Christophe
Detrembleur
*a,
Antoine
Debuigne
a,
Ozcan
Altintas
b,
Matthias
Conradi
c,
Edgar H. H.
Wong‡
b,
Christine
Jérôme
a,
Christopher
Barner-Kowollik
*b and
Tanja
Junkers
*c
aCenter for Education and Research on Macromolecules (CERM), University of Liege, Belgium. E-mail: Christophe.Detrembleur@ulg.ac.be; Fax: (+32) 4 3663497; Tel: (+32) 4 3663465
bPreparative Macromolecular Chemistry, Institut für Technische Chemie und Polymerchemie, Karlsruhe Institute of Technology (KIT), Engesserstr. 18, 76128, Karlsruhe, Germany. E-mail: christopher.barner-kowollik@kit.edu; Fax: (+49) 721 608-45740; Tel: (+49) 721 608-45642
cInstitute for Materials Research (IMO), Polymer Reaction Design Group, Universiteit Hasselt, Agoralaan, Gebouw D, BE-3590, Diepenbeek, Belgium. E-mail: tanja.junkers@uhasselt.be; Fax: (+32) 11 26-8399; Tel: (+32) 11 26-8318
First published on 12th September 2011
Via consecutive cobalt-mediated radical polymerization (CMRP), nitrone-mediated radical coupling (NMRC) and copper catalyzed azide-alkynecycloaddition (CuAAC), polymers with mikto-arm star and H-shape architecture were synthesized. Poly(vinyl acetate)40-block-poly(acrylonitrile)78-Co(acac)2polymers were synthesized viaCMRC and subsequently coupled using an alkyne functional nitrone. The coupling efficiency of the NMRC process was assessed employing N-tert-butyl α-phenyl nitrone (PBN), which is structurally very similar to the later employed coupling agent. Generally, coupling efficiencies of close to 90% or higher were observed in all cases. Since the coupling reaction yields triblock copolymers bearing an alkoxyamine functionality (and thus also an alkynegroup) in the middle of the chain, well defined PEG conjugates could be obtained viaCuAAC. Miktoarm star polymers of the structure (PVAc-b-PAN)2-PEG were generated as well as H-shaped material of the structure (PVAc-b-PAN)2-PEG-(PVAc-b-PAN)2viaconjugation with bifunctional PEG. In all cases, very narrow molecular weight material was obtained. Molecular weight analysis of the intermediate and the final products reveals that the hydrodynamic volume of the miktoarm star and the H-shaped materials is not substantially increased during the final conjugation reaction despite the fact that the absolute molecular weight increases by more than a factor of two in the latter case. Success of the conjugation reactions was confirmed via composition analysis viaNMR.
In the NMRC reaction, nitrones mediate the radical coupling reaction. Such compounds are excellent radical spin traps and are often used in ESR studies to transform transient species into stable counterparts that can be analyzed over extended times. Since they add rapidly to transient, propagating chains in radical polymerizations, nitrones can be employed to mediate polymerizations, either via in situ formation of a nitroxide mediating agent in in situ NMP24–29 or via direct control of the average chain length in so-called enhanced spin capturing polymerization (ESCP).30,31
In NMRC, macroradicals react readily with the mediator to form a macronitroxide which subsequently quenches other macroradicals via a persistent radical effect instead of undergoing bimolecular termination, eventually forming a symmetric coupling adduct with an alkoxyamine functionality in the middle of the chain.22 As an activation step to generate the macroradicals, abstraction of the terminal brominegroup from an ATRP-made polymer by Cu0 species is a suitable reaction pathway. In principle, however, no prerequisite is given for the activation and other reactions may be compatible with NMRC. In CMRC19–21polymers are coupled in a very similar fashion. In this case, macromolecules prepared by organometallic-mediated radical polymerization (OMRP)32 based on cobalt complexes, namely the cobalt-mediated radical polymerization (CMRP),33 present a cobalt-carbon end-group that can be activated to form macroradicals. Similarly to NMRC, combination of chains is thereby promoted by the addition of isoprene (or another conjugated diene), which will be built in a mid-chain position.19CMRC (and therewith the underpinning polymerization process CMRP)33 has the advantage over other coupling techniques that it allows for activation of radical chains that are not accessible via the ATRP route. Monomers such as vinyl acetate (VAc)34 and N-vinyl pyrrolidone (NVP)35 are not readily controlled via the conventional polymerization techniques such as ATRP, but are readily polymerizable in a controlled fashion viacobalt-mediated polymerizations. Thus, PVAc and PNVP with defined molecular weight are accessible that are available for radical coupling reactions. So far, these polymers but also poly(acrylonitrile) (PAN)37 were only coupled via the CMRC route.19–21 While an insertion of distinct chemical functionality into the chains is possible in principle, a combination with the nitrone technique seems highly advantageous since with nitrones it was already shown that secondary functionalities can be introduced into the product at a defined mid-chain location. Polyacrylates and polystyrene were synthesized according to the nitrone-mediated radical coupling procedure while introducing alkynegroups.36 In addition—in an attempt to transform the coupling reaction into a synthesis tool for multi-sequential polymers in a step growth approach—alkynes were introduced in regular intervals on the polymer backbone via a nitrone serving as a functional carrier.37
In here, we report the combination of both CMRP and NMRC as a novel synthetic tool for providing unprecedented copolymers with precise architectures. PVAc and PAN, obtained from CMRP, are coupled by means of nitrone-mediation. Homopolymers are obtained as well as block copolymers starting from PVAc-block-PAN precursors. An alkyne moiety is introduced into the products via functional nitrones, which subsequently served as an additional anchor point for further conjugation reactions. Via the alkyne, azide-functional polyethylene glycol (PEG) chains are conjugated resulting in complex three-armed polymer structures as well as H-shaped polymers when bifunctional PEG was employed (see Scheme 1). The results will be presented and discussed in a bottom-up approach: First, we will describe the activation step of model oligomers end-capped with cobalt followed by the nitrone coupling reactions of the polymeric species. In the last step, the assembly of the building blocks viaCuAAc is discussed to demonstrate the efficiency of the underlying reactions.
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Scheme 1 Schematic representation of the synthesis of H-shaped polymersvia combination of CMRP and NMRC followed by CuAACconjugation. |
To the PVAc-Co(acac)2 a solution of N-tert-butyl phenyl nitrone (PBN, 0.053 g PBN in 1 mL of toluene; 3 × 10−4 mol) was added under argon. Once the polymer was dissolved, the reaction mixture was heated at 40 °C overnight. An aliquot was subsequently withdrawn to determine the molecular weight and polydispersity of the coupled polymer (Mn = 7200 g mol−1; Mw/Mn = 1.07; coupling efficiency = 92%). The final product was precipitated 2 times in heptane and dried at 40 °C under vacuum overnight.
To the PAN-Co(acac)2 solution, a solution of N-tert-butyl phenyl nitrone (PBN; 0.065 g PBN in 1 mL of DMF; 3.7 10−4 mol) was added under argon at 0 °C. The reaction mixture was stirred at 40 °C overnight. An aliquot was then withdrawn to determine the molecular weight and polydispersity of the coupled polymer by SECDMF/LiBr calibrated by PS standards (Mn = 66200 g mol−1; Mw/Mn = 1.03). The final product was deactivated by adding an excess TEMPO, precipitated 2 times in methanol and dried at 40 °C under vacuum overnight. Absolute molecular parameters were determined by SEC/MALLS (Mn,abs = 9700 g mol−1; Mw/Mn = 1.02; coupling efficiency = 92%).
To the PVAc-Co(acac)2 dry and degassed DMF (4 mL) was then added under argon at 0 °C followed by AN (4 mL). The mixture was subsequently stirred at 0 °C until the conversion reached close to 50% (after about 24h). An aliquot was withdrawn for the determination of the molecular weight and polydispersity by SEC in DMF/LiBr (Mn = 50700 g mol−1; Mw/Mn = 1.03). The residual monomer was removed under vacuum at rt.
To the PVAc-b-PAN-Co(acac)2 solution a solution of the nitrone (0.23 g PBN in 2 mL of DMF; 8.88 10−4 mol) was added under argon. The reaction mixture was subsequently heated at 40 °C overnight. An aliquot was then withdrawn to determine the molecular weight and polydispersity of the coupled polymer by SECDMF/LiBr using PS calibration (Mn = 81400 g mol−1; Mw/Mn = 1.04). The final product was precipitated 3 times in a methanol/water (20/80) mixture heptane and dried at 40 °C under vacuum overnight.
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Scheme 2 Nitrones employed for coupling polymers end-capped by Co(acac)2. |
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Scheme 3 Radical coupling of PVAc-Co(acac)2 by nitrone1. |
Using a two molar excess of nitrone1 (N-tert-butyl α-phenyl nitrone, PBN) compared to PVAc-Co(acac)2, Fig. 1 shows that the coupling reaction is effective indicated by the shift of the SEC chromatogram of the PVAc-Co(acac)2 precursor to higher molecular weights. The extent of coupling is calculated as xc = 2[1 − (Mn,0/Mn)] in which Mn,0 and Mn are the molar masses of the polymer precursor and the coupled product, respectively. The extent of coupling is high and reaches 92% (Table 1, entry 1), the small tailing at the low molar mass side of the SEC chromatogram accounts for some small amounts of unreacted PVAc. It should be noted that the nitrone coupling, at least for polyacrylates, was shown to proceed also under equimolar conditions.36 Nevertheless, higher amounts can be used to increase the efficiency of the coupling.
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Fig. 1 Size exclusion chromatograms of poly(vinyl acetate) before (right) and after (left) reaction with nitrone1. |
Entry | PVAc-Co(acac)2 | Radical coupling | |||||
---|---|---|---|---|---|---|---|
M n a (g mol−1) | M w/Mna | [PVAc-Co(acac)2]/[nitrone] | Nitrone | M n b (g mol−1) | M w/Mnb | x c c | |
a Number-average molecular weight and polydispersity of PVAc-Co(acac)2 determined by SEC analysis in THF calibrated by polystyrene standards. b Number-average molecular weight and polydispersity of coupled PVAc determined by SEC analysis in THF calibrated by polystyrene standards. c The extent of coupling calculated as xc = 2[1 − (Mn,0/Mn)] in which Mn,0 and Mn are the molar masses of the polymer precursor and the coupled product, respectively. d Solvent = toluene. e Solvent = DMSO. | |||||||
1d | 3900 | 1.04 | 1/2 | 1 | 7200 | 1.07 | 0.92 |
2e | 3450 | 1.04 | 1/2 | 1 | 6400 | 1.06 | 0.93 |
3d | 4700 | 1.05 | 1/4 | 1 | 8700 | 1.10 | 0.92 |
4d | 5500 | 1.07 | 1/2 | 2 | 9200 | 1.17 | 0.84 |
5d | 6300 | 1.06 | 1/2 | 3 | 11050 | 1.14 | 0.88 |
6d | 5650 | 1.06 | 1/4 | 3 | 10900 | 1.08 | 0.88 |
Two approaches are envisaged to improve the coupling efficiency. The first one consists of carrying out the coupling reaction in dimethylsulfoxide (DMSO) instead of in toluene. Indeed, it is known that DMSO activates the C–Co bond cleavage and should therefore accelerate the generation of PVAc macroradicals that might affect the coupling efficiency. Table 1 shows that identical radical coupling efficiencies are observed in both solvents (comparison of entries 1 and 2). The second strategy consists of increasing the amount of nitrone compared to PVAc-Co(acac)2 since the increase of nitrone concentration compared to the macroradical precursor has been shown to be beneficial to the coupling reaction. Higher nitrone concentrations increase the likelihood of macronitroxides formation and thus reduce the rate of random termination events. Since a persistent radical effect controls the formation of AA′ macroalkoxyamines, higher nitrone and thus slightly larger nitroxide concentrations may be used without problems in a relatively broad concentration window. However, the coupling efficiency remains identical irrespective of the PVAc-Co(acac)2/PBN molar ratio (comparison of entries 1 and 3, Table 1).
1H NMR analysis of PVAc (see Fig. 2) coupled by 1 (Table 1, entry 2) shows the typical peaks of PVAc at 4.8 ppm (CH2–C–OCOCH3), 1.9 ppm (CH2–CH–OCOC
3) and at 1.75 ppm (C
2–CH–OCOCH3) but also the methoxy group of the initiator at the α- and ω-positions at 3.15 ppm. Importantly, the presence of the alkoxyamine in the polymer chain is observed by the presence of the phenyl group originating from 1 at 7.1–7.55 ppm. The comparison of the integration of this peak corresponding to 5 protons with that of the methoxy groups of the initiator at both chain ends corresponding to 6 protons allows to confirm the presence of one phenyl group per polymer chain. The degree of polymerization can also be calculated by 1H-NMR by comparing the integral of CH2–C
–OCOCH3 of the polymer backbone with the methoxy group of the initiator at both chain-ends at 3.15 ppm. This degree of polymerization (DPNMR = 70) is very close to that determined by SEC (DPSEC = 74).
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Fig. 2 400MHz 1H-NMRspectrum of the coupling product from PVAc-Co(acac)2 mediated by PBN (Table 1, entry 2). |
To dispel any doubt about the insertion of nitrone1 during the coupling process, the alkyl-cobalt(III) adduct that was described above to start the VAcpolymerization and that is in fact just a very short PVAc-chain end-capped by Co(acac)2 itself, is coupled by nitrone1. Thereby a product is formed that is of sufficiently small molecular weight to be analyzed by soft ionization mass spectrometry such as electrospray ionization mass spectrometryESI-MS.
For the ease of the analysis, the ESI measurement was carried out on the crude mixture of the coupling reaction of very low molecular weight PVAc-[CoIII] precursors, i.e. [Co(acac)2(–CH(OCOCH3)CH2)<4–R]. In this case, 1.6 equivalents of PBN were used compared to the organometallic species. Fig. 3 shows a typical ESI spectrum acquired using DCM/methanol 2:
1 as solvent and no specific cationization agent resulting in Na adducts. Highly uniform oligomers are detected with a repeat unit corresponding to a 86 Da interval and thus according to the mass of VAc. The measured m/z ratios demonstrate that the PVAc coupling product incorporates one PBN unit. For instance, the most intense signal (X6Na+) is observed at m/z 996 and can be attributed to sodium-cationized oligomers containing six VAc units, one PBN moiety and two V-70 initiating residues and thus the expected product. No signal corresponding to a PVAc chain without PBN unit (e.g.X6Na+, m/z 819, X7Na+, m/z 905) is detected, which confirms that the PVAc precursors do not undergo a direct coupling by combination. Also, uncoupled PVAc is not detected in significant amounts.
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Fig. 3 ESI-MS spectrum of a PVAc sample prepared by the coupling reaction of [Co(acac)2(–CH(OCOCH3)CH2)<4–R0]) with PBN. |
In order to introduce an alkynegroup at the middle of the PVAc chain, nitrone2 functionalized by a protected alkynegroup was then tested for the radical coupling. A protected alkyne was first used to avoid any suspected side reactions between alkyne and radicals. The radical coupling occurs in similar conditions established for 1, i.e. in toluene using a two molar excess of nitrone2 compare to PVAc-Co(acac)2 at 40 °C. The coupling efficiency tends to decrease when using the functional nitronevs. the unsubstituted one since xc is limited to 0.84 (entry 4, Table 1). Steric hindrance might account for this loss of coupling efficiency when nitrone1 is replaced by the more bulky nitrone2. Such a hindrance may result in lower addition rates of macroradicals to the nitrone as well as reduced combination rates of the macronitroxides towards other radicals. With polyacrylates, no reduction in efficiency was observed when exchanging 1 for 2,23,36 however PVAc macroradicals have a different reactivity and lead to more profound changes in the addition rate due to steric hindrance.
For the sake of comparison, a nitrone with an alkynegroup that is not protected (3) was subsequently tested under identical conditions. The coupling efficiency remains high (around 90%; Table 1, entry 5), suggesting that side reactions between the PVAc macroradical and alkynegroup are limited. Purification of the polymer by dialysis against methanol (SpectraPore 3000 dialysismembrane) allows removing excess nitrone and most of the uncoupled PVAc (see Fig. 4). A clear shift of the distribution towards double molecular weight is observed, whereby small amounts of material are apparently not reacted in the coupling reaction as is seen from the tailing towards higher elution volumes of the product distribution. Doubling the amount of nitrone in the reaction medium does not increase nor decrease further the extent of coupling and also similar distributions are obtained (Table 1, entry 6).
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Fig. 4 Size exclusion chromatography of poly(vinyl acetate) before (right) and after (left) reaction with nitrone 3 followed by dialysis against methanol (Table 1, entry 5). |
1H NMR analysis evidences the presence of the alkoxyamine in the middle of the polymer chain by the signals typical of protons of the phenyl group at 7.5–8.0 ppm (see Figure S1 in the supporting information section). Comparison of the integral of this signal corresponding to 4 protons to that of methoxy groups of chain-ends corresponding to 6 protons at 3.15 ppm confirms the presence of one phenyl group per polymer chain. The methylene group (O–C2–C≡CH) of the alkoxyamine is also observed at 4.94 ppm and its integral perfectly fits to the expected structure.
In the next step, the radical coupling of poly(acrylonitrile) end-capped by Co(acac)2 (PAN-Co(acac)2) was explored employing nitrone1 and using a PAN-Co(acac)2 to nitrone molar ratio = 1:
2. In contrast to the previous experiments, the reaction is carried out in a DMF/DMSO (2/1) mixture, as PAN is insoluble in toluene. At 40 °C, the coupling is efficient as shown by the SEC chromatogram of PAN-Co(acac)2 that is almost completely shifted towards the higher molecular weight side (see Fig. 5). Only a small amount of unreacted PAN is present at the low molar mass side of the SEC chromatogram. Analysis of the PAN precursor and the coupled product by SEC equipped with a multi-angle laser light scattering (MALLS) detector allows determining the absolute molar masses of the polymers and thus to precisely calculate the extent of coupling to xc = 0.91. As observed for PVAc, the doubling of the PBN amount does not affect the coupling efficiency (Table 2, entry 2). 1H NMR spectroscopy shows the typical signals of the methyne and methyleneprotons of the PAN main chain at 3.14 ppm and 2.04 ppm, respectively. Typical peaks of the phenyl group of nitrone1 inserted at the middle of the polymer chain are observed at 7.3–7.65 ppm, clearly confirming the incorporation of PBN in the chain (see Fig. S2, ESI†). It should be noted that based on the results obtained on PVAc, very similar coupling efficiencies are also expected for PAN employing the nitrones 1–3, given that the type of activation as well as the general structure of the nitrones is very similar.
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Fig. 5 Size exclusion chromatography of poly(acrylonitrile) before (dotted line) and after (solid line) reaction with nitrone1. |
Entry | PAN-Co(acac)2 | Radical coupling | ||||
---|---|---|---|---|---|---|
M n a (g mol−1) | M w/Mna | [PAN-Co(acac)2]/[nitrone] | M n b (g mol−1) | M w/Mnb | x c c | |
a Absolute number-average molecular weight and polydispersity of PAN-Co(acac)2 determined by SEC analysis in DMF/LiBr using a MALLSdetector with the specific refractive index increment (dn/dc) of PAN = 0.076 ml g−1. b Absolute number-average molecular weight and polydispersity of coupled PAN determined by SEC analysis in DMF/LiBr using a MALLSdetector with the specific refractive index increment (dn/dc) of PAN = 0.076 ml g−1. c The extent of coupling calculated as xc = 2[1 − (Mn,0/Mn)] in which Mn,0 and Mn are the molar masses of the polymer precursor and the coupled product, respectively. | ||||||
1 | 5300 | 1.02 | 1/2 | 9700 | 1.02 | 0.91 |
2 | 5400 | 1.02 | 1/4 | 9800 | 1.02 | 0.91 |
As an illustration, when nitrone3 bearing the unprotected alkynegroup is added to a PVAc40-b-PAN78-Co(acac)2diblock copolymer prepared by CMRP, the symmetrical PVAc40-b-PAN156-b-PVAc40triblock copolymer mid-chain functionalized by the alkynegroup is formed (see Scheme 4).
Again, the high efficiency of the coupling reaction is also here demonstrated by the clear shift of the SEC chromatogram of the diblock copolymer towards the higher molecular weight side with almost no residual diblock copolymer being left over. Moreover, a very low polydispersity (Mw/Mn = 1.04) is maintained after this reaction. Fig. 6 depicts the successive growth of the polymer chains. On the right, the PVAc-Co(acac)2polymer is shown with the dashed line representing the distribution of the chain extended PVAc-PANdiblock copolymer. Finally, the ABA triblock copolymer that is directly obtained from the nitrone coupling reaction is shown at the lowest retention time.
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Fig. 6 Size exclusion chromatography of PVAc-Co(acac)2 (right; Mn,SEC DMF = 15900 g mol−1; Mw/Mn = 1.04), PVAc-b-PAN-Co(acac)2 (middle; Mn,SEC DMF = 50700 g mol−1; Mw/Mn = 1.03) and PVAc-b-PAN-b-PVAc (left; Mn,SEC DMF = 81400 g mol−1; Mw/Mn = 1.04) formed by coupling PVAc-b-PAN-Co(acac)2 with nitrone3. |
1H NMR analysis of the coupled copolymer evidences the presence of signals that are typical of PVAc and PAN but also the presence of protons of the phenyl group of the alkoxyamine at 7.6–7.9 ppm (see Fig. S3, ESI†), attesting the successful incorporation of the functional nitrone in the copolymer. Comparison of the integrals of C–O(C
O)–CH3 of PVAc at 4.78 ppm to that of the phenylprotons at 7.6–7.8 ppm allows to determine the experimental VAc unit/alkoxyamine ratio in the copolymer. This VAc/alkoxyamine molar ratio is 90 and thus close to the theoretical value ([VAc]/[alkoxyamine]th = 80) determined from the absolute molecular weight of PVAc used for the synthesis of the copolymer (Mn,abs = 3400 g mol−1) and taking into account that one alkoxyamine is formed per chain during coupling as depicted in Scheme 4. This corresponds to a coupling efficiency of approximately 90% (assuming a perfect block extension).
Sample | Endgroups | M n, SEC THF a | M n/Mw | M n, NMR b | Functionalityc |
---|---|---|---|---|---|
a THF GPC directly calibrated with polystyrene standards. b Calculated based on integration of –CH2–N3NMR peak compared to backbone –CH2–. c Calculated based on residual tosylate observed in spectrum. | |||||
PEG 1 | CH3O, N3 | 7040 | 1.03 | 6400 | 93% |
PEG 2 | 2x N3 | 5860 | 1.03 | 5120 | 92% |
To assess the coupling efficiency of the CuAAC reaction, first conjugations were carried out on the simplest available system, i.e. the midchain functional PVAc as also shown in Fig. 4. Fig. 7 depicts the molecular weight distributions before and after polymerconjugation. The dotted line represents the PVAcpolymer with the embedded alkyne functionality ion midchain location. The dashed line shows PEG 1. As already seen in the elugram discussed above in the context of PVAcNMRC, a small amount of uncoupled starting material is still visible in the distribution, which consequently also does not react in the CuAAC reaction. The main distribution, however, shifted and a number average molecular weight of 10800 g mol−1 is obtained by SEC in dimethylacetamide solution (for a list of all molecular weights involved in the CuAAC reactions, refer to Table 4). It should be noted that no match of the measured molecular weight with the addition of the individual building blocks must be expected since block copolymers and star-shaped materials in particular do not allow for accurate molecular weight distributions when the universal calibration principle is applied. Nevertheless, the clear shift of the distribution is indicative of a successful click reaction. Due to the overlapping low-molecular weight shoulder of the PVAc material, it is unclear if some of traces of PEG 1 are still present in the polymer after reaction. Inspection of the product distribution, however, suggests that an almost quantitative conjugation has occurred.
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Fig. 7 Distributions of alkyne-midchain functional PVAc, PEG-1 and the conjugation product (PVAc)2-PEG. |
Polymer | M n,GPC/g mol−1a | M w/Mn |
---|---|---|
a Measured on a SEC with DMAc as the eluent, calibrated directly with polystyrene standards. | ||
PVAc-alkyne-PVAc | 9400 | 1.10 |
PVAc-b-PAN-alkyne-PAN-b-PVAc | 38700 | 1.05 |
(PVAc)2PEG | 10800 | 1.09 |
(PVAc-b-PAN)2PEG | 45200 | 1.05 |
(PVAc)2PEG(PVAc)2 | 12600 | 1.09 |
(PVAc-b-PAN)2PEG(PVAc-b-PAN)2 | 43200 | 1.05 |
With the success of the above reaction largely confirmed, the mid-chain functionalized ABA triblock copolymer was subjected to the CuAACconjugation. The outcome of such reaction is depicted in Fig. 8. Again, a clear shift of the whole distribution is observed with the apparent Mn changing from 38700 to 45200 g mol−1, indicating an efficient polymerconjugation reaction. Since the PEG 1 is significantly smaller in size than the PVAc-b-PAN-b-PVAc triblock, no overlap of the product distribution is observed and complete disappearance of the PEG can be confirmed. Thus, it can be concluded that the reaction—as expected—proceeds well in equimolar conditions.
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Fig. 8 Distributions of alkyne-midchain functional pVAc-b-PAN-b-PVAc, PEG-1 and the conjugation product (PVAc-b-PAN)2-PEG. |
In the present case relatively small PEG chains were attached to the PVAc-PAN triblocks. Even though not tested, there is, however, only little doubt that also larger chains could be coupled since CuAAC usually allows for conjugations also between larger macromolecules. Instead of conjugation of higher molecular weight compounds, we choose a different route and aimed at conjugation of the same PVAc and PVAc-PAN blocks with bifunctional PEG 2, thus creating H-shaped polymers. Analogue reactions to PEG 1 were carried out and the resulting molecular weight distributions are given in Fig. 9 and Fig. 10.
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Fig. 9 Distributions of alkyne-midchain functional PVAc, PEG 2 and the conjugation product (PVAc)2-PEG-(PVAc)2. |
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Fig. 10 Distributions of alkyne-midchain functional PVAc-b-PAN-b-PVAc, PEG 2 and the conjugation product (PVAc-b-PAN)2-PEG-(PVAc-b-PAN)2. |
Overall, a very similar outcome to the conjugations with PEG 1 is observed for the PVAchomopolymer as well as the triblock copolymer. Uniform molecular weight distributions with low polydispersities are obtained. While the molecular weight distributions indicate a success of the reaction based alone on occurrence of a symmetrical shift of the distributions, closer inspection of the apparent molecular weights raises questions. As detailed in Table 4, only a slightly higher molecular weight is observed for the PVAc H-shaped polymer when compared to the three-arm star. With the coupling of the triblocks, even a slightly smaller apparent Mn is observed for the H-shaped vs. the miktostar product. Thus, at a first glance, failure of the reaction might be expected. Closer analysis indicates, however, that hydrodynamic volume effects are most likely responsible for the lack of larger shifts in the apparent molecular weight. By comparison of the midchain functionalized PVAc with the corresponding 3-arm star, one can see that the addition of PEG has only a small effect on the apparent average molecular weight, an effect that was observed before, in some cases even causing an apparent reduction of molecular weight after conjugation.43 Thus, when discussing the H-shaped material, one may assume in a good approximation that the polymer might be regarded as a four-arm star with respect to the hydrodynamic volume of the molecule. A reduction in hydrodynamic volume of chains in solution at constant molecular weight is well known to occur when going from linear polymers to n-armed star polymers. Radke et al. found that a correction factor of 1.4 or higher applies (depending on the type of polymer) when a 4-arm star (homo)polymer is analyzed using universal calibration with linear standards.44 Taking such correction into account, almost a doubling in molecular weight is observed when going from the alkyne-functional starting material to the H-shaped product. Another indication for the success of the reaction is the practically unchanged polydispersity of the product distribution. If only partial conjugation would have occurred (resulting in a mixture of unreacted precursor, three-arm and H-shape material), then a significant broadening of the distribution would need to be observed. The lack of such thus is highly indicative for an efficient conjugation.
With the larger PVAc-b-PAN-b-PVAcconjugation, similar considerations apply, even though it needs to be noted that a significantly larger correction factor would need to be applied (∼1.8) in order to explain the comparatively low apparent molecular weight of the final product. While such a high value might in principle be possible (the PVAc-PAN block composition adds to the complexity of the hydrodynamic volume effect), it cannot be proven by the present data. Thus, in order to confirm the target structure, the monomer composition of the product was analyzed viaNMR. Comparison of characteristic peaks in the 1H-NMRspectrum of the miktoarm star polymer reveals a composition (in monomer units) of PVAc:PAN:PEG of 1:
1.86
:
2.6 (by integrating the peaks around 4.8 ppm (VAc), 3.5 (PEG) and 3.2 (AN), see supporting information section for details). Based on the number of VAc monomer units present in the polymer (see NMR analysis above), a molecular weight of 6550 g mol−1 is calculated for the PEG arm, which is in almost perfect agreement with the analysis of the starting materials (6400 g mol−1, see Table 3). For the H-shape polymer, a composition of 1
:
0.87
:
2.6 is obtained, confirming the constant composition of VAc:AN and concomitantly the expected reduction of the number of PEG units in the product. Calculation of the molecular weight of the PEG block yields a molecular weight of 6100 g mol−1 and thus a result that is only slightly larger than the molecular weight of the bifunctional starting material (5120 g mol−1, see Table 3). Considering the increasing inaccuracy of the calculation method and the partial overlap of solvent peaks, also in this case a good agreement between both values is obtained. It should be noted, that while both the miktoarm and the H-shaped polymer show a constant VAc:AN content, the number of AN units is slightly overestimated. Closer inspection of this peak reveals, however, the presence of small peaks overlapping with the characteristic peak region, which might stem from the cycloaddition product. This overestimation is however inconsequential for the relative determination of the PEG content. In summary, for both polymers—despite the only small change in apparent molecular weight derived by conventional SEC analysis—successful formation of the target structures can hence be largely confirmed.
Footnotes |
† Electronic supplementary information (ESI) available: NMR spectra of the building blocks and the final products. See DOI: 10.1039/c1py00297j |
‡ Current address: Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia. |
This journal is © The Royal Society of Chemistry 2012 |