Conception and Evaluation of a Library of Cleavable Mass Tags for Digital Polymers Sequencing

A library of phosphoramidite monomers containing a main-chain cleavable alkoxyamine and a side-chain substituent of variable molar mass (i.e. mass tag) was prepared in this work. These monomers can be used in automated solid-phase phosphoramidite chemistry and therefore incorporated periodically as spacers inside digitally-encoded poly(phosphodiester) chains. Consequently, the formed polymers contain tagged cleavable sites that guide their fragmentation in mass spectrometry sequencing and enhance their digital readability. The spacers were all prepared via a seven steps synthetic procedure. They were afterwards tested for the synthesis and sequencing of model digital polymers. Uniform digitally-encoded polymers were obtained as major species in all cases, even though some minor defects were sometimes detected. Furthermore, the polymers were decoded in pseudo-MS³ conditions, thus confirming the reliability and versatility of the spacers library.     

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions

Artificially performing chemical reactions in living biosystems to attain various physiological aims remains an intriguing but very challenging task. In this study, the Schiff base reaction was conducted in cells using Sc(OTf)₃ as a catalyst, enabling the in situ synthesis of a hollow covalent organic polymer (HCOP) without external stimuli. The reversible Schiff base reaction mediated intracellular Oswald ripening endows the HCOP with a spherical, hollow porous structure and a large specific surface area. The intracellularly generated HCOP reduced cellular motility by restraining actin polymerization, which consequently induced mitochondrial deactivation, apoptosis, and necroptosis. The presented intracellular synthesis system inspired by the Schiff base reaction has strong potential to regulate cell fate and biological functions, opening up a new strategic possibility for intervening in cellular behavior.     

Molecular Architecture and Function of Polymeric Oriented Systems: Models for the Study of Organization,Surface Recognition,and Dynamics of Biomembranes

The Part and the Whole. The principle of self-organization for the creation of functional units is not an invention of modern natural sciences. It was already a basic idea of the ancient philosophies in Asia and Europe: only the mutuality of the parts creates the whole and its ability to function. Translated into the language of chemistry this means: the self-organization of molecules leads to supramolecular systems and is responsible for their functions. Thermotropic and lyotropic liquid crystals are such functional units, formed by self-organization. As highly oriented systems, they exhibit new properties. The importance of lyotropic liquid crystals for the life sciences has been known for a long time. They are a prerequisite for the development of life and the ability of cells to function. In materials sciences this concept of function through organization led to the development of new liquid-crystalline materials. From the point of view of macromolecular chemistry, this review tries to combine these two different fields and especially hopes to stimulate their interaction and joint treatment. To exemplify this, the molecular architecture of polymeric organized systems will be discussed. Polymeric liquid crystals combine the ability to undergo spontaneous self-organization–typical of liquid-crystalline phases–with the polymer-specific property of stabilizing these ordered states. As new materials, polymeric liquid crystals have already been investigated intensively. As model systems for biomembranes as well as for the simulation of biomembrane processes, they so far have been little discussed. The intention of this review article is to show that polymer science is able to contribute to the simulation of cellular processes such as the stabilization of biomembranes, specific surface recognition, or even the “uncorking” of cells. Polymer science, having an old tradition as an inter-disciplinary field, can no longer restrict itself to common plastics. Attempts to reach new horizons have already begun. The borderland between liquid crystals and cells will certainly play an important role. Basic requirements to work in this frontier area between organic chemistry, membrane biology, life science, and materials science will be the delight in scientific adventures as well as the courage to go ahead. The most important prerequisite will be the willingness to cooperate with disciplines which so far have not really accepted each other. From this point of view, this review does not aim at giving defined answers. It wants instead to encourage the scientific venture: too often we cling to painfully acquired knowledge, fearing adventures.     

Grafted Polymeric Microspheres: A Synthetic Approach to Structurally Well-Defined Brush Polymers

Abstract

A simple method for the surface grafting of crosslinked polystyrene latex particles of narrow size distribution as core is described. Amino groups were generated on the surface of these microspheres by a two-step process of nitration and subsequent reduction. Polyethylene glycol chain of desired molecular weight was covalently linked to the surface amino group using diiso-cyanate-coupling reaction. The method is appropriate for designing brush polymers.

     

分子印迹聚合物研究:从小分子到生物大分子

分子印迹技术是一项制备功能聚合物材料的方法,其对印迹分子的专一性选择识别能力引起了人们的广泛关注。随着方法的基本确立和技术的逐渐成熟,其应用领域和范围不断扩大。本文在总结以往研究结果的基础上,对迄今为止进展相对缓慢的生物大分子印迹研究予以了特别关注,对相关的水环境下的分子识别问题进行了仔细的讨论,认真的分析了生物大分子印迹研究工作的难点和不利因素,对分子印迹技术的未来发展和应用前景进行了展望。     

From Random Coil to Extended Nanocylinder: Dendrimer Fragments Shape Polymer Chains

Wedgelike dendrimer fragments , “dendrons”, attached to linear polymers as side groups, can be used to create anisotropic “nanocylinders”, leading to uncoiling and extension of the polymer chains. Synthetic macromolecules of this type can be visualized directly on surfaces and their contour length determined from scanning force micrographs. Unexpected acceleration effects in the polymerization of dendron monomers as well as the structural consequences of dendritic “pieces of cake” (shown schematically) on linear polymer chains are discussed.     

From Glucose to Polymers: A Continuous Chemoenzymatic Process

Efforts to synthesize degradable polymers from renewable resources are deterred by technical and economic challenges; especially, the conversion of natural building blocks into polymerizable monomers is inefficient, requiring multistep synthesis and chromatographic purification. Herein we report a chemoenzymatic process to address these challenges. An enzymatic reaction system was designed that allows for regioselective functional group transformation, efficiently converting glucose into a polymerizable monomer in quantitative yield, thus removing the need for chromatographic purification. With this key success, we further designed a continuous, three-step process, which enabled the synthesis of a sugar polymer, sugar poly(orthoester), directly from glucose in high yield (73 % from glucose). This work may provide a proof-of-concept in developing technically and economically viable approaches to address the many issues associated with current petroleum-based polymers.     

Protein-based Nanoparticles: From Drug Delivery to Imaging,Nanocatalysis and Protein Therapy

Proteins and enzymes are versatile biomaterials for a wide range of medical applications due to their high specificity for receptors and substrates, high degradability, low toxicity, and overall good biocompatibility. Protein nanoparticles are formed by the arrangement of several native or modified proteins into nanometer-sized assemblies. In this review, we will focus on artificial nanoparticle systems, where proteins are the main structural element and not just an encapsulated payload. While under natural conditions, only certain proteins form defined aggregates and nanoparticles, chemical modifications or a change in the physical environment can further extend the pool of available building blocks. This allows the assembly of many globular proteins and even enzymes. These advances in preparation methods led to the emergence of new generations of nanosystems that extend beyond transport vehicles to diverse applications, from multifunctional drug delivery to imaging, nanocatalysis and protein therapy.     

Nano and dendritic structured carboranes and metallacarboranes: From materials to cancer therapy

An account of the current research carried out in our laboratories is presented. Included is the incorporation of several group 14 elements into charge-compensated carboranes. These species present a bonding pattern not found in other main group carboranes. In addition to our continuing studies of the syntheses and structures of organometallic compounds, the use of these compounds as catalysts and catalyst precursors has been investigated. The isotopic exchange reactions between ¹⁰B enriched boron hydrides with naturally abundant boranes catalyzed by Ru(0) nanoparticles has been studied. The Ru(0) nanoparticles were obtained by the reduction of [CpRuCp^∗RuCp^∗]PF₆ (Cp^∗ = C₅Me₅) with hydrogen and stabilized by the ionic liquid trihexyltetradecylphosphonium dodecylbenzenesulfonate [THTdP][DBS]. This was found to be an excellent, long lived catalyst for the exchange reaction of B-10 enriched diborane and naturally abundant decaborane(14). Other approaches to the production and use of nano-metal catalysts have also been explored. The reduction of the iridium carborane, (PPh₃)₂IrH(7,8-C₂B₉H₁₁) with hydrogen in the presence of trihexyltetradecylphosphonium methylsulfonate, [THTdP][MS], produced an Ir(0) nanoparticles that catalyzed the phenylborolation as did our Ir(sal = N-R = salicylaldiminato; COD = cyclooctadiene complex. Progress in the use of single wall carbon nanotubes (SWCNT) as boron delivery agents was also discussed.     

循环肿瘤DNA的检测:从数字化到测序

液体活检的主要检测对象——循环肿瘤DNA(circulating tumor DNA, ctDNA)是人体血液循环系统中具有一定特征的(包括突变、缺失、插入、重排、拷贝数变异、甲基化等)来自肿瘤细胞基因组的DNA片段,其主要来源于凋亡或坏死的肿瘤细胞。ctDNA 的检测和分析能够提供肿瘤中的基因组信息,例如,基因组中的拷贝数变异、突变和甲基化富集等。相较于其他的肿瘤标志物,ctDNA相对稳定,提取技术相对成熟,与肿瘤的大小和发展具有一定的相关性,是一种新兴的、有前景的肿瘤生物标志物,在精准医疗中发挥着越来越重要的作用。不过ctDNA含量极低,背景游离DNA(cell free DNA, cfDNA)含量高,个体间差异大,且需要提前预判检测的位点和突变,因此,利用新方法和新技术对它进行全面检测分析是必不可少的。目前,针对 ctDNA 的检测方法和平台种类繁多,在此,我们总结了从数字PCR到下一代测序的ctDNA检测的研究进展,包括一些商业化的仪器和一些仍在实验室发展中的设备并对利用这些新兴技术分析检测ctDNA的发展趋势做了展望。     

Coordination Polymers: From Metal–Organic Frameworks to Spheres

Sphere of destiny : Metal–organic spheres with remarkable encapsulation properties are readily prepared and their ability to host a wide range of guest species, including nanoparticles, fluorescent dyes, and quantum dots, is demonstrated. Both the metal–organic spheres and the encapsulated species maintain their fluorescent or magnetic properties, highlighting the importance of these systems as new multifunctional materials.

     

Thiocoumarins: From the Synthesis to the Biological Applications

Coumarin is a privilege scaffold in medicinal chemistry. Coumarin derivatives are still an emerging class of highly potent pharmaceutical drugs, best known in the field of antimicrobials and anticoagulants. Thiocoumarins are a particular class of coumarins in which one or two of the oxygen atoms are replaced by a sulfur. They are chemically subdivided in three groups: Thiocoumarins, 2-thioxocoumarins, and dithiocoumarins. This review emphasizes the rationale behind the synthesis and biological applications of the most relevant publications related to this family of compounds. Particular attention has been given to their potential as drug candidates, with particular emphasis in the last 5 years. This article is based on the most relevant information collected from multiple electronic databases, including SciFinder, Pubmed, Espacenet, and Mendeley.     

Study of Molecular Orientation by Vibrational Spectroscopy: From Polymers to Silk

Infrared and Raman spectroscopies are very efficient techniques to characterize molecular orientation in macromolecular systems. In the present paper, two examples of the application of vibrational spectroscopy to the study of molecular orientation in synthetic and natural macromolecules will be presented. In the first example, the dynamics of orientation and relaxation of stretched films of bimodal blends of polystyrene (PS) and deuterated polystyrene (dPS) has been studied in situ by polarization modulation infrared linear dichroism while, in the second one, polarized Raman microspectroscopy has been used to determined quantitatively the orientation of β-sheet domains in single filaments of Bombyx mori silk.     

Two-Dimensional Covalent and Supramolecular Polymers: From Monolayer to Bilayer and the Thicker

Selective preparation of two-dimensional polymers (2DPs) and supramolecular polymers (2DSPs) with defined thickness is crucially important for controlling and maximizing their functions, yet it has remained as a synthetic challenge. In the past decade, several approaches have been developed to allow selective preparation of discrete monolayer 2DPs and 2DSPs. Recently, crystal exfoliation and self-assembly strategies have been employed to successfully prepare bilayer 2DP and 2DSP, which represent the first step towards the controlled “growth” of 2D polymers from the thinnest monolayers to thicker few-layers along the third dimension. This Concept review discusses the concept of accurate synthesis of 2D polymers with defined layers. Advances in this research area will pave the way to rational synthetic strategies for 2D polymers with controlled thickness.     

Cucurbituril‐Modulated Supramolecular Assemblies: From Cyclic Oligomers to Linear Polymers

Employing bis(p‐sulfonatocalix[4]arenes) (bisSC4A) and N′,N′′hexamethylenebis(1‐methyl‐4,4′‐bipyridinium) (HBV⁴⁺) as monomer building blocks, the assembly morphologies can be modulated by cucurbit[n]uril (CB[n]) (n=7, 8), achieving the interesting topological conversion from cyclic oligomers to linear polymers. The binary supramolecular assembly fabricated by HBV⁴⁺ and bisSC4A units, forms an oligomeric structure, which was characterized by NMR spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), dynamic light scattering (DLS), isothermal titration calorimetry (ITC), and gel permeation chromatography (GPC) experiments. The ternary supramolecular polymer participated by CB[8] is constructed on the basis of host–guest interactions by bisSC4A and the [2]pseudorotaxane HBV⁴⁺@CB[8], which is characterized by means of AFM, DLS, NMR spectroscopy, thermogravimetric analysis (TGA), UV/Vis spectroscopy, and elemental analysis. CB[n] plays vital roles in rigidifying the conformation of HBV⁴⁺, and reinforcing the host–guest inclusion of bisSC4A with HBV⁴⁺, which prompts the formation of a linear polymer. Moreover, the CB[8]‐participated ternary assembly could disassemble into the molecular loop HBV²⁺@CB[8] and free bisSC4A after reduction of HBV⁴⁺ to HBV²⁺, whereas the CB[7]‐based assembly remained unchanged after the reduction. CB[8] not only controlled the topological conversion of the supramolecular assemblies, but also improved the redox‐responsive assembly/disassembly property practically.     

Blending to Make Nonhealable Polymers Healable: Nanophase Separation Observed by CP/MAS 13C NMR Analysis

Can commodity polymers are made to be healable just by blending with self-healable polymers? Here we report the first study on the fundamental aspect of this practically challenging issue. Poly(ether thiourea) (PTUEG₃; T_g=27 °C) reported in 2018 is extraordinary in that it is mechanically robust but can self-heal even at 12 °C. In contrast, poly(octamethylene thiourea) (PTUC₈; T_g=50 °C), an analogue of PTUEG₃, cannot heal below 92 °C. We found that their polymer blend self-healed in a temperature range above 32 °C even when its PTUEG₃ content was only 20 mol %. Unlike PTUEG₃ alone, this polymer blend, upon exposure to high humidity, barely plasticized, keeping its excellent mechanical properties due to the non-hygroscopic nature of the PTUC₈ component. CP/MAS ¹³C NMR analysis revealed that the polymer blend was nanophase-separated, which possibly accounts for why such a small amount of PTUEG₃ provided the polymer blend with humidity-tolerant self-healable properties.     

Hard and Soft Capsules: From Branched Polymers to Controlled Release via Gels

Summary: Supramolecular gels, made from the combination of telechelic poly (ethyleneglycols) (PEG's) and trivalent poly(isobutylenes) with terminal matching hydrogen bonds were prepared and their rheological properties were investigated. Addition of poly(N-isopropylacrylamide) as thermosensitive polymer was included into the gel-capsules in amounts of 10 w%, producing gels with strongly thermally- responsive properties. Additionally, dansyl-dyes with two different endgroups (either an hydrophobic endgroup or a multiple hydrogen bond) were encapsulated into the gels as mimicks for pharmaceutically active substances. Monitoring their diffusion by UV-dependent measurements allowed to tune the diffusion and thus the release properties of the gel. The generated supramolecular gels will allow the selective encapsulation and triggered release of various pharmaceuticals and biologically active targets.     

Polymer Nanoassembly as Delivery Systems and Anti‐Bacterial Toolbox: From PGMAs to MSN@PGMAs

Researches on cargo delivery systems have received burgeoning attention and advanced rapidly. For synthetic nanodevices, polymer nanoassemblies and their inorganic‐organic hybrid materials, especially smart mesoporous silica nanoparticle (MSN)‐polymer hybrids (e. g., MSN@PGMAs), have attracted increasing attention in recent years. Their superior characteristics and unique features such as dynamic transition of morphology endow them the ability to efficiently entrap cargo molecules and undergo smart cargo delivery and release in response to various external stimuli. In this Personal Account, we present our recent research progress in the construction of cargo delivery systems based on polymers, poly(glycidyl methacrylate) (PGMA) and its derivatives in particular, ranging from polymer nanoparticles, reverse micelles, to vesicles and reverse vesicles, and their performance in the delivery and controlled release of model molecules and therapeutic agents. Significantly, MSN‐PGMA hybrid nanoassemblies (MSN@PGMAs), constructed with the aid of atom transfer radical polymerization, host‐guest interactions, or layer‐by‐layer self‐assembly techniques, and their potential bio‐related applications and anti‐bacterial applications as new nanocarriers are reviewed. Finally, the prospects and challenges of such nanoplatforms are also discussed.