Supramolecular Self-Assembly with Precisely Control and Potential Biological Application

Self-assembly is one of the most interesting phenomena in the field of life science. Inspired by life system, taking advantage of non-covalent interaction to construct artificial self-assembly systems with different functions has become a hot topic in interdisciplinary research. This work is devoted to the design and synthesis of new building blocks based on BCPs or amino acid to build 1D chiral and 2D platelet micelles with controllable morphology and exploring the potentially biology and optoelectronics application.

In chapter 2 and 3, block copolymers of PPV-b-P2VP were employed as building units for supramolecular self-assembly. By the introduction of chlorine, morphological transformation from rod-like micelles to diamond-like micelles was achieved by the thermally induced nucleation process that lets the kinetically trapped 1D nanostructures to transform as the 2D nanostructures in the thermodynamic state. Then the crystalline groups as TIPS group was introduced into the copolymers, which caused the morphology transition from 2D square to rectangular or rod-like micelles with controllable aspect ratios. These nanomaterials with controllable shapes that possess fluorescent and semiconducting properties could be potential candidates for biological and optoelectronics applications.

Chapter 4 and 5 describes the study of amino acid derivatives based on thiophene core with different amino acid arms as building blocks. After supramolecular self-assembly, the helices with controllable chirality and 2D rectangular microsheets were obtained. In addition, by utilizing co-assembly, helicity appearance and inversion were observed for the TDAP-MA system, which was used to provide a feasible detection approach for melamine.

[1] Whitesides, G. M.; Grzybowski, B., Self-assembly at all scales. Science 2002, 295, 2418.
[2] Service, R. F., How far can we push chemical self-assembly? Science 2005, 309, 95.
[3] Qi R.; Zhu Y.; Han L.; Wang M.; He F., Rectangular Platelet Micelles with Controlled Aspect Ratio by Hierarchical Self-Assembly of Poly(3-hexylthiophene)-b-poly (ethylene glycol). Macromolecules 2020, 53 (15), 6555-6565.
[4] Alexandridis P.; Lindman B., Amphiphilic Block Copolymers: Self-assembly and Applications. Amsterdam: Elsevier, 2000.
[5] Bates F. S.; Fredrickson G. H., Block copolymers-designer soft materials. Phys. Today 1999, 52: 32-38.
[6] Kim J. K.; Yang S. Y.; Lee Y.; Kim Y., Functional nanomaterials based on block copolymer self-assembly. Prog. Polym. Sci. 2010, 35(11): 1325-1349.
[7] Orilall M. C.; Wiener U., Block copolymer based composition and morphology control in nanostructured hybrid materials for energy conversion and storage: Solar cells, batteries, and fuel cells. Chem. Soc. Rev. 2011, 40(2): 520-535.
[8] Zhang L.; Eisenberg A., Multiple morphologies and characteristics of crew-cut micelle-like aggregates of polystyrene-b-poly (acrylic acid) diblock copolymers in solution. Science 1995, 268(5218): 1728-1731.
[9] Chen D.; Jiang M., Strategies for constructing polymeric micelles and hollow spheres in solution via specific intermolecular interactions. Acc. Chem. Res. 2005, 38 (6): 494-502.
[10] Cui H.; Chen Z.; Zhong S.; Wooley K.L.; Pochan D. J., Block copolymer assembly via kinetic control. Science 2007, 317 (5838): 647-650.
[11] Zhang L.; Eisenberg A., Multiple morphologies and characteristics of "crew-cut" micelle-like aggregates of polystyrene-b-poly (acrylic acid) diblock copolymers in aqueous, solutions. J. Am. Chem. Soc. 1996, 118 (13): 3168-3181
[12] Wang X.; Guerin G.; Wang H.; Wang Y.S.; Manners I.; Winnik A. M., Cylindrical block copolymer micelles and co-micelles of controlled length and architecture. Science 2007, 317 (5838): 644-647.
[13] Harada A.; Kataoka K., Chain length recognition: Core-shell supramolecular assembly from oppositely charged block copolymers. Science 1999, 283 (5398): 65-67.
[14] Förster S.; Antonietti M., Amphiphilic block copolymers in structure-controlled nanomaterial hybrids. Adv. Mater. 1998, 10 (3): 195-217.
[15] Gädt T.; leong N. S.; Cambridge G.; Winnik M. A.; Manners I., Complex and hierarchical micelle architectures from diblock copolymers using living, crystallization-driven polymerizations. Nat. Mater. 2009, 8 (2): 144-150.
[16] Gillies E. R.; Jonson T. B.; Fréchet J. M. J., Stimuli-responsive supramolecular assemblies of linear-dendritic copolymers. J. Am. Chem. Soc. 2004, 126 (38): 11936-11943.
[17] Goodwin A. P.; Mynar J. L.; Ma Y.; Fleming R. G.; Fréchet M. J. J., Synthetic micelle sensitive to IR light via a two-photon process. J. Am. Chem. Soc. 2005, 127 (28): 9952-9953.
[18] Hu J.; Liu G.; Nijkang G., Hierarchical interfacial assembly of ABC triblock copolymer. J. Am. Chem. Soc. 2008, 130 (11): 3236-3237.
[19] Qiu H.; Gao Y.; Boott C. E.; Gould O. E.; Harniman R. L.; Miles M. J.; Webb S. E. D.; Winnik M. A.; Manners I., Uniform patchy and hollow rectangular platelet micelles from crystallizable polymer blends. Science 2016, 352 (6286): 697-701.
[20] Kataoka K.; Harada A.; Nagasaki Y., Block copolymer micelles for drug delivery: Design, characterization and biological significance. Adv. Drug. Deliv. Rev. 2001, 47 (1): 113-131.
[21] Mai Y.; Eisenberg A., Chem. Soc. Rev. 2012, 41, 5969-5985.
[22] Shen H.; Zhang L.; Eisenberg A., Thermodynamics of crew-cut micelle formation of polystyrene-b-poly (acrylic acid) diblock copolymers in DMF/H2O mixtures. J. Phys. Chem. B. 1997, 101(24):4697-4708.
[23] F ̈orster S.; Antonietti M., Amphiphilic Block Copolymers in Structure-Controlled Nanomaterial Hybrids. Adv. Mater. 1998, 10, 195–217.
[24] Ganda, S.; Dulle, M.; Drechsler, M.; Förster, B.; Förster, S.; Stenzel, M. H., Two-Dimensional Self-Assembled Structures of Highly Ordered Bioactive Crystalline-Based Block Copolymers. Macromolecules 2017, 50 (21), 8544-8553.
[25] Schacher F. H.; Rupar P. A.; Manners I., Functional block copolymers: nanostructured materials with emerging applications. Angew. Chem. Int. Ed. 2012, 51, 7898–7921.
[26] Riess G., Micellization of block copolymers. Prog. Polym. Sci. 2003, 28(7): 1107-1170.
[27] Cameron N. S.; Corbierre M. K.; Eisenberg A., Asymmetric amphiphilic block copolymers in solution: a morphological wonderland. Can. J. Chem. 1999, 77, 1311–1326.
[28] Tritschler U.; Pearce S.; Gwyther J.; Whittell G. R.; Manners I., Functional nanoparticles from the solution self-Assembly of block copolymers. Macromolecules 2017, 50, 3439–3463.
[29] Hayward R. C.; Pochan D. J., Tailored assemblies of block copolymers in solution: It is all about the process. Macromolecules 2010, 43, 3577–3584.
[30] Macfarlane L.; Zhao C.; Cai J.; Qiu H.; Manners I., Emerging applications for living crystallization- driven self-assembly, Chem. Sci. 2021,12, 4661-4682.
[31] Lin Y. Y.; Thomas M. R.; Gelmi A.; Leonardo V.; Pashuck E. T.; Maynard S. A.; Wang Y.; Stevens M. M., Self-Assembled 2D Free- Standing Janus Nanosheets with Single-Layer Thickness. J. Am. Chem. Soc. 2017, 139, 13592−13595.
[32] Zhuo M. P.; Tao Y. C.; Wang X. D.; Wu Y. C.; Chen S.; Liao L. S.; Jiang L., 2D Organic Photonics: An Asymmetric Optical Waveguide in Self-Assembled Halogen-Bonded Cocrystals. Angew. Chem., Int. Ed. 2018, 57, 11300−11304.
[33] Han L.; Wang M. J.; Jia X. M.; Chen W.; Qian H. J.; He F., Uniform two-dimensional square assemblies from conjugated block copolymers driven by pi-pi interactions with controllable sizes. Nat. Commun. 2018, 9, No. 865.
[34] Ganda S.; Dulle M.; Drechsler M.; Forster B.; Forster S.; Stenzel M. H., Two-Dimensional Self-Assembled Structures of Highly Ordered Bioactive Crystalline-Based Block Copolymers. Macromolecules 2017, 50, 8544−8553.
[35] Hudson Z. M.; Boott C. E.; Robinson M. E.; Rupar P. A.; Winnik M. A.; Manners I., Tailored hierarchical micelle architectures using living crystallization-driven self-assembly in two dimensions. Nat. Chem. 2014, 6, 893−898.
[36] Nazemi A.; He X. M.; MacFarlane L. R.; Harniman R. L.; Hsiao M. S.; Winnik M. A.; Faul C. F. J.; Manners I., Uniform “Patchy” Platelets by Seeded Heteroepitaxial Growth of Crystallizable Polymer Blends in Two Dimensions. J. Am. Chem. Soc. 2017, 139, 4409−4417.
[37] Wang M. J.; Han L.; Zhu Y. L.; Qi R.; Tian L. L.; He F., Formation of Hierarchical Architectures with Dimensional and Morphological Control in the Self-Assembly of Conjugated Block Copolymers. Small Methods 2020, 4, 1900470.
[38] Zhu C.; Liu L.; Yang Q.; Lv F.; Wang S., Water-soluble conjugated polymers for imaging, diagnosis, and therapy. Chem. Rev. 112, 4687–4735 (2012).
[39] Tao D.; Feng C.; Cui Y.; Yang X.; Manners I.; Winnik, M. A.; Huang, X., Monodisperse Fiber-like micelles of controlled length and composition with an oligo (p-phenylenevinylene) core via “living” crystallization-driven self-assembly. J. Am. Chem. Soc. 2017, 139, 7136−7139.
[40] Sun H.; Liu J.; Li S.; Zhou L.; Wang J.; Liu L.; Lv F.; Gu Q.; Hu B.; Ma Y.; Wang S., Reactive Amphiphilic Conjugated Polymers for Inhibiting Amyloid b Assembly. Angew. Chem., Int. Ed. 2019, 58, 5988−5993.
[41] Wang M.; Han L.; Zhu Y.; Qi R.; Tian L.; He F., Inky flower-like supermicelles assembled from π-conjugated block copolymers. Polym. Chem. 2020, 11, 61-67.
[42] Han L.; Fan H.; Zhu Y. L.; Wang M.J.; Pan F.; Yu, D. P.; Zhao, Y.; He, F., Precisely Controlled Two-Dimensional Rhombic Copolymer Micelles for Sensitive Flexible Tunneling Devices. CCS Chemistry 2020, 3 (5), 1399-1409.
[43] Schmelz J.; Schedl A. E.; Steinlein C.; Manners I.; Schmalz H., Length control and block-type architectures in worm-like micelles with polyethylene cores. J. Am. Chem. Soc. 2012. 134(34): 14217-14225.
[44] Desbaumes L.; Eisenberg A., Single-solvent preparation of crew-cut aggregates of various morphologies from an amphiphilic diblock copolymer. Langmuir 1999, 15(1): 36-38.
[45] Shen H.; Eisenberg A., Morphological phase diagram for a ternary system of block copolymer PS310-b-PAA52/dioxane/H2O. J. Phys. Chem. B 1999. 103(44): 9473-9487.
[46] Yu Y.; Zhang L.; Eisenberg A., Morphogenic effect of solvent on crew-cut aggregates of amphiphilic diblock copolymers. Macromolecules 1998, 31(4): 1144-1154
[47] Lehn J. M., Supramolecular chemistry. Science 1993, 260(5115): 1762-1764.
[48] Whitesides G. M.; Grzybowski, B., Self-assembly at all scales. Science 2002, 295(5564): 2418-2421.
[49] Aizenberg J.; Fratzl P., Biological and biomimetic materials. Adv. Mater. 2009, 21(4): 387-388.
[50] Sanchez C.; Arribart H.; Guille M. M. G., Biomimetism and bioinspiration as tools for the design of innovative materials and systems. Nat. Mater. 2005, 4(4): 277-288.
[51] Palmer L. C.; Newcomb C. J.; Kaltz S. R.; Spoerke E. D.; Stupp S. I., Biomimetic systems for hydroxyapatite mineralization inspired by bone and enamel. Chem. Rev. 2008, 108(11): 4754-4783.
[52] Ariga K.; Hill J. P.; Lee M. V.; Vinu A.; Charvet R.; Acharya S., Challenges and breakthroughs in recent research on self-assembly. Sci. Technol. Adv. Mater. 2008, 9(1): 1468-1565.
[53] Nie Z.; Kumacheva E., Patterning surfaces with functional polymers. Nat. Mater. 2008, 7(4): 277-290.
[54] Ajayaghosh A.; Praveen V. K.; Vijayakumar C., Organogels as scaffolds for excitation energy transfer and light harvesting(J]. Chem. Soc. Rev. 2008, 37(1): 109-122.
[55] He Q.; Duan L.; Qi W.; Wang K.; Cui Y.; Yan X.; Li J., Microcapsules containing a biomolecular motor for atp biosynthesis. Adv. Mater. 2008, 20(15): 2933-2937.
[56] Ligthart G.; Ohkawa, H.; Sijbesma, R. P.;Meijer E. W., Complementary quadruple hydrogen bonding in supramolecular copolymers . J. Am. Chem. Soc. 2005, 127(3): 810-811.
[57] Burattini S.; Greenland B. W.; Hayes, W.; Mackay M. E.; Rowan S. J.; Colquhoun H. M., A supramolecular polymer based on tweezer-type π-π interactions: molecular design for healability and enhanced toughness. Chem. Mater. 2011, 23(1): 6-8.
[58] Ko I. K.; Kean T. J.; Dennis J. E. Targeting mesenchymal stem cells to activated endothelial cells. Biomaterials 2009, 30: 3702-3710.
[59] Xu X. D.; Li X.; Chen, H.; Qu Q.; Zhao L.; Agren H.; Zhao Y., Host-guest interaction-mediated construction of hydrogels and nanovesicles for drug delivery. Small 2015, 11(44): 5901-5906.
[60] Minakawa M. ; Nakagawa M.; Wang K. H.; Imura Y.; Kawai T., Controlling Helical Pitch of Chiral Supramolecular Nanofibers Composed of Two Amphiphiles. Bull. Chem. Soc. Jpn. 2020, 93 (10), 1150-1154.
[61] Ghosh D., Farahani A. D., Martin A. D.; Thordarson P.; Damodaran K. K., Chem. Mater. 2020, 32, 3517.
[62] Sorrenti A.; Illa O.; Ortuno R. M., Amphiphiles in aqueous solution: Well beyond a soap bubble[J]. Chem. Soc. Rev. 2013, 42(21): 8200-8219.
[63] Yui H.; Minamikawa H.; Danev R.; Nagayama K.; Kamiya S.; Shimizu T., Growth process and molecular packing of a self-assembled lipid nanotube: Phase-contrast transmission electron microscopy and XRD analyses. Langmuir 2008, 24(3): 709-713.
[64] Kamiya S.; Minamikawa, H.; Jung, J. H.; Yang B.; Masuda M.; Shimizu T., Molecular structure of glucopyranosylamide lipid and nanotube morphology. Langmuir 2005, 21(2): 743-750.
[65] Barclay T. G.; Constantopoulos, K.; Zhang, W., Fujiki M; Petrovsky N.; Matisons J. G., Chiral self-assembly of designed amphiphiles: Influences on aggregate morphology. Langmuir 2013, 29(32): 10001-10010.
[66] Fuhrhop J. H.; Helfrich W., Fluid and solid fibers made of lipid molecular bilayers. Chem. Rev. 1993, 93(4): 1565-1582.
[67] Fujita N.; Shinkai S., Design and function of low molecular-mass organic gelators (Imogs) bearing steroid and sugar groups. Molecular gels: materials with self-assembled fibrillar networks, 2006: 553-575.
[68] Shimizu T.; Masuda M.; Minamikawa H., Supramolecular nanotube architectures based on amphiphilic molecules. Chem. Rev. 2005, 105(4): 1401-1443.
[69] Wang X.; Liu M., Vicinal solvent effect on supramolecular gelation: Alcohol controlled topochemical reaction and the toruloid nanostructure. Chem. A Euro. J. 2014, 20(32): 10110-10116.
[70] Takafuji M. Kira Y.; Tsuji H., Sawada S.; Hachisako H.; Ihara H., Optically active polymer film tuned by a chirally self-assembled molecular organogel. Tetrahedron 2007, 63(31): 7489-7494.
[71] Shirosaki T.; Chowdhury S.; Takafuji M., Alekperov D.; Popova G.; Hachisako H.; Ihara H., Functional organogels from lipophilic 1-glutamide derivative immobilized on cyclotriphosphazene core. J. Mater. Res. 2006, 21(5): 1274-1278.
[72] Kira Y.; Okazaki Y.; Sawada T.; Takafuji M.; Ihara H., Amphiphilic molecular gels from omega-aminoalkylated I-glutamic acid derivatives with unique chiroptical properties. Amino Acids 2010, 39(2): 587-597.
[72] Jintoku H.; Sagawa T.; Sawada T., Takafuji M.; Hachisako H.; Ihara H., Molecular organogel-forming porphyrin derivative with hydrophobic 1-glutamide. Tetrahedron Lett. 2008, 49(25): 3987-3990.
[73] Hifsudheen M.; Mishra R. K.; Vedhanarayanan B., Praveen V. K.; Ajayaghosh A., The helix to super-helix transition in the self-assembly of pi-systems: Superseding of molecular chirality at hierarchical level. Angew. Chem. Int. Ed. 2017, 56(41): 12634-12638.
[74] Garoff R. A.; Litzinger E. A.; Connor R. E., Fishman I., Armitage B. A., Helical Aggregation of Cyanine Dyes on DNA Templates: Effect of Dye Structure on Formation of Homo- and Hetero aggregates. Langmuir 2002, 18(16):6330-6337.
[75] Crusats J.; El-Hachemi Z.; Ribo J. M.; Hydrodynamic effects on chiral induction. Chem. Soc. Rev. 2010, 39(2): 569-577.
[76] Micali N.; Engelkamp H.; van Rhee P. G., Chiristianen P. C. M.; Scolaro L. M.; Mann J. C., Selection of supramolecular chirality by application of rotational and magnetic forces. Nat. Chem. 2012, 4(3): 201-207.
[77] Ribo J. M.; Crusats J.; Sagues F., Claret J.; Rubires R., Chiral sign induction by vortices during the formation of mesophases in stirred solutions. Science 2001, 292(5524): 2063-2066.
[77] Yuan, J.; Liu, M. H., Chiral molecular assemblies from a novel achiral amphiphilic 2-(heptadecy) naphtha 2,3 imidazole through interfacial coordination. J. Am. Chem. Soc. 2003, 125(17): 5051-5056.
[78] Huang, X.; Li, C.; Jiang, S. G., Wang X.; Zhang B.; Liu M. H., Self-assembled spiral nanoarchitecture and supramolecular chirality in langmuir-blodgett films of an achiral amphiphilic barbituric acid. J. Am. Chem. Soc. 2004, 126(5): 1322-1323.
[79] Oiu Y.: Chen P.: Liu M., Evolution of various porphyrin nanostructures via an oil/aqueous medium: Controlled self-assembly, further organization, and supramolecular chirality. J. Am. Chem. Soc. 2010, 132(28): 9644-9652.
[80] Zhang S.; Yang S.; Lan J., Yang S.; You J., Helical nonracemic tubular coordination polymer gelators from simple achiral molecules. Chem. Commun. 2008, 46: 6170-6172.
[81] Song B.; Liu B.; Jin Y.; He X.; Tang D.; Wu G.; Yin S., Controlled self-assembly of helical nano-ribbons formed by achiral amphiphiles. Nanoscale 2015, 7(3): 930-935.
[82] Link D. R.; Natale G.; Shao R.; Maclennan J. E.; Clark N. A.; Korblova E.; Walba D. M., Spontaneous formation of macroscopic chiral domains in a fluid smectic phase of achiral molecules. Science 1997, 278(5345): 1924-1927.
[83] Hough L. E.; Spannuth M.; Nakata M.; Coleman D. A.; Jones C. D.; Danlgraber G.; Tschierske C.; Watanabe J.; Korblova E.; Walba D. M.; Maclennan J. E.; Glaser M. A.; Clark N. A., Chiral isotropic liquids from achiral molecules. Science 2009, 325(5939): 452-456.
[84] Dressel C.; Liu F.; Prehm M., Zeng X.; Ungar G.; Tschierske C., Dynamic mirror-symmetry breaking in bicontinuous cubic phases. Angew. Chem. Int. Ed. 2014, 53(48): 13115-13120.
[85] Sang Y.; Yang D.; Duan P.; Liu M., Towards homochiral supramolecular entities from achiral molecules by vortex mixing-accompanied self-assembly. Chem. Sci. 2019, 10(9): 2718-2724.
[86] Wang X.; Li M.; Song, P., Lv X.; Liu Z.; Huang J.; Yan Y., Reversible manipulation of supramolecular chirality using host-guest dynamics