The Coil-to-Globule Transition of Single-Chain Polymeric

Article pubs.acs.org/Macromolecules

The Coil-to-Globule Transition of Single-Chain Polymeric Nanoparticles with a Chiral Internal Secondary Structure Gijs M. ter Huurne, Martijn A. J. Gillissen, Anja R. A. Palmans,* Ilja K. Voets,* and E. W. Meijer Institute for Complex Molecular Systems, Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands S Supporting Information *

ABSTRACT: The intramolecular folding of chiral single polymeric chains into single-chain polymeric nanoparticles (SCPNs) via πstacking was investigated. To this end, hydrophilic polymers grafted with structuring, chiral 3,3′-bis(acylamino)-2,2′-bipyridine-substituted benzene-1,3,5-tricarboxamides (BiPy-BTAs) units were prepared via ring-opening metathesis polymerization (ROMP). A combination of spectroscopic and scattering techniques was employed to obtain a better understanding of the folding behavior and the chiral internal structure of these systems. Circular dichroism spectroscopy showed that the folding of the polymer is highly dependent on the solvent quality and temperature. The folding process in water was finetuned via the addition of a good cosolvent (tetrahydrofuran), resulting in an optimal balance between the conformational freedom of the polymer’s backbone and the stability of the π-stacked units. Small-angle X-ray scattering (SAXS) experiments showed that the shape of the SCPNs is controlled by the formation of a chiral internal secondary structure.

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and in water.20,23,27,37 In a recent study, we investigated the shape and size of SCPNs in water and assessed the effect of temperature and cosolvent on their formation.47 In the research presented here, we extend this study to amphiphilic polymers that fold in aqueous media as a result of hydrophobic forces and π-stacking of the pendant groups. In this study we selected ringopening metathesis polymerization (ROMP) for the synthesis of polymers with a tunable number of chiral pendant functional groups because precise control over the molecular weight and molar-mass dispersity can be obtained, and a high tolerance toward functional groups is possible with this approach.48,49 As structuring motif, we opted for chiral 3,3′-bis(acylamino)-2,2′bipyridine-substituted benzene-1,3,5-tricarboxamides (BiPyBTAs)discotic molecules known to self-assemble into helical structures with a preferred handedness via solvophobic forces and π-stacking.50 This self-assembly process proceeds in solution via an isodesmic mechanism and results in supramolecular structures that emit bright green fluorescence.51−55 To allow polymer folding in aqueous media, the hydrophobic discotic units were copolymerized with hydrophilic monomers that are capable of shielding the hydrophobic structuring core and provide solubility in aqueous media. The effect of a good cosolvent and temperature on the folding process of polymeric chains grafted with structuring BiPy-BTA moieties was studied using circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS). We show that the folding of the polymer into a SCPN is

INTRODUCTION Reproducing the specific way in which Nature folds its linear polymers into perfectly defined nanostructures by using synthetic systems is a major goal in the field of synthetic macromolecular design. A new route to obtain such structures makes use of precisely engineered polymers to construct singlechain polymeric nanoparticles (SCPNs).1−6 In this biomimetic approach, linear polymers are folded into nanometer-sized objects via intramolecular cross-links between the polymer’s cross-linkable grafts. So far, several types of intramolecular cross-links have been explored, ranging from covalent7−13 to dynamic covalent14−17 to noncovalent.18−27 The structure-forming elements are usually attached as side chains to a linear polymer backbone either via direct copolymerization or by postfunctionalization.7,15,28−30 The introduction of click chemistry31,32 and advances in the field of synthetic polymer chemistry,33−36 introducing robust controlled/living polymerization techniques tolerant toward functional groups, have both been crucial to obtain tailored polymeric chains, which resulted in the flourishing field of SCPNs. The modular nature of the single chain approach allows the design of nanoparticles that have potential in various applications via the implementation of specific active groups. Rudimentary enzyme analogues have already been prepared using SCPNs, by incorporation of catalytically active groups in the foldable polymer chain. 37−42 Furthermore, SCPNs functioning as chemosensors, contrast agents, and drug carriers have been prepared.13,43−46 Since structure and function are closely related, we studied in detail how a polymer with pendant, hydrogen-bond-based supramolecular motifs folds into a SCPN in organic solvents © XXXX American Chemical Society

Received: March 23, 2015 Revised: May 29, 2015

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DOI: 10.1021/acs.macromol.5b00604 Macromolecules XXXX, XXX, XXX−XXX

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Scheme 1. Schematic Representation of the Folding of a Hydrophilic BiPy-BTA Containing Copolymer into Single-Chain Polymeric Nanoparticles as a Function of Solvent Quality

Scheme 2. Synthesis of Monomers 3 and 7 and Their Subsequent Random Copolymerization

accompanied by π-stacking of the BiPy-BTAs. In addition, the formation of small helical aggregates within the SCPNs is governed by a compromise between the polymer’s flexibility and the stability of the π-stacking. Experimental evidence for the appearance of this internal structure within the ordered SCPN could, for the first time, be probed by SAXS, presumably due to the high electron density of the BiPy-BTAs.

monomer 3, which is highly soluble in aqueous media. In addition, cis-5-norbornene-exo-2,3-dicarboxylic anhydride (1) was coupled to N-Boc-1,12-dodecanediamine (4).43 Subsequent deprotection of the Boc group resulted in the corresponding amine, which was coupled to the acid chloride of the asymmetric monoacid BiPy-BTA (6),43 resulting in BiPyBTA-based monomer 7. All compounds were fully characterized using 1H NMR, 13C NMR, DSC, and MALDI-TOF MS (see Supporting Information Section 3). Monomers 3 and 7 were copolymerized via ROMP using a third-generation Grubbs catalyst to produce random copolymers.43,57 Polymers with a degree of polymerization (DP) of approximately 100 were synthesized, incorporating 0, 5, or 10 mol % BiPy-BTA, which afforded p0%, p5%, and p10%, respectively. The degree of polymerization (DP) was estimated from the initiator-to-monomer ratio (1/100) and the monomer conversion as determined by 1H NMR of the crude reaction mixture. After purification of the polymers, the 1H NMR spectra of p5 and p10% (see Figure 1 for p5%) clearly show the

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RESULTS Synthesis and Characterization of Amphiphilic (Co)polymers. To access random copolymers that fold into welldefined single-chain polymeric nanoparticles, norbornene-based monomers comprising either a water-soluble chain or a BiPyBTA supramolecular motif were synthesized (Scheme 2). In previous studies we used oligo(ethylene glycol)-based side chains to impart water solubility in a series of amphiphilic block copolymers;27,37,39 here we focus on Jeffamines. Coupling of cis-5-norbornene-exo-2,3-dicarboxylic anhydride (1)56 with Jeffamine M-1000 polyetheramine (2) resulted in hydrophilic B


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Figure 1. 1H NMR spectrum for p5% in CDCl3.

and temperature-dependent circular dichroism (CD) spectroscopy. CD spectroscopy is an excellent method to monitor the aggregation behavior of BiPy-BTAs. When peripheral chiral information is present, BiPy-BTAs form helical aggregates that show a characteristic CD effect.53,58 For p5% and p10%, the appearance of a CD effect indicates that the pendant BiPyBTAs are capable of inter- or intrachain aggregation. In contrast, the hydrodynamic radius (RH) as obtained by DLS permits to assess whether the polymers are present as single chains or multichain aggregates in solution.23,24,26,37−39,43 Combining both techniques thus allows to monitor the folding of a single amphiphilic polymer chain in aqueous media. The reference polymer (p0%), which only consists of hydrophilic monomer 3, proved to be readily soluble in water, and DLS showed that objects with an RH of 8.0 nm were formed. The functionalized polymers (p5% and p10%), however, were not directly soluble in water due to their increased hydrophobicity. Small nanoparticles for p5% and p10% in water could only be obtained via controlled solvent exchange using stepwise dialysis.59 Hereto, a membrane filled with a solution of the polymer in THF was placed in a THF/ water mixture with a low volume fraction of water (ϕTHF = 0.8). After an hour the outer solvent was replaced with a ϕTHF = 0.6 mixture. The THF content of the solution was slowly decreased by repeating this procedure until the polymers were dissolved in pure water. This treatment resulted in aqueous solutions of p5% and p10% with an RH of 6.4 and 11.3 nm, respectively (Table 1). The CD effect observed in the CD spectra for the functionalized polymers (p5% and p10%) in water indicates the presence of a helical aggregate (Figure 2). The spectrum is different from those typically observed for helically stacked BiPy-BTAs51,58 but closely resembles the CD spectra observed for the asymmetric BiPy-BTAs that contain two chiral bipyridine arms and one aliphatic dodecyl chain.53 Furthermore, the intensity of the signal at 386 nm in p5% and p10%

aromatic protons of the bipyridine moiety between 15.5 and 7.5 ppm, while the protons arising from the water-soluble part are found around 3.5 ppm. The amount of BiPy-BTAs incorporated (mol % BiPy-BTA) was estimated from the ratio between the peaks corresponding to the aromatic BiPy-BTA protons (δ 9.63−8.28, 11H) and those related to the double bonds in the polymer backbone (δ 6.10−5.08, 4H). The values obtained for the mol % BiPy-BTA and the DPs correspond well to the targeted values (Table 1 and Supporting Information Section Table 1. Overview of Degree of Polymerization (DP), Number-Average Molecular Weight (Mn), Molar Mass Dispersity (ĐM), BiPy-BTA Incorporation (mol % BiPy), and Hydrodynamic Radius (RH) Obtained for p0−10%

polymer

feed mol % 7 [%]

p0% p5% p10%

0 5 10

conv [%]

obsd mol % BiPya [%]

DPa

Mnb [kDa]

ĐMb

RHc [nm]

100 100 100

0 4.9 10.2

97 94 96

49.0 44.7 44.3

1.29 1.23 1.30

8.0 ± 0.1 6.4 ± 0.6 11.3 ± 0.2

a

a

Based on the conversion as determined using 1H NMR. bDetermined using SEC in DMF. cDetermined by DLS in water c = 1 mg mL−1.

3). Size exclusion chromatography (SEC), calibrated with poly(ethylene oxide) standards using DMF as eluent, showed Mn values ranging from 44.3 to 49.0 kDa and narrow molarmass dispersities (ĐM) (1.23−1.30) for p0%, p5%, and p10%. Folding of the Copolymers in Water. Previous research showed that a series of BiPy-BTA pendant polynorbornenes form compartmentalized structures in organic media43 while amphiphilic BTA-pendant polymethacrylates fold in water into compact conformations with a hydrophobic interior.26,27,37,47 Here, the behavior of both the homopolymer (p0%) and the amphiphilic copolymers (p5% and p10%) was studied in aqueous environments using dynamic light scattering (DLS) C


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Supporting Information Section 4 for details), indicating that one polymer forms one SCPN across the entire range of THF/ water compositions. CD spectroscopy measurements on p10% were conducted at different ϕTHF (Figure 3A). The rather small CD effect observed at low ϕTHF changes in shape and magnitude upon an increase in ϕTHF. Upon the addition of THF, the spectra become more defined and start to correspond to the spectrum typically observed for the helically self-assembled “free” BiPyBTAs.51,58 At a certain point, however, the addition of too much THF results in a loss of the CD effect, although the shape remains unchanged, indicating that the interactions that stabilize BiPy-BTA association start to be disrupted (see Supporting Information Section 5 for details). Plotting the CD effect at a single wavelength (λ = 386 nm) versus ϕTHF at different temperatures reveals the importance of solvent composition and temperature on π-stacking between the BiPy-BTAs (Figure 3B). The minimum at ϕTHF = 0.4 and 0 °C is indicative for an optimal stacking between the BiPy-BTA moieties. In addition, temperature-dependent CD measurements show a maximal responsiveness to changes in temperature at ϕTHF = 0.4 (Figure 3B,C). In this solvent composition, the compromise between the strength of π-stacking and the conformational flexibility of the polymer allows optimal πstacking between the pendant BiPy-BTAs. Effect of Chain Length and BiPy-BTA Loading on the Copolymer Folding. To elucidate the importance of chain length and BiPy-BTA concentration on the folding behavior of the amphiphilic polymers, four additional polymers with DP = 200 and 400 with both 5 and 10 mol % BiPy-BTA incorporation were prepared (see Supporting Information Sections 3 and 5 for details). The temperature-dependent CD studies showed that the CD effect increases as a function of the BiPy-BTA incorporation. The normalized cooling curves for the polymers are, however, superimposable when only the DP or concentration is varied. This indicates that the folding behavior of polymers is influenced by its BiPy-BTA incorporation but independent of its degree of polymerization and concentrationbehavior that is similar to that previously observed in BTA-based polymethacrylates.22,37 Shape, Size, and Structure of Polymers p0%−p10% in Solution. Although there are many ways to prepare welldefined, functional nanoparticles, the precise relation between the internal structure and the overall particle shape of SCPNs is not yet clear. In fact, Pomposo et al. recently reported that apart from our previously reported BTA-based SCPNs23,27,47 many SCPNs adopt open, sparse morphologies resembling those of intrinsically disordered proteins, instead of globular

Figure 2. CD spectra of p10% in water at various temperatures (cBiPy‑BTA = 3 × 10−5 M).

(Δε = −1.7 and −3.4 M−1 cm−1, respectively) is significantly lower than the Δε = −35.6 M−1 cm−1 previously observed for “free” symmetric BiPy-BTA.41 We attribute this to hampered πstacking between the BiPy-BTAs grafted to a polymer compared to the unhindered “free” analogues. When increasing the temperature to 95 °C (Figure 2), Δε changes from −4 to −2 M−1 cm−1. This is remarkable since similar systems consistently showed a complete disappearance of the CD signal at these high temperatures, indicating a complete loss of the internal structure.37,40,47 Here, helical aggregates remain present even at 95 °C, suggesting that the aggregates are kinetically trapped within a glass-like polymer matrix. Folding of the Copolymers in THF/Water Mixtures. Recently, we showed that both temperature and the addition of a cosolvent control the global conformations and folding of SCPNs.27,47 Hence, the effect of the THF volume fraction (ϕTHF) on the folding behavior and size of p10% was further investigated via CD spectroscopy and DLS as a function of temperature and THF content. THF was selected as the cosolvent because it proved to be a good solvent for the polymers during their synthesis and is expected to increase the mobility of the polymer backbone in solution. Polymer p10% was dissolved in THF/water mixtures with different volume fractions of THF (ϕTHF) by first dissolving the polymer in the desired amount of THF, followed by slowly injecting this solution into the required amount of water. The RH of p10% was determined in all mixtures using global triexponential decay fitting (see Supporting Information Section 4 for details). This was necessary to correct for the inhomogeneous nature of the THF/water mixture due to the presence of small THF/water clusters.60 The RH values obtained via this method ranged from 5 to 11.3 nm (see

Figure 3. (A) Comparison of the CD spectra for p10% in various in ϕTHF = 0.1, 0.4, and 1.0 (cBiPy‑BTA = 3 × 10−5 M). (B) CD effect at 386 nm as a function of solvent composition and temperature (cBiPy‑BTA = 3 × 10−5 M). (C) CD spectra of p10% at various temperature in the optimal solvent composition (ϕTHF = 0.4). D


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Figure 4. Scattering curve for (A) p0% fitted with the generalized Gaussian coil model (5 mg mL−1, ϕTHF = 0.4), (B) p10% fitted with a combined generalized Gaussian coil and sphere model (5 mg mL−1, ϕTHF = 0.4), and (C) PEG-BiPy-BTA fitted with a sphere model (1 mg mL−1, ϕTHF = 0.4). For more details on the form factor models used to fit the SAXS data, see the Supporting Information Section 6.

conformations.61 Thus, we performed SAXS measurements on p0%, p5%, and p10% to study the effect of BiPy-BTA incorporation and solvent composition on the shape and internal structure of the BiPy-BTA-based SCPNs. The SAXS profile collected for p0% in the optimal solvent composition (ϕTHF = 0.4) resulted in a rather featureless scattering curve, typical for polymers in solution (Figure 4A). The scattering curve of polymer p10% (ϕTHF = 0.4), however, clearly contains an additional feature around q = 1−2 nm−1 (Figure 4B). This additional feature suggests the presence of an approximately 0.5−1 nm sized structure within the SCPNs. To elucidate the origin of this unknown feature in p10%, SAXS measurements were performed on a 9-fold oligoethylene oxidesubstituted BiPy-BTA (PEG-BiPy-BTA) discotic in ϕTHF = 0.4.62 The SAXS profile (Figure 4C) displays a q-independent intensity in the same q-regime, suggesting that the additional feature in p10% is related to the aggregates of the incorporated BiPy-BTAs. The profile obtained for the “free” PEG-BiPy-BTA in ϕTHF = 0.4 fits well to a sphere model (Figure 4C) while the SAXS profile for p0% fits to a generalized Gaussian coil model.32 Subsequently, the entire scattering curve for p10% was successfully fitted by combining the generalized Gaussian coil and sphere models. The radius of the sphere was determined to be approximately 1.1 nm via global parameter fitting of the curves corresponding to p10% and the PEG-BiPy-BTA. Assuming a typical interdisc distance for BiPy-BTA stacks (3.4 Å), the SCPNs contain 2−3 BiPy-BTA stacks, each consisting of 3−4 BiPy-BTA discs.51 The effect of the amount of BiPy-BTA incorporation on the shape of the SCPNs was evaluated by comparing polymers p0%, p5%, and p10%, which differ in the amount of pendant BiPy-BTAs in ϕTHF = 0.4 (Figure 5). The curves obtained were fitted using the combined generalized Gaussian coil and sphere model with a fixed sphere radius of 1.1 nm (Figure 5). Comparison of the curves for the various polymers shows that the additional feature, attributed to the aggregates formed by the incorporated BiPy-BTA, is the most pronounced in p10% containing the 10 mol % BiPy-BTAs, which is in line with the higher value for Δε observed in the CD experiments. From the scattering curves, values can be extracted for the radius of gyration (RG), the excluded volume parameter from the Flory mean field theory (ν), and a prefactor α, related to the electron length density difference between the sphere and polymer matrix and the abundance of spheres. These values are collected in Table 2.

Figure 5. Curves for p0%, p5%, and p10% fitted with the combined generalized Gaussian coil and fixed radius sphere model (5 mg mL−1, ϕTHF = 0.4, 20 °C).

Table 2. Data Corresponding to the Fitted SAXS Curves of Polymers p0%, p5%, and p10% in ϕTHF = 0.4 polymer

RG [nm]

ν

Rsphere [nm]

α [cm−2]

RHa [nm]

ρ

p0% p5% p10%

4.9 5.9 7.1

0.36 0.36 0.26

1.1 1.1

5.4 × 10−6 1.0 × 10−5

8.4 ± 0.3 6.5 ± 0.4 7.1 ± 0.5

0.6 0.9 1.0

a

The hydrodynamic radius as determined by DLS.

The presence of the nanometer-sized feature is described by the sphere model with a fixed radius of 1.1 nm. If the additional feature is connected to the internal structure formed by BiPyBTA moieties, the abundance of the internal structure (α) should increase with an increasing BiPy-BTA incorporation in the polymers. In fact, as seen in Table 2, α increases from 5.4 × 10−6 in p5% to 1.0 × 10−5 in p10%, strongly suggesting that the additional nanometer-sized feature is connected to BiPy-BTAbased helical aggregates within the SCPN. As earlier indicated by the CD experiments, optimal selfassembly of the pendant BiPy-BTAs was observed in a ϕTHF = 0.4 solvent mixture, while hardly any self-assembly was observed in pure water or THF. Therefore, p10% was studied in various solvent compositions (ϕTHF = 0.1, 0.4, and 1.0) using SAXS. We used ϕTHF = 0.1 instead of pure water, as it proved to be nearly impossible to obtain the required polymer concentration in pure water. The combined generalized Gaussian coil and sphere model, with a fixed sphere radius of E


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Macromolecules 1.1 nm, was used to fit the obtained scattering profiles (Figure 6). The SAXS curve for ϕTHF = 1.0 does not show a plateau at

Interestingly, the nanometer-sized feature is only observed in the ϕTHF = 0.4 mixturethe same solvent composition that gives the most pronounced CD effect in the CD measurements. This suggests that a compromise between the stabilizing πstacking and solvophobic interactions between BiPy-BTAs and the flexibility of the polymer backbone determines the folding behavior of the polymers.

solvent for the polymer backbone, improves the conformational flexibility of the polymer, resulting in enhanced π-stacking of the BiPy-BTA units. In addition, the responsiveness to temperature changes of the SCPN is improved. However, THF destabilizes the π-stacking at high ϕTHF. Whereas the BiPy-BTA content, the amount of THF added (ϕTHF), and the temperature all affect the amount of π-stacking between BiPyBTAs, the degree of polymerization does not. Scattering techniques (DLS and SAXS) provide information on the size and shape of the amphiphilic polymers in water. Comparing the RGs of the systems studied here with those reported in the literature indicates that the BiPy-BTA-based amphiphilic polymers are likely present as single-chain polymeric nanoparticles in water (Table 2).23,27,47 An increase in the BiPy-BTA incorporation results in an increase of the RG. Although this is typically attributed to the swelling of the polymer chain, the observed decrease in ν-value indicates a decrease in solvent quality, which precludes swelling of the system (Table 2). Using the RG from SAXS and the RH from DLS, we computed the particle’s shape factor (ρ = RG/RH). While p0% is present as a compact globule, p5% and p10% seem to adopt a more asymmetric shape in ϕTHF = 0.4 as the νvalues are low while the ρ-values are significantly higher. This trend is similar to what has been observed for BTA-containing SCPNs.39,40 The trends observed in the RG and RH also indicate that the conformation of the polymer depends on the solvent composition. Compared to p10% in ϕTHF = 0.4, p10% is slightly smaller in ϕTHF = 0.1 but larger in pure THF. This trend is in line with the strong impact of the good solvent THF and bad solvent water on the conformation of the polymer backbone. Remarkably, a nanometer-sized structure feature was observed in the SAXS profiles of p10%. The fact that this additional feature in the SAXS profile is only observed in the optimal solvent mixture, ϕTHF = 0.4, and its abundance increases as a function of the BiPy-BTA incorporation prompts us to conclude that the BiPy-BTA-related internal structure within the SCPN is observed. Assuming a typical interdisc distance for BiPy-BTA stacks (3.4 Å) suggests the SCPNs contain 2−3 separate BiPy-BTA stacks each with 3−4 BiPyBTA discs.32 This isas far as we knowthe first time the structured interior of a SCPN is visualized by SAXS. Presumably, the higher electron density and mass in BiPyBTAs provide the local contrast needed for visualization. It is noteworthy that similar additional features reflecting the inner structure of a BTA stack have never been observed in any of the scattering profiles for the BTA-based SCPNs we studied before.23,27,47

DISCUSSION Investigating the folding behavior of amphiphilic chiral BiPyBTA-based polymers, which only relies on π-stacking and solvophobic interactions in water−THF mixtures, reveals that these interactions drive the formation of compartmentalized structures in water. In addition, an interesting compromise was found between the conformational flexibility of the polymer and the ability of the chiral BiPy-BTA units to stack helically via π-stacking. CD spectroscopy showed that these two counteracting effects lead to optimal polymer folding in a ϕTHF = 0.4 solvent mixture. At lower ϕTHF, the formed SCPNs contain a chiral BiPy-BTA structure that is kinetically trapped in the nanoparticle’s glass-like polymer matrix, preventing the formation of helical aggregates. The addition of THF, a good

CONCLUSIONS A new step has been taken in elucidating the relation between the folding of a chiral single-chain polymeric nanoparticle via noncovalent interactions and its final conformation, by using a combination of circular dichroism spectroscopy and small-angle X-ray scattering. These techniques showed that the folding of hydrophilic poly(norbornene-imide)-based polymers by using π-stacking is highly dependent on temperature and solvent composition. While CD spectroscopy revealed the formation of the SCPN’s chiral stabilizing core, SAXS showed that the formation of such a local structure desymmetrizes the SCPN’s global conformation. Furthermore, the use of the electron-rich BiPy-BTA groups allowed the visualization of the synthetic nanoparticle’s internal structure using SAXS.

Figure 6. SAXS profiles of polymer p10% in various THF/water compositions fitted with the combined generalized Gaussian coil and sphere models. For more details on the form factor models used to fit the SAXS data, see the Supporting Information Section 6.

the smallest accessible q-value, indicating that the particles are larger than the probed length scale (RG > 10 nm). The observed slope (ν = 0.47) confirms that pure THF is a Θsolvent, which explains the swelling of the polymer. In both ϕTHF = 0.1 and 0.4 the polymers have a smaller RG (7.0 and 7.1 nm, respectively) and adopt a more compact conformation (ν = 0.31 and 0.26, respectively). Although the differences in RH are small, they are consistent with a more globular shape in ϕTHF = 0.1 and a slightly more asymmetric shape in a ϕTHF = 0.4 mixture (Table 3). Table 3. Data Corresponding to the Fitted SAXS Curves of Polymer p10% in Various THF/Water Compositions (ϕTHF) ϕTHF

RG [nm]

ν

0.1 0.4 1.0

7.0 7.1 >10

0.31 0.26 0.47

Rsphere [nm] 1.1

α [cm−2]

RH [nm]

ρ

1.0 × 10−5

6.9 ± 0.3 7.1 ± 0.5 7.8 ± 0.2

1.0 1.0 >1.2

■

■

F


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Macromolecules

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Control over the polymeric architectures in combination with detailed conformational studies of the formed SCPNs is crucial to achieve systems that show protein-like functions in the areas of catalysis and sensing. This research further increases our understanding of the folding behavior of precisely engineered polymers into single-chain polymeric nanoparticles with defined conformations. Our next step is to understand the relationship between polymer sequence, folding of the polymer, and how structure translates into function.

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ASSOCIATED CONTENT

S Supporting Information *

Detailed experimental procedure, 1H NMR spectroscopy, dynamic light scattering, circular dichroism spectroscopy, and small-angle X-ray scattering. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.5b00604.

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AUTHOR INFORMATION

Corresponding Authors

*(A.R.A.P.) E-mail [email protected], tel 0031 40 247 3105. *(I.K.V.) E-mail [email protected], tel 0031 40 247 4427. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is financed by The Netherlands Organization for Scientific Research (NWO-TOP grant 10007851), the Dutch Ministry of Education, Culture and Science (Gravity program 024.001.035), and the European Research Council (FP7/20072013, ERC Grant Agreement 246829). I.K.V. is grateful for financial support from The Netherlands Organization for Scientific research (NWO VENI grant 700.10.406, ECHOSTIP 717.013.005) and the European Union through the Marie Curie 5 Fellowship program FP7-PEOPLE-2011-CIG (contract no. 293788). We gratefully thank Jolanda Spiering for providing the BiPy-BTA wedge. The ICMS Animation Studio (Eindhoven University of Technology) is acknowledged for providing the artwork.

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The Coil-to-Globule Transition of Single-Chain Polymeric

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