Stimuli-Responsive Principles of Supramolecular Organizations Emerging from Self-Assembling and Self-Organizable Dendrons, Dendrimers, and Dendronized Polymers

Abstract

All activities of our daily life, of the nature surrounding us and of the entire society and its complex economic and political systems are affected by stimuli. Therefore, understanding stimuli-responsive principles in nature, biology, society, and in complex synthetic systems is fundamental to natural and life sciences. This invited Perspective attempts to organize, to the best of our knowledge, for the first time the stimuli-responsive principles of supramolecular organizations emerging from self-assembling and self-organizable dendrons, dendrimers, and dendronized polymers. Definitions of stimulus and stimuli from different fields of science are first discussed. Subsequently, we decided that supramolecular organizations of self-assembling and self-organizable dendrons, dendrimers, and dendronized polymers may fit best in the definition of stimuli from biology. After a brief historical introduction to the discovery and development of conventional and self-assembling and self-organizable dendrons, dendrimers, and dendronized polymers, a classification of stimuli-responsible principles as internal- and external-stimuli was made. Due to the enormous amount of literature on conventional dendrons, dendrimers, and dendronized polymers as well as on their self-assembling and self-organizable systems we decided to discuss stimuli-responsive principles only with examples from our laboratory. We apologize to all contributors to dendrimers and to the readers of this Perspective for this space-limited decision. Even after this decision, restrictions to a limited number of examples were required. In spite of this, we expect that this Perspective will provide a new way of thinking about stimuli in all fields of self-organized complex soft matter.

Keywords: dendrimers; dendronized polymers; dendrons; external-stimuli; internal-stimuli; self-assembling and self-organizable; stimuli-responsive principles; supramolecular organizations.

Figure 1

Divergent and convergent methodologies for the synthesis of dendrimers and dendrons displaying the number of reactions (left side); Examples of amorphous or liquid dendrons and self-assembling dendrons (right side) [60]. The parts of the Figure were adapted from [111] combined and modified. Copyright © 2009, American Chemical Society.

Figure 2

Structural and retrostructural analysis of supramolecular assemblies formed via the self-assembly and self-organization of dendrons help to discover and predict by generational strategy [60]. The Figure was adapted and modified from [60]. Reproduced with permission from [60]. Copyright © 2009, American Chemical Society.

Figure 3

The deconstruction strategy of third-generation dendron (3,4BpPr-(3,4,5BpPr)₂)12G3-X (shown in the middle) led to the discovery of new self-assembling minidendrons marked in yellow, where X = –CO₂CH₃ for 6a and –CH₂OH for 6b. In each step of the deconstruction (solid arrows), the fragment highlighted by the wedge of the corresponding color (red or gray) is removed, and the remaining unmarked dendron is synthesized and structurally analyzed. Yellow highlights form a molecular switch and a ribosome-size supramolecular dendrimer [135]. The Figure was adapted from [135] and modified. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 4

(a) A diversity of supramolecular assemblies generated from the primary structures designed by the deconstruction strategy. Novel structures from deconstructed dendritic esters (blue arrows) and alcohols (purple dotted arrows). (b) Reconstructed relative electron density distributions of the Φ_h and Φ_h^3D-SL phases generated from 9b indicating the reversible transition with temperature. (c) The potential role as a supramolecular switch. [135]. The parts of the Figures were adapted from [135] and modified. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 5

Structural and retrostructural analysis of supramolecular dendrimers self-assembled from a library of symmetric constitutional isomeric AB₂ to AB₉ self-assembling sp²-sp² dendrons [86]. Reproduced with permission from [86]. Copyright © 2021, American Chemical Society.

Figure 6

The classifications of internal- and external-stimuli in self-organized dendrimers generated from self-assembling and self-organizable dendrons, dendrimers, and dendronized polymers.

Figure 7

Chemical composition affecting the structure of self-organized supramolecular dendrimers. Structures, self-assembly, and self-organization of the second generation dendrons: (a) all-trans cone conformation of (3,4,5)²12G2-CO₂Me; (b) all gauche-crown conformation of (3,4,5)²12F8G2-CO₂Me; (c) all trans-taper conformation of (3,4,5)²12F8G2-CO₂Me [136]. Parts of this Figure were adapted from [136] and modified. Copyright © 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 8

(a) Dendrons with identical chemical composition but different sequence forming different kinds of supramolecular structures. Supramolecular dendrimers self-assembled from (4-3,4,5-4³)12G1-CH₂OH and (4²-3,4,5)12G1-CH₂OH. (b) An example in which constitutional isomeric structures with identical composition but a different sequence of a combination of linear n-nonyl and branched chiral or racemic groups provide different supramolecular assemblies with different rates of heating and cooling. DSC traces of PBIs with sequence-defined hybrid r/n-nonyl dendrons were recorded upon second heating and first cooling at 10 °C/min. Phases determined by fiber XRD, transition temperatures (in °C), and associated enthalpy changes (in parentheses, in kcal/mol) are indicated. Phase notation: Φ_h^k1, columnar hexagonal crystal with offset dimers; Φ_h^k2, columnar hexagonal crystal with cogwheel assembly; Φ_c–o^k, columnar centered orthorhombic crystal; Φ_m^k, columnar monoclinic crystal, i, isotropic liquid [127,140]. Parts of the Figure were adapted, combined, and modified from [127,140]. Copyright © 2004, American Chemical Society. Copyright © 2020, American Chemical Society.

Figure 9

An example that demonstrates the role of the multiplicity of the branching point during the self-organization of a supramolecular assembly. Structural and retrostructural analysis of supramolecular dendrimers self-assembled from AB₃ 3,4,5-trisubstituted monodendrons of generation 2 and 3 are shown on the left side and from a generation 3 AB₂ 3,5-disubstituted dendron on the right side [126]. Parts of the Figure were adapted, combined, and modified from [126]. Copyright © 2004, American Chemical Society.

Figure 10

An example demonstrating the constitutional isomerism of the branching point affecting the supramolecular organizations. Structural and retrostructural analysis of supramolecular dendrimers self-assembled from AB₂ 3,5-disubstituted dendron is shown on the left side and of its constitutional isomeric AB₂ 3,4-disubstituted dendron is shown on the left side [126]. Parts of the Figure were adapted, combined, and modified from [126]. Copyright © 2004, American Chemical Society.

Figure 11

Hierarchical self-organization of the same self-assembling dendron at two different generations. (4-(3,4,5)²12G2-X is second generation (top), and (4-(3,4,5)³12G3-X is third generation (bottom) self-assembling dendron self-assembling columnar and, respectively, spherical assemblies generating columnar hexagonal and cubic Pm$\stackrel{-}{3}$n or A15 Frank–Kasper phases [124]. Parts of the Figure were adapted and modified from [124]. Copyright © 1998, American Chemical Society.

Figure 12

Examples of constitutional isomerism of the focal point. 1,3,5-trihyhdroxybenzene (THB), triphenylene, cyclotetraveratrylene (CTTV), cyclotriveratrylene (CTV).

Figure 13

(a) Illustration of the concept of the helical dendritic dipeptide and of its self-assembly into hydrophobic helical pores. Structure, conformation and hydrogen-bonding of (4-3,4-3,5)12G2-CH₂-Boc-L-Tyr-L-Ala-OMe and (4-3,4-3,5)12G2-CH₂-Boc-L-Tyr-D-Ala-OMe during self-assembly. Self-assembly of homochiral dendritic dipeptides in porous supramolecular columns via a helical cooperative growth. Schematic and analysis of self-assembly via supramolecular polymerization in solution and the corresponding side-view and cross-section of the porous supramolecular columns determined from XRD analysis in the solid state. (b) A hat-like homochiral or racemic column is generated by a dendronized cyclotriveratrylene (CTV). The deracemization process between enantiomerically rich columns assembled from the hat-shaped dendronized CTV. Illustration of homochiral columns constructed by a chiral self-sorting supramolecular helical organization of hat-shaped molecules (S), (R)-(3,4Bn)dm8*G1-CTV; comparison of wide-angle XRD patterns before and after thermal annealing; demonstration of chiral self-sorting mechanism [161,167,171]. Parts of the Figure were adapted, combined and modified from [160,166,171]. Copyright © 2004, Macmillan Magazines Ltd. Copyright © 2011, American Chemical Society.

Figure 14

The diversity of possibilities for the attachment of a self-assembling dendron or dendrimer to a covalent or supramolecular backbone. Topologies generated from linear covalent and supramolecular polymers dendronized with self-assembling dendrons, twin dendritic molecules, and Janus dendrimers [185]. Dendron directly attached to the polymer backbone via apex (a), with a flexible spacer (b), attached via non-covalent interactions (c), supramolecular polymers dendronized (d), dendron directly attached to the polymer backbone via its periphery (e), via its periphery and a flexible spacer (f), covalent polymers dendronized with twin-dendrimers (g), and with Janus dendrimers (h,i). This Figure is reproduced with permission from [185]. Copyright © 2012, American Chemical Society.

Figure 15

Self-assembly and self-organization of crown-like, cone-like and taper-like dendrons and other corresponding self-organizable dendronized polymers. Shape of secondary and tertiary structure mediated bt temperature and/or degree of polymerization of the dendronized polymer backbone.

Figure 16

Summary of periodic and quasiperiodic arrays self-organized from assemblies of poly[(3,4)17G1-Oxz] at different degrees of polymerization (DP) and temperature [144]. This Figure is reproduced with permission from [144]. Copyright © 2018, American Chemical Society.

Figure 17

Molecular machine self-organized from dendronized helical polyphenylacetylenes. Illustration of the helix–coil transition and its transformation into a helix–helix transition that mediates expansion and contraction of the helical structure with temperature (a); expanded images collected by a digital camera at 25 °C and at 80 °C of the oriented fiber (b); variable-temperature CD spectrum (c); comparison of the fiber length change from optical microscopy and column diameter from the fiber XRD for the library of the polyphenylacetylenes with different peripheral alkyl chain length in the dendron (m) (d) [97,100]. The Figure is adapted from [97,100]. Copyright © 2005, American Chemical Society. Copyright © 2008, American Chemical Society.

Figure 18

Schematic illustration of complex electronic supramolecular materials mediated by dendrons containing donor (D) and acceptor (A) groups, and their co-assembly with complementary amorphous polymers containing D and A side groups (a). The different systems form hexagonal columnar (Φ_h), centred rectangular columnar (Φ_r-c), and simple rectangular columnar (Φ_r-s) arrays; a and b are lattice dimensions. The self-repairing process of back-folded (brown) electronically active supramolecular helical pyramidal columns self-assembled by semifluorinated minidendron attached to the acceptor groups (b) [200]. The Figure is adapted and modified from [201]. Copyright © 2002, Macmillan Magazines Ltd.

Figure 19

General molecular structure of dendritic monomers and dendronized polymers, and the top and tilt views of the supramolecular column [41,42,204]. The Figure was adapted and modified from reference [112]. Copyright © The Royal Society of Chemistry.

Figure 20

The development and structures of liposomes, stealth liposomes, polymersomes, dendrimersomes, onion-like dendrimersomes, glycopolymers, glycodendrimers, glycoliposomes, glycodendrimersomes, and onion-like glycodendrimersomes.

Figure 21

Encoding biological recognition in a bicomponent cell-membrane mimic. (a) Sequence-defined JGDs with different Lac densities, sequence, and linker length. (b) Schematic representation of JGD building blocks. (c) Summary of aggregation assay data using GDSs from self-assembly of sequence-defined JGDs (Lac = 0.1 mM, 900 μL) with Gal-1 (1 mg·mL⁻¹, 100 μL), Gal-8S (1 mg·mL⁻¹, 100 μL), and (Gal-1)4–GG (1 mg·mL⁻¹, 100 μL). Color codes for galectins: Gal-1, red; Gal-8S, blue; (Gal-1)4–GG, green. N and C represent the N and C termini of proteins. For selected examples symbols used for significant difference (p values by Student’s t-test) are: “n.s.” for p > 0.05 (for statistically nonsignificant) and “*” for p < 0.05 (for statistically significant) [226]. Copyright (2019) National Academy of Sciences USA.

Figure 22

Modular tethering of DNA to SNAP-tagged dendrimersomes. (a) Schematic showing layering of a protein and DNA coat to dendrimersome vesicle. (b) His-SNAP proteins bind to RH-NTA to form the initial protein layer. SNAP binds to a BG conjugated to the DNA, allowing for the modular formation of a second layer, composed of nucleic acids. The DNA aptamer is labeled with FAM to enable imaging. (c) schematic of multilayer dendrimersome containing DNA and protein coat [230]. Copyright (2019) National Academy of Sciences USA.

Figure 23

Illustration of (a) the preparation of giant DSs, (b) the preparation of BMV expressing YadA bacterial adhesin protein, and (c) coassembly of giant hybrid vesicles from giant DSs and E. coli BMV expressing YadA bacterial adhesin protein [222]. Copyright (2016) National Academy of Sciences USA.

Figure 24

Schematic illustration of (a) the preparation of giant DSs, (b) the preparation of HMV from human kidney cells 293 (HEK293), and (c) coassembly of giant hybrid vesicles from giant DSs, and HMV from HEK293 labeled with GFP [218]. Copyright (2019) National Academy of Sciences USA.

Figure 25

CLSM images show the process of engulfment of bacteria (blue) by DSs (red). (a) Adhesion of E. coli to the DS membrane. (b,c) Invagination of E. coli into the interior of the DS. (d) Formed endosome with living bacteria inside. (e) 3D reconstruction of 150 confocal scans for the whole (left) and 80 confocal scans for half (right) of the DS with engulfed E. coli. The white dashed line on a whole DS indicates the place of intersection for the presentation of half of the DS to show the interior of an endosome with engulfed bacteria [232]. The Figure was adapted from [233]. Copyright © 2019, American Chemical Society.

Figure 26

Schematic representation of four-component LNPs, one-component IAJDs based DNPs, and the cell transfection mechanism of LNPs and DNPs encapsulating Luc-mRNA (A) Four-component LNPs. (B) One-component IAJDs and their DNPs. (C) Cell transfection mechanism of LNPs and DNPs encapsulating Luc-mRNA.

Figure 27

Summary of the supramolecular orientational memory (SOM) effect with selected examples of new bundles of columnar arrays and new molecular bundles of columnar hexagonal arrays generated by SOM [86,179]. SOM from Φ_h to (a) Pm$\stackrel{-}{3}$n (A15); (b) Im$\stackrel{-}{3}$m (BCC); (c) Pm$\stackrel{-}{3}$n (A15); (d) Pm$\stackrel{-}{3}$n (A15); and (e) P4₂/mnm (σ). This Figure is reproduced with permission from [178]. © 2022 The Author(s). Published by Elsevier Ltd.

Figure 28

Mechanism of disassembly of large dendrimersomes by photocleavage and their reassembly into smaller dendrimersomes [245]. Copyright © The Royal Society of Chemistry.

Figure 29

(a) Molecular structure of dendrimers G4(D3); (b) Molecular structure of dendron G2(OH) (anti), and (c) Molecular structure of dendrimers G2(OH) (gauche). (d) Molecular model of the smectic phase of G2(OH). The magnetic field is almost horizontal [249].