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Kinetics-Controlled Amphiphiles Self-Assembly Processes Xiaoyan Zheng, Lizhe Zhu, Xiangze Zeng, Luming Meng, Lu Zhang, Dong Wang, and Xuhui Huang J. Phys. Chem. Lett., Just Accepted Manuscript • DOI: 10.1021/acs.jpclett.7b00160 • Publication Date (Web): 02 Apr 2017 Downloaded from http://pubs.acs.org on April 4, 2017

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The Journal of Physical Chemistry Letters

Kinetics-Controlled Amphiphiles Self-Assembly Processes Xiaoyan Zheng§,¶, Lizhe Zhu§, Xiangze Zeng§, Luming Meng§, Lu Zhang§, Dong Wang#, Xuhui Huang*,§,¶ §

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research

Center for Tissue Restoration & Reconstruction, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong ¶

HKUST-Shenzhen Research Institute, Nanshan, Shenzhen 518057, P.R. China

#

Key Laboratory of Organic OptoElectronics and Molecular Engineering, Department of

Chemistry, Tsinghua University, Beijing 100084, P. R. China

Corresponding Author *Email: [email protected]

ACS Paragon Plus Environment

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ABSTRACT: Amphiphiles self-assembly is an essential bottom-up approach of fabricating advanced functional materials. Self-assembled materials with desired structures are often obtained through thermodynamic control. Here, we demonstrate that the selection of kinetic pathways can lead to drastically different self-assembled structures, underlining the significance of kinetic control in self-assembly. By constructing kinetic network models from large-scale molecular dynamics simulations, we show that two largely similar amphiphiles PYR and PYN prefer distinct kinetic assembly pathways. While PYR prefers an incremental growth mechanism and forms a nanotube, PYN favors a hopping growth pathway leading to a vesicle. Such preference was found to originate from the subtle difference in the distributions of hydrophobic and hydrophilic groups in their chemical structures, which leads to different rates of the adhesion process among the aggregating micelles. Our results are in good agreement with experimental results, and accentuate the role of kinetics in the rational design of amphiphiles self-assembly.

TOC GRAPHICS


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Amphiphiles are natural or synthetic compounds (surfactants, peptides or block copolymers) that possess both hydrophilic and lipophilic (hydrophobic) components. They can self-assemble into a variety of nanostructures in solution, and thus provide an essential bottom-up approach to fabricate functional supramolecular nanomaterials of desired morphology1-11. Importantly, such fabrication requires a precise control of the self-assembly process, either by fine tuning the environmental conditions such as the solvent conditions12-16, external stimuli4, 17 or by manipulating the amphiphilicity of the building block amphiphiles17. However, it remains highly non-trivial to precisely predict the outcome of amphiphiles self-assembly purely based on the conformations of the monomeric building blocks. In spite of the early success for conventional surfactants18-22, such prediction is particularly challenging for amphiphiles with non-canonical distributions of hydrophobic and hydrophilic groups1,

23-24

, because the increased

complexity in the structure of the non-canonical amphiphiles introduces an additional level of complexity in their intermolecular interactions. Hence, all these attributes render the assembly process of non-canonical amphiphiles significantly more complex and hierarchal than that of conventional surfactants. Non-canonical amphiphiles with very similar chemical structures can assemble into entirely different nanostructures, even under identical solvent conditions25-28. This can be exemplified by two systems with nearly identical chemical structure: 1-[11-oxo-11(pyren-1-ylmethoxy)-undecyl]

pyridinium

bromide

(PYR),

and

1-(11-((5a1,8a-

dihydropyren-1-yl)methylamino)-11-oxoundecyl) pyridinium bromide (PYN). As shown in Figure 1a-1b (Figure S1 in the Supporting Information (SI)), both PYR and PYN consist of the pyrenyl groups, the alkyl chains, and the pyridinium groups. The only chemical


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structural difference is that while PYR contains the ester group, PYN bears a more polar amide group. Strikingly, Zhang and co-workers show by experiments that, in aqueous solution, this seemingly subtle difference has led to dramatically different fates of their

Figure 1. Amphiphiles PYR and PYN and their assembly pathways. In the structure of (a) PYR and (b) PYN, transparent circles denote the coarse-graining beads that represent the amphiphiles in this study. Sharing with PYR the same hydrophobic pyrenyl group, alkyl chain (grey) and positively charged pyridinium group (magenta), PYN bears an amide group (magenta, dashed circle) instead of the ester group in PYR (grey, dashed circle). The top two assembly pathways of the preferred path channel for (c) PYR (incremental growth channel, blue) and (d) PYN (the hopping growth channel, red) are given with the snapshots of all conformational states on top-view. An enlarged side-view of the final assembled structure is given for each system. The population of the incremental and hopping growth channel are given in (e) for PYR and (f) for PYN, respectively. See details of conformational states in Tables S3 and S4 in SI.


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self-assembly. That is, PYRs self-assemble into nanotubes with a diameter of ca. 250 nm, whereas PYNs aggregate into vesicles with the same diameter29-30. Purely thermodynamic considerations seem highly difficult to explain why PYNs selfassemble into drastically different nanostructures from PYRs. Although subtle differences are found in the equilibrium conformations of the free monomers of PYR and PYN, such differences are far from adequate to predict the difference in their final assembled nanostructures (see Fig.S2, Table S1 in SI), largely due to the elaborate interplay of the intermolecular interactions and the hierarchical nature of their assembly processes1, 31-32. On one hand, the introduction of the more hydrophilic amide group in PYN breaks the extended hydrophobic tail, and thus weakens the hydrophobic interactions that drive monomers to aggregate. On the other hand, this amide group in PYN can form favourable inter-molecular polar-polar interactions, stabilizing the PYN aggregates in the aqueous solution. Such elaborate interplay among these interactions will lead to various intermediate states, thus necessitating the kinetic characterizations of these heterogeneous self-assembly processes. In a more general context, realizing the precise prediction and control of the kinetic pathways of self-assembly has been increasingly recognized as the central challenge for fabricating functional nanostructures from the building blocks with ever-greater complexity33-37. To understand the striking difference in the assemblies between PYR and PYN, we systematically explored the kinetic pathways during the early assembly stages of amphiphiles. This is achieved by constructing kinetic network models (KNMs) on top of the large-scale coarse-grained molecular dynamics simulations (CGMD)38-42 of 125 PYRs and PYNs respectively (see Figures S5-S6 in SI). The CG force-field were rigorously parametrized from the


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all-atom molecular dynamics simulations of the amphiphiles (see details in Figures S3-S4 and the Supplementary Methods and Discussions in SI). Unlike the conventional methods that rely on visual inspection and analysis of the individual simulation trajectories43, KNMs provide a statistical picture that covers the transition pathways among all conformational states during the assembly processes. As a result, direct connections can then be made between KNMs and experimental measurements, such as the temperature-jump experiments.44 Based on the KNMs, we identified two path channels that coexist for both PYR and PYN: an incremental channel and a hopping channel (see Figure 1c-d and Figure S11 in SI). Due to the heterogeneous nature of the self-assembly process, numerous parallel pathways coexist. The two path channels were identified by grouping multiple parallel pathways according to their kinetic similarity using a path lumping algorithm (built upon the Transition Path Theory45-46, see more details in the Supplementary Methods and Discussions in SI). Here, the kinetic similarity is measured by the accumulated interpathway flux among the parallel pathways. Each path channel reflects a specific growth mechanism for the amphiphiles assembly. In the incremental channel, the aggregate size grows incrementally by fusing with small aggregate (the size increases with ∆N < 35 throughout the assembly pathways, see Figure S11a-S11b). The size N of the intermediate states is widely distributed along the incremental channel (5-110), which is consistent with the many aggregation steps (Figure 1c). By contrast, in the hopping channel, the aggregate grows in a hopping manner by fusing itself with an aggregate of similar size (∆N almost doubles at each step). For example, a sudden jump in size (∆N = 55-63) is observed immediately before the final step (Figure 1d). Accordingly, a smaller number of aggregation steps occurs in the hopping channel than in the incremental one. Notably,


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almost all steps are accompanied by a rod-to-disk aggregate morphology transition (see Figure 1c-d, and Figures. S12 and S13 in SI). The morphology (rod, disk or sphere) was quantified by the asphericity parameter Ap (see more details in the Computational Methods and the Supplementary Methods and Discussions section in SI). Most interestingly, we observed a distinct preference over the incremental and hopping growth channels by PYR and PYN. For PYR, the ratio between the probability of the incremental and hopping growth channel is 69%:31%, while the corresponding ratio for PYN is 41%:59% (Figure 1e-f). Thus, PYR tends to assemble incrementally while PYN favors the hopping growth. We also observed that the overall assembly of PYN is faster than that of PYR (see Figure S14c in SI). To understand the surprisingly different preference for the path channels of PYR and PYN, we performed a detailed analysis of the kinetic parameters in the assembly processes. After the formation of small micelles, all subsequent growth steps can be regarded as the fusion events between two micelles. Such fusion of micelles typically consists of three stages: collision, adhesion and merging.47 Collision is a diffusion-controlled encountering event of two micelles. Adhesion is the subsequent adjustment of the two micelles that have formed a super-micelle upon collision (Figure 2a). Merging is a further rod-to-disk morphology switching process to relax the unfavourable super-micelle. Among these three events, the timescales of both collision (Te) and merging (Tt) can be explicitly computed from our KNMs. We observed that both Te and Tt increase monotonically as the assembly proceeds, and that Tt is always much smaller than Te, indicating that micelles have sufficient time to switch morphology from rod to disk before it collapses with another aggregate (Figure S14a-S14b). However, throughout all assembly stages, no significant difference in Tt or in Te was observed between PYR and PYN. This suggests that


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the mean first passage time (MFPT) of the assembly (Figure S14c) is only determined by the total number of aggregation steps in the self-assembly processes, which is consistent with the small MFPT of PYNs that prefer the hopping growth with less number of aggregation steps. More importantly, this observation directly points to the decisive role of the two micelles adhesion process, which is known to be the rate-limiting step of the micelle fusion47-50, in the preference of path channels of the two amphiphiles. During adhesion, two micelles have to overcome a free energy barrier that originates from the electrostatic repulsions among the positively charged pyridinium groups on their surface so as to form a super-micelle (Figure 2a). Explicit calculations of the adhesion

Figure 2. (a) Schematics of two micelles adhesion process, with waters (cyan), positive charged pyridinium groups (pink), negative charged counter-ions: Br- (light orange) and the hydrophobic tails (green). (b) The calculated adhesion rate for two micelles adhesion. (c) and (d) plots the surface positive charge density and the packing density of the pre-adhesion micelles (aggregate size: 30), respectively.


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rate between two micelles (see more details in the Supplementary Methods and Discussions in SI) show that the adhesion rate for PYR micelles is considerably (about twice) lower than that of PYN micelles (Figure 2b). This difference is due to their distinct amphiphilicity. Because of the clearer separation of the hydrophobic and hydrophilic groups in PYR monomers, it is more difficult for PYR aggregates to expose their hydrophobic groups and to form super-micelle during the adhesion process than PYN (see Figure S15 in SI). This is supported by the larger positive charge density on the surface of PYR micelles than PYN micelles (see Figure 2c and Figure S17a). For PYNs, the more polar amide group weakens their intermolecular hydrophobic interactions, and thus reduces the packing density of PYN micelles (see Figure 2d and Figure S17b). A higher free energy barrier caused by the higher electrostatic repulsions on the two micelles surface during adhesion for PYR increases the population of their small-sized micelles. Therefore, PYR favors to grow incrementally by fusing with small-sized micelle, while PYN with more large-sized aggregates, tends to assemble via the hopping channel (Figure 1e-f). Furthermore, the preference over the growth mechanism by PYR and PYN were found to directly dictate the fate of their assembly. Morphology analysis revealed that all assembled nanostructures by PYRs are planar disk-like micelles, regardless of the assembly mechanisms (Figure S19a and S19c in SI). By contrast, PYNs assemble into planar disks (Figure S19b in SI) in the incremental channel, but into highly curved disks (Figure S19d in SI) in the dominant hopping channel. This is because an aggregate formed by the incremental growth channel via gradually absorbing the small-sized aggregates (incremental growth) is likely to form a planar structure, while an aggregate


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fused by micelles with identical size (hopping growth) tends to form a curved structure, due to the different orientations of two fusing micelles. In addition, such dictation of the final structure by the aggregation mechanism seems irrelevant to the monomeric conformations within the aggregates. This is because the monomeric conformations of PYR and PYN only differ at the very early assembly stages (aggregate size

Kinetics-Controlled Amphiphile Self-Assembly ... - ACS Publications

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