Single Polymer Chain Research Articles

Shotgun Sequencing of 512‐mer Copolyester Allows Random Access to Stored Information

AbstractDigital information encoded in polymers has been exclusively decoded by mass spectrometry. However, the size limit of analytes in mass spectrometry restricts the storage capacity per chain. In addition, sequential decoding hinders random access to the bits of interest without full‐chain sequencing. Here we report the shotgun sequencing of a 512‐mer sequence‐defined polymer whose molecular weight (57.3 kDa) far exceeds the analytical limit of mass spectrometry. A 4‐bit fragmentation code was implemented at aperiodic positions during the synthetic encoding of 512‐bit information without affecting storage capacity per chain. Upon activating the fragmentation code, the polymer chain splits into 18 oligomers, which could be individually decoded by tandem‐mass sequencing. These sequences were computationally reconstructed into a full sequence using an error‐detection method. The proposed sequencing method eliminates the storage limit of a single polymer chain and allows random access to the bits of interest without full‐chain sequencing.

Carbon bowls induce single-chain polymer to form DNA-like double-stranded helical structures

Carbon materials have played an important role in the long history of human development. In this manuscript, we introduce a carbon material with a ‘bowl’-like structure, i.e., a carbon bowl, and explore its induced self-assembly process of single-chain polyphenyl. It is found that single-stranded polyphenyl can self-assemble into a double-stranded helix structure similar to DNA in the presence of two carbon bowls. Both the van der Waals potential well and the π–π stacking interaction between carbon bowls and polyphenyl chain play a major role in the self-assemble process. Too few carbon bowls or too lengthy a polyphenyl chain reduced the contact force between the bowls and the polyphenyl chain, preventing self-assembly. In addition, it was discovered that varied positions of the carbon bowls in the polyphenyl chain result in distinct final configurations. Both high and low temperatures did not favour the self-assembly process. Carbon bowls with varying layers remain stable and can induce self-assembly of the polyphenyl chain. This research result will provide an important theoretical basis for the development of new carbon nanomaterials and the construction of new carbon composites.

Stereospecific supramolecular polymerization of nanoclusters into ultra-long helical chains and enantiomer separation

During the construction of supramolecular polymers of smaller nanoparticles/nanoclusters bearing hierarchy and homochirality, the mechanism understanding via intuitive visualization and precise cross-scale chirality modulation is still challenging. For this goal, a cooperative self-assembly strategy is here proposed by using ionic complexes with uniform chemical composition comprising polyanionic nanocluster cores and surrounded chiral cationic organic components as monomers for supramolecular polymerization. The single helical polymer chains bearing a core-shell structure at utmost length over 20 μm are demonstrated showing comparable flexibility resembling covalent polymers. A nucleation-elongation growth mechanism that is not dealt with in nanoparticle systems is confirmed to be accompanied by strict chiral self-sorting. A permeable membrane prepared by simple suction of such supramolecular polymers displays high enantioselectivity (e.e. 98% after four runs) for separating histidine derivatives, which discloses a benefiting helical chain structure-induced functionalization for macroscopic supramolecular materials in highly efficient racemate separation.

Near-Infrared Emissive Super Penetrating Conjugated Polymer Dots for Intratumoral Imaging in 3D Tumor Spheroid Models.

This study describes the formation of single-chain polymer dots (Pdots) via ultrasonic emulsification of nonionic donor-acceptor-donor type (D-A-D) alkoxy thiophene-benzobisthiadiazole-based conjugated polymers (Poly BT) with amphiphilic cetyltrimethylammonium bromide (CTAB). The methodology yields Pdots with a high cationic surface charge (+56.5mV ± 9.5) and average hydrodynamic radius of 12nm. Optical characterization reveals that these Pdots emit near-infrared (NIR) light at a maximum wavelength of 860nm owing to their conjugated polymer backbone consisting of D-A-D monomers. Both colloidal and optical properties of these Pdots make them promising fluorescence emissive probes for bioimaging applications. The significant advantage of positively charged Pdots is demonstrated in diffusion-limited mediums such as tissues, utilizing human epithelial breast adenocarcinoma, ATCC HTB-22 (MCF-7), human bone marrow neuroblastoma, ATCC CRL-2266 (SH-SY5Y), and rat adrenal gland pheochromocytoma, CRL-1721 (PC-12)tumor spheroid models. Fluorescence microscopy analysis of tumor spheroids from MCF-7, SH-SY5Y, and PC-12 cell lines reveals the intensity profile of Pdots, confirming extensive penetration into the central regions of the models. Moreover, a comparison with mitochondria staining dye reveals an overlap between the regions stained by Pdots and the dye in all three tumor spheroid models. These results suggest that single-chain D-A-D type Pdots, cationized via CTAB, exhibit long-range mean free path of penetration (≈1µm) in dense mediums and tumors.

Shotgun Sequencing of 512-mer Copolyester Allows Random Access to Stored Information.

Digital information encoded in polymers has been exclusively decoded by mass spectrometry. However, the size limit of analytes in mass spectrometry restricts the storage capacity per chain. In addition, sequential decoding hinders random access to the bits of interest without full-chain sequencing. Here we report the shotgun sequencing of a 512-mer sequence-defined polymer whose molecular weight (57.3 kDa) far exceeds the analytical limit of mass spectrometry. A 4-bit fragmentation code was implemented at aperiodic positions during the synthetic encoding of 512-bit information without affecting storage capacity per chain. Upon activating the fragmentation code, the polymer chain splits into 18 oligomers, which could be individually decoded by tandem-mass sequencing. These sequences were computationally reconstructed into a full sequence using an error-detection method. The proposed sequencing method eliminates the storage limit of a single polymer chain and allows random access to the bits of interest without full-chain sequencing.

Self-Adaptive Synthesis of Non-Covalent Crosslinkers while Folding Single-Chain Polymers.

Peptide folding is a dynamic process driven by non-covalent cross-linking leading to functional nanostructures for essential biochemical activities. However, replicating this process in synthetic systems is challenging due to the difficulty in mimicking nature's real-time regulation of non-covalent crosslinking for single-chain polymer folding. Here, we address this by employing anionic dithiol building blocks to create macrocyclic disulfides as non-covalent crosslinkers that adapted to the folding process. Initially, small macrocycles facilitated a low degree folding of a polycation. Then, this preorganized structure catalysed the production of larger macrocycles that enhanced the folding conversely. The self-adaptive synthesis was verified through the encapsulation of an anticancer drug, showing an updated production distribution of non-covalent crosslinkers and maximizing drug-loading efficiency against drug-resistant cancer in vitro. Our research advances the understanding of molecular systems by exploring species evolution via the structural dynamics of polymer folding. Additionally, adaptive synthesis enables controlled, sequential folding of synthetic polymers, with the potential to mimic protein functions.

Instability of single polymer chain in an electroelastic problem

Under electric loading produced by compliant electrodes, a dielectric elastomer is prone to material instabilities which, in a microstructural level, may connect to single polymer chain instability. To reveal if such connection exists, we aim to use an electroelastic energy model for single polymer chain to study the chain instability. We approximate curvature shape of the chain under the electric loading by using trigonometry series in a spatial coordinate. The Rayleigh–Ritz method is then applied to solve the energy equation formed by the trigonometry series. We demonstrate in the numerical examples that the instability of the chain may occur at the value of electric field with corresponding configuration of the chain close to its full length.

Biodynamers: applications of dynamic covalent chemistry in single-chain polymer nanoparticles

Dynamic Covalent Chemistry (DCC) enables the development of responsive molecular systems through the integration of reversible bonds at the molecular level. These systems are thermodynamically stable and capable of undergoing various molecular assemblies and transformations, allowing them to adapt to changes in environmental conditions like temperature and pH. Introducing DCC into the field of polymer science has led to the design of Single-Chain Nanoparticles (SCNPs), which are formed by self-folding via intramolecular crosslinking mechanisms. Defined by their adaptability, SCNPs mimic biopolymers in size and functionality. Biodynamers, a subclass of SCNPs, are specifically designed for their stimuli-responsive and tunable, dynamic properties. Mimicking complex biological structures, their scope of application includes target-specific and pH-responsive drug delivery, enhanced cellular uptake and endosomal escape. In this manuscript, we discuss the integration of DCC for the design of SCNPs, focusing particularly on the characteristics of biodynamers and their biomedical and pharmaceutical applications. By underlining their potential, we highlight the factors driving the growing interest in SCNPs, providing an overview of recent developments and future perspectives in this research field.Graphical

Dual-reactive single-chain polymer nanoparticles for orthogonal functionalization through active ester and click chemistry

Glucose has been extensively studied as a targeting ligand on nanoparticles for biomedical nanoparticles. A promising nanocarrier platform are single-chain polymer nanoparticles (SCNPs). SCNPs are well-defined 5–20 nm semi-flexible nano-objects, formed by intramolecularly crosslinked linear polymers. Functionality can be incorporated by introducing labile pentafluorophenyl (PFP) esters in the polymer backbone, which can be readily substituted by functional amine-ligands. However, not all ligands are compatible with PFP-chemistry, requiring different ligation strategies for increasing versatility of surface functionalization. Here, we combine active PFP-ester chemistry with copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) click chemistry to yield dual-reactive SCNPs. First, the SCNPs are functionalized with increasing amounts of 1-amino-3-butyne groups through PFP-chemistry, leading to a range of butyne-SCNPs with increasing terminal alkyne-density. Subsequently, 3-azido-propylglucose is conjugated through the glucose C1- or C6-position by CuAAC click chemistry, yielding two sets of glyco-SCNPs. Cellular uptake is evaluated in HeLa cancer cells, revealing increased uptake upon higher glucose-surface density, with no apparent positional dependance. The general conjugation strategy proposed here can be readily extended to incorporate a wide variety of functional molecules to create vast libraries of multifunctional SCNPs.

Amphiphilic Single-Chain Polymer Nanoparticles as Imaging and Far-Red Photokilling Agents for Photodynamic Therapy in Zebrafish Embryo Xenografts.

This work introduces rationally designed, improved amphiphilic single-chain polymer nanoparticles (SCNPs) for imaging and photodynamic therapy (PDT) in zebrafish embryo xenografts. SCNPs are ultrasmall polymeric nanoparticles with sizes similar to proteins, making them ideal for biomedical applications. Amphiphilic SCNPs result from the self-assembly in water of isolated synthetic polymeric chains through intrachain hydrophobic interactions, mimicking natural biomacromolecules and, specially, proteins (in size and when loaded with drugs, metal ions or fluorophores also in function). These ultrasmall, soft nanoparticles have various applications, including catalysis, sensing, and nanomedicine. Initial in vitro experiments with nonfunctionalized, amphiphilic SCNPs loaded with a photosensitizing Zn phthalocyanine with four nonperipheral isobutylthio substituents, ZnPc, showed promise for PDT. Herein, the preparation of improved, amphiphilic SCNPs containing ZnPc as highly efficient photosensitizer encapsulated within the nanoparticle and surrounded by anthracene units is disclosed. The amount of anthracene groups and ZnPc molecules within each single-chain nanoparticle controls the imaging and PDT properties of these nanocarriers. Critically, this work opens the way to improved PDT applications based on amphiphilic SCNPs as a first step toward ideal, long-term artificial photo-oxidases (APO).

Dynamic Implications of Noncovalent Interactions in Amphiphilic Single-Chain Polymer Nanoparticles.

Single-chain polymer nanoparticles (SCNPs) combine the chemical diversity of synthetic polymers with the intricate structure of biopolymers, generating versatile biomimetic materials. The mobility of polymer chain segments at length scales similar to secondary structural elements in proteins is critical to SCNP structure and thus function. However, the influence of noncovalent interactions used to form SCNPs (e.g., hydrogen-bonding and biomimetic secondary-like structure) on these conformational dynamics is challenging to quantitatively assess. To isolate the effects of noncovalent interactions on SCNP structure and conformational dynamics, we synthesized a series of amphiphilic copolymers containing dimethylacrylamide and monomers capable of forming these different interactions: (1) di(phenylalanine) acrylamide that forms intramolecular β-sheet-like cross-links, (2) phenylalanine acrylamide that forms hydrogen-bonds but lacks a defined local structure, and (3) benzyl acrylamide that has the lowest propensity for hydrogen-bonding. Each SCNP formed folded structures comparable to those of intrinsically disordered proteins, as observed by size exclusion chromatography and small angle neutron scattering. The dynamics of these polymers, as characterized by a combination of dynamic light scattering and neutron spin echo spectroscopy, was well described using the Zimm with internal friction (ZIF) model, highlighting the role of each noncovalent interaction to additively restrict the internal relaxations of SCNPs. These results demonstrate the utility of local scale interactions to control SCNP polymer dynamics, guiding the design of functional biomimetic materials with refined binding sites and tunable kinetics.

Designing a Naturally Inspired Conductive Copolymer to Engineer Wearable Bioadhesives for Sensing Applications.

The design of adhesive and conductive soft hydrogels using biopolymers with tunable mechanical properties has received significant interest in the field of wearable sensors for detecting human motions. These hydrogels are primarily fabricated through the modification of biopolymers to introduce cross-linking sites, the conjugation of adhesive components, and the incorporation of conductive materials into the hydrogel network. The development of a multifunctional copolymer that integrates adhesive and conductive properties within a single polymer chain with suitable cross-linking sites eliminates the need for biopolymer modification and the addition of extra conductive and adhesive components. In this study, we synthesized a copolymer based on poly([2-(methacryloyloxy)ethyl] trimethylammonium chloride-co-dopamine methacrylamide) (p(METAC-DMA)) using a controlled radical polymerization, allowing for the efficient conjugation of both adhesive and conductive units within a single polymer chain. Subsequently, our multifunctional hydrogel named Gel-MD was fabricated by mixing the p(METAC-DMA) copolymer with non-modified gelatin in which cross-linking took place in an oxidative environment. We confirmed the biocompatibility of the Gel-MD hydrogel through in vitro studies using NIH 3T3 cells as well as in vivo subcutaneous implantation in rats. Furthermore, the Gel-MD hydrogel was effective and sensitive in detecting various human motions, making it a promising wearable sensor for health monitoring and diagnosis.

A Chain Scission-Induced Anisotropic Damage Constitutive Model for Double Network Hydrogels

This work develops a chain scission-induced anisotropic damage constitutive model for double network (DN) hydrogels while considering the damage cross effect. A free energy of a single polymer chain comprising the configuration entropy of the polymer chain and the internal energy of persistent segments is proposed to avoid the force singularity caused by chain stretch limit. Then, a distribution function of the initial stretch ratio of polymer chains in DN hydrogels is derived to consider the randomness of chain length. Based on the micro-sphere full-network model and an energy-form fracture criterion of polymer chains, the damage evolution model of polymer chains in a certain orientation is formulated by the critical initial stretch ratio of the polymer chain, showing that only polymer chains with the initial stretch ratio lower than the critical initial stretch ratio survive in a certain chain stretch. The critical initial stretch ratio is determined by the maximum chain stretch and the maximum first invariant of the deformation state by considering the damage cross effect. Using the developed damage constitutive model, we describe the stress softening, strain hardening behavior and the nonmonotonic stress–strain curve of DN hydrogels. It also reveals that the residual strain of DN hydrogels in the loading cycles is caused by the anisotropic damage of polymer chains in DN hydrogels.

Estimating Poly(N-isopropylacrylamide) size in solution below the LCST using fluorescence correlation spectroscopy with non-covalent bound fluorophores

Accurate size measurements of nanosized polymer chains in dilute solutions is important for understanding polymer behavior, however, these measurements can be challenging to implement accurately, and are technique dependent. Here we explore the use of Fluorescence Correlation Spectroscopy (FCS) to determine the size of single polymer chains in dilute solutions (<2 wt%). FCS, a technique with single molecule sensitivity, generally requires the use of covalently labelled polymers which can distort physicochemical behavior. Here, FCS based size measurements were based on the non-covalent interaction of fluorophores (Alexa 405, Atto 390, and Atto 425) with PNIPAm in water at 25 °C (below the Lower Critical Solution Temperature).FCS estimated size (hydrodynamic radius) of three different MW PNIPAm samples in water were: 5.0 ± 1.0 nm (28.5 kDa), 5.0 ± 1.0 nm (38 kDa), 3.3 ± 0.5 nm (55.5 kDa), in reasonable agreement with theoretical calculations. Accuracy was directly related to the fraction of PNIPAm-bound fluorophore, which were, for 1 wt% PNIPAm solutions in water: ∼11.5 % (Atto 390), ∼8.1 % (Atto 425), and 4 % (Alexa 405). This method has several advantages in that it does not require a covalent labelling of PNIPAm, it can be implemented on very small sample volumes, and allows for in-situ measurements.

Machine-learning-assisted searching for thermally conductive polymers: A mini review

Polymers, known for their lightweight, high strength, and ease of processing, serve as a key component in engineering materials. Polymers with high thermal conductivity (TC) present enormous potential applications in thermal management for high-performance electronic devices. However, the discovery of thermally conductive polymers is still in a time-consuming and labor-intensive trial-and-error process, which undoubtedly hinders the progress in related applications. Fortunately, machine learning (ML) enables to overcome this obstacle by building precise models to predict the TC of polymers through learning from a large volume of data and it can quickly identify polymers with high TC and provide significant insights to guide further design and innovation. In this mini review, we briefly describe the general process of using ML to predict polymers with high TC and then give guidance for the selection and utilization of three important components: database, descriptor, and algorithm. Furthermore, we summarize the predicted thermally conductive single polymer chains, amorphous polymers, and metal-organic frameworks via ML and identify the key factors that lead to high TC. Finally, we touch on the challenges faced when utilizing ML to predict the TC of polymer and provide a foresight into future research endeavors.

Directly visualizing individual polyorganophosphazenes and their single-chain complexes with proteins

Polyorganophosphazenes are water-soluble macromolecules with immunoadjuvant activity that self-assemble with proteins to enable biological functionality. Direct imaging by cryogenic electron microscopy uncovers the coil structure of those highly charged macromolecules. Here, we successfully visualize individual polymer chains within the vitrified state in the absence of additives for contrast enhancement which is attributed to the high mass contrast of the inorganic backbone. Upon assembly with proteins, multiple protein copies bind at the single polymer chain level resulting in structures reminiscent of compact spherical complexes or stiffened coils. The outcome depends on protein characteristics and cannot be deduced by commonly used characterization techniques, such as light scattering, thus revealing direct morphological insights crucial for understanding biological activity. Atomic force microscopy supports the morphology outcomes while advanced analytical techniques confirm protein-polymer binding. The chain visualization methodology provides tools for gaining insights into the processes of supramolecular assembly and mechanistic aspects of polymer-enabled vaccine delivery.

Controlling of electro-optical properties of cobalt phthalocyanine formed single chain polymer: Sudan III and nanographene based its composites

The synthesis of poly[4-(4-vinylbenzyl)oxy)phthalonitrile-co-styrene] [P(VBOPN5 %-co-St)] was carried out by free radical polymerisation at 60 °C. The successful formation of a green coloured single-chain polymer molecule with the formation of cobalt phthalocyanine (SCP-CoPc) was performed at 140–150 °C in the presence of dilute cyclohexanol. The characterization of SCP-CoPc was confirmed by FT-IR and UV/vis spectroscopic techniques. The absorption filtration process of the SCP-CoPc polymer/Sudan III composite was investigated. The introduction of Sudan III into the SCP-CoPc polymer matric strongly affected the optical transmission spectrum of the composite films. The optical transmission measurements of the SCP-CoPc/Sudan III thin film show a high absorption in the visible region (400–800 nm). In the SCP-CoPc/Sudan III composites, the optical band gaps (Eg1 and Eg2) of each of its components has changed significantly. The Eg1 and Eg2 were found to be between 1.90 and 2.83 eV, respectively. Depending on the sudan III content, a wide range from 600 nm to 730 nm indicates complete absorption filtration. The dc electrical conductivity and dielectric behavior of the SCP-CoPc/Nanografene (NG) 6 wt% nanocomposite increased with increasing temperature. From the dc conductivity plot, the Ea values of I. and II. regions were found to be 0.75 eV and 0.27 eV, respectively and it was found that the calculated activation energy obeyed the Arrhenius relationship. The refractive index and the optical permittivity of SCP-CoPc/NG 6 wt% have been estimated.

The Soft Nanodots as Fluorescent Probes for Cell Imaging: Analysis of Cell and Spheroid Penetration Behavior of Single Chain Polymer Dots.

This study describes the formation, size control, and penetration behavior of polymer nanodots (Pdots) consisting of single or few chain polythiophene-based conjugated polyelectrolytes (CPEs) via nanophase separation between good solvent and poor solvent of CPE. Though the chain singularity may be associated with dilution nanophase separation suggests that molecules of a good solvent create a thermodynamically driven solvation layer surrounding the CPEs and thereby separating the single chains even in their poor solvents. This statement is therefore corroborated with emission intensity/lifetime, particle size, and scattering intensity of polyelectrolyte in good and poor solvents. Regarding the augmented features, Pdots are implemented into cell imaging studies to understand the nuclear penetration and to differentiate the invasive characteristics of breast cancer cells. The python based red, green, blue (RGB) color analysis depicts that Pdots have more nuclear penetration ability in triple negative breast cancer cells due to the different nuclear morphology in shape and composition and Pdots have penetrated cell membrane as well as extracellular matrix in spheroid models. The current Pdot protocol and its utilization in cancer cell imaging are holding great promise for gene/drug delivery to target cancer cells by explicitly achieving the very first priority of nuclear intake.

Light-driven folding of single polymer chains via metal-complexation

We introduce a light-driven methodology (λmax = 365 nm) to fold single polymer chains into single chain nanoparticles (SCNPs) via metal-complexation.

Visible-light-mediated Diels-Alder reactions under single-chain polymer confinement: investigating the role of the crosslinking moiety on catalyst activity.

Macromolecular scaffolds are rapidly emerging in catalysis owing to the ability to control catalyst placement at precise locations. This spatial proximity allows for enhanced catalyst activity that may not be observed using small molecules. Herein, we describe a triphenylpyrylium (TPT)-based visible-light active single-chain polymer nanoparticle (SCNP) that facilitates the radical cation [4 + 2]-cycloaddition. We find that the catalytic activity is highly dependent on the styrylarene comonomer used, wherein it can act as a redox mediator under confinement, increasing the catalytic turnover (TON) by up to 30 times in comparison to free TPT in solution. Mechanistic studies indicate that TPT excited states are quenched by the acene, with the resultant radical cation formed from naphthalene-based SCNPs able to proceed in oxidizing the dienophile in the elementary step of the reaction, while leading to near quantitative yields of the cycloadduct. The TPT-SCNP demonstrates enhanced photocatalyst efficiency compared to molecular TPT, and is able to be recycled and reused in three iterations of the reaction prior to decreased performance from photobleaching. Our results overall suggest that the confined nature of the SCNP and spatial proximity of acene-based pendants enforces their participation as cocatalytic redox mediators that impart enhanced photoredox catalysis under confinement.