Monoalkyl Poly(2-methyl-2-oxazoline) Micelles. A Small-Angle

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Monoalkyl Poly(2-methyl-2-oxazoline) Micelles. A Small-Angle Neutron Scattering Study Gise`le Volet,*,† Loı¨c Auvray,‡,§ and Catherine Amiel† Syste`mes Polyme`res Complexes, Institut de Chimie et des Mate´riaux Paris-Est, 2 rue Henri Dunant, 94320 Thiais, France, Laboratoire León Brillouin, CEA CNRS, CEN Saclay, 91191 Gif sur YVette cedex, France, and Laboratoire Mate´riaux Polyme`res aux Interfaces, UniVersite´ d’EVry Val d’Essonne, Rue du Pe`re Jarland, 91025 EVry cedex, France ReceiVed: April 1, 2009; ReVised Manuscript ReceiVed: July 24, 2009

This paper presents a SANS study of hydrophobically end-modified poly(2-methyl-2-oxazoline) (POXZ-Cn) micelles in aqueous solutions. Strong long-range repulsive interactions between the micelles are evidenced by correlation peaks present at concentrations as low as 0.5 wt %. Due to the dissymmetry in size between the hydrophobic and hydrophilic parts of the chains, the micelles have been analyzed using a model of starlike micelles. Large extension of the POXZ arms into the micelles can explain the original SANS behavior. The dissociation of the micellar structures by adding a complexing agent of the alkyl groups, hydroxypropyβ-cyclodextrin (HPβ-CD), has been followed by SANS. The micelles are progressively disrupted by the addition of increasing amounts of HPβ-CD, and the SANS behavior of free chains is recovered in the presence of an excess of the complexing agent. Introduction Mixtures of anionic and cationic surfactants self-assemble into various microstructures such as micelle, vesicle, lamellar, columnar, and cubic mesophases, depending on the strength of intra- and intermolecular interactions, the relative fractions of different groups within the molecules, and the shape of the molecules.1-3 Polymeric micelles or vesicles derived from amphiphilic polymers in aqueous solution offer several advantages relative to such conventional surfactants. Nonionic polymers demonstrate lower pH and saline sensitivity than ionic surfactants, and micelles or vesicles produced from these polymers would be expected to show this same reduced sensitivity.4 Additionally, amphiphilic polymers are of great interest due to their potential application in detergency, dispersion stabilization, foaming, emulsification, lubrication, separation technologies, drug delivery systems, and protection of microorganisms against mechanical damages in bioreactors.5-7 Most amphiphilic polymers are block or graft copolymers based on poly(ethylene oxide) used as the hydrophilic moiety, and the hydrophobic moiety is made of poly(propylene oxide), polyesters, polystyrene, poly(amino acids), or polyalkanes.8-12 Other amphiphilic copolymers are made from poly(N-acylethylenimine) or poly(2-substituted-2-oxazoline), and the lipophilic/ hydrophilic balance is introduced by changing the nature of the acyl group.13-16 An important new class of block copolymer is based on poly(2-alkyl-2-oxazoline). Diblock copolymers were synthesized based on poly(2-ethyl-2-oxazoline) as the hydrophilic block and poly(L-lactide) or poly(ε-caprolactone) as the hydrophobic block.17 Other diblock copolymers were synthesized based on poly(2-methyl-2-oxazoline) (POXZ).18-22 This hydrophilic polymer contains an amide function in its unit (also present in proteins), which justifies its use in biomimetic polymer systems because it constitutes a pseudopeptide chain. * To whom correspondence should be addressed. Tel.:+33-1-49 78 12 35. Fax: +33-1-49 78 12 08. E-mail: [email protected]. † Institut de Chimie et des Mate´riaux Paris-Est. ‡ CEN Saclay. § Universite´ d’Evry Val d’Essonne.

Another interest in POXZ is that it shows comparable properties to those of poly(ethylene oxide), particularly its nontoxicity and its good biocompatibility,18,23-25 and no immunoresponse has been reported even in complex biological matrixes.25 Consequently, poly(2-methyl-2-oxazoline) is widely studied for biomedical applications such as drug-delivery systems and for the construction of artificial membranes.26 Previously, we have reported the synthesis and the micellar structures of a monoalkyl end-capped poly(2-methyl-2-oxazoline) (POXZ-C12 and POXZC18).27 It was found that critical micelle concentrations are between 7 × 10-4 and 4 × 10-2 wt % and are dependent on the hydrophilic/lipophilic balance. This study evaluates the structural properties of the aggregates by small-angle neutron scattering (SANS). It will be shown that the micelles have an original behavior, with correlation peaks present at low concentration well described by a model of interacting star-like micelles. The parameters that will be studied are the chains’ molecular weights (between 3 × 103 and 7 × 103), the nature of the end groups (C12 and C18), and the concentrations (from 0.1 to 2%). A second part will be devoted to the SANS study of the micelles dissociation by addition of a β-cyclodextrin compound, hydroxypropy-β-cyclodextrin (HPβ-CD). Indeed, HPβ-CD, by making inclusion complexes with the alkyl groups, compete with the process of self-association of the alkyl groups, which is responsible for the micelle formation. It will be shown that the behavior of free chains is recovered by addition of HPβCD in excess. Experimental Section Materials. The monomer 2-methyl-2-oxazoline (Aldrich, Milwaukee WI, U.S.A., purity 99%) was dried overnight over calcium hydride and purified by distillation under a nitrogen atmosphere. Acetonitrile (SDS, Peypin, France) was distilled over calcium hydride before use. Iodomethane (purity 99%), 1-iodododecane (purity 98%), and 1-iodooctadecane (purity 95%) were purchased from Aldrich and used as received. Methanolic KOH was prepared from methanol (SDS) and pellets of KOH, used as purchased. Hydroxypropylβ-cyclodextrin HPβ-

10.1021/jp9029634 CCC: $40.75  2009 American Chemical Society Published on Web 09/21/2009

Monoalkyl Poly(2-methyl-2-oxazoline) Micelles

Figure 1.

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J. Phys. Chem. B, Vol. 113, No. 41, 2009 13537

H spectrum of POXZ-C12-B.

TABLE 1: Synthesis and Characteristics of POXZ-Cn polymer

initiator

[M]0/[I]0 feed ratio

time (h)

yield (%)

POXZ POXZ-C12-A POXZ-C12-B POXZ-C18-A POXZ-C18-B

CH3I CH3(CH2)11I CH3(CH2)11I CH3(CH2)18I CH3(CH2)18I

60 29 58 35 88

18 18 18 18 24

95 99 95 95 90

a

MRMN 4.9 ×103 a 2.5 × 103 5.5 × 103 3.4 × 103 6.6 × 103

SANS MCD 2Cl2

2Cl2 (Å) RCD g

3.3 × 103 2.1 × 103 6.0 × 103 2.7 × 103 6.7 × 103

24 15 71 24 47

Estimated by SEC and a refractometric detector.

CD (with molar substitution of 0.8) was purchased from Aldrich. Deuterated methylene chloride CD2Cl2 and D2O (Eurisotop, CEA Saclay) were used as received. Synthesis of Monoalkyl End-Capped Poly(2-methyl-2oxazoline). C18- or C12-POXZ were prepared by cationic polymerization according to the procedure reported elsewhere.27 Briefly, the monomer 2-methyl-2-oxazoline was polymerized in dry acetonitrile under dry nitrogen. Different alkyl iodides were used as the initiator, iodomethane, 1-iodododecane, or 1-iodooctadecane. A typical procedure with iodomethane as the initiator is given as follows. To 30 mL of dried acetonitrile, 10 mL (1.18 × 10-1 mol) of 2-methyl-2-oxazoline was introduced, and 0.12 mL (1.93 × 10-3 mol) of iodomethane was added. After stirring for 18 h, at 80 °C, the polymerization was stopped by pouring methanolic KOH into the reaction mixture. The polymer was purified by precipitation in diethyl ether and then dried under vacuum. The other polymers with a hydrophobic group were prepared similarly using 1-iodododecane or 1-iodooctadecane as the initiator. Characterization of Polymers. The polymers were characterized by 1H NMR on a Bru¨ker Avance 400 spectrometer, in deuterated chloroform. Size exclusion chromatography (SEC) was performed on a chromatograph equipped with a pump P 100 (Spectra-Physics, Fremont, CA, U.S.A.), a Rheodyne injector, a set of two columns, PL-aquagel OH-30 and OH-40 (Polymer Laboratories, Shropshire, U.K.), and a differential refractometer RI 71 (Shodex, Japan) connected at the end of the columns. The chromatographic analysis of polymers was done in an aqueous 0.1 mol · L-1 LiNO3 solution after calibration of the columns with a set of poly(ethylene oxide) (PEO) standards with a range of molecular weights from 2 × 102 to 6.45 × 105 g · mL-1. The polymer solutions were prepared at a concentration of 10 mg · mL-1.

Neutron Scattering Measurements. Small-angle neutron scattering (SANS) measurements were performed at the Laboratoire León Brillouin (ORPHEE reactor, CEN Saclay) on the PACE spectrometer. The experimental scattering vector q (q ) (4π/λ) sin(θ/2)) range was 0.0032 < q (Å-1) < 0.12 and was covered by two sample-to-detector distances (3 m at the neutron wavelength of 6 Å-1 and 4.6 m at 13 Å-1). The samples were loaded into Hellma quartz cells with a 2 mm optical path length. The cells were placed in a sample changer, and the scattering for each sample was measured for about 2 h at room temperature. Scattering intensities from solutions were corrected for empty cell scattering, solvent scattering, and sample transmission. I(q) is on the absolute scale (cm-1). All of the polymer solutions were prepared by weight at a concentration of 1 or 2 wt % in D2O or in deuterated methylene chloride, respectively. These solutions were kept under stirring for 24 h before measurement by small-angle neutron scattering (SANS). Results and Discussion Synthesis and Characterization of POXZ-Cn. The polymers POXZ-Cn were prepared by cationic polymerization with good yields (>90%). The alkyl end group (C12 or C18) were structurally incorporated in the chain by the use of a specific alkyl iodide initiator. The experimental conditions of the synthesis are reported in Table 1. This synthesis was described in detail in a previous paper.27 The molecular weights of the polymers POXZCn are over the range from 2 × 103 to 7 × 103. The polydispersity indexes Mw/Mn are between 1.1 and 1.2, giving narrow molecular weight distributions. A typical 1H NMR spectrum of POXZ-C12-B polymer is shown in Figure 1, where characteristic peaks have been assigned. Molecular weights were determined from the peak integration ratios of methyl protons in a POXZ repeating unit at 2.01 ppm and methyl protons of

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C12-B at 0.77 ppm. In the case of POXZ, the NMR molecular weight determinations could not be done since the terminal methyl group could not be isolated on the spectra. Instead of that, it has been analyzed by size exclusion chromatography in aqueous solvent. The determination, based on a PEO calibration curve and using a refractometric detector, gives Mn ) 4.9 × 103 and Mw ) 6.9 × 103 g · mol-1, in the same range as the ones determined by NMR. The polymers were also characterized by SANS in CD2Cl2, which is a solvent of the macromolecular chain POXZ and of the end group Cn. At small angles, the scattering intensity can be approximated by the Zimm eq 1a or by the Guinier eq 1b, yielding a radius of gyration

(

ln I(q) ) ln I0 -

Figure 2. Scattering from different POXZ in D2O at 1 wt %.

)

(1a)

R2g 2 q 3

(1b)

R2g 1 1 1 + q2 ) I I0 3

In the plots 1/I versus q2 (not shown), only the linear part of the scattering data has been taken into account for the analysis. From the extrapolated scattered intensity at q close to zero (I0), the polymers’ molecular weight was calculated according to eqs 2 and 3.

I0 ) φVPOXZNPOXZ(nPOXZ - ns)2

(2)

where φ is the volume fraction, VPOXZ is the partial volume of a unit, NPOXZ is the degree of polymerization, and nPOXZ (or ns) is the scattering length density of the polymer (or solvent). The contribution of the alkyl group to the scattering is neglected. The scattering length density of the POXZ has been calculated assuming densities equal to 1 g/cm3, nPOXZ ) 1.10 × 1010 cm-2.

Mw ) NPOXZMOXZ + MCn

(3)

MOXZ and MCn are the molar mass of the OXZ unit and hydrophobic end group, respectively. The molecular weights determined by NMR and SANS can be compared from Table 1. The values are generally in good agreement. The radius of gyration Rg has been determined from the slope of the Zimm plot. For the same molecular weight, the radii of gyration Rg of POXZ-C12 and POXZ-C18 are similar and are close to the one of the precursor polymer POXZ. The Rg values for the polymers range from 15 to 70 Å, depending mainly on molecular weight. Behavior of POXZ and POXZ-Cn in D2O. The amphiphilic nature of the polymers POXZ-Cn consisting of hydrophilic POXZ and hydrophobic alkyl end group provides an opportunity to form micellar aggregates above a critical concentration in a selective solvent like water. The presence of hydrophobic microdomains which may constitute the micellar cores groups has been probed by fluorescence measurements in a previous work.27 Critical micelle concentrations (cmc) were in the range of 7 × 10-4 to 4 × 10-2 wt % and were dependent on the hydrophilic/lipophilic balance. Indeed, the value of cmc increased with the molecular weight of the macromolecular chain and decreased when the length of the alkyl end group increased.27

Figure 3. Plot ln(I) versus ln(q) for different POXZ in D2O at 1 wt % (scale of ln(I) shifted by (-0.8) for POXZ).

Aqueous solutions of POXZ and POXZ-Cn at concentrations above the cmc have been studied by SANS. Figure 2 shows the SANS scattering intensity I(q) as a function of q obtained from POXZ-Cn in D2O at a concentration of 1% w/w and of POXZ at the same concentration. The scattering of POXZ corresponds to the one of nonassociated chains. The analysis of the low q intensity dependence allows determination of the molecular weight and the radius of gyration using the Zimm eq 1a. Mw ) 3.7 × 103 is in good agreement with the value determined by SANS in CD2Cl2 (Table 1), proving that the POXZ chains are not aggregated in water. The radius of gyration Rg ) 50 Å is larger than that in CD2Cl2. Figure 3, which is a ln(I) versus ln(q) representation, emphasizes the behavior at large q. I varies with a power law q-1.1 at large q. The close to -1 exponent value shows that the POXZ have local rod conformations and behave as semiflexible chains28 with a persistence length Lp on the order of 1/qc, where qc is the crossover of the q-1.1 regime, as indicated in Figure 3. This gives Lp ∼ 20 Å. Thus, both the low q behavior, which shows an expansion of the chains, and the large q behavior, evidencing a local rod conformation, are in agreement with a phenomenom of chain structuring in aqueous solvent. Semiflexible behavior of polyoxazolines has not been reported yet in the literature. The origin of this phenomenon could be due to helical conformations of the POXZ chains, water molecules being used to stabilize the helices by making hydrogen bonds between two units.29,30 Contrary to the scattering pattern of the unmodified POXZ, where the intensity decreases monotoneously with q, correlation peaks are clearly observed for all of the POXZ-Cn samples studied at 1 wt % concentration (Figure 2). Similar correlation peaks have been observed in the case of the micelles of neutral



Figure 4. (a) Scattering from POXZ-C12-B in D2O at different concentrations (wt %). (b) Scattering from POXZ-C18-B in D2O at different concentrations (wt %).

diblock copolymers22,31 and in aqueous solutions of poly(ethylene oxide)-based alkyl-terminated polymers (PEO-Cn or Cn-PEO-Cn).32,33 These last amphiphilic copolymers are architecturally similar to the ones of this study. The appearance of correlation peaks in the case of POXZ-Cn is not surprising and may result from micelle-micelle interactions at concentrations close to or above the micelle overlap concentrations. However, we must emphasize that it is quite surprising to observe correlation peaks in the case of low-molecular-weight polymers (2 × 103 to 6 × 103) at low concentration (less than 1%). For comparison, PEO-Cn of larger molecular weight (1.6 × 104) and bearing C16 end groups had a micelle overlap concentration of 5%.32,33 Recently, short diblock amphiphilic copolymers bearing a POXZ block of molecular weight around 3 × 103 were shown to form micellar structures, but correlation peaks were only observed at concentrations larger than 6 wt %.22 Varying the concentration from 0.1 to 2 wt % enables us to cross the boundary of the dilute to the semidilute regime. Scattering intensities in this concentration range are shown in Figure 4 for POXZ-C12-B and POXZ-C18-B. In the case of POXZC12-B (Figure 4a), the scattering corresponds to one of the nonassociated chains at 0.1 wt %, and correlation peaks have been observed for upper concentrations. In the case of POXZC18-B (Figure 4b), at the lowest concentration (0.1 wt %), the data are more noisy, but the micellar suspension is clearly located in the dilute regime as the intensity is decreasing monotoneously with q. A Zimm plot analysis (eq 1a) allows determination of the weight average molecular weight of the aggregates Mw ) 1.58 × 105 and its radius of gyration Rg ) 225 Å. In this analysis, it has been assumed that all of the chains belong to the micelles, the concentration 0.1% being much larger than the cmc (2 × 10-3 wt %). An estimate of the aggregation number can be deduced from the molecular weight of the unassociated chains (6.7 × 103), Nagg ) 23. This number is in good qualitative agreement with the ones determined for monoalkyl-terminated PEO chains.34 The critical overlapping concentration of the aggregates defined as

c* )

Mw 4 Na π(Rg)3 3

(4)

can thus be calculated; c* ) 0.55 wt % and seems to be in good agreement with the results of Figure 4b. Indeed, a change in the intensities versus q behavior occurs between the concentrations of 0.1 and 0.5 wt %. The appearance of a correlation

TABLE 2: Value of qmax Determined from the Curves Ic(q)/I0.1(q) versus q for POXZ-C18-B [polymer] (%)

qmax (Å-1) 2.2 × 10-2 2.5 × 10-2 2.6 × 10-2

0.5 1 2

peak in the 0.5 wt % sample shows that the micelles are already experiencing repulsive interactions due to their close contact in solution. The scattering intensities are related to the form factor P(q) of the micelles and to their structure factor S(q) via the following relationship

I(q) ) I0 · P(q) · S(q)

(5)

where I0 ) φVPOXZN(nPOXZ - ns)2 (as in eq 2) and N is the number of POXZ units in the micelles. Before trying to fit the SANS results through a model, a first analysis of the peak maxima can give an estimate of the sizes in the interacting system. Making the rough approximation that the form factor can be deduced from intensity measurements at low concentration (0.1 wt % in the case of POXZ-C18-B), the structure factor Sc(q) of a sample at a concentration c should be simply proportional to the ratio Ic(q)/I0.1(q). Due to the low precision of the measurements at 0.1 wt %, the points are relatively scattered, but the peak maxima qmax(c) of the structure factors can be determined unambiguously. The results for concentrations ranging from 0.5 to 2 wt % are reported in Table 2 for POXZC18-B. The peak position qmax(c) should be of the same order as R-1 g . More precisely, if we assume a model based on a distorded face-centered cubic lattice,35 the mean distance D between the particle centers is related to qmax(c), D ) 1.22(2π/qmax(c)). Close to the critical overlapping concentration c*, where a close packing of the aggregates should occur, D should be approximately 2Rg. At c ) 1%, this gives Rg ) 155 Å, a value in good agreement with the Rg determined in the dilute regime. Many attempts to model the structure of polymeric micelles have already been made. In the case of block copolymers, corescorona models of particles interacting via a hard sphere potential have generally been used.31,36 In the case of the POXZCn samples, the hydrophobic block (alkyl group) is very small compared to the hydrophilic block (POXZ), and a core-corona model should poorly describe our system as the size of the core should be very small compared to the one of the corona. The structure of the POXZ-Cn micelles should be close to the one

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TABLE 3: Fit Parameters of the Four Samples at 1 wt % Concentration and Contour Lengths (Lc) polymer (at 1 wt %)

RHS(Å)

F (Å)

φS

E (cm)-1

F (cm)-1

ξ (Å)

Lc (Å)

112 173 146 228

66.8 82 62.9 126

0.021 0.02 0.078 0.022

0.31 0.10 1.29 1.04

0.053 0.27 0.16 0.102

10 26 18.1 15

100 260 130 300

POXZ-C12-A POXZ-C12-B POXZ-C18-A POXZ-C18-B

of star polymers. Dilute and semidilute solutions of star polymers have been analyzed by SANS by many authors,37-39 and correlation peaks have also been reported, the critical volume fraction above which peaks were observed being dependent on the number of arms of the star. Theoretically, the behavior of star polymers has been studied by Daoud and Cotton,40 Birshtein et al.,41,42 Witten et al.,43 and Marques et al.44 Micelles and flowers of PEO-Cn and Cn-PEO-Cn have been analyzed in terms of star polymers,32 and the same model will be used to fit the SANS data of the present work. We will consider that the hydrophobic core of the micelles contribute negligibly to the scattering and that the main contribution is due to the POXZ chains. In the semidilute regime, the star-like micelles are overlapping, and two regions can be defined, unperturbed internal regions of the stars of radius F, which are embedded in a sea of blobs of constant size ξ. The intensity can be decomposed into two contributions,32,44 I(q) ) Is(q) + Ib(q) where Is(q) expresses correlation between the different stars, and Ib(q) accounts for density fluctuations in the inner parts of the stars and in the sea of blobs. According to Beaudouin and al,32 I(q) can be expressed by the following relationship, under θ-solvent conditions

I(q) )

∆b22 N2a

[

Nm MwNagg

( RF ) ] [ 6[qF -q Fsin(qF)] ] S(q) + 2 2

2

3 3

K1jc2(∆b2)2

ξ3 1 + q2ξ2

(6)

The structure factor S(q) is the Percus-Yevick approximation of the hard sphere of radius RHS and volume fraction φs. Nm is the number of stars per unit volume, Nagg the aggregation number, R the maximum extension of the stars (in dilute solution), F the radius of the unperturbed part of the stars, and Mw the polymer molecular weight. The ∆b2 is the contrast length in cm/g. K1 is a numerical prefactor and c the polymer concentration (g/cm3). Na is Avogradro’s number. Equation 6 can be rewritten as

[

I(q) ) E

]

6[qF - sin(qF)] 2 F S(q) + q3F3 1 + q2ξ2

(7)

where E and F correspond to eqs 8 and 9

E)

∆b22 N2a

[

Nm MwNagg

( RF ) ]

F ) K1jc2(∆b2)2ξ3

2 2

(8)

(9)

The SANS data have been fitted using eq 6 and using the following parameters, RHS, φs, F, ξ, E, and F. The fit parameters are given for the four polymer samples at 1 wt % concentration in Table 3, whereas the fits are shown

in Figure 5. It appears that the SANS results cannot be fitted with φs values larger than 0.08 for all of the samples studied. However, as the aggregation number has been estimated for POXZ-C18-B at low concentration (Nagg ) 23), the expected value of φs calculated from the following relationship, φs ) Na · C · 4/3π(RHS)3/(Nagg · Mw(chain)), is on the order of 0.5, several times larger than the value deduced from the fit. A possible explanation of this discrepancy could come from the model of monodisperse star-like micelles which has been used. It is known that introduction of polydispersity dampens the oscillations in a similar way as those obtained with lower volume fractions. For this reason, it has not been possible to extract aggregation numbers from the fits. The correlation lengths are not obtained with a good sensitivity and thus will not be discussed extensively. The parameters RHS and F are the ones which are more precisely determined and depend only in a limited way on the fit procedure (parameters φs and ξ being imposed at different values). In all cases, the radius F, which represents the size of the nonoverlapping part of the stars, is smaller than RHS by a factor of ∼2. The contour lengths (Lc) of the chains have been calculated as the sum of the contributions from the alkyl group and POXZ chain, the contour lengths of C12 and C18 groups being, respectively, 17 and 24 Å and the size of a POXZ unit being 3.5 Å. As shown in Table 3, the hard sphere radius RHS and Lc are quite comparable. Figure 6 shows the variation of RHS and F with the concentration for POXZ-C18-B. These two quantities show qualitative variations in agreement with the models of stars, that is, RHS and F decrease with the concentration above the critical overlapping concentration c*, which should be in the range of 0.1 < c* < 0.5 wt %. More precisely, the star model predicts the relationship F R (c/ c*)-a for c > c*, where the exponent a is equal to 3/4 or 1 in good or θ-solvent conditions.33,44 The relative changes in F at concentrations of 1 and 2 wt % (larger than c*) are smaller than expected from the above relationships. This discrepancy can be attributed to the semirigid behavior of the polyoxazoline micellar arms (as evidenced by the large q behavior of unmodified polyoxazoline and by the large extension of the micelles). This should modify the interpenetration of the stars and explain the milder variations in F than expected. It should be noted that, in the low concentration range (0.1 wt %), F (200 Å) is the size of the star in dilute solution (R) and is in good agreement with the Rg value calculated from a Guinier analysis (Rg ) 225 Å; see above). The fact that F is of the same order as Lc (300 Å) shows that the chains in the stars are largely extended. This large extension can be at the origin of the unusual behavior observed for the POXZ-Cn micelles compared to the similar PEO-based systems and to the micelles of POXZ-based diblock copolymers.22 Dissociation of Micellar Structures by Adding Cyclodextrins. In order to dissociate the micellar structures, hydroxypropy-β-cyclodextrin (HPβ-CD) was added into the polymer solutions, in variable excess compared to the alkyl groups. Indeed, one of the most characteristic features of cyclodextrins is their ability to form inclusion complexes with various hydrophobic or amphiphilic species by capturing different guest molecules inside of their hydrophobic cavities.45 This charac-



Figure 5. Fits (red lines) of the SANS results (blue cross) for the four samples at 1 wt % concentration, POXZ-C12-B, POXZ-C12-A, POXZ-C18-B, and POXZ-C18-A.

Figure 6. Influence of the concentration on radius: RHS ([) and F (9) for POXZ-C18-B.

teristic has been used to inhibit polymer-polymer associations in aqueous solutions of amphiphilic polymers, to control the rheology of polymer-surfactant systems, and, more recently, to decompact DNA surfactant complexes.36,46-50 In a previous work, β-cyclodextrin was used to reduce the viscosity of a dilute aqueous POXZ-Cn solution.27 The dissociation of aggregates was ensured by the complexation of the hydrophobic end groups inside of the hydrophobic cavities of β-CD. Intrinsic viscosities of the complexes POXZ-Cn/β-CD were comparable to the ones of free precursor POXZ chains when β-CD was added in large excess (3 β-CD for 1 alkyl), showing the efficiency of the dissociation. In this study, another β-cyclodextrin compound (HPβ-CD) has been used instead of β-CD since it is totally soluble under the conditions of the SANS experiments, whereas the solubility limit of β-CD is around 10-18 g/L. Moreover, HPβ-CD has comparable affinities for the alkyl end groups as β-CD, as shown in the literature.51,52 Aqueous solutions of POXZ-Cn (1 wt %) containing various amounts of HPβ-CD have been studied by SANS (Figure 7). The correlation peaks are clearly affected by the molar ratio HPβ-CD/alkyl. Adding increasing amounts of HPβ-CD de-

creases continuously the structure factor contribution to the scattering until the disappearance of the correlation peak at a large HPβ-CD/alkyl molar ratio. It is apparent in Figure 7 that the rates of disappearance of the peaks depend on the alkyl length, larger excess being needed in the cases of POXZ-C18-A (Figure 7c) and POXZ-C18-B (Figure 7d) than in the cases of POXZC12-A (Figure 7a) and POXZ-C12-B (Figure 7b). It should be noted that the strongest effect is observed for the lower-molecular-weight polymer bearing C12 end groups (POXZ-C12-A), where the scattered intensity becomes comparable to that of the precursor POXZ at a HPβ-CD/alkyl molar ratio of 1. It means that a majority of the micelles have been dissociated at this ratio. Previous works have shown that C12 surfactant micelles were completely dissociated by adding β-cyclodextrins, proving that the competitive mechanism of association of the C12 groups (inclusion complexes with the cyclodextrins versus self-associations) is in favor of the inclusion complexes. The C12 groups mainly form 1/1 inclusion complexes with β-cyclodextrins.53 The affinity constant K of dodecyltrimethylammonium bromide for HPβCD is K ) 5.5 × 103 L/mol.54 Assuming a complexation constant of the same order in the case of POXZ-C12-A allows one to calculate the fraction of C12 groups bound to cyclodextrins at the conditions of the SANS experiment, and it is equal to 1. Thus, the results of Figure 7a give a good indication that the complexation constant of POXZ-C12-A for HPβ-CD is comparable to the one of C12 surfactants. In the case of POXZ-C12-B, the behavior is similar, except that the scattered intensities are larger than the ones of the precursor POXZ at a HPβ-CD/C12 molar ratio of 1. This can be due to the lower complexation constant of POXZ-C12-B than POXZ-C12-A because of it largest molecular weight. Indeed, it has been shown in the case of hydrophobically modified PEO that the complexation constants decreased with the PEO molecular weight due to entropic effects.55 The two other polymer samples bearing the C18 end groups behave quite differently as a larger amount of HPβ-CD

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Volet et al.

Figure 7. (a) Scattering from POXZ-C12-A in D2O with various ratios nHPβ-CD/nC12. (b) Scattering from POXZ-C12-B in D2O with various ratios nHPβ-CD/nC12. (c) Scattering from POXZ-C18-A in D2O with various ratios nHPβ-CD/nC18. (d) Scattering from POXZ-C18-B in D2O with various ratios nHPβ-CD/nC18.

is needed to recover a scattering behavior similar to the one of the precursor POXZ. A previous SANS study on PEO-PPO-PEO copolymers36 has shown that adding β-CD dissociated the copolymer micelles, and the authors have quantified the dissociation by assuming that the total scattered intensity was the sum of the micelle and free chain intensities. In this work, the model used is the one of semidilute star-like micelles, which has been applied above (eq 6). The assumptions are that the polymer system remains at semidilute conditions and that the dissociated chains participate to the scattering by the sea of blobs (second term in eq 6). Dissociation of the micelles by adding HPβ-CD should thus induce change in the fit parameters E and F but also should have an influence on the other ones RHS, φs, F, and ξ as the overlapping conditions are expected to vary when the number of micelles decreases. However, some parameters have been kept constant (φs, ξ) in order to lower the number of variables in the fits. It has been found that increasing amounts of HPβ-CD on the same polymer sample induce mainly a decrease of E and an increase of F. This comes with a slight decrease of RHS combined with a slight increase of F. As E is proportional to the number of chains belonging to micelles (Nm · Nagg), the decrease of E with the HPβ-CD excess is a direct expression of the progressive dissociation of the micelles by making inclusion complexes with HPβ-CD. Figure 8 represents the relative variation of E (E/E0, where E0 is the value without HPβ-CD) with the HPβ-CD/C18 molar ratio for the two polymer samples POXZ-C18-A and POXZ-C18-B. Figure 8 shows similar behavior for the two polymers, independently on the molecular weights. There is only partial dissociation of the micelles at a ratio of 1 HPβ-CD to 1 C18, and ratios larger than 2 HPβ-CD to 1 C18 are necessary to ensure a complete dissociation. Again, this can be interpreted in terms of the stoichiometry of complexation of C18 into HPβ-CD cavities, which can be 1/1

Figure 8. Influence of the molar ratio HPβ-CD/C18 on the micellar term E/E0 for POXZ-C18-A (9) and POXZ-C18-B ([) (1 wt %).

or 1/2.53 However 2 HPβ-CDs are needed to cap perfectly the C18 groups and to protect them from self-association. Thus, the SANS experiments show that is possible to dissociate the micelles by adding cyclodextrin compounds in excess compared to the alkyl groups. The inclusion complexes formed between the cyclodextrin cavities and the alkyl groups help extract the POXZ-Cn chains from the micelles. At a large excess of HPβ-CD, the scattering should majorly be due to the POXZ-Cn/CD complexes, the free HPβ-CD giving a negligible contribution. Figure 9 shows a ln(I) versus ln(q) representation of POXZ-C12-B/HPβ-CD in a HPβ-CD/alkyl molar ratio of 4. It is superimposed on the one of POXZ-C12-B without HPβ-CD. In this representation, the more apparent difference is in the large q behavior. The power law q-a gives an exponent close to 1 for the complex, whereas it is 1.7 for POXZ-C12-B. It appears that having capped the C12 alkyl group into β-cyclodextrin cavities and thus preventing it from aggregation help to recover


Figure 9. Plot ln(I) versus ln(q) for POXZ-C12-B in D2O at 1 wt % with an excess of HPβ-CD (nHPβ-CD/nC12 ) 4) and without HPβ-CD.

the semiflexible structure of the precursor POXZ chains discussed in the beginning of the Experimental Section (see Figure 3). Conclusion This work has shown that POXZ compounds, which are considered to be analoguous to PEO compounds because of their hydrophilicity and biocompatibility, behave quite differently from PEO in aqueous solution. First of all, POXZ structuralizes in water and has the behavior of a semiflexible polymer with a persistence length on the order of 20 Å. POXZ-Cn self-associate into micellar structures, which show correlation peaks at much lower concentrations than PEO-Cn of the same molecular weights. The SANS results have been analyzed in the frame of a model of semidilute star-like micelles. The analysis as a function of the concentration and extrapolated to dilute solutions allowed proof that the POXZ chains were quite extended in the micelles, and this seems to be at the origin of the original behavior of the POXZ-Cn micelles. The addition of a β-cyclodextrin compound, HPβ-CD, induces progessive disruption of the micelles. This is traduced in the SANS results by a smearing out of the correlation peaks as the concentration of HPβ-CD is increased. The analysis using the model of star-like micelles allowed quantification of the rate of dissociation of the chains into the micellar structures as a function of the molar ratio HPβ-CD/Cn. In the case of the C12 groups, almost all of the chains were dissociated at a ratio larger than 1. This is coherent with the mechanism of the 1/1 C12/ HPβ-CD inclusion complex generally reported in the literature. The polymers bearing C18 groups need larger amounts of HPβ-CD for a complete dissociation of the micelles, and at a molar ratio HPβ-CD/Cn of 1, only 40-60% of the chains have been extracted from the micelles. This different behavior of the POXZ-C18 polymers can be explained by the necessity to add 2 HPβ-CD for 1 C18 in order to cap it perfectly and protect it against self-association. At a large excess of HPβ-CD, when all of the chains are dissociated, the semiflexible behavior of POXZ is again visible. Acknowledgment. The authors would like to thank Oleg Borisov for interesting discussions. References and Notes (1) Oberdisse, J.; Regev, O.; Porte, G. J. Phys. Chem. B 1998, 102, 1102–1108. (2) Jung, H. T.; Kim, S. O.; Ko, Y. K.; Yoon, D. K.; Hudson, S. D.; Percec, V.; Holerca, M. N.; Cho, W. D.; Mosier, P. E. Macromolecules 2002, 35, 3717–3721.

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