Multicomponent supramolecular copolymerization promises to construct complex nanostructures with emergent properties. However, even with two monomeric components, various possible outcomes such as self-sorted supramolecular homopolymers, a random (statistical) supramolecular copolymer, an alternate supramolecular copolymer, or a complex supramolecular block copolymer can occur, determined by their intermolecular interactions and monomer exchange dynamics and hence structural prediction is extremely challenging. Herein, we target this challenge and demonstrate unprecedented two-component sequence controlled supramolecular copolymerization by manipulating thermodynamic and kinetic routes in the pathway complexity of selfassembly of the constitutive monomers. Extensive molecular dynamics simulations provided useful mechanistic insights into the monomer exchange rates and free energy of interactions between the monomers that dictate the self-assembly pathway and sequence. The fluorescent nature of core-substituted naphthalene diimide monomers has been further utilized to characterize the three sequences via Structured Illumination Microscopy (SIM).

Supramolecular block copolymerzation with optically or electronically complementary monomers provides an attractive bottomup approach for the non-covalent synthesis of nascent axial organic heterostructures, which promises to deliver useful applications in energy conversion, optoelectronics, and catalysis. However, the synthesis of supramolecular block copolymers (BCPs) constitutes a significant challenge due to the exchange dynamics of non-covalently bound monomers and hence requires fine microstructure control. Furthermore, temporal stability of the segmented microstructure is a prerequisite to explore the applications of functional supramolecular BCPs. Herein, we report the cooperative supramolecular block copolymerization of fluorescent monomers in solution under thermodynamic control for the synthesis of axial organic heterostructures with light-harvesting properties. The fluorescent nature of the core-substituted naphthalene diimide (cNDI) monomers enables a detailed spectroscopic probing during the supramolecular block copolymerization process to unravel a nucleation−growth mechanism, similar to that of chain copolymerization for covalent block copolymers. Structured illumination microscopy (SIM) imaging of BCP chains characterizes the segmented microstructure and also allows size distribution analysis to reveal the narrow polydispersity (polydispersity index (PDI) ≈ 1.1) for the individual block segments. Spectrally resolved fluorescence microscopy on single block copolymerized organic heterostructures shows energy migration and light-harvesting across the interfaces of linearly connected segments. Molecular dynamics and metadynamics simulations provide useful mechanistic insights into the free energy of interaction between the monomers as well as into monomer exchange mechanisms and dynamics, which have a crucial impact on determining the copolymer microstructure. Our comprehensive spectroscopic, microscopic, and computational analyses provide an unambiguous structural, dynamic, and functional characterization of the supramolecular BCPs. The strategy presented here is expected to pave the way for the synthesis of multi-component organic heterostructures for various functions.

Chirality-driven self-sorting is envisaged to efficiently control functional properties in supramolecular materials. However, the challenge arises because of a lack of analytical methods to directly monitor the enantioselectivity of the resulting supramolecular assemblies. Presented herein are two fluorescent core-substituted naphthalene-diimide-based donor and acceptor molecules with minimal structural mismatch and they comprise strong self-recognizing chiral motifs to determine the self-sorting process. As a consequence, stereoselective supramolecular polymerization with an unprecedented chirality control over energy transfer has been achieved. This chirality-controlled energy transfer has been further exploited as an efficient probe to visualize microscopically the chirality driven self-sorting.

Stereoselective and temporally controlled supramolecular polymerizations are ubiquitous in nature and are desirable attributes for the design of chiral, well-defined functional materials. Kinetically controlled, living supramolecular polymerization (LSP) has emerged recently for the synthesis of supramolecular polymers with controlled length and narrow dispersity. On the other hand, stringent design requirements for chiral-discriminating monomers precludes the stereoselective control of the supramolecular polymer structure. Herein, a synergetic stereo-and structural control of supramolecular polymerization by the realization of an unprecedented stereoselective seed-induced LSP is reported. Homochiral and seeded growth is demonstrated with bischromophoric naphthalene diimide (NDI) enantiomers with a chiral binaphthyl amine core, exhibiting strong self-recognition abilities and pathway complexity.

Synthesis of supramolecular blockc o-polymers (BCP) with small monomers and predictive sequence requires elegant molecular design and synthetic strategies.H erein we report the unparalleled synthesis of tri-component supramolecular BCPs with tunable microstructure by ak inetically controlled sequential seeded supramolecular polymerization of fluorescent p-conjugated monomers.C ore-substituted naphthalene diimide (cNDI) derivatives with different core substitutions and appended with b-sheet forming peptide side chains providep erfect monomer design with spectral complementarity,p athway complexity and minimal structural mismatcht os ynthesize and characterize the multi-component BCPs.T he distinct fluorescent nature of various cNDI monomers aids the spectroscopic probing of the seeded growth process and the microscopic visualization of resultant supramolecular BCPs using Structured Illumination Microscopy (SIM). Kinetically controlled sequential seeded supramolecular polymerization presented here is reminiscent of the multistep synthesis of covalent BCPs via living chain polymerization. These findings provide ap romising platform for constructing unique functional organic heterostructures for various optoelectronic and catalytic applications.

Nature's fuel-driven approach as a generic concept for structural and temporal regulation over biomimetic synthetic supramolecular polymerization.

Bioinspired, kinetically controlled seeded growth has been recently shown to provide length, dispersity, and sequence control on the primary structure of dynamic supramolecular polymers. However, command over the molecular organization at all hierarchical levels for the modulation of higher order structures of supramolecular polymers remains a formidable task. In this context, a surface-catalyzed secondary nucleation process, which plays an important role in the autocatalytic generation of amyloid fibrils and also during the chiral crystallization of small monomers, offers exciting possibilities for topology control in synthetic macromolecular systems by introducing secondary growth pathways compared to the usual primary nucleation−elongation process. However, mechanistic insights into the molecular determinants and driving forces for the secondary nucleation event in synthetic systems are not yet realized. Herein, we attempt to fill this dearth by showing an unprecedented molecular chirality control on the primary and secondary nucleation events in seed-induced supramolecular polymerization. Comprehensive kinetic experiments using in situ spectroscopic probing of the temporal changes of the monomer organization during the growth process provide a unique study to characterize the primary and secondary nucleation events in a supramolecular polymerization process. Kinetic analyses along with various microscopic studies further reveal the remarkable effect of stereoselective nucleation and seeding events on the (micro)structural aspects of the resulting multicomponent supramolecular polymers.

In a three-dimensional (3D) representation, each protein molecule displays a specific pattern of chemical and topological features, which are altered during its misfolding and aggregation pathway. Generating a recognizable fingerprint from such features could provide an enticing approach not only to identify these biomolecules but also to gain clues regarding their folding state and the occurrence of pathologically lethal misfolded aggregates. We report here a universal strategy to generate a fluorescent fingerprint from biomolecules by employing the pan-selective molecular recognition feature of a cucurbit[7]­uril (CB[7]) macrocyclic receptor. We implemented a direct sensing strategy by covalently tethering CB[7] with a library of fluorescent reporters. When CB[7] recognizes the chemical and geometrical features of a biomolecule, it brings the tethered fluorophore into the vicinity, concomitantly reporting the nature of its binding microenvironment through a change in their optical signature. The photophysical properties of the fluorophores allow a multitude of probing modes, while their structural features provide additional binding diversity, generating a distinct fluorescence fingerprint from the biomolecule. We first used this strategy to rapidly discriminate a diverse range of protein analytes. The macrocyclic sensor was then applied to probe conformational changes in the protein structure and identify the formation of oligomeric and fibrillar species from misfolded proteins. Notably, the sensor system allowed us to differentiate between different self-assembled forms of the disease-specific amyloid-β (Aβ) aggregates and segregated them from other generic amyloid structures with a 100% identification accuracy. Ultimately, this sensor system predicted clinically relevant changes by fingerprinting serum samples from a cohort of pregnant women.