Modulating the Molecular Geometry and Solution Self-Assembly of Amphiphilic Polypeptoid Block Copolymers by Side Chain Branching Pattern

Abstract

Solution self-assembly of coil-crystalline diblock copolypeptoids has attracted increasing attention due to its capability to form hierarchical nanostructures with tailorable morphologies and functionalities. While the N-substituent (or side chain) structures are known to affect the crystallization of polypeptoids, their roles in dictating the hierarchical solution self-assembly of diblock copolypeptoids are not fully understood. Herein, we designed and synthesized two types of diblock copolypeptoids, i.e., poly( N -methylglycine)- b -poly( N -octylglycine) (PNMG- b -PNOG) and poly( N -methylglycine)- b -poly( N -2-ethyl-1-hexylglycine) (PNMG- b -PNEHG), to investigate the influence of N-substituent structure on the crystalline packing and hierarchical self-assembly of diblock copolypeptoids in methanol. With a linear aliphatic N-substituent, the PNOG blocks pack into a highly ordered crystalline structure with a board-like molecular geometry, resulting in the self-assembly of PNMG- b -PNOG molecules into a hierarchical microflower morphology composed of radially arranged nanoribbon subunits. By contrast, the PNEHG blocks bearing bulky branched aliphatic N-substituents are rod-like and prefer to stack into a columnar hexagonal liquid crystalline mesophase, which drives PNMG- b -PNEHG molecules to self-assemble into symmetrical hexagonal nanosheets in solution. A combination of time-dependent small/wide-angle X-ray scattering and microscopic imaging analysis further revealed the self-assembly mechanisms for the formation of these microflowers and hexagonal nanosheets. These results highlight the significant impact of the N-substituent architecture (i.e., linear versus branched) on the supramolecular self-assembly of diblock copolypeptoids in solution, which can serve as an effective strategy to tune the geometry and hierarchical structure of polypeptoid-based nanomaterials.

Solution Self-Assembly of Coil-Crystalline Diblock Copolypeptoids Bearing Alkyl Side Chains

“…In addition, they also have shown that well-defined block copolypeptoids, e.g., poly(N-methyl glycine)- b -poly(N-butyl glycine) (PNMG- b -PNBG), can be produced by controlled ROP with sequential monomer addition [ 61 , 62 ]. In our previous studies [ 60 , 70 , 79 , 84 ], a variety of well-defined amphiphilic diblock copolypeptoids that comprised of at least one crystallizable block with relatively low PDIs have been synthesized via benzyl amine-initiated ROPs of R-NCAs in a sequential manner, allowing us to further investigate their CDSA behaviors in solution. There are several aliphatic N-substituents can be readily used for the molecular design ( Figure 1 ).…”

“…For example, in the case of racemic 2-ethyl-l-hexyl side chains, it was found that relatively short poly (N-2-ethyl-1-hexyl glycine) (PNEHG) molecules with DP n ≤ 20 are amorphous with no first-order transition observed by DSC [ 90 , 91 ]. On the other hand, longer PNEHG chains, e.g., DP n ≥ 100, exhibit a single first-order thermal transition with a small enthalpic change, but are still in sharp contrast with poly (N-octyl glycine) (PNOG) homopolymer which also possesses eight carbon atoms on their side chains [ 84 , 97 ]. Our recent WAXD measurements on PNOG and PNEHG homopolymers with similar DP n (DP n ≈ 100) revealed the effect of side chain branching on the molecular geometry and supramolecular assembly [ 84 ].…”

“…Recent developments in the controlled polymerization and solid-phase synthesis have enabled access to a variety of polypeptoids with tailorable chain length, N-substituent structures, sequence, and architecture [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. In the past several years, solution self-assembly of block copolypeptoids have especially attracted increasing attention due their capability to form various self-assembled nanostructures with tailorable structure, morphology, and functionality [ 60 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. Given their molecular tunability, polypeptoid-based BCPs are considered as a promising biomimetic platform for macromolecular and supramolecular engineering for biomedical and biotechnological applications.…”

Patchy Micelles with a Crystalline Core: Self-Assembly Concepts, Properties, and Applications

“…Next to BCPs with a PFS block, a variety of other crystallizable polymer blocks were employed in CDSA, e.g. polyethylene (PE) [ 68 , 92 , 93 , 94 ], poly(ethylene oxide) [ 95 ], polyesters (poly( ε -caprolactone) (PCL) or poly( L -lactide) (PLLA)) [ 86 , 96 , 97 , 98 , 99 , 100 , 101 ], polycarbonate [ 102 ], poly(2- iso -propyl-2-oxazoline) (P i PrOx) [ 103 , 104 ], liquid crystalline polymers [ 71 , 105 ], poly(vinylidene fluoride) [ 106 ], polypeptoids [ 107 , 108 ], and various conjugated polymers (e.g., poly(3-hexyl thiophene) (P3HT) and OPV) [ 75 , 109 , 110 , 111 , 112 , 113 ].…”

Hierarchical assemblies of polypeptoids for rational design of advanced functional nanomaterials

“…This work provides an understanding of the relationship between peptoid sequences, assembly nanostructures, and its crystallization pathways. A recent work [ 35 ] compares the crystalline packing and hierarchical assembly pathways of PNMG‐ b ‐PNDG and a similar PNMG‐ b ‐PNEHG (poly‐( N ‐methylglycine)‐ b ‐poly( N ‐2‐ethyl‐1‐hexylglycine)) in Figure 4B. With linear N‐alkyl substituents, PNDG blocks pack into lamellar‐like crystalline structures which drives PNMG‐ b ‐PNDG assemble into a hierarchical microflower‐like particles.…”