,
β-CD; 6H, diethylene glycol).
Synthesis of Partially Adamantane Functionalized Poly-
(organophosphazene) (16) (PPhos-Ad). To an anhydrous DMF
solution (30 mL) of polymer 13 (0.40 g, 1.57 mmol) was added an
anhydrous DMF solution (5 mL) of 1-adamantyl isocyanate (0.06 g,
0.31 mmol). Then a trace amount of TEA (0.04 mL, 0.31 mmol) was
added. The mixture was stirred at 90 °C for 2 d. The polymer solution
was then purified by dialysis versus methanol/acetone (40/60) for 3 d
(Spectra/Por dialysis membrane; MWCO = 12 000−14 000). The
solution was concentrated to 1/3 of its original volume, and
precipitated into diethyl ether (200 mL). The pale brown adhesive
precipitate was isolated and dried under vacuum to give polymer 16
(yield: 67%). 31P NMR (D2O): δ −7.21 (s). 1H NMR (D2O): 4.14 (s,
2H, diethylene glycol), 3.89−3.47 (bm, 6H, diethylene glycol), 2.08−
1.53 (bm, 15H, adamantane).
Micelle Preparation. To prepare micelle solutions, nanopure
water (80 mL) with a conductivity of 18.2 MΩ/cm was added
dropwise to a mildly stirred solution of the 1:1 host (7) (0.10 g, 0.005
mmol) and guest (5) (0.06 g, 0.005 mmol) polymers in THF (5 mL).
Once the host−guest pseudo−block copolymer was formed, all the
THF was removed under reduced pressure to give a 2 g/L of micelle
aqueous solution. Then, the solution was diluted with water to obtain
a micelle concentration in the range of 2 g/L to 1 × 10−5 g/L. For
fluorescence measurements, a pyrene solution in THF (1.2 × 10−3 M)
was added to nanopure water to give a final pyrene concentration of 12
× 10−7 M. Following dilution, the THF was removed under reduced
pressure. The pyrene solution was then mixed with the pseudo-block
copolymer solutions to obtain copolymer concentrations ranging from
1 g/L to 5 × 10−6 g/L, while the pyrene concentration of the all
samples was maintained at 6 × 10−7 M. The samples were sonicated
for 10 min and were allowed to stand for 1 day before fluorescence
measurements.
Supramolecular Gelation. PPhos-β-CD (15) (200 mg) was
dissolved in 2 mL of nanopure water (10% w/v) as a macromolecular
host component. Then, PPhos-Ad (16) (200 mg) was dissolved in 2
mL of nanopure water (10% w/v) as a macromolecular guest
component. The two components were mixed and shaken
mechanically at room temperature to allow the formation of the
supramolecular gels (18). To study the competitive dissociation of the
obtained gels, 1 mL of a saturated β-CD aqueous solution was added
to the gel and the system was shaken mechanically for 10 min.
polymerization was initiated unidirectionally with a target of 30
repeating units. Then, the adamantyl modified phosphorani-
mine was added to quench the living chain-end. Subsequently,
the resultant polymer was treated with an excess of
NaOCH2CF3 to replace the chlorine atoms and yield the
hydrophobic phosphazene guest block. The final product was
soluble in acetone, DMF and THF, but insoluble in CHCl3,
CH2Cl2, methanol or water. The chain-end phosphorus signal
was detected by 31P NMR, and the adamantyl moiety appeared
in the 1H NMR spectrum (Supporting Information, Figure S1).
The calculation of the number of the repeating units from the
31P NMR spectra (from integrations of end-phosphorus −2.71
ppm and repeating unit phosphorus −7.74 ppm, 27 repeating
1
units) and from H NMR (from integrations of OCH2CF3
4.36−4.81 ppm and adamantane 1.97 ppm, 34 repeating units)
were close to the target of 30 repeating units. The difference in
the number of repeating units calculated by GPC (Mn∼12 300
g/mol, repeating units∼50, PDI∼1.23) is due to the different
hydrodynamic radii between Ad-PTFE and polystyrene stand-
ards (for the GPC calibration curve).
Synthesis of Branched-Star Shaped Organic Polymers
Containing β-CD at the Chain-end (β-CD-PmPEGMA). Atom
transfer radical polymerization (ATRP) is one of the most
robust controlled/living radical polymerization techniques as it
functions with a diversity of monomers, molecular weight
control, and narrow polydispersity.25 Since its development,
RESULTS AND DISCUSSION
■
Polymer Synthesis and Characterizations. Synthesis of
Adamantane Terminated Linear Phosphazene (Ad-PTFE).
The development of the PCl5-induced living cationic polymer-
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this technique has stimulated research and exploration of the
synthetic boundaries of new polymeric structures, especially for
synthesizing block copolymers.26,27 In this work, a β-CD based
macroinitiator with four bromo-initiation sites on the primary
face of β-CD (primary hydroxyl groups) was obtained following
a well established method.4 With an increasing degree of
substitution of 2-bromoisobutyryl bromide units, the solubility
of the modified β-CD decreased dramatically in water, but
increased distinctly in acetone. Tetra-substituted β-CD is at the
boundary of solubility which makes it slightly soluble in both
water and acetone. Hence, if treated with four equivalents of
the bromo-substituent, the esterification reaction products can
be purified by repeatedly washing the crude product with water
and acetone. ATRP was carried out using the CuBr/PMDETA
complex as a catalyst, with poly(ethylene glycol) methyl ether
grafted methyl methacylate as a monomer (Scheme 2). A small
Figure 2. GPC traces of a series of β-CD-PmPEGMA.
Scheme 2. Synthetic Chart of β-CD-PmPEGMA (7)
challenging prospect because the mutliple hydroxyl functional
groups on β-CDs may require serious synthetic efforts to
prevent unwanted cross-linking. Moreover, the possibility also
exists that the resultant polymers will have poor solubility, or
that sterically induced low reactivity will be experienced during
the secondary macromolecular modifications.28,29 In order to
solve these problems, two strategies were employed for
designing the polymeric structure and the synthesis protocols.
First, one of the 21 hydroxyl groups on the β-CD must be
converted to a different functional group, leaving the remaining
hydroxyl groups unmodified. The new functional group should
be able to undergo a distinct reaction while the other hydroxyl
groups are inert under the reaction conditions. Second, a long
and flexible spacer group must connect the polymer backbone
to the β-CD to increase the accessibility of the functional
groups in the bulky β-CDs. Meanwhile, the spacer groups
should not change the water solubility or increase the potential
toxicity of the resultant polymers depending on their
applications.
Progress on modification techniques for CDs, especially for
monofunctionalization, has greatly accelerated the diversity of
compounds based on β-CD containing polymers in recent
years.30 Also, since Sharpless and co-workers introduced the
“click” chemistry concept in 2001,31 this copper-catalyzed
azide−alkyne cycloaddition (CuAAC) has proved to be an
extremely useful tool for construction of polymer networks due
to its mild reaction conditions, high reactivity, solvent and
functional group tolerance, and lack of byproducts.32 Thus,
based on earlier work,33 β-CD was monoazidified (10) on the
primary face to selectively react with alkyne functional groups
introduced as side units on the polyphosphazene backbone. In
order to enhance the reactivity of the “click” reaction,
diethylene glycol groups were used as spacer units to increase
the side chain flexibility and lower steric hindrance.
Monoprotection of the hydroxyl groups on diethylene glycol
(8) was carried out before macromolecular substitution to
prevent polymer cross-linking (Scheme 3). Dihydropyran was
selected as the protecting group due to the ease of
macromolecular deprotection under acidic conditions.
amount of DMF was added to dissolve the macroinitiator, and
the polymerization conditions were optimized for the control of
molecular weight and polydispersity. Because the presence of
trace quantities of oxygen could oxidize the Cu(I) catalyst and
quench the living radical, oxygen was carefully excluded from all
reagents and the reactions were carried out under an inert
atmosphere. In this work, the molar ratio of monomer to one
initiation site (4 initiation sites on each ring) was 200:1. This
large excess of monomer was intended to produce a narrower
polydispersity by lowering radical concentrations and minimiz-
ing chain terminations. A series of guest blocks (β-CD-
PmPEGMA) with increasing molecular weights were prepared
by varying the polymerization time from 2 to 6 h (Figure 2).
The proton resonances of both the chain-end β-CD and four
armed PmPEGMA units were detected in the 1H NMR
spectrum (Supporting Information, Figure S2).
Synthesis of Graft Phosphazenes with Pendent β-CD
Units: Macromolecular Hosts (PPhos-β-CD). Generally speak-
ing, the substitution reactions of poly(dichlorophosphazene)
become more challenging as the structures of the chlorine-
replacement nucleophiles become more complex. Large side
groups generate more steric hindrance with a corresponding
decrease in reactivity. Meanwhile, the solubilities of the
polymers usually decrease after the attachment of large or
complex side groups. This tends to hinder their synthesis,
characterization and processability. Complex or multifunctional
side groups also necessitate multistep protection and
deprotection reactions in order to prevent cross-linking or
side reactions during the macromolecular substitutions. Thus,
linkage of β-CD units to polyphosphazene side-chains is a
Thus, as shown in Scheme 4, poly(dichlorophosphazene),
prepared by the thermal ring-opening polymerization of
hexachlorocyclotriphosphazene, was treated with the sodium
salt of monoprotected diethlyene glycol to give polymer 12
with a molecular weight (g/mol) of 520 000 (∼2720 repeat
units). The side group deprotection reaction was carried out in
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Scheme 3. Synthesis Chart of Small Molecules for
Macromolecular Reactions
1
Scheme 4. Synthetic Scheme Leading to PPhos-β-CD (15)
Figure 3. H NMR of polymers 12−15.
phosphorus atoms (Supporting Information, Figure S3).
Meanwhile, 31P NMR spectra of 12−15 showed similar signal
peaks without significant broadening. This implies that
degradation of the polymer was minimal during the multistep
macromolecular side-chain modifications. PPhos-β-CD (15)
showed no evidence of cross-linking since it was soluble in
DMF, DMSO (room temperature), and water (heated), but
insoluble in less polar organic solvents.
DSC measurements provide additional evidence of the
successful linkage of β-CD to the polyphosphazene backbone
(Supporting Information, Figure S4). Polymer 14 with flexible
diethylene glycol side chains had a low glass transition
temperature (Tg) at around −47 °C. After clicking 10% of β-
CD onto the polymer side-chains, the Tg of PPhos-β-CD (15)
increased substantially to about 50 °C. This major increase in
Tg is attributed to an increase in side chain steric hindrance
which prevents network movement, together with assisting the
formation of additional hydrogen bonding from the multiple
hydroxyl groups on the β-CD. The significant change in Tg
could also be detected directly by the different textures of 14
(adhesive gum) and 15 (glassy powder) at room temperature.
No melting behavior was detected for 15 up to 220 °C. Above
that temperature, intense signal fluctuation was detected from
the DSC experiments due to the thermal decomposition.
Synthesis of Graft Phosphazene Containing Adamantane
Units at the Termini of the Side-Chains: Macromolecular
Guests (PPhos-Ad). For the macromolecular guests, around
10% of the adamantyl moieties were linked to the
polyphosphazene side-chain. The diethylene glycol spacer
groups were required to utilize more flexible side-chains in
order to better interact with the host component during “host−
guest” complexations. Initial attempts following the same
method for synthesizing polymer 14, by reacting polymer 13
with NaH and 1-bromoadamantane, were not successful,
probably due to the low reactivity of bulky 1-bromoadaman-
tane. Later, 1-adamantyl isocyanate was used for the formation
of a carbamate linkage (Scheme 5). New peaks appeared at
2.08−1.53 ppm indicating the successful introduction of the
adamantyl group by this method (Supporting Information,
Figure S5). The resultant adhesive polymer 16 was soluble in
water and DMSO.
aqueous trifluoroacetic acid to release the free hydroxyl groups
for further reaction (13). The success of the deprotection
reaction was easily verified by the disappearance of the peaks at
1.92−1.47 ppm (dihydropyran) in the H NMR spectrum
(Figure 3). Thus 10% of the hydroxyl groups were activated to
1
alkyne group 14 to further react with β-CD-N3. A new peak at
1
2.8 ppm from H NMR indicated the success of the alkyne
activation at the terminus of the polymer side-chains. A
maximum of 10% of β-CD could be “clicked” to the side chains
even though the alkyne-activation in the prior step was more
than 10%. Because the size of β-CD is significantly larger than
the repeating units of the polyphosphazene backbone, a
substantial increase in steric hindrance occurred after the β-
CD units were introduced. This sheltered the remaining
functional groups on the polymer from access to additional β-
CD. Meanwhile, the azide functional group on the bulky β-CD
can only interact effectively with alkyne functional groups on
the polymer from one direction (at the primary face), which
further decreases the overall reactivity. New peaks assigned to
1
β-CD from the H NMR spectra indicated the presence of the
β-CD in the polymer. The peak of one end-proton of the
alkyne at 2.8 ppm shifted to around 8.3 ppm and represented
the formation of a triazole bridge. The new polymer, PPhos-β-
CD, shows no obvious shift in the 31P NMR spectra (−7 ppm)
because the modifications were too distant from the backbone
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Scheme 5. Synthetic Scheme for PPhos-Ad (16)
Table 1. Summary of PmPEGMA-pb-PTFE Micelles
Mn
(g/mol)
(Ad-
Mn (g/mol) (β-
CD-
PmPEGMA)
cmc
(mg/L) r (nm)
entry
PTFE)
PmPEGMA-pb-PTFE-1
PmPEGMA-pb-PTFE-2
PmPEGMA-pb-PTFE-3
12 300
12 300
12 300
19 450
34 660
49 310
4.6
8.1
32
44
60
28.2
(1 g/L) due to the formation of amphiphilic pseudoblock
copolymers (Figure 4). Meanwhile, the hydrodynamic radius of
Assembly of Organo−Phosphazene Structures by
Host−Guest Interactions. Host−Guest Interactions at the
terminus of the Main-chain. Palm tree-like pseudoblock
copolymer structures (PmPEGMA-pb-PTFE, 17) were ob-
tained by exploiting the supramolecular interaction between
adamantane guest 5 and β-CD host 7 in water. Previous studies
have showed that the association constant for adamantane and
β-CD is high in the presence of water (104−105 M−1).34
Meanwhile, the host−guest interaction between β-CD and
oligo(ethylene glycol) is minimal due to the inappropriate
size.35 The 2D 1H NOESY spectrum was obtained after mixing
equimolar quantities of the host block and the guest block in
DMSO-d6 with a few drops of D2O (Supporting Information,
Figure S6). The cross-peaks at around 3.5 and 1.9 ppm are
assigned to the inner protons of β-CD and the protons of the
adamantyl moiety, respectively. This indicates the close
proximity of these protons, which is direct evidence in favor
of the host−guest interactions.
Micelles were prepared by dissolving host and guest blocks in
THF. Then a large amount of water was added dropwise to
reach a target block copolymer concentration of 2 g/L,
followed by the removal of THF at reduced pressure. This
stock micelle solution was further diluted to various lower
concentrations. The formation of micelles was demonstrated by
four methods, fluorescence, dynamic light scattering, TEM, and
AFM. The critical micelle concentrations (cmc) of PmPEG-
MA-pb-PTFE (17) were studied by a standard fluorescence
technique using pyrene as a fluorescence probe.34,36,37
Although pyrene is a guest molecule for β-CD as well, the
partition of pyrene in the β-CD cavity is negligible due to the
presence of the adamantyl moiety since adamantane is a better
guest with a much higher association constant.4,38 In the
excitation fluorescence spectra of pyrene, the peak initially at
333 nm at low polymer concentrations red-shifted to 336 nm
when the polymer concentrations increased to a certain point.
At the same time, the intensity of the pyrene fluorescence
increased substantially. This turning point of the pyrene’s
fluorescence behavior is due to the inclusion of pyrene from
aqueous solution into the hydrophobic core of the micelles,
which indicates the lowest concentration of the pseudoblock
copolymer required for the formation of micelles (cmc). The
cmc value can then be calculated by plotting the ratios of the
peak intensities at 336 to 333 nm (I336/I333) versus the
logarithum of the polymer concentrations (Supporting
Information, Figure S7). The threshold concentration at the
turning point of I336/I333 reflected the shift of pyrene from an
aqueous environment into the hydrophobic environment in the
micelle core. The cmc values summarized in Table 1 showed
that higher cmc values were obtained with an increase in the
molecular weight of the hydrophilic block.
Figure 4. AFM (a), TEM (b), and DLS (c) of micelles formed by
PmPEGMA-pb-PTFE-3; TEM (d) after the addition of pure β-CD
guests.
the aggregations increased with an increase in molecular weight
of β-CD-PmPEGMA. The sizes and shapes of the micelles
were also examined by TEM and AFM as shown in Figure 4.
The average micelle diameter measured by TEM and AFM was
in agreement with the mean diameter measured by DLS. The
existence of larger micelles with diameters in excess of several
hundred nanometers resulted from intermicellar aggregations
with the resultant formation of multicore micelle structures.39
Because of the noncovalent connection between the hydro-
philic and the hydrophobic blocks, the micelles showed
competing guest−responsive self-disassembly behavior. Thus,
the addition of pure β-CD host to the micelle solutions induced
the dissociation of the micelle structure. β-CD competed with
β-CD-PmPEGMA to associate with the adamantyl group on
the phosphazene block, thus breaking the noncovalent
connections. The TEM results in Figure 4 showed the contours
of the micelle becoming diffuse, and the spherical shape evident
in image b no longer existed after the addition of β-CDs. DLS
also confirmed the dissociation since the previous narrow size
distribution became broad, with a decrease of average radius.
Host−Guest Interaction on the Side-Chain. Pyrene was
introduced as a probe guest molecule to study the interaction
between the hydrophobic guest and the hydrophobic cavity of
β-CD on the side-chains. As shown in the excitation spectra
(Figure 5), the fluorescence peak of pyrene was red-shifted with
an increased intensity in the presence of PPhos-β-CD.
Dynamic light scattering (DLS) suggested an absence of self-
aggregation for any of the three host blocks in water. However,
when Ad-PTFE was introduced as a guest block (PmPEGMA-
pb-PTFE), self-aggregations were detected for all of variations
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Figure 5. Fluorescence studies of side-chain host−guest interactions: excitation spectra (a), emission spectra (b).
Meanwhile, the intensity ratio of the first and third vibrational
bands (I1/I3) of pyrene from the emission spectra changed
substantially from I1 > I3 to I1 < I3, and the overall fluorescence
intensity increased after the addition of PPhos-β-CD. This
indicated that the pyrene was transferred from the aqueous
environment to the hydrophobic β-CD cavities pendent to the
polyphosphazene backbone.
A supramolecular gel was obtained by mixing the “guest
component” PPhos-Ad and the “host component” PPhos-β-
CD. Host−guest interactions between the side chains of the
two polyphosphazenes formed noncovalent cross-links. As
shown in Figure 6, a gel (18) could be obtained within 1 h at
main-chain and on the side-chains. Amphiphilic palm-tree like
pseudoblock copolymers were obtained through the host−
guest coupling of an adamantane end-functionalized poly-
phosphazene and 4-armed β-CD initiated poly[poly(ethylene
glycol) methyl ether methacylate]. The micelle properties of
the noncovalent amphiphiles were studied by various
techniques. β-CD or adamantane were also introduced onto
the side-chains of polyphosphazenes to form macromolecular
hosts or macromolecular guests. The β-CD containing
polyphosphazene functions as a macromolecular host demon-
strated its capability to carry hydrophobic molecules and the
ability to form supramolecular gel when mixed with a
macromolecular guest. The success of constructing these new
poly(organophosphazene) structures not only extends the
synthetic boundary of phosphazene related materials but,
more important, could endow the new materials aggregative,
stimulus-responsive, guest−carrying/releasing, and gelation
properties which could extend the areas of application for
this system.
ASSOCIATED CONTENT
* Supporting Information
Experimental section including NMR spectra, DSC plots, and a
plot of I336/I333 vs log C. This material is available free of charge
via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*(H.R.A.) E-mail: hra@chem.psu.edu.
■
Figure 6. Formation of a supramolecular gel by “host−guest”
interactions.
Notes
higher host polymer and guest polymer concentrations (a, 10%
w/v), while only a viscous solution was generated if the
concentrations of the two components were lower. Rheological
measurement demonstrated the formation of a soft gel, since
the storage modulus (G′ = 5.1 kPa) surpassed the loss modulus
(G″ = 1.8 kPa). The soft gel (18) showed no injectable
behavior due to a high association constant between
adamantane and β-CD. The soft gel (a) turned into viscous
solution (b) if a pure β-CD host aqueous solution was added
with mechanical shaking for a certain time. The small-molecule
host, β-CD, competes with macromolecular host PPhos-β-CD
to interact with PPhos-Ad leading to dissociation of some of the
physical cross-links. Moreover, the formation of gel was also
inhibited if the macromolecular guest component PPhos-Ad
was premixed with pure β-CD before mixing with PPhos-β-CD.
The authors declare no competing financial interest.
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