Kinetically Controlling the Length of Self-Assembled Polymer Nanofibers Formed by Intermolecular Hydrogen Bonds

Abstract

Strong directional hydrogen bonds represent a suitable supramolecular force to drive the one-dimensional (1D) aqueous self-assembly of polymeric amphiphiles resulting in cylindrical polymer brushes. However, our understanding of the kinetics in these assembly processes is still limited. We here demonstrate that the obtained morphologies for our recently reported benzene tris-urea and tris-peptide conjugates are strongly pathway-dependent. A controlled transfer from solutions in organic solvents to aqueous environments enabled a rate-dependent formation of kinetically trapped but stable nanostructures ranging from small cylindrical or spherical objects (<50 nm) to remarkably large fibers (>2 μm). A detailed analysis of the underlying assembly mechanism revealed a cooperative nature despite the steric demands of the polymers. Nucleation is induced by hydrophobic interactions crossing a critical water content, followed by an elongation process due to the strong hydrogen bonds. These findings open an interesting new pathway to control the length of 1D polymer nanostructures.

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

“…Correlating well with the AF4 results, cryoTEM images of both samples (Figure 4B and 1D) showed mainly short cylinders after a cumulated US time of 30 s, with an average fiber length of 124 ± 65 nm and 69 ± 41 nm for BTU and BTP, respectively (Figure S8, Supporting Information File 1). It is important to note that all obtained fibers remained unchanged over several months after the top-down processing, demonstrating the previously described excellent kinetic stability of these supramolecular aggregates (Figures S15 and S16, Supporting Information File 1) [21].…”

“…While the hydrogen bonding moieties are either urea-based or peptide-based (i.e., phenylalanine) units, the dodecyl chains act as hydrophobic shields to induce the amphiphilic assembly in water and prevent the surrounding water from interfering with the hydrogen bonds in the interior [29]. Attaching a hydrophilic PEO chain (2 kg⋅mol −1 ), the compounds self-assemble into long fiber structures consisting of 2-4 lateral core units upon transfer into water, as reported previously [19][20][21]. A slow solvent change from a THF solution to water resulted in µm-long fibers in both cases (BTU or BTP).…”

“…This could further be supported by AF4 measurements ( Figure 3A and 3B). Here, fibers featuring an average radius of gyration of R g ≈ 20 nm and a weight-average molar mass of M w = 3,099,000 g⋅mol −1 , corresponding to a number of aggregation of N agg ≈ 1,200 and a length of 110 nm for BTU (assuming four units per cross-section), as well as a weight-average molar mass of M w = 4,406,000 g⋅mol −1 , corresponding to a number of aggregation of N agg ≈ 490 and a length of 120 nm (assuming two units per cross-section) for BTP, could be observed after 10 min at 1,000 rpm (Figure S12A and S12B, Supporting Information File 1 ) [ 19 , 21 ].…”

“…The resulting fibers featured an average R g value of ≈15 nm (Figure S14, Supporting Information File 1 ) and a weight-average molar mass of M w = 3,633,000 g⋅mol −1 , corresponding to a number of aggregation of N agg = 1400 and a length of 125 nm for BTU (assuming four units per cross-section). For BTP, a weight-average molar mass of M w = 2,910,000 g⋅mol −1 , corresponding to a number of aggregation of N agg = 440 and a length of 80 nm (assuming two units per cross-section) was calculated [ 19 , 21 ]. Correlating well with the AF4 results, cryoTEM images of both samples ( Figure 4B and 1D) showed mainly short cylinders after a cumulated US time of 30 s, with an average fiber length of 124 ± 65 nm and 69 ± 41 nm for BTU and BTP, respectively (Figure S8, Supporting Information File 1 ).…”

“…The resulting amphiphilic character of the materials facilitated a control of the kinetic assembly, which provided access to stable nanostructures on a broad length range (<100 nm–2 µm). While the process enables a good adjustment of the length, it relies on a precise control of the assembly pathway and requires the use of organic solvents, such as THF and DMF, which limits the applicability in pharmaceutical formulations [ 21 ]. For an application in nanomedicine, a length in the range of 100–200 nm is particularly attractive to ensure cellular uptake and to access the known size window for a potential enhanced permeability and retention effect (EPR) [ 22 – 23 ].…”