Low Molecular Weight Counterparts Research Articles

Post-Sterilization Physicochemical Characterization and Biological Activity of Cellulose Nanocrystals Coated with PDDA.

The rapid expansion of medical nanotechnology has significantly broadened the potential applications of cellulose nanocrystals (CNCs). While CNCs were initially developed for drug delivery, they are now being investigated for a range of advanced biomedical applications. As these applications evolve, it becomes crucial to understand the physicochemical behavior of CNCs in biologically relevant media to optimize their design and ensure biocompatibility. Functionalized CNCs can adsorb biomolecules, forming a "protein corona" that can impact their physicochemical properties, including alterations in particle size, zeta potential, and overall functionality. In this study, CNCs were coated with low (8500 Da)- and high (400,000-500,000 Da)-molecular-weight cationic polymer (poly(diallyldimethylammonium chloride-(PDDA) via non-covalent grafting, and their physicochemical characteristics, as well as their biological effects, were assessed in physiologically relevant media after sterilization. Our findings show that autoclaving significantly alters the physicochemical properties of CNC-PDDA, particularly when coated with low-molecular-weight (LMW) polymer. Furthermore, we observed that CNC-PDDA of a high molecular weight (HMW) has a greater impact on cell viability and blood biocompatibility than its LMW counterpart. Moreover, cellular immune responses to both CNC-PDDA LMW and HMW vary in the presence or absence of serum, implying that protein adsorption influences cell-nanomaterial recognition and their biological activity. This study provides valuable insights for optimizing CNC-based nanomaterials for therapeutic applications.

Self-assembling butyric acid prodrug acts as a sensitizer for cancer radiotherapy

Butyric acid, is reported to radiosensitize cancer cell lines in vitro. Their short systemic half-lives may explain their lack of in vivo efficacy. To manage the unsuitable pharmacokinetics of low-molecular-weight (LMW) butyric acid, we have designed a new polymeric prodrug comprising amphiphilic block copolymers, [poly(ethylene glycol)-b-poly(vinyl butyrate)s] (PEG-b-PV(BA)), with tens of butyric acid units conjugated through enzymatically metabolizable ester linkages as side chains in the hydrophobic segment. PEG-b-PV(BA) spontaneously forms self-assembling nanoparticles (NanoBA) with diameters of tens of nanometers. Pharmacological studies of intraperitoneal administration revealed that the retention of NanoBA in the plasma and tumors was extended up to 48–72 h compared to its LMW counterparts, as evidenced using in vivo imaging, immunoblotting of the PEG segment of the block copolymers, and radioisotope techniques. These results corroborated the LC-MS/MS-based study, validating the prominent in vivo liberation of butyric acid for a prolonged period (24 h) in NanoBA administered group compared to the LMW butyric acid, which cleared within approximately 0.5 h post-administration. Furthermore, radiation treatment after 24 h of intraperitoneal NanoBA administration toward tumor (B16-F10)-bearing mice exhibited significantly slower tumor growth in comparison with control irradiated tumors and LMW butyric acid-treated group, which was attributable to attenuated radioresistance Cox-2 and NF-κβ survival pathways. Current findings demonstrate that our self-assembling nanoparticle NanoBA prodrug substantially enhances the radiosensitizing effect of butyric acid in solid tumors in vivo, supporting the use of NanoBA for future clinical ramifications.

Impact of the functional coating of silver nanoparticles on their in vivo performance and biosafety

Objective and significance Silver nanoparticles (AgNPs) have become an interesting therapeutic modality and drug delivery platform. Herein, we aimed to investigate the impact of functional coating on the in vivo performance of AgNPs as an economic and scalable method to modulate their behavior. Methods AgNPs were coated with chitosan (CHI) as a model biopolymer using a one-pot reduction-based method, where CHI of two molecular weight ranges were investigated. The resultant CHI-coated AgNPs (AgNPs-CHI) were characterized using UV-VIS spectroscopy, DLS, and TEM. AgNPs were administered intravenously to rats and their biodistribution and serum levels of hepato-renal function markers were monitored 24 h later compared to plain AgNO3 as a positive control. Results UV-VIS spectroscopy confirmed the successful coating of AgNPs with CHI. DLS revealed the superiority of medium molecular weight CHI over its low molecular weight counterpart. AgNPs-CHI demonstrated a semi-complete clearance from the systemic circulation, a liver-dominated tissue tropism, and limited renal exposure. On the other hand, AgNO3 was poorly cleared from the circulation, with relatively high renal exposure and a non-specific tissue tropism. AgNPs-CHI were well-tolerated by the liver and kidney without signs of toxicity or inflammation, in contrary with AgNO3 which resulted in a significant elevation of Creatinine (CRE), Urea, and Total Protein (TP), suggesting a significant nephrotoxicity and inflammation. Conclusions Functional coating of AgNPs with CHI substantially modulated their in vivo behavior, promoting their hepatic selectivity and biotolerability, which can be invested in the development of drug delivery systems for the treatment of liver diseases.

Variation in physicochemical properties and bioactivities of Morinda citrifolia L. (Noni) polysaccharides at different stages of maturity.

Morinda citrifolia L. (Noni) as an evergreen plant is a rich source of natural polysaccharides. The present work aims to investigate the maturation-related changes in polysaccharides of Morinda citrifolia L. (Noni) at five stages of maturity (stages from the lowest to highest degree - 1, 2, 3, 4, and 5). The chemical composition (carbohydrate, protein, uronic acid, and sulfate radical) of Noni polysaccharides was determined by different chemical assays. Ion chromatography system was used to analyze the monosaccharide composition, and the molecular weight was measured by HPGPC. The polysaccharides were also analyzed by FT-IR and their radical scavenging effect against DPPH, hydroxyl radicals and ABTS was evaluated. The UV-vis assay and gel electrophoresis assay were performed to investigate the DNA damage protective effect. Results indicated the significant effect of fruit maturities on the extraction yields, molecular weights, uronic acid contents, sugar levels, monosaccharide compositions and proportions, antioxidant capacities, and DNA protective effects of Noni polysaccharides. However, no fruit maturity stage had prominent impact on the sulfuric radical contents and preliminary structure characteristics. Noni polysaccharides extracted at stage 5 (N5) had the largest extraction yield (8.26 ± 0.14%), the highest sugar content (61.94 ± 1.86%) and the most potent scavenging effect on DPPH (IC50: 1.06 mg/mL) and ABTS (IC50: 1.22 mg/mL) radicals. The stronger DPPH and ABTS radical scavenging activities of N5 might be contributed by its higher content of fucose and rhamnose and smaller molecular weight. Noni polysaccharides extracted at stage 4 (N4) showed the highest uronic acid content (4.10 ± 0.12%), and the superior performance in scavenging hydroxyl radicals and protecting DNA. The greater hydroxyl radical scavenging effect of N4 might be attributed to its higher percentage of the low molecular weight counterpart. Moreover, the DNA protective effects of N4 displayed a positive correlation with its hydroxyl radical scavenging ability. Overall, stage 4 and stage 5 could be ideal stages of fruit maturity aiming at high-quality Noni polysaccharides extraction. This study provided valuable information for the selection of suitable Noni polysaccharides to cater for various industrial applications.

Exploration of changes in the chemical composition of sedimentary organic matter and the underlying processes during biodegradation through advanced analytical techniques

Environmental context Organic matter (OM) biodegradation plays a key role as it is one of the main processes causing changes in the amount, composition and properties of OM in sediment. However, a complete understanding of its processes and mechanisms is still not reached. In this study, we aim to explore the chemical composition changes during biodegradation and identify underlying processes. Rationale Although the scientific community has widely investigated organic matter biodegradation processes, only a limited number of studies have explored the molecular changes of this material, whereas its structure, composition and origin play a key role in these processes. Methodology We decided to examine the effects of biodegradation on the chemical composition of sedimentary organic matter and to explore the underlying mechanisms. We conceived a laboratory-based degradation experiment utilising organic-rich sediments artificially composed of two contrasting organic matter end-members (i.e. soil and algae) under two oxygen conditions. The sediment samples before and after incubation were then analysed by laser desorption ionisation–Fourier-transform–ion cyclotron resonance–mass spectrometry for molecular characterisation and by thermally assisted hydrolysis and methylation gas chromatography–mass spectrometry in order to offer insights into the mechanisms driving the biodegradation processes. Results Our results from molecular characterisation unveiled distinct pathways of biodegradation contingent upon the source material. Moreover, they hinted at a predilection for altering high molecular weight compounds like lignin & carboxylic-rich alicyclic molecules (CRAM) and condensed aromatic structures (CAS), manifesting as a conversion into lower molecular weight counterparts. Furthermore, the complementary findings from biomarker analyses underscored the influence of environmental factors – specifically oxygen conditions and microbial communities – on organic matter decomposition. Discussion Although this study is a controlled laboratory experiment and more studies are needed, it demonstrates the intricate interplay among chemical, biological and environmental factors that profoundly shape the reactivity of organic matter. This study underscores the critical need for persistent inquiry, aimed at unravelling the factors and conditions governing the diverse pathways of biodegradation.

Molecular weight-dependent adsorption heterogeneities of humic acid on microplastics in aquatic environments: Further insights from fluorescence spectra combined with two-dimensional correlation spectroscopy and site energy distribution analysis

Microplastics as emerging environmental contaminants have attracted global attention. Ubiquitous dissolved organic matter (DOM), a heterogeneous mixture with various organic components and continuous molecular weight (MW) distribution, can significantly influence the fate, bioavailability and toxicity of microplastics in aquatic environments. However, to date, understanding of the MW-dependent adsorption heterogeneities of DOM on microplastics in aquatic environments has remained unknown. In this study, the soil humic acid (HA), a representative DOM, was fractionated into > 100 kDa HA, 30–100 kDa HA, 10–30 kDa HA, 3–10 kDa HA and < 3 kDa HA, whose adsorption behaviors on polystyrene microplastics (PSMPs) under different electrolytes at pH6.0 investigated by multispectral techniques, as well as two-dimensional correlation spectroscopy and site energy distribution analysis. High molecular weight MW-fractionated HAs dominated the soil HA. Compared to the lower molecular weight MW-fractionated HAs, the higher molecular weight counterparts exhibited higher aromaticity, showing higher adsorption affinities onto PSMPs in aquatic environments. Adsorption isotherms and kinetics of the MW-fractionated HAs onto PSMPS can be reasonably explained by Langmuir models and the linear driving force (LDF) model, respectively. Enhanced aromaticity in residual solutions was observed, suggesting that the preferable adsorption of the higher aromatic moieties in the pristine and MW-fractionated HAs on PSMPs could be subsequently replaced by the lower aromatic moieties for the limited binding sites. Combined, the humic-like materials in MW-fractionated HAs could be significantly impacted the complexation of PSMPs in aquatic environments. The heterogeneous/complicated distributions of active adsorption sites in the humic-like materials of the MW-fractionated HAs, and the subsequent subtle changes of these sites to PSMPs were characterized by synchronous fluorescence spectroscopy coupled with two-dimensional correlation spectroscopy. High molecular weight MW-fractionated HAs provided more active adsorption sites than those in the low molecular weight counterparts, which also possessed stronger adsorption affinities and higher complexation capacities to PSMPs. The site energy distributions for the adsorption of the MW-fractionated HAs on PSMPs were calculated based on Langmuir model. The adsorption heterogeneities of PSMPs at the experimental conditions were close. This study provides deep insights into the MW-dependent adsorption heterogeneities of HA on PSMPs, and the results are of significance to understand the biogeochemical behaviors of DOM and MPs in aquatic environments.

Crystallization and phase separation in PEDOT:PSS/PEO blend thin films: Influence on mechanical and electrical properties at the nanoscale

Thin films of polymeric blends composed of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) and polyethylene oxide (PEO) were investigated by varying the concentration of the two components over the entire range of compositions and the molecular weight of PEO. Phase separation and crystallization have been studied at different length scales by combining Atomic Force Microscopy (AFM) and Grazing Incidence Wide Angle X-ray Scattering (GIWAXS) using synchrotron light. Several different arrangements in the thin films of the two polymers constituting the blend were observed and discussed in detail, providing information about their reciprocal influence at the micro- and nano-scale. In addition to that, we were able to estimate quantitative nanomechanical and nanoelectrical properties via AFM and finally revealing the dependence of the thin films' physical properties on their composition and structure. By varying the blend composition, we achieved different coating capability, mechanical properties, and electrical conductivity. Furthermore, depending on the PEO molecular weight, the electrical response of the resulting blends’ thin films shows some differences. In the low range concentration, the blend thin films with high molecular weight PEO present coarser conducting paths than in those with the low molecular weight counterparts. For intermediate concentrations, a more effective phase segregation of PEDOT:PSS and PEO is achieved for high molecular weight PEO. These differences are also translated to different electrical conductivity.

Supramolecular Hydrogels Based on Cyclodextrins: Progress and Perspectives

AbstractHydrogels have emerged as one of the best studied, widely applied and most versatile classes of soft materials. Hydrogels are important biomimetic nanomaterials comparable to extracellular matrices in terms of water content, porosity, and rigidity. In this regard, self‐assembled hydrogels based on supramolecular host‐guest interactions have enabled unique characteristics like stimuli response, self‐healing, shape memory and self‐regulation. In particular, the use of cyclodextrins and their host‐guest chemistry is a powerful tool for the development of functional hydrogels with unprecedented properties. In this article, recent advances on hydrogels based on supramolecular chemistry of cyclodextrins are reviewed to provide an overview of the manifold design strategies, material properties and areas of application. We contrast the progress on cyclodextrin containing polymer gels to that of their low molecular weight counterparts by highlighting selected publications from each of these subcategories.

Metal binding by dissolved organic matter in hypersaline water: A size fractionation study using different isolation methods

The influence of dissolved organic matter (DOM) on mineral extraction from salt lake brines depend on DOM quality. This study contributes to our knowledge of DOM’s metal binding behavior in hypersaline environments by characterization of DOM from lakes in the Qaidam Basin, i.e., Qarhan Lake (LQDOM), Da Qaidam (DQDOM) and West Ginair Salt Lake (WGDOM). The DOM was fractionated based on solid phase extraction (SPE) and ultrafiltration (UF), and the spectral and metal binding behavior of these fractions were studied by absorption spectroscopy, Pb(II) titration techniques and fluorescence parallel factor (PARAFAC) analysis. The results showed that bulk DOM generally contained more dissolved organic carbon (DOC), lower specific UV absorbance (SUVA254), higher fluorescence and biological indices, comparable humification index, and lower condition stability constants compared to the other nature waters. Compared with UF, SPE-derived DOM exhibited higher DOC recovery and aromaticity and lower carbohydrate yield. It appeared that the SPE procedure used affects the spectral composition of bulk DOM to a larger extent than UF. Source and molecular weight (MW)-dependent differences in abundance and quality of brine DOM was indicated by higher SUVA254 in high MW DOM, for LQDOM and DQDOM, and humic-like fluorophores were mainly in high MW-DOM in each lake. Moreover, the high MW humic-like component exhibited higher metal binding potential than the bulk and low MW counterparts for LQDOM and DQDOM, while the inverse was observed for WGDOM. This study revealed the effects of isolation techniques on interpretation of DOM characteristics, and meanwhile highlighted the importance of origin- and MW-dependent DOM in manipulating the behavior, fate, and bioavailability of heavy metals in salt lake brine.

Management of tumor growth and angiogenesis in triple-negative breast cancer by using redox nanoparticles

In cancer, angiogenesis is a critical phenomenon of nascent blood vessel development to facilitate the oxygen and nutrient supply prerequisite for tumor progression. Therefore, targeting tumors at the angiogenesis step may be significant to prevent their advanced progression and metastasis. Although angiogenesis inhibitors can limit the further growth of tumors, complete eradication of tumors may not be possible by monotherapy alone. Therefore, a therapeutic regimen targeting both tumor growth and its vasculature is essential. Because reactive oxygen species (ROS) are fundamental to both angiogenesis and tumor growth, the use of antioxidants may be an effective dual approach to inhibit tumors. We previously confirmed that our original antioxidant nitroxide radical-containing nanoparticles (RNPs) such as pH-sensitive RNPN, and pH-insensitive RNPO, effectively attenuates the tumorigenic and metastasis potentials of triple-negative breast cancer. In this study, we further investigated the efficacy of RNPs to limit the tumor progression by inhibiting the ROS-regulated cancer angiogenesis in a triple-negative breast cancer model. Here, we confirmed that RNPs significantly inhibited in vitro angiogenesis, attributed to the downregulation of the ROS-regulated angiogenesis inducer, vascular endothelial growth factor (VEGF) in the breast cancer cell line (MDA-MB231) and human umbilical vein endothelial cells (HUVEC), which was consistent with decreased cellular ROS. TEMPOL, a low-molecular-weight (LMW) control antioxidant, exhibited anti-angiogenic effects accompanied by cytotoxicity to the endothelial cells. In an in vivo xenograft model for breast cancer, RNPs exerted significant anti-tumor effect due to the decreased expression of tumor VEGF, which prevented accumulation of the endothelial cells. It should be noted that such efficacy of RNPs was obtained with negligible off-target effects. On the other hand, TEMPOL, because of its size, exerted anti-angiogenesis effect accompanied with injuries to the kidneys, which corroborated with previous reports. Our findings imply that RNPs are more potential antioxidants than their LMW counterparts, such as TEMPOL, for the management of breast cancers.

Kinetic Features of Elementary Events in the Radical Polymerization of Methyl Methacrylate under Conditions of Nitroxide-Mediated Reversible Inhibition

The kinetic features of the elementary events of initiation, reinitiation, and reversible termination in the radical polymerization of methyl methacrylate mediated by piperidine and imidazoline nitroxides are studied. The rate constants of these reactions and the constant of equilibrium between the dormant and growing chains are determined. In all the systems studied, the reinitiation rate constant and the equilibrium constant decrease during polymerization. The activity of imidazoline nitroxides in the termination reaction turns out to be an order of magnitude lower than that of piperidine ones, and the constant of interaction of both types of nitroxides with methyl methacrylate growing radicals is two and a half orders of magnitude lower than that with their low molecular weight counterparts.

Characterization, origin and aggregation behavior of colloids in eutrophic shallow lake

Stability of colloidal particles contributes to the turbidity in the water column, which significantly influences water quality and ecological functions in aquatic environments especially shallow lakes. Here we report characterization, origin and aggregation behavior of aquatic colloids, including natural colloidal particles (NCPs) and total inorganic colloidal particles (TICPs), in a highly turbid shallow lake, via field observations, simulation experiments, ultrafiltration, spectral and microscopic, and light scattering techniques. The colloidal particles were characterized with various shapes (spherical, polygonal and elliptical) and aluminum-, silicon-, and ferric-containing mineralogical structures, with a size range of 20–200 nm. The process of sediment re-suspension under environmentally relevant conditions contributed 78–80% of TICPs and 54–55% of NCPs in Lake Taihu, representing an important source of colloids in the water column. Both mono- and divalent electrolytes enhanced colloidal aggregation, while a reverse trend was observed in the presence of natural organic matter (NOM). The influence of NOM on colloidal stability was highly related to molecular weight (MW) properties with the high MW fraction exhibiting higher stability efficiency than the low MW counterparts. However, the MW-dependent aggregation behavior for NCPs was less significant than that for TICPs, implying that previous results on colloidal behavior using model inorganic colloids alone should be reevaluated. Further studies are needed to better understand the mobility/stability and transformation of aquatic colloids and their role in governing the fate and transport of pollutants in natural waters.

β-lactam resistance: The role of low molecular weight penicillin binding proteins, β-lactamases and ld-transpeptidases in bacteria associated with respiratory tract infections.

Disruption of peptidoglycan (PG) biosynthesis in the bacterial cell wall by β-lactam antibiotics has transformed therapeutic options for bacterial infections. These antibiotics target the transpeptidase domains in penicillin binding proteins (PBPs), which can be classified into high and low molecular weight (LMW) counterparts. While the essentiality of the former has been extensively demonstrated, the physiological roles of LMW PBPs remain poorly understood. Herein, we review the function of LMW PBPs, β-lactamases and ld-transpeptidases (Ldts) in pathogens associated with respiratory tract infections. More specifically, we explore their roles in mediating β-lactam resistance. Using a comparative genomics approach, we identified a high degree of genetic redundancy for LMW PBPs which retain the motifs, SxxN, SxN and KTG required for catalytic activity. Differences in domain architecture suggest distinct physiological roles, possibly related to bacterial cell cycle and/or adaptation to various environmental conditions. Many of the LMW PBPs play an important role in β-lactam resistance either through mutation or variation in abundance. In all of the bacterial genomes assessed, at least one β-lactamase homologue is present, suggesting that enzymatic degradation of β-lactams is a highly conserved resistance mechanism. Furthermore, the presence of Ldt homologues in the majority of species surveyed suggests that alternative PG crosslinking may further mediate β-lactam drug resistance. A deeper understanding of the interplay between these different mechanisms of β-lactam resistance will provide a framework for new therapeutics, which are urgently required given the rapid emergence of antimicrobial resistance. © 2018 IUBMB Life, 70(9):855-868, 2018.

Petroleum hydrocarbons (PH) in groundwater aquifers: An overview of environmental fate, toxicity, microbial degradation and risk-based remediation approaches

Abstract Petroleum hydrocarbon (PH) contamination of soil and aquatic ecosystems is a serious global issue. PH are classified as xenobiotics and emerging priority pollutants. When released into the environment, fate and behavior of PH varies widely with the particular composition and physicochemical properties. Usually, PH with higher molecular weight are toxic and seldom mobilizes in subsurface plumes when compared to their low molecular weight counterparts. Due to the toxic, mutagenic and carcinogenic nature of PH, various remediation approaches are currently employed for their clean-up from the environment. Degradation of PH by the activity of native microbes is considered as a significant eco-friendly and cost effective approach for the remediation of PH contaminated sites. Changes in the microbial adaptations and dynamics are important indicators for monitoring the effects of PH contamination. Several analytical techniques are available for the identification and quantification of PH present in contaminated sites. Also, toxicity tests are widely employed to monitor the effect of remediated sites where analytical techniques fall short to identify certain PH due to the lack of standardized methods and low concentrations. Consequently, this review provides an overview of environmental fate, toxicity, and remediation of PH with particular emphasis on risk-based remediation which considers the use of both analytical and toxicological studies for effective management and remediation of PH contaminated sites.

In-vitro starch hydrolysis of chitosan incorporating whey protein and wheat starch composite gels

The study examined the influence of chitosan, incorporated into whey protein and wheat starch thermo gels, on the in-vitro hydrolysis of the polysaccharide. Gels were subjected to the following external conditions containing α-amylase at constant incubation temperature of 37 °C: In the first procedure, they were immersed in phosphate buffer (0.05 M) and maintained at pH 6.9 throughout the entire digestion. In the second instance, they were introduced into a salt solution, with pH and total volume adjusted at times in sync with the human gastrointestinal tract. Results indicate that low and medium molecular weight chitosan, in combination with whey protein, were effective at enhancing the protective barrier against starch degradation. Less maltose was liberated from gels containing medium molecular weight chitosan, as opposed to the low molecular weight counterpart, and results compare favorably with the outcome of the in-vitro digestion of binary whey protein and wheat starch composites.

Oral nanotherapeutics: Redox nanoparticles attenuate ultraviolet B radiation-induced skin inflammatory disorders in Kud:Hr- hairless mice.

The active participation of an anti-inflammatory drug in the biological pathways of inflammation is crucial for the achievement of beneficial and therapeutic effects. This study demonstrated the development of redox nanoparticles that can circulate in the blood at significantly high levels, thus increasing their efficacy as an oral treatment against the deleterious effects of reactive oxygen species (ROS) in an invivo inflammatory skin model. To confirm the blood bioavailability of the nanoparticles, mice were injected with the nanoparticles solution (RNPN) via oral gavage. Using electron spin resonance and radioactive labeling techniques, the blood circulation of the redox polymer that forms the nanoparticles was confirmed 24h after oral administration. This contrasted with its low molecular weight counterpart (NH2-TEMPO), which peaked 15min post injection and was found to be cleared rapidly within minutes after the peak. We then tested its efficacy in the inflammatory skin model. Kud:Hr-hairless mice were irradiated with UVB (302nm) to induce skin damage and inflammation. Throughout the entire period of UVB irradiation, RNPN was administered to mice by free drinking. NH2-TEMPO was used as the control. The results showed that oral supplementation of RNPN significantly improved the therapeutic effects of the core nitroxide radical compared with its low molecular weight counterpart. Furthermore, RNPN significantly reduced UVB-induced skin aging, epidermal thickening, edema, erythema, skin lesions, and various pathological skin inflammatory disorders invivo. From the obtained data, we concluded that the use of long-circulating redox nanoparticles (RNPN) provided an effective treatment against the damaging effects of excessive ROS in the body.

Highly conductive solvent-free polymer electrolyte membrane for lithium-ion batteries: Effect of prepolymer molecular weight

The present article demonstrates the effects of molecular weight of network precursor on properties of solid-state polymer electrolyte membrane (PEM) comprised of poly (ethylene glycol) diacrylate (PEGDA) prepolymer, succinonitrile (SCN) plasticizer, and lithium bis(trifluoromethane sulphonyl) imide (LiTFSI) salt using two different PEGDA molecular weights. To provide guidance for crosslinking reaction, ternary phase diagrams of the PEM precursor mixtures were established. Upon photopolymerization within the wide isotropic region, completely amorphous membranes were obtained in several compositions. The PEM having a higher PEGDA molecular weight (i.e., 6000g/mol) revealed both improved impact strength with an elongation at break of ~80 % and higher ambient temperature ionic conductivity (~1.4×10−3Scm−1) relative to the low molecular weight counterpart (i.e., 700g/mol). Both PEMs exhibited excellent electrochemical (4.8V/Li/Li+) and thermal (140°C) stabilities. Specific discharge capacities of the PEM containing half-cells using LiFePO4 or Li4Ti5O12 electrodes against lithium electrode reached the level of ~140mAhg−1 at 0.2°C, indicating potential applications in all solid-state lithium-ion batteries.

Conductivity Mechanism in Polymerized Imidazolium-Based Protic Ionic Liquid [HSO3–BVIm][OTf]: Dielectric Relaxation Studies

In this paper, we investigate the molecular dynamics and ions transport properties of polymerized imidazolium-based protic ionic liquid (HSO3−BVIm)(OTf)a new material with potential applications in energy storage and electrochemical devices. The results of dielectric measurements, analyzed in modulus M*(f) and conductivity σ*(f) formalisms, combined with temperature-modulated differential scanning calorimetry experiments, have revealed a fundamental difference between the conducting properties of the examined polymer membrane and its low-molecular weight counterpart. Our findings indicated a strong decoupling between conductivity relaxation times τσ (related to the ions migration through the polymer matrix) and segmental dynamics when the ionic transport is controlled by fast proton hopping through the dense hydrogen-bond network. Finally, we also discuss, for the first time, the effect of water content on the glass transition temperature value, relation between the charge and mass diffusion, reflected in the decoupling phenomenon, and the conductivity mechanism of examined poly(HSO3−BVIm)(OTf).

Biodegradable in situ gelling delivery systems containing pilocarpine as new antiglaucoma formulations: effect of a mercaptoacetic acid/N-isopropylacrylamide molar ratio

Ocular drug delivery is one of the most commonly used treatment modalities in the management of glaucoma. We have recently proposed the use of gelatin and poly(N-isopropylacrylamide) (PNIPAAm) graft copolymers as biodegradable in situ forming delivery systems for the intracameral administration of antiglaucoma medications. In this study, we further investigated the influence of carrier characteristics on drug delivery performance. The carboxyl-terminated PNIPAAm samples with different molecular weights were synthesized by varying the molar ratio of mercaptoacetic acid (MAA)/N-isopropylacrylamide (NIPAAm) from 0.05 to 1.25, and were determined by end-group titration. The preparation of gelatin-g-PNIPAAm (GN) copolymers from these thermoresponsive polymers was achieved using carbodiimide chemistry. Our results showed that the carboxylic end-capped PNIPAAm of high molecular weight may lead to the lower thermal phase transition temperature and slower degradation rate of GN vehicles than its low molecular weight counterparts. With a decreasing MAA/NIPAAm molar ratio, the drug encapsulation efficiency of copolymers was increased due to fast temperature-triggered capture of pilocarpine nitrate. The degradation of the gelatin network could greatly affect the drug release profiles. All of the GN copolymeric carriers demonstrated good corneal endothelial cell and tissue compatibility. It is concluded that different types of GN-based delivery systems exhibit noticeably distinct intraocular pressure-lowering effect and miosis action, thereby reflecting the potential value of a MAA/NIPAAm molar ratio in the development of new antiglaucoma formulations.

High throughput glutathione and Nrf2 assays to assess chemical and biological reactivity of cysteine-reactive compounds

Compounds that inhibit their target through covalent binding offer a number of unique advantages as potential therapeutic agents. They can achieve high ligand efficiency, and thus high potency, which can translate into a reduced drug dosage. In addition, covalent binding can result in a long duration of action of the compound and thus less frequent drug dosing. Despite these advantages, there are several safety concerns about this class of compounds because of their inherent reactivity and potential for non-specific binding to cellular proteins. The primary aim of this study was to establish the thiol reactivity of acrylamides and other cysteine-reactive groups by measuring reactivity against various cysteine-containing cellular components. Compounds were incubated with glutathione, bovine serum albumen (BSA) or human liver microsomes (HLM), and the reduction in thiol levels was quantitated using Ellman's reagent. In addition, the ability of compounds to induce Nrf2 activity in a reporter gene assay was used as a functional readout of compound reactivity. The assays were validated using known thiol-reactive compounds and Nrf2 inducers such as sulforaphane (SFP) and 1,2-dithiole-3-thione (D3T). Our results demonstrate that acrylamides possess low reactivity unless activated by electron-withdrawing N-substituents. Analogous propynamides and vinyl sulphones were more reactive than acrylamides with respect to glutathione activity but were less reactive in the Nrf2 assay. Large drug-like molecules, including irreversible kinase inhibitors targeting BTK and EGFR, were far less reactive than their lower molecular weight counterparts, suggesting that the presence of an electrophile is not sufficient to predict thiol reactivity. These studies demonstrate the utility of multiple thiol sources in addition to glutathione when assessing the thiol reactivity of covalent inhibitors. These studies demonstrate the utility of multiple assays for determining the glutathione reactivity and off-target reactivity of cysteine-reactive compounds.