Synthetic Macromolecules Research Articles

"Is macromolecular crowding overlooked?"--Effects of volume exclusion on DNA-amino acids complexes and their reconstitutes.

Biological macromolecules evolve and function within intracellular environments that are crowded with other macromolecules. Crowding results in surprisingly large quantitative effects on both the rates and the equilibria of interactions involving macromolecules, but such interactions are commonly studied outside the cell in uncrowded buffers. The addition of high concentrations of natural and synthetic macromolecules to such buffers enables crowding to be mimicked in vitro, and should be encouraged as a routine variable to study. In this study, we propose to understand the changes in DNA character and its modulation in presence of macromolecules such as PEG with reference to binding parameters to amino acids using fluorescence enhancement.

Targeted delivery of Dicer-substrate siRNAs using a dual targeting peptide decorated dendrimer delivery system

Small interfering RNAs (siRNA) are emerging as novel therapeutic agents, providing competent delivery systems that are available. Dendrimers, a special family of synthetic macromolecules, represent an exciting delivery platform by virtue of their well-defined dendritic structure and unique multivalency and cooperativity confined within a nanoscale volume. Here, we report a Dicer-substrate siRNA (dsiRNA) which, when delivered using a structurally flexible triethanolamine-core poly(amidoamine) dendrimer of generation 5 as the nanocarrier, gives rise to a much greater RNAi response than that produced with conventional siRNA. Further decoration of the dsiRNA/dendrimer complexes with a dual targeting peptide simultaneously promoted cancer cell targeting through interacting with integrins and cell penetration via the interaction with neuropilin-1 receptors, which led to improved gene silencing and anticancer activity. Altogether, our results disclosed here open a new avenue for therapeutic implementation of RNAi using dendrimer nanovector based targeted delivery. From the Clinical EditorThis study demonstrates superior therapeutic properties of siRNA when combined with a dendrimer-based targeted nano-delivery system. Similar approaches may eventually gain clinical utility following additional studies determining safety and efficacy.

Temperature‐sensitive elastin‐mimetic dendrimers: Effect of peptide length and dendrimer generation to temperature sensitivity

Dendrimers are synthetic macromolecules with unique structure, which are a potential scaffold for peptides. Elastin is one of the main components of extracellular matrix and a temperature-sensitive biomacromolecule. Previously, Val-Pro-Gly-Val-Gly peptides have been conjugated to a dendrimer for designing an elastin-mimetic dendrimer. In this study, various elastin-mimetic dendrimers using different length peptides and different dendrimer generations were synthesized to control the temperature dependency. The elastin-mimetic dendrimers formed β-turn structure by heating, which was similar to the elastin-like peptides. The elastin-mimetic dendrimers exhibited an inverse phase transition, largely depending on the peptide length and slightly depending on the dendrimer generation. The elastin-mimetic dendrimers formed aggregates after the phase transition. The endothermal peak was observed in elastin-mimetic dendrimers with long peptides, but not with short ones. The peptide length and the dendrimer generation are important factors to tune the temperature dependency on the elastin-mimetic dendrimer.

Progress of quartz crystal microbalance in chiral analysis.

Chiral analysis is one of the most important/challenging analytical tasks due to the necessity for differentiation of very slight differences in the molecular configurations between chiral isomers. It consists of two processes, chiral recognition and signal transduction. Quartz crystal microbalance (QCM) holds a great promise for the next-generation sensors, due to its remarkable mass sensitivity, fast response, capable of online detection and low cost. It has been the focus of academic and practical research on chiral analysis during the last two decades. This review provides a detailed overview of recent advances made in chiral analysis based on QCM detection with regard to the recognition elements, which include synthetic macromolecules, molecular imprinting polymers (MIPs), proteins, amino acids and their derivatives, etc. The prospects of using QCM for chiral analysis are also put forward.

Recent Advances in Molecular Recognition Based on Nanoengineered Platforms

Nanoparticles and nanoengineered platforms have great potential for technologies involving biomoleuclar detection or cell-related biosensing, and have provided effective chemical interfaces for molecular recognition. Typically, chemists work on the modification of synthetic polymers or macromolecules, which they link to the nanoparticles by covalent or noncovalent approaches. The motivation for chemical modification is to enhance the selectivity and sensitivity, and to improve the biocompatibility for the in vivo applications. In this Account, we present recent advances in the development and application of chemical interfaces for molecular recognition for nanoparticles and nanoengineered platforms, in particular single-walled carbon nanotubes (SWNTs). We discuss emerging approaches for recognizing small molecules, glycosylated proteins, and serum biomarkers. For example, we compare and discuss detection methods for ATP, NO, H2O2, and monosaccharides for recent nanomaterials. Fluorometric detection appears to have great potential for quantifying concentration gradients and determining their location in living cells. For macromolecular detection, new methods for glycoprofiling using such interfaces appear promising, and benefit specifically from the potential elimination of cumbersome labeling and liberation steps during conventional analysis of glycans, augmenting the currently used mass spectrometry (MS), capillary electrophoresis (CE), and liquid chromatography (LC) methods. In particular, we demonstrated the great potential of fluorescent SWNTs for glycan-lectin interactions sensing. In this case, SWNTs are noncovalently functionalized to introduce a chelated nickel group. This group provides a docking site for the His-tagged lectin and acts as the signal modulator. As the nickel proximity to the SWNT surface changes, the fluorescent signal is increased or attenuated. When a free glycan or glycosylated probe interacts with the lectin, the signal increases and they are able to obtain loading curves similar to surface plasmon resonance measurements. They demonstrate the sensitivity and specificity of this platform with two higher-affined glycan-lectin pairs: fucose (Fuc) to PA-IIL and N-acetylglucosamine (GlcNAc) to GafD. Lastly, we discuss how developments in protein biomarker detection in general are benefiting specifically from label-free molecular recognition. Electrical field effect transistors, chemi-resistive and fluorometric nanosensors based on various nanomaterials have demonstrated substantial progress in recent years in addressing this challenging problem. In this Account, we compare the balance between sensitivity, selectivity, and nonspecific adsorption for various applications. In particular, our group has utilized SWNTs as fluorescence sensors for label-free protein-protein interaction measurements. In this assay, we have encapsulated each nanotube in a biocompatible polymer, chitosan, which has been further modified to conjugate nitrilotriacetic acid (NTA) groups. After Ni(2+) chelation, NTA Ni(2+) complexes bind to his-tagged proteins, resulting in a local environment change of the SWNT array, leading to optical fluorescence modulation with detection limit down to 100 nM. We have further engineered the platform to monitor single protein binding events, with an even lower detection limit down to 10 pM.

Determination of polyethylene glycol end group functionalities by combination of selective reactions and characterization by matrix assisted laser desorption/ionization time-of-flight mass spectrometry

End groups play a critical role in macromolecular coupling reactions for building complex polymer architectures, yet their identity and purity can be difficult to ascertain using traditional analytical technique. Recent advances in mass spectrometry techniques have made matrix-assisted laser desorption/ionization time-of-fight (MALDI-TOF) mass spectrometry a rapid and powerful tool for providing detailed information about the identity and purity of homopolymer end groups. In this work, MALDI-TOF mass spectrometry was used to study end groups of linear polyethylene glycols. In particular, the identifications of alcohol, amine and thiol end groups are investigated because these nucleophilic moieties are among the most common within biological and synthetic macromolecules. Through comparative characterization of alcohol, amine, and thiol end groups, the exact identification of these end groups could be confirmed by selective and quantitative modification. The precision of this technique enables the unambiguous differentiation of primary amino groups relative to hydroxyl groups, which differ by only 1 mass unit. In addition, the quantitative conversion of various polyethylene glycol end groups using highly efficient coupling reactions such as the thiol-ene and azide-alkyne click reactions can be confirmed using MALDI-TOF mass spectrometry.

Fluorescent labelled dual-stimuli (pH/thermo) responsive self-assembled side-chain amino acid based polymers

Pyrene labelled chain transfer agent, py-CTA, was synthesized and employed for the reversible addition-fragmentation chain transfer (RAFT) polymerization of Boc-phenylalanine/alanine methacryloyloxyethyl ester (Boc-F/A-EMA) based monomers, for obtaining α-pyrene labelled homopolymers, pyrene-poly(Boc-phenylalanine/alanine methacryloyloxyethyl ester) (py-P(Boc-F/A-EMA)), with controlled molecular weight, narrow polydispersity and precise chain-end functionality. Subsequent Boc-deprotection produced pH-responsive cationic homopolymers with side-chain primary amino groups. Furthermore, py-P(Boc-F/A-EMA) was utilized as macro-CTA for the polymerization of di(ethylene glycol) methyl ether methacrylate (DEGMA) to afford block copolymers, which upon Boc-deprotection provided dual pH- and thermo-responsive polymers. An interplay of hydrophobicity of the incorporated amino acid residue as well as pH value of the solution were determined as the tunable parameter for the alteration of lower critical solution temperature (LCST) of these block copolymers. Functionalization of carbon nanotube (CNT) via non-covalent interactions, and unique morphologies generated from the self-assembly of these synthetic macromolecules were also investigated.

Regulation of Photophysical Properties for Naphthyl Decorated PAMAM Dendrimers by Pseudorotaxane Formation at Periphery

Abstract Dendrimers are regularly and hierarchically branched synthetic macromolecules with monodispersity, globular shape, interior pockets, and numerous peripherial functionality, which endow them with great potential in miscellaneous applications such as host-guest chemistry, chemosensor, catalysis, drug delivery, microreactor and light-harvesting systems. In the present work, a series of naphthyl terminal-decorated polyamidoamine (PAMAM) dendrimers Gn-NA (n=1~3) and model compound were synthesized. The water-soluble PAMAM backbone was constructed by the classic divergent method and the terminal modification of dendrimers by naphthyl groups was accomplished through a reaction of peripheral amino units with naphthyl succinimidyl ester efficiently. The average functionalization extents of the peripheral groups were 100%, 97% and 93% for G1~G3, respectively. The structures of Gn-NA (n=1~3) were characterized by H NMR, C NMR, MALDI-TOF mass spectra and IR. Steady state and time-resolved photophysical studies reveal that strong interactions among peripheral naphthyls occur within Gn-NA, resulting in the excimer formation and the naphthyl fluorescence quenching. The quenching efficiency of naphthyl fluorescence increases with increasing generations. The assembly of the peripheral naphthyl group with cucurbit[7]uril (CB[7]) forms a pseudorotaxane with ratio of 1∶1 and association constants (an application of B-H equation) of 768, 887 and 823 mol•L from generation 1 to generation 3, respectively. The lifetime of the pseudorotaxane of NA-Model with CB[7] is slightly longer than that of NA-Model, indicating that the formation of pseudorotaxane can reduce the nonradiative decay at a certain degree. The lifetimes of naphthyl group and its pseudorotaxane with CB[7] of Gn-NA were resolved to be 2.5~2.7 and 11.4~11.7 ns, respectively, and the lifetimes of the intramolecular naphthyl excimer of Gn-NA were analyzed to be ca. 17 ns. Combining the results of the remarkably increased lifetime of the naphthyl group in its pseudorotaxane form and those of the NA-Model system, we conclude that the peripheral pseudorotaxane formation depresses both the formation of intramolecular naphthyl excimer and the excited state quenching by solvent, thus enhancing the fluorescence emission of naphthyl dramatically. This study provides a potential strategy for developing controllable light-emitting dendritic system with efficient synthesis and improvable photophysical properties.

A new insight into fluoride anion in electron transfer reactions

Recently, scientists have developed fluoride anion recognition synthetic macromolecules for potential applications in environmental monitoring. However, the actual role of fluoride anion remains highly debated in the reaction of anion-induced electron transfer (ET) to π-electron-deficient naphthalenediimides. The present study demonstrates that the ET reaction is induced by the complexation of F− with the cation radical formed with the assistance of polar aprotic solvent. The results present an alternative mechanism of the actual role of F− in ET reactions in polar aprotic solvents that could provide novel implications for anion-mediated ET reactions.

Advantages of Monodisperse and Chemically Robust “SpheriCal” Polyester Dendrimers as a “Universal” MS Calibrant

The utilization of dendrimer calibrants as an alternative to peptides and proteins for high mass calibration is explored. These synthetic macromolecules exhibited a number of attractive advantages, including exceptional shelf-lives, broad compatibility with a wide range of matrices and solvents, and evenly spaced calibration masses across the mass range examined, 700-30,000 u. The exceptional purity of these dendrimers and the technical simplicity of this calibration platform validate their broad relevance for high molecular weight mass spectrometry.

Synthesis of temperature‐dependent elastin‐like peptide‐modified dendrimer for drug delivery

Dendrimers are synthetic macromolecules with a unique structure that are potential unimolecular drug carriers and potential scaffolds for peptides. Elastin is one of the main components of the extracellular matrix, as well as a temperature-sensitive biomacromolecule. Val-Pro-Gly-Val-Gly repeats, an elastin-like peptide, have been used for designing artificial elastin molecules. In this study, we have synthesized a novel type of temperature-dependent drug carrier by conjugating Ac-Val-Pro-Gly-Val-Gly to a dendrimer, named elastin-mimetic dendrimer. The elastin-mimetic dendrimer formed β-turn structure by heating. The elastin-mimetic dendrimer exhibited the inverse phase transition, depending on pH and NaCl concentration in addition to temperature. The elastin-mimetic dendrimer could encapsulate a model drug, rose bengal, even though the complex stability was similar to the dendrimer without elastin-like peptide. Therefore, the elastin-mimetic dendrimer is a potential drug carrier with temperature- and pH-dependent properties.

Separation and characterization of natural and synthetic macromolecules

This topical collection is dedicated to the separation and characterization of natural and synthetic macromolecules. The international symposia on separation and characterization of natural and synthetic macromolecules, abbreviated to SCM, were born in 2003 with a series of conferences organized in Amsterdam, and very quickly a lively international community developed with a main emphasis on separation techniques for macromolecules. The area of interest expanded with time to include complementary techniques for characterization of macromolecules, which makes powerful analysis of macromolecular systems possible. The idea to collect representative contributions in a special issue of Analytical and Bioanalytical Chemistry arose during the planning of the first SCM held in Dresden, in 2013. Today, SCM is a platform for discussion and collaboration among scientists with different scientific backgrounds interested in separation techniques and characterization methods for macromolecules and it represents a forum of experts in chemical analysis, polymer research and the life sciences. Macromolecules, independent of their origin, synthetic or natural, are essential in our life. Complex polymer architectures with tailored designs are increasingly used in highpriority areas, such as microelectronics and medicine. Along with synthetic strategies, the control and analysis of their properties are of great significance for understanding the structure–property relationships. In this context, the need for accurate, reliable and efficient characterization methods is obvious. For effective and successful research in polymer separation science, interdisciplinarity is essential. SCM provides a platform for promising characterization techniques in an early stage of their development, but also for hot topics related to synthetic and natural polymers on a fundamental or application-oriented level. This is reflected in this special issue. It starts with a Trends article and a Critical Review followed by Research Papers covering subjects such as human health, smart materials, and polymers/oligomers for food, cosmetics, additives, etc. The macromolecular systems discussed in this collection of articles are of synthetic or natural origin, ranging from glucose polymers, substituted cellulose ethers, Diels-Alder polymers with dynamic bonding, branched polymers, block copolymers, smart polymer brushes and biopolymers all the way to peptide surfaces. We place strong emphasis on the development and improvement of separation methods, for example temperaturedependent size-exclusion chromatography and the coupling of different separation techniques to solve special problems, such as in situ reaction kinetics or structure elucidation of olefin copolymers. The separation techniques used in polymer science are nowadays far more diverse than size-exclusion chromatography. Techniques such as liquid adsorption chromatography, capillary electrophoresis (under critical conditions), hydrodynamic chromatography, field-flow fractionation (in all its variations) and the well-known temperature-rising elution fractionation are creatively used for solving specific issues. In combination with new detection techniques, such as light scattering and electrospray ionization mass spectrometry, and with complementary spectroscopic, microscopic and thermal analysis, comprehensive state-of the-art investigations are performed. Apart from the latest developments in polymer separations, this issue features a contribution on polymer characterization at surfaces using time-of-flight secondary ion mass spectrometry, X-ray atomic force microscopy and in situ spectroscopic ellipsometry. Published in the topical collection Separation and Characterization of Natural and Synthetic Macromolecules with guest editors Albena Lederer and Peter J. Schoenmakers.

Filtrodynamics: Time Dependent Trans-Filter Pressure Signals for Early Detection and Monitoring of Particulates During Chemical Processing

In many chemical manufacturing processes particulates often appear in addition to the desired products. Frequently, these particulates are undesirable and ubiquitous in macromolecular reactors that produce and process both synthetic and natural macromolecules. In some cases, however, particulates are necessary, such as bacteria in a biotechnology reactor. This work presents ‘filtrodynamics’, a means for early detection and monitoring of particulates in chemical processes. Time-dependent pressure signals across filters yield information on particulate populations. Moreover, a characteristic loading model has been proposed that self-consistently interlinks the particle concentration, flow rates, and filter properties via a characteristic loading parameter Lc. Filtrodynamics may yield a low cost alternative to delicate and difficult to maintain online optical sensors.

Efficiency of non-protein solutions using hydroxypropyl cellulose on survival of bovine and human oocytes and embryos after vitrification

Vitrification is an alternative method of cryopreservation in ART, resulting in significantly improved survival rates of oocytes and embryos, and with excellent clinical outcomes. To reduce risk of viral contamination, government regulators have stipulated that non-serum substitutes must be used ART. The purpose of this study was to test the efficacy of a synthetic macromolecule, hydroxypropyl cellulose (HPC), for use as a supplement in vitrification solutions. In vitro survival and clinical outcome of bovine and human oocytes and blastocysts after vitrification using non-protein vitrification solutions containing HPC were examined and compared with conventional vitrification method. Four experiments were conducted to assess the efficacy of non-protein VS for oocytes and blastocysts. Four-hundred and twenty bovine oocytes and 300 blastocysts and 154 human oocytes were vitrified by the Cryotec method(Kuwayama, 2013). The solutions for vitrification were supplemented with 0.06 mg/ml HPC or with 10%SSS or with no added macromolecule (NA). Some HPC solutions and SSS solutions were stored at 4ºC or -80ºC for 12months before vitrification. The survival rates of bovine oocytes vitrified in HPC, SSS and NA were 100%, 100% and 86% and the respective blastocyst rates were 22%, 18% and 8%, respectively. The survival rates of bovine blastocysts vitrified in HPC, SSS and NA were 99%, 93% and 88%, respectively.The survival rate of bovine oocytes vitrified in HPC solutions stored for 12 months at 4°C or -80°C was 100%; the rates for those vitrified in SSS solutions were somewhat lower than HPC. The survival rates of human oocytes vitrified in HPC, SSS and NA were 100%, 98% and 92%, respectively. High morphological in vitro survival and growth of bovine and human oocytes, and also bovine blastocysts after vitrification using the solutions containing HPC suggest that this supplement can be effective for human oocytes and embryos vitrification.

Sequence-Controlled Polymers

Sequence-controlled polymers are macromolecules in which monomer units of different chemical nature are arranged in an ordered fashion. The most prominent examples are biological and have been studied and used primarily by molecular biologists and biochemists. However, recent progress in protein- and DNA-based nanotechnologies has shown the relevance of sequence-controlled polymers to nonbiological applications, including data storage, nanoelectronics, and catalysis. In addition, synthetic polymer chemistry has provided interesting routes for preparing nonnatural sequence-controlled polymers. Although these synthetic macromolecules do not yet compare in functional scope with their natural counterparts, they open up opportunities for controlling the structure, self-assembly, and macroscopic properties of polymer materials.

Effect of polyoxyethylene and polyoxypropylene nonionic block copolymers on performance and recruitment of immune cell subsets in weaned pigs

BackgroundBecause European-wide directives are restricting the non-clinical use of antibiotics as in-feed growth promotors in swine production, there is an intensive search for alternative strategies for control and prevention of losses among young pigs. With the growing knowledge of the porcine immune system and its endogenous modulation, it has been clearly established that exogenous immunomodulation using adjuvants and immune response modifiers (IRMs) represents an important prophylactic/therapeutic approach in the prevention/treatment of both stress- and microbial-induced disorders that accompaning weaning. However, it is essential to select a fully evaluated agent which may act either as a nonspecific IRM or synergistically as an adjuvant with vaccines. The synthetic macromolecules with a long history as adjuvant and IRM are nonionic block copolymers which consist of polyoxyethylene (POE) and polyoxypropylene (POP) molecules.MethodsThe aim of this work was to evaluate the effectiveness of POE-POP given as a single peroral dose on productivity parameters such as body weight gain, feed intake and feed conversion ratio, and systemic and intestinal immune parameters by assessing the proportions of CD45+ lymphoid cells, CD4+ and CD8+ T cells, and CD21+ B cells in the peripheral blood as well as the number of CD45RA+ naive lymphoid cells residing in the ileal mucosa in weaned pigs during a follow-up study 5 weeks after the treatment.ResultsPigs treated with POE-POP had better feed intake (+ 14.57%), higher average body mass at the end of the experiment (20.91 kg vs. 17.61 kg), and higher body weight gain in relation to Day 0 (191.63% vs. 144.58%) as well as in relation to nontreated pigs (+ 18.74%), with a lower feed conversion ratio (− 30.26%) in comparison to the control pigs. A much lower diarrhea severity score (5 vs. 54) was recorded in pigs treated with POE-POP (− 90.74%) than in the control pigs. A higher average diarrhea severity (ADS) was recorded in the control pigs (1.54 vs. 0.14), whereas the treatmant group had much a lower ADS ratio (− 90.91%) after 35 days of the experiment. The pigs that were treated with POE-POP had an increased proportion of CD45+, CD4+ and CD8+ cells at Day 21 (at p < 0.05, p < 0.05 or p < 0.01, respectively), Day 28 (at p < 0.01, respectively) and Day 35 (at p < 0.01, p < 0.05 or p < 0.01, respectively) as well as of CD21+ cells at Day 28 (p < 0.05) and Day 35 of the experiment (p < 0.01). Also, these pigs had more numerous CD45RA+ cells in interfollicular (p < 0.05) and follicular areas (p < 0.01) of the ileal Peyer’s patches than did control pigs.ConclusionThis property of POE-POP to induce recruitment of circulating and intestinal immune cell subsets in weaned pigs may allow the use of IRM-active block copolymers as adjuvants for vaccines, particularly those orally delivered and targeted to the gut-associated lymphoid tissues that are well known to promote rather tolerogenic than protective immune responses.

Amperometric sensing — Bioelectroanalysis

It seems quite timely that Analytical and Bioanalytical Chemistry (ABC) is devoting a special issue to sensing. Less obvious is that the issue is limited to electrochemical sensing, even less so to amperometric sensing, bioelectrosensing included. Actually, electroanalysis is not the most widely applied analytical technique. Optical methods definitely overwhelm the electrochemical ones in popularity; once mass spectrometry, chromatography, and the relevant hyphenated techniques, are taken into account together with the optical ones, only a restricted room is seemingly left to electrochemical methods of analysis. However, especially in the field of biosensors, this general description does not alway hold and electroanalytical techniques are presently dominating successful commercial applications of biosensors. A big change in electroanalysis has occurred in the last 30 years, caused by the invention of modified electrodes. The modification of electrode surfaces has also led to improved anchoring of highly specific biological recognition elements, allowing unprecedented performance in electrocatalytic biosensing. Electrode systems have attained increasing complexity and a large variety of electrode modifiers have been proposed, such as synthetic and natural macromolecules, different types of nanoparticles and conducting polymers or clays. Among the novel materials developed in the last 20 years, only a limited number have been tested and used in an electrochemical context, and an even much lower number have been considered for electroanalysis. This encourages analytical chemists to closely follow developments in the field of material chemistry, basic studies in electrochemistry and electrochemical applications to potentially transfer this knowledge to effective electroanalytical systems. Concomitantly with the development of novel electrode materials, optimization of the overall system structure has become more complex, requiring its characterization using a large number of spectroscopic, microscopic and electrochemical techniques. Consequently, interdisciplinarity has become a must for the effective development of novel modified electrodes for electroanalysis. Only combinations of analytical techniques provide sufficient insight into the in-depth functioning of modified electrodes for electroanalysis and the interplay between the different components ultimately composing the complex electrode architecture. Complete knowledge, in the widest sense, is necessary to achieve the best performance of an envisaged sensor as a whole. A lot of time has passed since the years in which ‘bare’ electrodes were used in molecular electrochemistry studies, which were subsequently transferred to electroanalysis. More or less complex electrode mechanisms were studied only by electrochemical techniques that allowed the electrode mechanism to be fully elucidated from a qualitative and even quantitative point of view. Such a ‘simple’, though rigorous approach is not possible with more complex modified electrode systems any more, owing to the enormous variety of possible structures, depending on a number of possible compositions and the conditions under which the system has been realized. A danger lies in the tendency to separate the field into two ‘different kinds’ of scientists doing electroanalysis: those strictly following an ‘it works!’ approach describing often useful effects which cannot be given an in-depth account, owing to the too great complexity of the system, Published in the topical collections Amperometric Sensing with guest editors Renato Seeber, Fabio Terzi, and Chiara Zanardi and Bioelectroanalysis with guest editors Nicolas Plumere, Magdalena Gebala, and Wolfgang Schuhmann. R. Seeber (*) : F. Terzi :C. Zanardi Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Via G. Campi, 183, 41100 Modena, Italy e-mail: renato.seeber@unimore.it

Solid-State NMR in Macromolecular Systems: Insights on How Molecular Entities Move

The function of synthetic and natural macromolecularsystems critically depends on the packing and dynamics of the individual components of a given system. Not only can solid-state NMR provide structural information with atomic resolution, but it can also provide a way to characterize the amplitude and time scales of motions over broad ranges of length and time. These movements include molecular dynamics, rotational and translational motions of the building blocks, and also the motion of the functional species themselves, such as protons or ions. This Account examines solid-state NMR methods for correlating dynamics and function in a variety of chemical systems. In the early days, scientists thought that the rotationalmotions reflected the geometry of the moving entities. They described these phenomena as jumps about well-defined axes, such as phenyl flips, even in amorphous polymers. Later, they realized that conformational transitions in macromolecules happen in a much more complex way. Because the individual entities do not rotate around well-defined axes, they require much less space. Only recently researchers have appreciated the relative importance of large angle fluctuations of polymers over rotational jumps. Researchers have long considered that cooperative motions might be at work, yet only recently they have clearly detected these motions by NMR in macromolecular and supramolecular systems. In correlations of dynamics and function, local motions do not always provide the mechanism of long-range transport. This idea holds true in ion conduction but also applies to chain transport in polymer melts and semicrystalline polymers. Similar chain motions and ion transport likewise occur in functional biopolymers, systems where solid-state NMR studies are also performed. In polymer science, researchers have appreciated the unique information on molecular dynamics available from advanced solid-state NMR at times, where their colleagues in the biomacromolecular sciences have emphasized structure. By contrast, following X-ray crystallographers, researchers studying proteins using solution NMR introduced the combination of NMR with computer simulation before that became common practice in solid-state NMR. Today's simulation methods can handle partially ordered or even disordered systems common in synthetic polymers. Thus, the multitechnique approaches employed in NMR of synthetic and biological macromolecules have converged. Therefore, this Account will be relevant to both researchers studying synthetic macromolecular and supramolecular systems and those studying biological complexes.

Sequence‐Controlled Multi‐Block Glycopolymers to Inhibit DC‐SIGN‐gp120 Binding

Glycan–protein interactions are essential for many physiological processes including cell–cell recognition, cell adhesion, cell signalling, pathogen identification, and differentiation. Dendritic cell-specific intercellular adhesion molecule3-grabbing non-integrin (DC-SIGN; CD209) is a C-type lectin (carbohydrate-binding protein) present on both macrophages and dendritic cell subpopulations and plays a critical role in many cell interactions. DC-SIGN binds to microorganisms and host molecules by recognizing surface-rich mannose-containing glycans through multivalent glycan– protein interactions and serves as a target for several viruses, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Carbohydrate-binding proteins (CBP) have been suggested as potential microbicides for the prevention of HIV infection. However, the isolation of natural CBPs is relatively difficult because of their hydrophilic nature and low affinity for the virus. 4] Thus, synthetic lectins are of interest for carbohydrate recognition studies. Alternatively, noncarbohydrate inhibitors of mammalian lectins can be used to prevent the interaction between DC-SIGN and gp120. The structures of these multivalent ligands have a great effect on carbohydrate binding to lectins, and the use of linear polymers to effectively inhibit lectin binding has been demonstrated by several research groups. Synthetic polymer chemistry has developed rapidly in recent years. Currently, polymerization of functional monomers with the desired chain length, structure, and composition is straightforward; whereas producing polymers with monomer sequence control remains challenging, which has implications for the controlled folding of synthetic macromolecules. There are a few recent reports where sufficient control has been achieved in controlling the monomer sequence along the polymer chain. To the best of our knowledge, this is the first report where some control over the relative position of the sugars is exhibited and their binding to the human lectin DC-SIGN is demonstrated. We have used a controlled polymerization technique, single-electron transfer living radical polymerization (SET-LRP), to polymerize glycomonomers, which are prepared by copper catalyzed azide–alkyne click (CuAAC) reaction prior to polymerization. A series of glycomonomers were prepared by reaction of 3-azidopropylacrylate (APA) and alkylated mannose, glucose, and fucose using a Fischer–Helferich glycosylation. This was performed using CuSO4 and sodium ascorbate in a methanol/water mixture (see the Supporting Information). SET-LRP of the glucose monomer (GluA) was performed in dimethylsulfoxide (DMSO) using a copper(0)/copper(II) and tris[2-(dimethylamino)ethyl]amine (Me6TREN)-derived catalyst. Polymerization reached over 90 % monomer conversion in six hours whilst maintaining a narrow molecular weight distribution with increasing molecular weight. (Supporting Information, Figure S4). The obtained polymers were characterized by size exclusion chromatography (SEC) and MALDI-TOF mass spectroscopy (MS) or high-resolution electrospray ionization mass spectroscopy (HR-ESI MS), which indicated very high chain-end fidelity allowing for sequential monomer addition. We designed a polymerization reaction starting with one equivalent of initiator (I) and two equivalents of mannose glycomonomer (ManA; Figure 1a). ManA was fully consumed after 12 hours; then two equivalents of GluA in DMSO were added to the reaction mixture and GluA was consumed in 16 hours. Two equivalents of ManA in DMSO were subsequently added to the reaction mixture, and this cycle was continued until six short blocks of glycopolymers were produced (the degree of polymerization (DP) = 2 for each block, (mannose)2-(glucose)2-(mannose)2-(glucose)2(mannose)2-(glucose)2). No purification steps were required prior to addition of the subsequent monomer. The conversion of the first four blocks, as analyzed by H NMR spectroscopy, reached 100 %, shown by the complete disappearance of vinyl groups at 5.7–6.5 ppm. The glycomonomers were dissolved in purged DMSO prior to their addition and this resulted in further dilution of the reaction mixture upon each monomer addition. Traces of vinyl groups could still be detected after [*] Q. Zhang, J. Collins, A. Anastasaki, Dr. C. R. Becer, Prof. D. M. Haddleton Department of Chemistry, University of Warwick Gibbet Hill Road, Coventry, CV4 7AL (UK) E-mail: d.m.haddleton@warwick.ac.uk Homepage: http://www.warwick.ac.uk/go/polymers Dr. R. Wallis Department of Biochemistry, University of Leicester Leicester, LE1 9HN (UK) Dr. D. A. Mitchell Clinical Sciences Research Institute, Warwick Medical School, University of Warwick Coventry, CV2 2DX (UK) [**] We acknowledge financial support from the University of Warwick and the China Scholarship Council. Equipment used in this research was funded by the Innovative Uses for Advanced Materials in the Modern World (AM2) with support from AWM and ERDF. D.M.H. is a Royal Society/Wolfson Fellow and C.R.B. is a Science City Senior Research Fellow. Dr. Christopher N. Scanlan has provided the gp120. Supporting information for this article (syntheses of all materials and details of the characterization methods) is available on the WWW under http://dx.doi.org/10.1002/anie.201300068. Angewandte Chemie

Cu(II)-triggered release of paclitaxel from a supramolecular complex

The research on the stimuli-responsive property of biological or synthetic macromolecules in a wide range of scientific fields is a crucial subject for the achievements of the targeted drug release and the precise control of the functions of the supramolecules at a molecular level. We used an anthraquinone-functioned cyclodextrin (1) bridged by an aza-arm to solubilise paclitaxel (PTX) by forming a supramolecular complex (1/PTX). The possible inclusion mode was given based on the experimental results of ultraviolet–visible spectroscopy, Fourier transform infrared, X-ray diffraction, fluorescence spectra, nuclear magnetic resonance, transmission electron microscope, scanning electron microscope and dynamic light scattering characterisations. The controlled release of PTX can be achieved by adding Cu2+ to the solution. This study provides useful references in developing stimuli-responsive drug-carrying and drug-releasing materials.