Bioinspired Polymer Vesicles Based on Hydrophilically Modified Polybutadienes Zofia Hordyjewicz-Baran, Liangchen You, Bernd Smarsly, Reinhard Sigel, and Helmut Schlaad* Max Planck Institute of Colloids and Interfaces, Colloid Chemistry, Research Campus Golm, 14424 Potsdam, Germany ReceiVed February 9, 2007 ReVised Manuscript ReceiVed April 4, 2007 Bioinspired polymers are raising more and more attention as advanced materials for key applications in materials science or biomedicine. Especially interesting are the so-called “bio- hybrids” or “molecular chimeras”, 1 which are polymers being made of biological (peptide, sugar, or nucleic acid) and synthetic parts. Polymers with main-chain biological segments can nowadays be synthesized by design in high quality 2-4 sbut often in low quantity. Polymers with pendent biofunctionalities, on the other hand, are easily available through chemical modifica- tion, basically without limitation in quantity. The most promising strategies involve “click chemistry”, i.e., Cu(I)-catalyzed Huis- gen 1,3-dipolar cycloaddition of azides onto alkyne side chain polymers, 5 or free-radical addition of mercaptans onto an alkene side chain polymers. 6,7 The latter approach enables one to generate a platform of “hydrophilically modified polybutadienes” from readily avail- able starting materials. Such hydrophilically modified poly- butadienes are random copolymers being, as can be recognized by the chemical structure in Figure 1, closely related to the polymeric amphiphiles introduced by Ringsdorf et al. 8 (also compare to amphiphilic homopolymers, 9 polysoaps, and hy- drophobically modified polymers 10 ). As such, they should be useable for the production of functional polymer colloids by design, especially for that of bioinspired polymer vesicles or membranessa field so far being reserved to block copoly- mers. 11,12 Four polymeric amphiphiles and biohybrids were produced by free-radical additions of ω-functional mercaptans onto a 1,2- polybutadiene with a number-average of 40 repeat units (see the list in Table 1). Details of synthetic procedures and analytics can be found elsewhere 13 and in the Supporting Information. The weak polyelectrolytes 1-3 could be dispersed in water (polymer concentration ∼0.1 wt %) at room temperature in a certain range of pH, as monitored by eye (clear solution) and by measurement of the light scattering intensity at an angle of 90° (Figure 2a). Flocculation or precipitation of polymer was recognized by a steep increase of turbidity and scattering intensity. The polyanion 1 readily dispersed in neutral to basic media when acid residues were in carboxylate form. The polymer started to precipitate when the pH was decreased (using 0.1 N HCl) to a value of 6.0 or lower. The polymer redispersed upon addition of 0.1 N NaOH. The scattering intensity was the same as at the beginning of the titration cycle, indicating that the process was fully reversible. Accordant observations were made for the polycation 2, which was disperable in neutral to acidic media (f ammonium form) and started to precipitate sharply at pH 8.2. The poly(amino acid) 3 dispersed in very acidic and in basic media; precipitation occurred around the isoelectric point (which for methionine is at pH 5.74) between pH 2.3 and ∼9. Evidently, 1-3 responded to changes in pH as would be expected for weak polyelectrolytes. The peculiarity is that the copolymer chains form aggregates rather than dissolve on a molecular level. Dynamic light scattering analyses (DLS, scattering angle 90°) of 0.3 wt % solutions of 1 and 3 in 0.1 N NaOH and of 2 and 3 in 0.1 N HCl showed the presence of aggregates with apparent hydrodynamic radii of R h app ∼ 170 nm (1 and 2) and R h app ∼ 130/120 nm (3, low/high pH) (Figure 2b). Aggregates with R h app ∼ 130 nm were also observed for the nonionic glucose-modified sample 4, directly dissolved in water at a concentration of 0.1 wt % (Figure 2c). Small-angle X-ray scattering (SAXS) indicated the presence of vesicles in 5 wt % solutions of 1-3 (Figure 3a). (Samples were directly dissolved in water, and then the pH of the solution was adjusted to either pH 7 (1 and 2) or pH 11 (3).) The asymptotes of scattering curves at low scattering vectors (s ) 2/λ sin Θ) obey the characteristic I(s) ∝ s -2 (I: scattering intensity). An additional local maximum arising at s ∼ 0.13 nm -1 suggests that the membrane has a multilamellar structure with a lamellar spacing of about 7 nm (Figure 3c). Evidently, the layers formed by the polymeric amphiphiles 1-3 are about as thick as a bilayered membrane of a liposome (∼5 nm). Note that the weight fractions of hydrophilic units of 1-3 (w hydro ) 0.11-0.31, Table 1) are smaller than or similar to that of, for instance, 1-palmityl-2-oleyl-phosphatidylcholine (w hydro ) 0.24) occurring in the membranes of higher organisms. 14 The nonionic sample 4 instead self-assembled into unilamellar vesicles (Figure 3c), as suggested by SAXS (10 wt % solution) and transmission electron microscopy (TEM) (see Figure 3a,b). SAXS data could be reasonably analyzed on the basis of a model * Corresponding author: Fax (+) 49.331.567.9502; e-mail schlaad@ mpikg.mpg.de. Figure 1. General chemical structure of the hydrophilically modified 1,2-polybutadienes prepared (R: see Table 1) and idealized sketch of a polymeric amphiphile. Table 1. List of Hydrophilically Modified Polybutadienes (See Chemical Structure in Figure 1) a Degree of functionalization, determined by elemental analysis. 13 b Fractions of comonomer units: n ) 2f - 1, m ) (1 - n)/2. c Weight fraction of hydrophilic groups. d Sample contains traces of double bonds ( 1 H NMR). 3901 Macromolecules 2007, 40, 3901-3903 10.1021/ma070347n CCC: $37.00 © 2007 American Chemical Society Published on Web 04/26/2007