Cooperative Polymerization Research Articles

Cooperative Covalent Polymerization of N-carboxyanhydrides: from Kinetic Studies to Efficient Synthesis of Polypeptide Materials

ConspectusPolypeptides, as the synthetic analogues of natural proteins, are an important class of biopolymers that are widely studied and used in various biomedical applications. However, the preparation of polypeptide materials from the polymerization of N-carboxyanhydride (NCA) is limited by various side reactions and stringent polymerization conditions. Recently, we report the cooperative covalent polymerization (CCP) of NCA in solvents with low polarity and weak hydrogen-bonding ability (e.g., dichloromethane or chloroform). The polymerization exhibits characteristic two-stage kinetics, which is significantly accelerated compared with conventional polymerization under identical conditions. In this Account, we review our recent studies on the CCP, with the focus on the acceleration mechanism, the kinetic modeling, and the use of fast kinetics for the efficient preparation of polypeptide materials.By studying CCP with several initiating systems, we found that the polymerization rate was dependent on the secondary structure as well as the macromolecular architecture of the propagating polypeptides. The molecular interactions between the α-helical, propagating polypeptide and the monomer played an important role in the acceleration, which catalyzed the ring-opening reaction of NCA in an enzyme-mimetic, Michaelis–Menten manner. Additionally, the proximity between initiating sites further accelerated the polymerization, presumably due to the cooperative interactions of macrodipoles between neighboring helices and/or enhanced binding of monomers. A two-stage kinetic model with a reversible monomer adsorption process in the second stage was developed to describe the CCP kinetics, which highlighted the importance of cooperativity, critical chain length, binding constant, [M]0, and [M]0/[I]0. The kinetic model successfully predicted the polymerization behavior of the CCP and the molecular-weight distribution of resulting polypeptides.The remarkable rate acceleration of the CCP offers a promising strategy for the efficient synthesis of polypeptide materials, since the fast kinetics outpaces various side reactions during the polymerization process. Chain termination and chain transfer were thus minimized, which facilitated the synthesis of high-molecular-weight polypeptide materials and multiblock copolypeptides. In addition, the accelerated polymerization enabled the synthesis of polypeptides in the presence of an aqueous phase, which was otherwise challenging due to the water-induced degradation of monomers. Taking advantage of the incorporation of the aqueous phase, we reported the preparation of well-defined polypeptides from nonpurified NCAs. We believe the studies of CCP not only improve our understanding of biological catalysis, but also benefit the downstream studies in the polypeptide field by providing versatile polypeptide materials.

Correction to “Rigid Triptycene-Based Di- and Trinuclear Salicylaldiminato Nickel Cooperative Polymerization Catalysts”

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to “Rigid Triptycene-Based Di- and Trinuclear Salicylaldiminato Nickel Cooperative Polymerization Catalysts”Jueqin YuJueqin YuMore by Jueqin Yu, Dao Zhang*Dao ZhangMore by Dao Zhanghttps://orcid.org/0000-0002-5853-748X, and Quanrui WangQuanrui WangMore by Quanrui Wanghttps://orcid.org/0000-0001-7593-9176Cite this: Organometallics 2023, 42, 10, 1037Publication Date (Web):May 4, 2023Publication History Received7 March 2023Published online4 May 2023Published inissue 22 May 2023https://doi.org/10.1021/acs.organomet.3c00127Copyright © 2023 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views651Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (708 KB) Get e-Alertsclose Get e-Alerts

Rigid Triptycene-Based Di- and Trinuclear Salicylaldiminato Nickel Cooperative Polymerization Catalysts

A multimetallic structure with a rigid linker can poise more than one catalytically active site in close proximity to control their reaction pathways in ethylene (co)polymerization by intermetallic cooperativity. This elegant concept was mainly limited to bimetallic systems. We report the synthesis of a series of mono-, bi-, and trinuclear salicylaldiminato Ni(II) catalysts based on a triptycene backbone. In ethylene (co)polymerization, the bimetallic nickel catalyst not only showed higher activity than the mononickel catalyst but also achieved an enhanced incorporation rate of α-olefin and the polar amino olefin, while the trimetallic nickel catalysts were thermally robust up to 100 °C and achieved a unique long-chain branching level up to an 81% mole ratio of all. Trinuclear nickel catalysts were found to be very less active for ethylene copolymerization with 1-hexene due to the increased steric hindrance. Although the catalytic result is worse than expected, especially for trinickel complexes, this work is still meaningful for the development of multinuclear catalysts that can mediate important catalytic reactions with enhanced efficiency and cooperativity.

Supramolecular alternating copolymers with highly efficient fluorescence resonance energy transfer.

This article reports alternating supramolecular copolymerization of two naphthalene-diimide (NDI)-derived building blocks (NDI-1 and NDI-2) under thermodynamic control. Both monomers contain a central NDI chromophore, attached to a hydrocarbon-chain and a carboxylic-acid group. The NDI core in NDI-2 is symmetrically substituted with two butane-thiol groups, which makes it distinct from NDI-1. In decane, a 1 : 1 mixture of NDI-1 and NDI-2 shows spontaneous gelation and a typical fibrillar network, unlike the behavior of either of the components individually. The solvent-dependent UV/vis spectrum of the mixed sample in decane shows bathochromically shifted sharp absorption bands and a sharp emission band (holds a mirror-image relationship) with a significantly small Stokes shift compared to those in CHCl3, indicating J-aggregation. In contrast, the aggregated spectra of the individual monomers show broad structureless features, suggesting ill-defined aggregates. Cooling curves derived from the temperature-dependent UV/vis spectroscopy studies revealed early nucleation and a signature of well-defined cooperative polymerization for the mixed sample, unlike either of the individual components. Molecular dynamics simulations predicted the greatest dimer formation tendency for the NDI-1 + NDI-2 (1 : 1), followed by pure NDI-1 and NDI-2. Theoretical studies further revealed a partial positive charge in the NDI ring of NDI-1 when compared to NDI-2, promoting the alternating stacking propensity, which is also favored by the steric factor as NDI-2 is core-substituted with alkyl thiols. Such theoretical predictions fully corroborate with the experimental results showing 1 : 1 stoichiometry (from Job's plot) of the two monomers, indicating alternate stacking sequences in the H-bonded (syn-syn catemer type) supramolecular copolymer. Such alternating supramolecular copolymers showed highly efficient (>93%) fluorescence resonance energy transfer (FRET).

Controlled synthesis of PEGylated polyelectrolyte nanogels as efficient protein carriers

Designing rational carriers for protein encapsulation and delivery is of great interest in a wide range of applications. Herein, we develop a type of PEGylated polyelectrolyte nanogel that enables efficient protein loading, protection and intracellular delivery. Our design relies on a one pot process involving cooperative electrostatic assembly and polymerization, which constructs polyion complex (PIC) micelles containing cross-linked cationic PDMAEMA network associated with anionic PAA. Further removing PAA chains leads to core–shell nanogels with a cationic network surrounded by poly (ethylene glycol) (PEG) blocks. The established strategy allows to fabricate well-defined nanogels with regulated size and swelling ability depending on pH, salt concentration and cross-link degree. More notably, the abundant positive charges and the thermo-response of PDMAEMA network realize sufficient encapsulation and protection of BSA proteins, while the PEG blocks endow appreciable biocompatibility and successful intracellular protein delivery. Our study establishes a facile and robust approach for preparing core–shell polyelectrolyte nanogels with regulated size and properties, as well as prominent capabilities for protein encapsulation and delivery.

Inside Back Cover: Kinetics‐Regulated Interfacial Selective Superassembly of Asymmetric Smart Nanovehicles with Tailored Topological Hollow Architectures (Angew. Chem. Int. Ed. 12/2022)

A kinetics-regulated cooperative polymerization induced interfacial superassembly strategy is used by Biao Kong and co-workers in their Research Article (e202200240) to construct a series of asymmetric hollow porous composites with tunable diameters, architectures, and compositions. Owing to their excellent photothermal conversion performance and unique nanostructures, the resulting nanoparticles can be utilized as NIR light triggered nanovehicles with controllable cargo release.

Kinetics‐Regulated Interfacial Selective Superassembly of Asymmetric Smart Nanovehicles with Tailored Topological Hollow Architectures

AbstractHollow nanoparticles featuring tunable structures with spatial and chemical specificity are of fundamental interest. However, it remains a significant challenge to design and synthesize asymmetric nanoparticles with controllable topological hollow architecture. Here, a versatile kinetics‐regulated cooperative polymerization induced interfacial selective superassembly strategy is demonstrated to construct a series of asymmetric hollow porous composites (AHPCs) with tunable diameters, architectures and components. The size and number of patches on Janus nanoparticles can be precisely manipulated by the precursor and catalyst content. Notably, AHPCs exhibit excellent photothermal conversion performance under the irradiation of a near infrared (NIR) laser. Thus, AHPCs are utilized as NIR light‐triggered nanovehicles and cargos can be controllably released. In brief, this versatile superassembly approach offers a streamlined and powerful toolset to design diverse asymmetric hollow porous composites.

Kinetics-Regulated Interfacial Selective Superassembly of Asymmetric Smart Nanovehicles with Tailored Topological Hollow Architectures.

Hollow nanoparticles featuring tunable structures with spatial and chemical specificity are of fundamental interest. However, it remains a significant challenge to design and synthesize asymmetric nanoparticles with controllable topological hollow architecture. Here, a versatile kinetics-regulated cooperative polymerization induced interfacial selective superassembly strategy is demonstrated to construct a series of asymmetric hollow porous composites (AHPCs) with tunable diameters, architectures and components. The size and number of patches on Janus nanoparticles can be precisely manipulated by the precursor and catalyst content. Notably, AHPCs exhibit excellent photothermal conversion performance under the irradiation of a near infrared (NIR) laser. Thus, AHPCs are utilized as NIR light-triggered nanovehicles and cargos can be controllably released. In brief, this versatile superassembly approach offers a streamlined and powerful toolset to design diverse asymmetric hollow porous composites.

Consequences of Amide Connectivity in the Supramolecular Polymerization of Porphyrins: Spectroscopic Observations Rationalized by Theoretical Modelling.

The correlation between molecular structure and mechanism of supramolecular polymerizations is a topic of great interest, with a special focus on the pathway complexity of porphyrin assemblies. Their cooperative polymerization typically yields highly ordered, long 1D polymers and is driven by a combination of π‐stacking due to solvophobic effects and hydrogen bonding interactions. Subtle changes in molecular structure, however, have significant influence on the cooperativity factor and yield different aggregate types (J‐ versus H‐aggregates) of different lengths. In this study, the influence of amide connectivity on the self‐assembly behavior of porphyrin‐based supramolecular monomers was investigated. While in nonpolar solvents, C=O centered monomers readily assemble into helical supramolecular polymers via a cooperative mechanism, their NH centered counterparts form short, non‐helical J‐type aggregates via an isodesmic pathway. A combination of spectroscopy and density functional theory modelling sheds light on the molecular origins causing this stunning difference in assembly properties and demonstrates the importance of molecular connectivity in the design of supramolecular systems. Finally, their mutual interference in copolymerization experiments is presented.

Rod-coil block copolymer aggregates via polymerization-induced self-assembly.

Polymerization-induced self-assembly (PISA), incorporating the polymerization with in situ self-assembly, can achieve nano-objects efficiently. However, the cooperative polymerization and self-assembly lead to unclear polymerization kinetics and aggregation behavior, especially for the systems forming rigid chains. Here, we used dissipative particle dynamics simulations with a probability-based reaction model to explore the PISA behavior of rod-coil block copolymer systems. The impact of the length of macromolecular initiators, the targeted length of rigid chains, and the reaction probability on the PISA behavior, including polymerization kinetics and self-assembly, were examined. The difference between PISA and traditional self-assembly was revealed. A comparison with experimental observations shows that the simulation can capture the essential feature of the PISA. The present work provides a comprehensive understanding of rod-coil PISA systems and may provide meaningful information for future experimental research.

Tuning the Length of Cooperative Supramolecular Polymers under Thermodynamic Control.

In the field of supramolecular (co)polymerizations, the ability to predict and control the composition and length of the supramolecular (co)polymers is a topic of great interest. In this work, we elucidate the mechanism that controls the polymer length in a two-component cooperative supramolecular polymerization and unveil the role of the second component in the system. We focus on the supramolecular copolymerization between two derivatives of benzene-1,3,5-tricarboxamide (BTA) monomers: a-BTA and Nle-BTA. As a single component, a-BTA cooperatively polymerizes into long supramolecular polymers, whereas Nle-BTA only forms dimers. By mixing a-BTA and Nle-BTA in different ratios, two-component systems are obtained, which are analyzed in-depth by combining spectroscopy and light-scattering techniques with theoretical modeling. The results show that the length of the supramolecular polymers formed by a-BTA is controlled by competitive sequestration of a-BTA monomers by Nle-BTA, while the obvious alternative Nle-BTA acts as a chain-capper is not operative. This sequestration of a-BTA leads to short, stable species coexisting with long cooperative aggregates. The analysis of the experimental data by theoretical modeling elucidates the thermodynamic parameters of the copolymerization, the distributions of the various species, and the composition and length of the supramolecular polymers at various mixing ratios of a-BTA and Nle-BTA. Moreover, the model was used to generalize our results and to predict the impact of adding a chain-capper or a competitor on the length of the cooperative supramolecular polymers under thermodynamic control. Overall, this work unveils comprehensive guidelines to master the nature of supramolecular (co)polymers and brings the field one step closer to applications.

Noncovalent Synthesis of Self-Assembled Nanotubes through Decoupled Hierarchical Cooperative Processes.

Because of their wide number of biological functions and potential applications, self-assembled nanotubes constitute highly relevant targets in noncovalent synthesis. Herein, we introduce a novel approach to produce supramolecular nanotubes with defined inner and outer diameters from rigid rod-like monomers programmed with complementary nucleobases through two distinct, decoupled cooperative processes of different hierarchy and acting in orthogonal directions: chelate cooperativity, responsible for the formation of robust Watson-Crick H-bonded cyclic tetramers, and nucleation-growth cooperative polymerization.

Colloidal fibers and rings by cooperative assembly

Janus colloids with one attractive patch on an otherwise repulsive particle surface serve as model systems to explore structure formation of particles with chemically heterogeneous surfaces such as proteins. While there are numerous computer studies, there are few experimental realizations due to a lack of means to produce such colloids with a well-controlled variable Janus balance. Here, we report a simple scalable method to precisely vary the Janus balance over a wide range and selectively functionalize one patch with DNA. We observe, via experiment and simulation, the dynamic formation of diverse superstructures: colloidal micelles, chains, or bilayers, depending on the Janus balance. Flexible dimer chains form through cooperative polymerization while trimer chains form by a two-stage process, first by cooperative polymerization into disordered aggregates followed by condensation into more ordered stiff trimer chains. Introducing substrate binding through depletion catalyzes dimer chains to form nonequilibrium rings that otherwise do not form.

Proximity-Induced Cooperative Polymerization in "Hinged" Helical Polypeptides.

Cooperative interactions and transitions are among the most important strategies utilized by biological systems to regulate a variety of physical and chemical processes. We report herein an auto-accelerated, rapid cooperative polymerization of N-carboxyanhydrides (NCAs) with initiators structurally as simple as linear aliphatic diamines for the synthesis of polypeptides. The polymerization initiated by diamines proceeds via the formation of "hinged" polypeptides, which are two blocks of helical chains connected head-to-head by the diamine molecules in the polymerization solution. The reactions follow a two-stage, cooperative polymerization kinetic; the cooperative interactions between the macrodipoles of the two hinged helical polypeptides dramatically accelerate the polymerization. Compared to the NCA polymerization initiated by the hexylamine (CH3(CH2)5NH2), the chain propagation rate of the NCA polymerization is increased by more than 600 times when initiated by its diamine analogue (1,6-diaminohexane, NH2(CH2)6NH2). This proximity-induced cooperative polymerization showcases the single helix as a remarkable cooperativity-enabling motif in synthetic chemistry.

Self-Sorting of Rosette-Forming Naphthalene Barbiturates into Distinct Toroidal Assemblies.

A unique narcissistic self-sorting system is composed of two structurally similar mono- and bisnaphthalene-based supramolecular monomers. Upon cooling the pure mono- and bisnaphthalene monomers in a nonpolar solvent, toroidal and helicoidally elongated supramolecular polymers were obtained, respectively, through the nucleation-elongation mechanism. When a 1 : 1 mixture of these monomers was similarly cooled, we obtained self-sorted mixtures of smaller and larger toroidal supramolecular polymers with diameters of 15 and 26 nm, respectively. Absorption spectroscopic studies revealed that the mononaphthalene monomers prevents the bisnaphthalene monomers from forming nuclei, leading to a less cooperative polymerization process.

Thermodynamics of amyloid fibril formation from chemical depolymerization.

Amyloid fibrils are homo-molecular protein polymers that play an important role in disease and biological function. While much is known about their kinetics and mechanisms of formation, the origin and magnitude of their thermodynamic stability has received significantly less attention. This is despite the fact that the thermodynamic stability of amyloid fibrils is an important determinant of their lifetimes and processing in vivo. Here we use depolymerization by chemical denaturants of amyloid fibrils of two different proteins (PI3K-SH3 and glucagon) at different concentrations and show that the previously applied isodesmic linear polymerization model is an oversimplification that does not capture the concentration dependence of chemical depolymerization of amyloid fibrils. We show that cooperative polymerization, which is compatible with the picture of amyloid formation as a nucleated polymerization process, is able to quantitatively describe the thermodynamic data. We use this combined experimental and conceptual framework in order to probe the ionic strength dependence of amyloid fibril stability. In combination with previously published data on the ionic strength dependence of amyloid fibril growth kinetics, our results provide strong evidence for the product-like nature of the transition state of amyloid fibril growth.

Equilibrium Ratio of Polymers to Monomers in Cooperative Polymerization of Amyloid-β Protein

Equilibrium Ratio of Polymers to Monomers in Cooperative Polymerization of Amyloid-β Protein

A Stereochemically Driven Supramolecular Polymerisation.

Anthracyclines self-assemble in water into dimers. In the presence of sufficiently high salt (NaCl) concentrations, solutions of the antibiotic doxorubicin, but not those of the closely related molecules daunomycin and epirubicin, turn into gels barely compatible with the presence of small oligomers. The use of spectroscopic, scattering, imaging and computational techniques, allowed light to be shed on the self-assembly process that triggered doxorubicin gelification. A complex picture emerged, with doxorubicin molecules assembled into long, highly chiral, supramolecular aggregates made of hundreds of units, showing redshifted fluorescence spectra, very short fluorescence lifetimes and small-angle X-ray scattering profiles compatible with long cylinders. The involvement of specific chemical groups and the need for a specific stereochemistry of the monomers in the formation of a hydrogen-bond network to stabilise the supramolecular aggregates was supported by molecular dynamics calculations. A salt-induced, temperature-dependent, cooperative nucleation-elongation supramolecular polymerisation of the doxorubicin molecules is deduced.

A clickable NHC-Au(i)-complex for the preparation of stimulus-responsive metallopeptide amphiphiles.

We report the synthesis of an alkyne functionalised NHC-Au(i)-complex which is conjugated with amphiphilic oligopeptides using a copper(i) catalysed cycloaddition. The resulting Au(i)-metalloamphiphiles are shown to self-assemble into charge-regulated stimulus-responsive supramolecular polymers in water via a weakly cooperative polymerisation mechanism.

Frontispiece: Solvent Geometry Regulated Cooperative Supramolecular Polymerization

In the present examples of self-assembly of a naphthalene–diimide building block, linear hydrocarbon solvents directly participate in the nucleation step owing to a geometry allowed, favorable mixing with peripheral alkyl chains of the monomer, which leads to a cooperative supramolecular polymerization pathway. In sharp contrast, lack of such efficient nucleation leads to ill-defined polymerization pathway in cyclic hydrocarbons. However, in the presence of a small amount of additive (preformed fiber in linear alkanes), cooperative polymerization pathway could be retrieved even in cyclic alkanes. For more information, see the Full Paper by S. Ghosh et al. on page 10536 ff.