A Spontaneous In Situ Thiol-Ene Crosslinking Hydrogel with Thermo-Responsive Mechanical Properties.

The thermo-responsive behavior of Poly(N-isopropylacrylamide) makes it an ideal candidate to easily embed cells and allows the polymer mixture to be injected. However, P(NiPAAm) hydrogels possess minor mechanical properties. To increase the mechanical properties, a covalent bond is introduced into the P(NIPAAm) network through a biocompatible thiol-ene click-reaction by mixing two polymer solutions. Co-polymers with variable thiol or acrylate groups to thermo-responsive co-monomer ratios, ranging from 1% to 10%, were synthesized. Precise control of the crosslink density allowed customization of the hydrogel's mechanical properties to match different tissue stiffness levels. Increasing the temperature of the hydrogel above its transition temperature of 31 °C induced the formation of additional physical interactions. These additional interactions both further increased the stiffness of the material and impacted its relaxation behavior. The developed optimized hydrogels reach stiffnesses more than ten times higher compared to the state of the art using similar polymers. Furthermore, when adding cells to the precursor polymer solutions, homogeneous thermo-responsive hydrogels with good cell viability were created upon mixing. In future work, the influence of the mechanical micro-environment on the cell's behavior can be studied in vitro in a continuous manner by changing the incubation temperature.

PoCOsteo: generic novel platform for bone turnover marker measurement & monitoring.

Despite the increasing efforts in improving bone health assessments, current diagnostics suffer from critical shortcomings. The present article therefore describes a multiplex label-free immunosensor designed and validated for the assessment of two bone turnover markers (BTMs), namely beta isomerized C-terminal telopeptide of type I collagen (CTx) and Procollagen I Intact N-Terminal (PINP), the combination of which is needed to illustrate an accurate overview of bone health. The immunosensor was then tested outside and inside of a microsystem, with the aim of becoming compatible with a point of care system fabricated for automated assessment of these biomarkers later-on at patient side. Custom-made monoclonal antibodies were specifically designed for this purpose in order to guarantee the selectivity of the immunosensor. In the final platform, a finger prick blood sample is introduced into the microfluidic manifolds without any need for sample preparation step, making the tool suitable for near patient and outside of the central laboratory applications. The platform was exploited in 30 real blood samples with the results validated using electrochemiluminescence immunoassay. The results revealed the platform was capable of measuring the target analyte with high sensitivity and beyond the recommended clinical reference range for each biomarker (CTx: 104-1028 ng L-1 and PINP: 16-96 µg L-1, correspondingly). They also showed the platform to have a limit of detection of 15 (ng L-1) and 0.66 (µg L-1), a limit of quantification of 49 (ng L-1) and 2.21 (µg L-1), and an inter- and intra-assay coefficient of variance of 5.39-6.97% and 6.81-5.37%, for CTx and PINP respectively, which is comparable with the gold standard. The main advantage of the platform over the state-of-the art was the capability of providing the results for two markers recommended for assessing bone health within 15 minutes and without the need for skilled personnel or costly infrastructure.

Efficient in vitro and in vivo transfection of self-amplifying mRNA with linear poly(propylenimine) and poly(ethylenimine-propylenimine) random copolymers as non-viral carriers.

Messenger RNA (mRNA) based vaccines have been introduced worldwide to combat the Covid-19 pandemic. These vaccines consist of non-amplifying mRNA formulated in lipid nanoparticles (LNPs). Consequently, LNPs are considered benchmark non-viral carriers for nucleic acid delivery. However, the formulation and manufacturing of these mRNA-LNP nanoparticles are expensive and time-consuming. Therefore, we used self-amplifying mRNA (saRNA) and synthesized novel polymers as alternative non-viral carrier platform to LNPs, which enable a simple, rapid, one-pot formulation of saRNA-polyplexes. Our novel polymer-based carrier platform consists of randomly concatenated ethylenimine and propylenimine comonomers, resulting in linear, poly(ethylenimine-ran-propylenimine) (L-PEIx-ran-PPIy) copolymers with controllable degrees of polymerization. Here we demonstrate in multiple cell lines, that our saRNA-polyplexes show comparable to higher in vitro saRNA transfection efficiencies and higher cell viabilities compared to formulations with Lipofectamine MessengerMAX™ (LFMM), a commercial, lipid-based carrier considered to be the in vitro gold standard carrier. This is especially true for our in vitro best performing saRNA-polyplexes with N/P 5, which are characterised with a size below 100 nm, a positive zeta potential, a near 100% encapsulation efficiency, a high retention capacity and the ability to protect the saRNA from degradation mediated by RNase A. Furthermore, an ex vivo hemolysis assay with pig red blood cells demonstrated that the saRNA-polyplexes exhibit negligible hemolytic activity. Finally, a bioluminescence-based in vivo study was performed over a 35-day period, and showed that the polymers result in a higher and prolonged bioluminescent signal compared to naked saRNA and L-PEI based polyplexes. Moreover, the polymers show different expression profiles compared to those of LNPs, with one of our new polymers (L-PPI250) demonstrating a higher sustained expression for at least 35 days after injection.

Water-dispersible X-ray scintillators enabling coating and blending with polymer materials for multiple applications.

Developing X-ray scintillators that are water-dispersible, compatible with polymeric matrices, and processable to flexible substrates is an important challenge. Herein, Tb3+-doped Na5Lu9F32 is introduced as an X-ray scintillating material with steady-state X-ray light yields of 15,800 photons MeV-1, which is generated as nanocrystals on halloysite nanotubes. The obtained product exhibits good water-dispersibility and highly sensitive luminescence to X-rays. It is deposited onto a polyurethane foam to afford a composite foam material with dose-dependent radioluminescence. Moreover, the product is dispersed into polymer matrixes in aqueous solution to prepare rigid or flexible scintillator screen for X-ray imaging. As a third example, it is incorporated multilayer hydrogels for information camouflage and multilevel encryption. Encrypted information can be recognized only by X-ray irradiation, while the false information is read out under UV light. Altogether, we demonstrate that the water-dispersible scintillators are highly promising for aqueous processing of radioluminescent, X-ray imaging, and information encrypting materials.

Self-indicating polymers: a pathway to intelligent materials.

Self-indicating polymers have emerged as a promising class of smart materials that possess the unique ability to undergo detectable variations in their physical or chemical properties in response to various stimuli. This article presents an overview of the most important mechanisms through which these materials exhibit self-indication, including aggregation, phase transition, covalent and non-covalent bond cleavage, isomerization, charge transfer, and energy transfer. Aggregation is a prevalent mechanism observed in self-indicating polymers, where changes in the degree of molecular organization result in variations in optical or electrical properties. Phase transition-induced self-indication relies on the transformation between different phases, such as liquid-to-solid or crystalline-to-amorphous transitions, leading to observable changes in color or conductivity. Covalent bond cleavage-based self-indicating polymers undergo controlled degradation or fragmentation upon exposure to specific triggers, resulting in noticeable variations in their structural or mechanical properties. Isomerization is another crucial mechanism exploited in self-indicating polymers, where the reversible transformation between the different isomeric forms induces detectable changes in fluorescence or absorption spectra. Charge transfer-based self-indicating polymers rely on the modulation of electron or hole transfer within the polymer backbone, manifesting as changes in electrical conductivity or redox properties. Energy transfer is an essential mechanism utilized by certain self-indicating polymers, where energy transfer between chromophores or fluorophores leads to variations in the emission characteristics. Furthermore, this review article highlights the diverse range of applications for self-indicating polymers. These materials find particular use in sensing and monitoring applications, where their responsive nature enables them to act as sensors for specific analytes, environmental parameters, or mechanical stress. Self-indicating polymers have also been used in the development of smart materials, including stimuli-responsive coatings, drug delivery systems, food sensors, wearable devices, and molecular switches. The unique combination of tunable properties and responsiveness makes self-indicating polymers highly promising for future advancements in the fields of biotechnology, materials science, and electronics.

New sorbent-based hydrophobic alginic acid derivatives for fat removal in multi-pesticide residues: analysis of a fatty food sample.

Hydrophobic alginic acid derivatives were synthesized with various aliphatic hydrocarbon chains for fat removal in an analysis of multi-pesticide residues in a fatty food sample. First, alginic acid was chemically modified using eco-friendly ultrasound-assisted esterification with different alcohols, namely, hydrophobic alginic acid-methanol (HAA-C1), hydrophobic alginic acid-butanol (HAA-C4), and hydrophobic alginic acid-octadecanol (HAA-C18). The degree of esterification (DE) was determined by titration, and the results ranged from 57.3% to 63.7%. The physicochemical properties of the synthesized hydrophobic alginic acids (HAAs) were studied using FT-IR, XRD, TGA, and FE-SEM. Subsequently, the performance of the HAAs was checked and evaluated for the removal of fat from a fatty food sample by calculating the fat removal percentage and the determination of 214 pesticide residues in the fatty food sample. For the fat removal percentage application, the HAAs were able to efficiently remove between 77% and 83% of the fat; HAA-C18 had the highest percentage. Regarding the pesticide residue application, HAAs were also able to remove the fat content from the fatty food sample without a significant effect on the pesticide substances. The recoveries of the detected pesticide compounds were between 80% and 120% for all HAAs. However, there were various missing pesticide compounds for HAAs. The number of missing pesticide compounds was 19, 6, and 33 for HAA-C1, HAA-C4, and HAA-C18, respectively. HAA-C4 had medium hydrophobicity and it lost fewer pesticides than the other HAAs. This was because the multi-pesticide mixture had various classes of chemical structure; hence, it had different polarity powers. We concluded that HAAs are developable and applicable to be safely used as a green material in diverse fatty food sample analysis applications.

Sustained release of a human PD-L1 single-domain antibody using peptide-based hydrogels.

Monoclonal antibodies (mAbs) targeting the immune checkpoint axis, which contains the programmed cell death protein-1 (PD-1) and its ligand PD-L1, revolutionized the field of oncology. Unfortunately, the large size of mAbs and the presence of an Fc fraction limit their tumor penetrative capacities and support off-target effects, potentially resulting in unresponsive patients and immune-related adverse events (irAEs) respectively. Single-domain antibodies (sdAbs) are ten times smaller than conventional mAbs and represent an emerging antibody subclass that has been proposed as next generation immune checkpoint inhibitor (ICI) therapeutics. They demonstrate favorable characteristics, such as an excellent stability, high antigen-binding affinity and an enhanced tumor penetration. Because sdAbs have a short half-life, methods to prolong their presence in the circulation and at the target site might be necessary in some cases to unfold their full therapeutic potential. In this study, we investigated a peptide-based hydrogel as an injectable biomaterial depot formulation for the sustained release of the human PD-L1 sdAb K2. We showed that a hydrogel composed of the amphipathic hexapeptide hydrogelator H-FQFQFK-NH2 prolonged the in vivo release of K2 after subcutaneous (s.c.) injection, up to at least 72 h, as monitored by SPECT/CT and fluorescence imaging. Additionally, after encapsulation in the hydrogel and s.c. administration, a significantly extended systemic presence and tumor uptake of K2 was observed in mice bearing a melanoma tumor expressing human PD-L1. Altogether, this study describes how peptide hydrogels can be exploited to provide the sustained release of sdAbs, thereby potentially enhancing its clinical and therapeutic effects.

From One-Dimensional Disordered Racemate to Ordered Racemic Conglomerates through Metal-Coordination-Driven Self-Assembly at the Liquid-Solid Interface.

In recent years, there has been significant focus on investigating and controlling chiral self-assembly, specifically in the context of enantiomeric separation. This study explores the self-assembly behavior of 4-dodecyl-3,6-di(2-pyridyl)pyridazine (DPP-C12) at the interface between heptanoic acid (HA) and highly oriented pyrolytic graphite (HOPG) using a combination of scanning tunneling microscopy (STM) and multiscale molecular modeling. The self-assembled monolayer structure formed by DPP-C12 is periodic in one direction, but aperiodic in the direction orthogonal to it. These structures resemble 1D disordered racemic compounds. Upon introducing palladium [Pd(II)] ions, complexing with DPP-C12, these 1D disordered racemic compounds spontaneously transform into 2D racemic conglomerates, which is rationalized with the assistance of force-field simulations. Our findings provide insights into the regulation of two-dimensional chirality.

Synergistic topological and supramolecular control of Diels-Alder reactivity based on a tunable self-complexing host-guest molecular switch.

Compartmentalization and binding-triggered conformational change regulate many metabolic processes in living matter. Here, we have synergistically combined these two biorelevant processes to tune the Diels-Alder (DA) reactivity of a synthetic self-complexing host-guest molecular switch CBPQT4+ -Fu, consisting of an electron-rich furan unit covalently attached to the electron-deficient cyclobis(paraquat-p-phenylene) tetrachloride (CBPQT4+ , 4Cl- ) host. This design allows CBPQT4+ -Fu to efficiently compartmentalize the furan ring inside its host cavity in water, thereby protecting it from the DA reaction with maleimide. Remarkably, the self-complexed CBPQT4+ -Fu can undergo a conformational change through intramolecular decomplexation upon the addition of a stronger binding molecular naphthalene derivative as a competitive guest, triggering the DA reaction upon addition of a chemical regulator. Remarkably, connecting the guest to a thermoresponsive lower critical solution temperature (LCST) copolymer regulator controls the DA reaction on command upon heating and cooling the reaction media beyond and below the cloud point temperature of the copolymer, representing a rare example of decreased reactivity upon increasing temperature. Altogether, this work opens up new avenues towards combined topological and supramolecular control over reactivity in synthetic constructs, enabling control over reactivity through molecular regulators or even mild temperature variations.

Multifunctional Poly(2-ethyl-2-oxazoline) Copolymers Containing Dithiolane and Pentafluorophenyl Esters as Effective Reactive Linkers for Gold Surface Coatings.

Surface functionalization with biological macromolecules is an important task for the development of sensor materials, whereby the interaction with other biological materials should be suppressed. In this work, we developed a novel multifunctional poly(2-ethyl-2-oxazoline)-dithiolane conjugate as a versatile linker for gold surface immobilization of amine-containing biomolecules, containing poly(2-ethyl-2-oxazoline) as antifouling polymer, dithiolane for surface immobilization, and activated esters for protein conjugation. First, a well-defined carboxylic acid containing copoly(2-ethyl-2-oxazoline) was synthesized by cationic ring-opening copolymerization of 2-ethyl-2-oxazoline with a methyl ester-containing 2-oxazoline monomer, followed by postpolymerization modifications. The side-chain carboxylic groups were then converted to amine-reactive pentafluorophenyl (PFP) ester groups. Part of the PFP groups was used for the attachment of the dithiolane moiety, which can efficiently bind to gold surfaces. The final copolymer contained 1.4 mol% of dithiolane groups and 4.5 mol% of PFP groups. The copolymer structure was confirmed by several analytical techniques, including NMR spectroscopy and size-exclusion chromatography. The kinetics of the PFP ester aminolysis and hydrolysis demonstrated significantly faster amidation compared to hydrolysis, which is essential for subsequent protein conjugation. Successful coating of gold surfaces with the polymer was confirmed by spectroscopic ellipsometry, showing a polymer brush thickness of 4.77 nm. Subsequent modification of the coated surfaces was achieved using bovine serum albumin as a model protein. This study introduces a novel reactive polymer linker for gold surface functionalization and offers a versatile polymer platform for various applications including biosensing and surface functionalization.

Reaching the Tumor: Mobility of Polymeric Micelles Inside an In Vitro Tumor-on-a-Chip Model with Dual ECM.

Degradable polymeric micelles are promising drug delivery systems due to their hydrophobic core and responsive design. When applying micellar nanocarriers for tumor delivery, one of the bottlenecks encountered in vivo is the tumor tissue barrier: crossing the dense mesh of cells and the extracellular matrix (ECM). Sometimes overlooked, the extracellular matrix can trap nanoformulations based on charge, size, and hydrophobicity. Here, we used a simple design of a microfluidic chip with two types of ECM and MCF7 spheroids to allow "high-throughput" screening of the interactions between biological interfaces and polymeric micelles. To demonstrate the applicability of the chip, a small library of fluorescently labeled polymeric micelles varying in their hydrophilic shell and hydrophobic core forming blocks was studied. Three widely used hydrophilic shells were tested and compared, namely, poly(ethylene glycol), poly(2-ethyl-2-oxazoline), and poly(acrylic acid), along with two enzymatically degradable dendritic hydrophobic cores (based on hexyl or nonyl end groups). Using ratiometric imaging of unimer:micelle fluorescence and FRAP inside the chip model, we obtained the local assembly state and dynamics inside the chip. Notably, we observed different micelle behaviors in the basal lamina ECM, from avoidance of the ECM structure to binding of the poly(acrylic acid) formulations. Binding to the basal lamina correlated with higher uptake into MCF7 spheroids. Overall, we proposed a simple microfluidic chip containing dual ECM and spheroids for the assessment of the interactions of polymeric nanocarriers with biological interfaces and evaluating nanoformulations' capacity to cross the tumor tissue barrier.

Hydrophobic carboxymethyl cellulose as a clean-up sorbent in the determination of nitrofuran metabolites in animal-fat samples.

Hydrophobic carboxymethyl cellulose (CMC) biopolymers were fabricated for the removal of fat from food sample matrices. The hydrophobic CMCs were synthesised via the esterification of CMC with three alcohols with carbon chains of different lengths, methanol, butanol, and octadecanol, in the presence of sulfuric acid. The structure of the three synthesised hydrophobic CMCs was verified using FT-IR, and the physicochemical properties were investigated by TGA, SEM, and X-ray. Characterization confirmed the successful synthesis of the hydrophobic CMCs and that the hydrophobic groups are embedded in the sorbent biopolymer to interact with fat and reduce the fat content of the sample extract. Moreover, the performance of the fabricated hydrophobic CMCs was studied in two applications: fat removal and the determination of nitrofuran (NF) metabolites in fat samples. In the first application, excellent results were observed for fat removal; the highest percentage of fat removed from food sample extracts was 94.2% and the lowest was 88.5%. Successful results were also observed in the determination of NF metabolites in fat samples, as the final extract was clear and pure using the hydrophobic CMCs, while it was turbid for the control sample. In addition, the recovery of four NF metabolites was in the range of 97-117%. In general, the hydrophobic CMCs showed promising and satisfactory results, with CMC-C18 exhibiting the best results. The NF detection method was validated using CMC-C18 in three spiking levels; 0.5, 1.0 and 1.5 µg kg-1. The average recoveries of NF range between 83.3 to 104.3%, and the intra-day precision was determined by coefficient of variation, which was below 10% for all NF. The limit of detection and limit of quantification were between 0.6 to 0.9 and 0.20 to 0.28 µg kg-1 respectively. For linearity, the correlation coefficient (r2) was higher than 0.99 for NF metabolites. Overall, the hydrophobic CMCs can be further developed and safely used as green sorbents in food analysis applications.

Cationic amino-acid functionalized polymethacrylamide vectors for siRNA transfection based on modification of poly(2-isopropenyl-2-oxazoline).

Poly(2-isopropenyl-2-oxazoline) (PiPOx) is a functional polymer showing great potential for the development of smart biomaterials. The straightforward synthesis and post-polymerization functionalization of PiPOx offers many opportunities for tailoring the properties of the polymer towards biomaterials. In this study we report for the first time PiPOx-based cationic charged polymethacrylamides with amino acid side chains that can complex siRNA and promote transfection in vitro. Therefore, PiPOx was fully modified via ring opening addition reactions with the carboxylic acid groups of a series of N-Boc-L-amino acids and their reaction kinetics were investigated. Based on the determined kinetic constants, another series of PiPOx-based copolymers with balanced hydrophilic/hydrophobic content of N-Boc-L-amino acids were obtained via one-pot modification reaction with two different N-Boc-L-amino acids. The N-Boc protected homopolymers and related copolymers were deprotected to obtain (co)polymers with the targeted side chain cationic charged units. The (co)polymers' structures were fully investigated via FT-IR and 1H NMR spectroscopy, size exclusion chromatography (SEC), and TGA-DSC-MS analysis. The polarimetry measurements revealed that the homopolymers retain their chiroptical properties after post-modification, and a sign inversion is noticed from (L) N-Boc-protected analogues to (D) for the TFA cationic charged homopolymers. Generally, cationically charged homopolymers with hydrophilic amino acids on the side chain showed efficient complexation of siRNA, but poor transfection while cationic copolymers having both tryptophan and valine or proline side chains revealed moderate siRNA binding, high transfection efficiency (> 90% of the cells) and potent gene silencing with IC50 values down to 5.5 nM. Particularly, these cationic copolymers showed higher gene silencing potency as compared to the commercial JetPRIME® reference, without reducing cell viability in the concentration range used for transfection, making this a very interesting system for in vitro siRNA transfection.

Smart hydrogels delivered by high pressure aerosolization can prevent peritoneal adhesions.

Postoperative peritoneal adhesions occur in the majority of patients undergoing intra-abdominal surgery and are one of the leading causes of hospital re-admission. There is an unmet clinical need for effective anti-adhesive biomaterials, which can be applied evenly across the damaged tissues. We examined three different responsive hydrogel types, i.e. a thermosensitive PLGA-PEG-PLGA, a pH responsive UPy-PEG and a shear-thinning hexapeptide for this purpose. More specifically, their potential to be homogeneously distributed in the peritoneal cavity by high pressure nebulization and prevent peritoneal adhesions was evaluated. Solutions of each polymer type could be successfully nebulized while retaining their responsive gelation behavior in vitro and in vivo. Furthermore, none of the polymers caused in vitro toxicity on SKOV3-IP2 cells. Following intraperitoneal administration, both the PLGA-PEG-PLGA and the hexapeptide hydrogels resulted in local inflammation and fibrosis and failed in preventing peritoneal adhesions 7 days after adhesion induction. In contrast, the pH sensitive UPy-PEG formulation was well tolerated and could significantly reduce the formation of peritoneal adhesions, even outperforming the commercially available Hyalobarrier® as positive control. To conclude, local nebulization of the bioresponsive UPy-PEG hydrogel can be considered as a promising approach to prevent postsurgical peritoneal adhesions.

Solvent electrospinning amorphous solid dispersions with high itraconazole, celecoxib, mebendazole and fenofibrate drug loading and release potential.

In this work, the feasibility of ultra-high drug loaded amorphous solid dispersions (ASDs) for the poorly soluble itraconazole, mebendazole and celecoxib via solvent electrospinning in combination with poly(2-ethyl-2-oxazoline) and fenofibrate in combination with polyvinylpyrrolidone is demonstrated. By lowering the polymer concentration in the electrospinning solution below its individual spinnable limit, ASDs with a drug content of up to 80 wt% are obtained. This is attributed to drug-polymer interactions not being limited by default to hydrogen bonds, as also Van der Waals interactions can result in high drug loadings. The theoretically predicted miscibility by the Flory-Huggins theory is corroborated by the experimental findings based on (modulated) differential scanning calorimetry and x-ray diffraction. Globally, the maximally obtained amorphous drug loadings are higher compared to the loadings found in literature. Additionally, non-sink dissolution tests demonstrate an increase in solubility of up to 50 times compared to their crystalline counterparts. Moreover, due to the lack of precipitation biocompatible PEtOx succeeds in stabilizing the dissolved drug and inhibiting its instant precipitation. The current work thus demonstrates the broader applicability of the electrospinning technique for the production of physically stable ASDs with ultra-high drug loadings, a result which has been validated for several Biopharmaceutics Classification System class II drugs.

Cell Guiding Multicomponent Nanoyarn Tendon Scaffolds with Tunable Morphology and Flexibility.

Nanofibrous scaffolds are widely investigated for tendon tissue engineering due to their porous structure, high flexibility, and the ability to guide cells in a preferred direction. Previous research has shown that providing a microenvironment similar to in vivo settings improves tissue regeneration. Therefore, in this work, ingenious multicomponent nanoyarn scaffolds that mimic the fibrillar and tubular structures of tendons are developed for the first time through electrospinning and bundling nanoyarns followed by electrospinning of a nanofibrous shell around the bundle. Multicomponent nanoyarn scaffolds out of poly(ε-caprolactone) with varying porosity, density, and diameter were successfully produced by coelectrospinning with water-soluble poly(2-ethyl-2-oxazoline) as a sacrificial component. The diameter and fiber orientation of the nanoyarns were successfully tuned based on parameter-morphology models obtained by the design of experiments. Cyclic bending tests were performed, indicating that the flexibility of the multicomponent nanoyarn scaffolds depends on the morphology and can be tuned through controlling the number of nanoyarns in the bundle and the porosity. Indirect and direct cell culture tests using mouse and equine tendon cells revealed excellent cytocompatibility of the nanofibrous products and demonstrated the potential of the nanoyarns to guide the growing cells along the nanofiber direction, which is crucial for tendon tissue engineering.

Explosives removal and quantification using porous adsorbents based on poly(2-oxazoline)s with various degree of functionalization.

Polymeric porous adsorbents are reported for removal of explosives, namely picric acid, 1,3,5-trinitro-1,3,5-triazinane (RDX), and pentaerythritol tetranitrate (PETN) and their subsequent quantification using direct analysis with ambient plasma mass spectrometry. The adsorbents are obtained by functionalization of short-chain poly(2-oxazoline)s with methyl ester side chains using 4-(aminomethyl)pyridine with a degree of functionalization equal to 0, 5, 10, and 20%. The subsequent step consist of cross-linking using a high internal phase emulsion procedure by further side-chain amidation with diethylenetriamine as crosslinker. Picric acid, RDX, and PETN were chosen as the model compounds as they belong to three different groups of explosives, in particular nitroaromatics, nitroamines, and nitrate esters, respectively. The adsorption isotherms, kinetics, as well as the influence of pH and temperature on the adsorption process was investigated. The porous adsorbents showed the highest maximum adsorption capacity towards picric acid, reaching 334 mg g-1, while PETN (80 mg g-1) and RDX (17.4 mg g-1) were less efficiently adsorbed. Subsequent quantification of the adsorbed explosives is performed by a specially designed ambient mass spectrometry setup equipped with a thermal heater. The obtained limits of detection were found to be 20-times improved compared to direct analysis of analyte solutions. The effectiveness of the proposed analytical setup is confirmed by successful quantification of the explosives in river water samples. The research clearly shows that functional porous adsorbents coupled directly with ambient mass spectrometry can be used for rapid quantification of explosives, which can be, e.g., used for tracking illegal manufacturing sites of these compounds.

Non-activated Esters as Reactive Handles in Direct Post-Polymerization Modification.

Non-activated esters are prominently featured functional groups in polymer science, as ester functional monomers display great structural diversity and excellent compatibility with a wide range of polymerization mechanisms. Yet, their direct use as a reactive handle in post-polymerization modification has been typically avoided due to their low reactivity, which impairs the quantitative conversion typically desired in post-polymerization modification reactions. While activated ester approaches are a well-established alternative, the modification of non-activated esters remains a synthetic and economically valuable opportunity. In this review, we discuss past and recent efforts in the utilization of non-activated ester groups as a reactive handle to facilitate transesterification and aminolysis/amidation reactions, and the potential of the developed methodologies in the context of macromolecular engineering.

Conformational Parameters and Hydrodynamic Behavior of Poly(2-Methyl-2-Oxazoline) in a Broad Molar Mass Range.

In this work, we report our results on the hydrodynamic behavior of poly(2-methyl-2-oxazoline) (PMeOx). PMeOx is gaining significant attention for use as hydrophilic polymer in pharmaceutical carriers as an alternative for the commonly used poly(ethylene glycol) (PEG), for which antibodies are found in a significant fraction of the human population. The main focus of the current study is to determine the hydrodynamic characteristics of PMeOx under physiological conditions, which serves as basis for better understanding of the use of PMeOx in pharmaceutical applications. This goal was achieved by studying PMeOx solutions in phosphate-buffered saline (PBS) as a solvent at 37 °C. This study was performed based on two series of PMeOx samples; one series is synthesized by conventional living cationic ring-opening polymerization, which is limited by the maximum chain length that can be achieved, and a second series is obtained by an alternative synthesis strategy based on acetylation of well-defined linear poly(ethylene imine) (PEI) prepared by controlled side-chain hydrolysis of a defined high molar mass of poly(2-ethyl-2-oxazoline). The combination of these two series of PMeOx allowed the determination of the Kuhn-Mark-Houwink-Sakurada equations in a broad molar mass range. For intrinsic viscosity, sedimentation and diffusion coefficients, the following expressions were obtained: η=0.015M0.77, s0=0.019M0.42 and D0=2600M-0.58, respectively. As a result, it can be concluded that the phosphate-buffered saline buffer at 37 °C represents a thermodynamically good solvent for PMeOx, based on the scaling indices of the equations. The conformational parameters for PMeOx chains were also determined, revealing an equilibrium rigidity or Kuhn segment length, (A) of 1.7 nm and a polymer chain diameter (d) of 0.4 nm. The obtained value for the equilibrium rigidity is very similar to the reported values for other hydrophilic polymers, such as PEG, poly(vinylpyrrolidone) and poly(2-ethyl-2-oxazoline), making PMeOx a relevant alternative to PEG.

Poly(N-allyl acrylamide) as a Reactive Platform toward Functional Hydrogels.

The synthesis of poly(N-allyl acrylamide) (PNAllAm) as a platform for the preparation of functional hydrogels is described. The PNAllAm was synthesized via organocatalyzed amidation of poly(methyl acrylate) (PMA) with allylamine and characterized by 1H NMR spectroscopy, size exclusion chromatography (SEC), and turbidimetry, which allowed an estimation of the lower critical solution temperature of ∼26 °C in water. The PNAllAm was then used to make functional hydrogels via photoinitiated thiol-ene chemistry, where dithiothreitol (DTT) was used to cross-link the polymer chains. In addition, mercaptoethanol (ME) was added as a functional thiol to modulate the hydrogel properties. A decrease of the volume-phase transition temperature of the resulting hydrogels was observed with increasing ME content. Altogether this work introduces a straightforward way for the preparation of PNAllAm from PMA and demonstrates its value as a reactive polymer platform for the generation of functional hydrogels.