Macromolecules
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was performed using an instrument consisting of a Waters 717 plus
autosampler, a TSP Spectra Series P 100 pump, and a set of three PSS
SDV columns (104/500/50 Å). Signal detection was achieved using a
UV (TSP Spectra System UV 2000, 254 nm) and a refractive index
(Agilent 1260) detector. Calibration was carried out using poly-
(styrene) standards provided by Polymer Standards Service.
removed by filtration, and the solvent was removed at reduced
pressure. Column chromatography (ethyl acetate:petroleum 1:2, Rf =
0.35) yielded the desired product (23.96 g, yield: 60%). H NMR
1
(CDCl3, ppm): δ 5.81 (ddt, J = 16.9, 10.2, 6.7 Hz, 2H, H2CCH−),
5.12−4.81 (m, 4H, H2CCH−), 4.13−3.86 (m, 4H, P−O−CH2),
2.17−1.92 (m, 4H, H2CCH−CH2), 1.74−1.57 (m, 4H, O−CH2−
1H, 13C, and 31P{H} NMR spectra were acquired using a 400 MHz
Bruker AMX system. The temperature was kept at 298.3 K and
CH2−), 1.46 (d, 2JPCH = 17.4 Hz, 3H, P−CH3), 1.28 (br s, 24H). 13
C
NMR (CDCl3, ppm): δ 139.32 (H2CCH−), 114.28 (H2CCH−),
65.70 (d, J = 6.0, P−O−CH2), 33.94 (CH−CH2), 30.68 (d, J = 6.0,
O−CH2−CH2), 29.58, 29.31, 29.24, 29.06, 25.68 (O−CH2−CH2−
1
calibrated with a standard H methanol NMR sample using Topspin
3.0 (Bruker). 13C NMR spectra were referenced internally to solvent
signals. 31P{H} NMR spectra were referenced externally to phosphoric
acid. The 13C NMR (101 MHz) and 31P{H} NMR (168 MHz)
measurements were obtained with an 1H power gate decoupling
method using 30° degree flip angle. 2D (1H, 31P HMBC) were
measured using a Bruker 400 AMX NMR spectrometer The spectra
were referenced to the residual proton signals of the deuterated
solvent (CDCl3 (1H) = 7.26 ppm; DMSO (1H) = 2.50 ppm). All 1D
and 2D spectra were processed with MestReNova 6.1.1-6384.
Differential scanning calorimetry (DSC) measurements were
performed using a PerkinElmer DSC 8500 equipped with a
PerkinElmer CLN2 in the temperature range from −100 to 80 °C
under nitrogen with a heating rate of 10 K min−1.
1
CH2), 10.14 (d, JCP = 144 Hz, P−CH3). 31P{H} NMR (CDCl3,
ppm): δ 30.7. ESI MS: 823 (2MNa+).
Synthesis of 2-Methyl-4,7-dihydro-1,3,2-dioxaphosphepine 2-
Oxide (5). Methylphosphonic dichloride (7.30 g, 55 mmol) was
dissolved in dry THF (500 mL), 8 equiv of triethylamine was added,
and the solution was cooled to 0 °C. A solution of cis-buten-1,4-diol
(5.47 g, 62 mmol) in THF (40 mL) was added slowly (4 h) to the
solution via a syringe pump. After complete addition the solution was
stirred for 2 h and stored overnight at −28 °C to facilitate the
precipitation of the hydrochloride salt. The precipitate was removed by
filtration, and the solvent was removed from the filtrate at reduced
pressure. Column chromatography (acetone, Rf = 0.65) yielded the
desired product (4.496 g, yield: 55%) .1H NMR (CDCl3, ppm): δ 5.75
(t, J = 1.8 Hz, 2H, CHCH), 4.91−4.66 (m, 2H, CH−CH2−O),
Nanoparticle Characterization. The average particle size and
particle size distribution were determined by dynamic light scattering
(DLS) in a submicron particle sizer NICOMP 380 equipped with a
detector to measure the scattered light at 90°. The zeta-potential of the
solutions were obtained using a Zetasizer NanoZ using as dispersive
phase an aqueous 1 × 10−3 M KCl solution. The particle morphology
was studied by scanning electron microscopy (SEM) using a
microscopy Zeiss LEO Gemini 1530. Prior to the measurement, a
thin carbon coating layer was deposited using a vacuum coating system
Leica EM MED020.
Calcium Phosphate Attachment Studies. The calcium
phosphate granules (MBCP+, 80−200 μm, Biomatlante) were
dispersed in ultrapure water (10 mg mL−1, Millipore) and washed
for 30 min under horizontal agitation (200 rpm) before use. The
poly(phosphonate) nanoparticle dispersion in deionized water at an
initial concentration of 1−3 wt % was diluted to application
concentrations of 0.01% with deionized water in 1.5 mL Eppendorf
centrifuge vials (1 mL nanoparticle solution volume). The calcium
phosphate granules were mixed with the nanoparticle dispersion and
placed on a shaker for 30 min. Then, the mixture was centrifuged at
1000 rpm for 5 min, the majority of the liquid was pipetted from the
tube and removed, and the tube was refilled with deionized water and
vortexed to remove the not bound nanoparticles from the mixture.
This process of centrifuging, removing, and replacing the supernatant
with fresh deionized water, and vortexing was repeated two additional
times. After the three rinses were complete, the samples were
centrifuged again, and stored in water before observation in the
scanning electron microscope (SEM, Zeiss LEO Gemini 1530). Prior
to the measurement, a thin carbon coating layer was deposited using a
vacuum coating system Balzer Union (BAE250).
Synthetic Procedures. Synthesis of Methylphosphonic Dichlor-
ide (1). The dichloride was synthesized as previously reported.42
Briefly, a mixture of 62.0 g of dimethyl methylphosphonate (0.5 mol)
and DMF (0.5 mL) was added dropwise to refluxing thionyl chloride
(90 mL). Strong gas evolution of methyl chloride and sulfur dioxide
indicated the progress of the reaction. After 12 h the gas evolution
declined. To complete the reaction, the bath temperature was
increased to 120 °C. Fractional distillation of the raw product yielded
the desired dichloride as colorless crystals (49.82 g, yield: 75%, bp 71−
73 °C/65 mbar). 1H NMR (SOCl2, ppm): δ 2.54 (d, 2JPCH = 15 Hz).
31P{H} NMR (SOCl2, ppm): δ 44.9.
Synthesis of Di(undec-10-en-1-yl) Methylphosphonate (2).
Methylphosphonic dichloride (13.29 g, 100 mmol) was dissolved in
dry THF (200 mL) and cooled to 0 °C. A solution of 3-undec-10-en-
1-ol (34.06 g, 200 mmol) and pyridine (15.82 g, 200 mmol) in THF
(50 mL) was added dropwise. After completion of the addition, the
solution was stirred for 2 h and stored overnight at −28 °C to facilitate
the precipitation of the pyridinium hydrochloride. The precipitate was
2
4.63−4.42 (m, 2H, CH−CH2−O), 1.59 (d, JPCH = 17.5 Hz, 3H, P−
CH3). 13C NMR (DMSO-d6, ppm): δ 127.66 (CHCH), 63.53 (d, J
1
= 7.0, CH−CH2−O), 9.07 (d, JPC = 142.4 Hz, P−CH3). 31P{H}
NMR (CDCl3, ppm): δ 36.11. ESI MS: 255 (MAg+).
Representative Procedure for the Acyclic Diene Metathesis
Polymerization of 2. Monomer 2 (220 mg, 1.08 mmol) was placed
in an oven-dried Schlenk tube, and Grubbs’ first generation catalyst
(7.1 mg, 8.6 μmol, 0.8 mol %) was added under an argon atmosphere
with stirring. The catalyst dissolved rapidly in the monomer, yielding a
purple liquid. Reduced pressure (2 × 10−2 mbar) was applied to
remove the evolving ethylene. The reaction mixture was stirred for 24
h at 60 °C and for another 48 h at 80 °C. The reaction mixture was
allowed to cool to room temperature, and the resulting viscous oil was
dissolved in 1 mL of dichloromethane. Ethyl vinyl ether (100 μL) was
added to cap the active chain end. After treatment with activated
charcoal the solution was filtered through Celite, and the polymer (3e)
was precipitated from dichloromethane into methanol and finally dried
at reduced pressure (136 mg, yield: 62%).1H NMR (CDCl3, ppm): δ
5.47−5.25 (m, CHCH), 4.12−3.87 (m, CH2−O−P), 2.19−1.78
(m, CH2−CH), 1.74−1.54 (m, CH2−CH2−O), 1.45 (d, J = 17.4 Hz,
P−CH3), 1.26 (s, backbone). 13C NMR (CDCl3, ppm): δ 130.43
(CHCH), 129.97 (CHCH), 65.7 (d, J = 6.1 Hz, CH2−O−P),
32.74, 30.69, 30.63, 29.89, 29.78, 29.75, 29.67, 29.63, 29.56, 29.52,
29.42, 29.32, 29.30, 29.23, 27.34, 25.67, 11.14 (d, 1JPC = 145.4 Hz, P−
CH3). 31P{H} NMR (CDCl3, ppm): δ 30.6.
Hydrogenation of 3f. A 300 mg sample of the polymer 3f, 10 mL
of THF, and 100 mg of 20 wt % Pd(OH)2/C catalyst were charged
into a 250 mL ROTH autoclave. Hydrogenation was performed with
vigorous stirring under a hydrogen pressure of 50 bar at room
temperature for 48 h. The solution was then filtered through Celite to
remove the catalyst. The product was isolated after precipitation into
methanol and dried at reduced pressure to give a solid polymer (4, 252
1
mg). H NMR (CDCl3, ppm): δ 4.15−3.87 (m, CH2−O−P), 1.73−
1.55 (m, CH2−CH2−O), 1.46 (d, J = 17.4 Hz, P−CH3), 1.24 (br m,
backbone). 13C NMR (CDCl3, ppm): δ 65.73 (d, J = 6.1 Hz, CH2−
O−P), 30.70, 30.65, 29.86, 29.81, 29.74, 29.69, 29.35, 25.69, 11.17 (d,
1JPC = 144.4 Hz, P−CH3). 31P{H} NMR (CDCl3, ppm): δ 30.6.
Representative Procedure for the Ring-Opening Metathesis
Polymerization of 5. The monomer 5 (or a mixture of 5 and freshly
distilled cis-cyclooctene) (114.5 mg, 773 μmol) was dissolved in 2 mL
of dry chlorobenzene under an argon atmosphere. A stock-solution of
third generation Grubbs’ catalyst was prepared in dry chlorobenzene
and added via syringe (0.3 mL, 0.4 mol %) to the stirring monomer
solution. The mixture was stirred at room temperature for 12 h
(homopolymer) or for 2 h (copolymers) before 100 μL of ethyl vinyl
ether was added to terminate the active chain end. After treatment
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dx.doi.org/10.1021/ma5013286 | Macromolecules 2014, 47, 4884−4893