Degradation Of Backbone Research Articles

Tetrazole-Containing Polyelectrolytes: A New Class of Ion-Solvating Membranes for Alkaline Water Electrolysis

Alkaline ion-solvating membranes, such as those based on polybenzimidazole (PBI), offer high ion conductivity and good gas barrier properties, making them promising for next-generation alkaline water electrolyzers.1 However, the stability of commonly used PBI derivatives is limited due to gradual backbone degradation. Consequently, alternative PBI chemistries and other polymer options like poly(vinyl alcohol),2 and carboxylate functionalized styrene-ethylene-butylene copolymers are being explored to address this inherent stability issue.3 In this study, we present the synthesis and characterization of a novel type of ion-solvating membranes for alkaline water electrolyzers. These membranes are based on tetrazole functionalized polymers derived from poly(styrene-co-acrylonitrile). A one-step click-type [3+2] cycloaddition reaction was utilized to introduce tetrazole pendants by converting acrylonitrile groups in poly(styrene-co-acrylonitrile). The degree of functionalization was controlled by adjusting the content of acrylonitrile units in the polymer. Subsequent treatment in aqueous KOH solution led to the formation of negatively charged tetrazolide pendants with high ionization degrees.The alkaline stability of the tetrazolides was evaluated using both DFT simulations and model compound studies, demonstrating remarkable stability with no degradation observed for over 3000 hours in 25 wt.% KOH at 80 °C. Physicochemical properties such as electrolyte uptake, swelling behavior, thermal stability, and ion conductivity were assessed for the synthesized polymers. The electrolyte-imbibed membranes exhibited high ion conductivity, reaching up to 90 mS cm-1 in 15 wt% KOH at 80 °C. Electrolysis operation using these membranes showed stable performance for 600 hours with no signs of degradation. 1 D. Aili, M. R. Kraglund, S. C. Rajappan, D. Serhiichuk, Y. Xia, V. Deimede, J. Kallitsis, C. Bae, P. Jannasch, D. Henkensmeier, J. O. Jensen, ACS Energy Letters, 2023, 1900–1910. 2 Y. Xia, S. C. Rajappan, D. Serhiichuk, M. R. Kraglund, J. O. Jensen, D. Aili, J Memb Sci 2023, 680, 121719. 3 D. Serhiichuk, D. Tian, M. R. Almind, Z. Ma, Y. Xia, M. R. Kraglund, C. Bae, J. O. Jensen, D. Aili ACS Applied Energy Materials 2024 7 (3), 1080-1091 Figure 1 Tetrazolation of poly(styrene-co-acrylonitrile) and formation of corresponding potassium tetrazolide following equilibration in aqueous KOH. Figure 1

Recyclable Polythioesters and Poly(thioester-co-peptoid)s via Ring-Opening Cascade Polymerization of Amino Acid N-Carboxyanhydrides.

Polythioesters (PTEs) are emerging sustainable polymers for their degradability and recyclability. However, low polymerizability of monomers and extensive side reactions often hampered the polymerization process. Moreover, copolymers containing both thioester and other types of functional groups in the backbone are highly desirable but rarely accomplished owing to several synthetic challenges. Here, we report the ring-opening cascade polymerization (ROCAP) of N-(2-(acetylthio)ethyl)-glycine N-carboxyanhydrides (TE-NCA) to afford recyclable PTEs and unprecedented poly(thioester-co-peptoid)s (P(TE-co-PP)s) in a controlled manner. By developing appropriated carboxylic acid-tertiary amine dual catalysts, intramolecular S-to-N acyl shift is coupled into the ROCAP process of TE-NA to yield products with dispersity below 1.10, molecular weight (Mn) up to 84.5 kDa, and precisely controlled ratio of thioester to peptoids. Random copolymerization of sarcosine NCA (Sar-NCA) and TE-NCA gives thioester-embedded polysarcosine with facile backbone degradation while maintaining the water solubility. This work represents a paradigm shift for the ROP of NCAs, enriches the realm of cascade polymerizations, and provides a powerful synthetic approach to functional PTEs and P(TE-co-PP)s that are otherwise difficult or impossible to make.

Effects of Bacillus altitudinis inoculants on cigar tobacco leaf fermentation.

Microbial succession and metabolic adjustment during cigar tobacco leaf (CTL) fermentation are key factors to improve the quality and flavor of CTLs. However, the interactions in the above processes remain to be further elucidated. Bacillus altitudinis inoculants were added to the CTLs, and metagenomics and metabolomics were used to analyze the effects of the inoculants on regulating microbial succession, metabolic shift, and aroma production during fermentation. The addition of the inoculants reinforced the CTL macromolecule transformation and facilitated the aroma production efficiently, and the total aroma production was increased by 43% compared with natural fermentation. The omics analysis showed that Staphylococcus was a main contributor to fatty acid degradation, inositol phosphate metabolism, energy supply (oxidative phosphorylation), nutrient transport (ABC transporter and phosphotransferase system [PTS]), and aroma production (terpenoid backbone biosynthesis, phenylalanine metabolism, and degradation of aromatic compounds). Furthermore, Staphylococcus was positively correlated with TCA cycle intermediates (citric acid, fumaric acid, and aconitic acid), cell wall components, peptidoglycan intermediates (GlcNAc-1-P and UDP-GlcNAc), and phytic acid degradation products (inositol). The characteristics collectively showed Staphylococcus to be the most dominant in the microbial community at the genus level during microflora succession. The addition of the inoculants supplemented the nutritional components of the CTLs, enhanced the metabolic activity and diversity of bacteria such as Corynebacterium, improved their competitive advantages in the microflora succession, and facilitated the richness of microbial communities. Additionally, a metabolic shift in nicotine degradation and NAD + anabolism from Staphylococcus to Corynebacterium in fermentation with inoculants was first observed. Meanwhile, the significantly correlative differential metabolites with Staphylococcus and Corynebacterium were a metabolic complement, thus forming a completely dynamic fermentation ecosystem. The results provided evidence for CTL fermentation optimization.

Precisely Programmable Degradation and Drug Release Profiles in Triblock Copolyether Hydrogels with Cleavable Acetal Pendants.

Hydrogels hold significant promise as drug delivery systems due to their distinct advantage of sustained localized drug release. However, the challenge of regulating the initial burst release while achieving precise control over degradation and drug-release kinetics persists. Herein, we present an ABA-type triblock copolymer-based hydrogel system with precisely programmable degradation and release kinetics. The resulting hydrogels were designed with a hydrophilic poly(ethylene oxide) midblock and a hydrophobic end-block composed of polyethers with varying ratios of ethoxyethyl glycidyl ether and tetrahydropyranyl glycidyl ether acetal pendant possessing different hydrolysis kinetics. This unique side-chain strategy enabled us to achieve a broad spectrum of precise degradation and drug-release profiles under mildly acidic conditions while maintaining the cross-linking density and viscoelastic modulus, which is unlike the conventional polyester-based backbone degradation system. Furthermore, programmable degradation of the hydrogels and release of active therapeutic agent paclitaxel loaded therein are demonstrated in an in vivo mouse model by suppressing tumor recurrence following surgical resection. Tuning of the fraction of two acetal pendants in the end-block provided delicate tailoring of hydrogel degradation and the drug release capability to achieve the desired therapeutic efficacy. This study not only affords a facile means to design hydrogels with precisely programmable degradation and release profiles but also highlights the critical importance of aligning the drug release profile with the target disease.

Development of reversibly photo-crosslinkable water-stable poly(2-ethyl-2-oxazoline) nanofibers via functionalization with cinnamoyl moieties

Poly(2-ethyl-2-oxazoline) (PEtOx) is a potent member of the versatile poly(2-oxazoline) polymer platform with its high hydrophilicity that could be beneficial in numerous biomedical applications, especially in the form of a nanofibrous membrane. However, its water-solubility limits its application in situations where a stable, nanofibrous morphology is required in aqueous environments. The present work offers a straightforward route towards water-stable PEtOx-based nanofibrous membranes, via post-polymerization functionalization with cinnamoyl moieties (PEtOx-Cin) and photo-crosslinking of the electrospun membranes. It is shown that a UVB treatment does not significantly affect the nanofibrous morphology, while successfully inducing the cinnamoyl dimerization process and hence the formation of a polymeric network, as evidenced by spectral analysis. The hereby crosslinked PEtOx-based nanofibers exhibit a prolonged water-stability (at least 45 days), while, interestingly, intermediate irradiation times yield the best results. Full disintegration of the photo-crosslinked nanofibers in aqueous media could be achieved by subsequent UVC exposure. This is not only due to decrosslinking of the cinnamoyl dimers, but was also found to be due to partial degradation of the polymeric backbone. The investigation of UVB/UVC exposure on pure PEtOx nanofibrous membranes confirmed the photo-degradation of the polymeric backbone by a significant decrease in molar mass as observed by size exclusion chromatography and supported by spectral analysis. The hereby proposed, straightforward route for reversible crosslinking of PEtOx-based nanofibrous membranes and their accessible disintegration will contribute to the promotion of these materials in biomedical applications where a water-stable, nanofibrous morphology combined with high hydrophilicity and easy removal is required.

A Light-Triggered J-Aggregation-Regulated Therapy Conversion: from Photodynamic/Photothermal Therapy to Long-Lasting Chemodynamic Therapy for Effective Tumor Ablation.

Reactive oxygen species (ROS) have become an effective tool for tumor treatment. The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) takes advantage of various ROS and enhances therapeutic effects. However, the activation of CDT usually occurs before PDT, which hinders the sustained maintenance of hydroxyl radicals (⋅OH) and reduces the treatment efficiency. Herein, we present a light-triggered nano-system based on molecular aggregation regulation for converting cancer therapy from PDT/photothermal therapy (PTT) to a long-lasting CDT. The ordered J-aggregation enhances the photodynamic properties of the cyanine moiety while simultaneously suppressing the chemodynamic capabilities of the copper-porphyrin moiety. Upon light irradiation, Cu-PCy JNPs demonstrate strong photodynamic and photothermal effects. Meanwhile, light triggers a rapid degradation of the cyanine backbone, leading to the destruction of the J-aggregation. As a result, a long-lasting CDT is sequentially activated, and the sustained generation of ⋅OH is observed for up to 48 hours, causing potent cellular oxidative stress and apoptosis. Due to their excellent tumor accumulation, Cu-PCy JNPs exhibit effective in vivo tumor ablation through the converting therapy. This work provides a new approach for effectively prolonging the chemodynamic activity in ROS-based cancer therapy.

A Light‐Triggered J‐Aggregation‐Regulated Therapy Conversion: from Photodynamic/Photothermal Therapy to Long‐Lasting Chemodynamic Therapy for Effective Tumor Ablation

AbstractReactive oxygen species (ROS) have become an effective tool for tumor treatment. The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) takes advantage of various ROS and enhances therapeutic effects. However, the activation of CDT usually occurs before PDT, which hinders the sustained maintenance of hydroxyl radicals (⋅OH) and reduces the treatment efficiency. Herein, we present a light‐triggered nano‐system based on molecular aggregation regulation for converting cancer therapy from PDT/photothermal therapy (PTT) to a long‐lasting CDT. The ordered J‐aggregation enhances the photodynamic properties of the cyanine moiety while simultaneously suppressing the chemodynamic capabilities of the copper‐porphyrin moiety. Upon light irradiation, Cu‐PCy JNPs demonstrate strong photodynamic and photothermal effects. Meanwhile, light triggers a rapid degradation of the cyanine backbone, leading to the destruction of the J‐aggregation. As a result, a long‐lasting CDT is sequentially activated, and the sustained generation of ⋅OH is observed for up to 48 hours, causing potent cellular oxidative stress and apoptosis. Due to their excellent tumor accumulation, Cu‐PCy JNPs exhibit effective in vivo tumor ablation through the converting therapy. This work provides a new approach for effectively prolonging the chemodynamic activity in ROS‐based cancer therapy.

Synthesis and characterization of amino-functional polyesters composed of lactic acids and serine amino acids

Functional polyesters with good biocompatibility are always important biomaterials. In this study, poly (latide-co-N-trityl serine ester)s (P (LA-co-TSL)s) were synthesized through the copolymerization of lactide (LA) and N-trityl serine lactone (TSL) in toluene under 90 °C with the catalysis of diethylzinc. The molecular weight (Mn) of P (LA-co-TSL) with different TSL molar ratios (4.5%, 8.8%, 25.2%, 41.7% and 100 mol%) ranged from 3.7 kDa to 7.2 kDa with the polydipersity index (PDI) from 1.40 to 1.57. The chemical structure of poly (LA-co-TSL)s was characterized by FTIR, 1H NMR and 13C NMR spectroscopy. As the proportion of TSL in P (LA-co-TSL) increased, the glass transition temperature (Tg) of P (LA-co-TSL) increased gradually, from 56 °C of PLA to 161 °C of Poly (TSL). The initial weitht loss temperature of P (LA-co-TSL) increased as the ratio of TSL increased, from 172 °C of PLA to 230 °C of Poly (TSL). Upon removal of the N-trityl protecting group, amino functional poly (latide-co-serine ester) (P (LA-co-SL)) was realized and confirmd by FTIR and 1H NMR spectra. GPC displayed approximately 19.5% polyester backbone degradation during deprotection with trifluoroacetic acid. DSC analysis illustrated better crystallization properties of the copolyester after amino group deprotection. Using mPEG as an initiator, a new type of block copolymer, mPEG-b-poly (latide-co-N-trityl serine ester)s (mPEG-b-P (LA-co-TSL)s), was obtained. After N-trityl removal, mPEG-b-P (LA-co-TSL) displayed excellent cytocompatibility in L929 cell culture experiments.

Elucidating the backbone degradation mechanism of poly(7-oxa-2,3-diazanorbornene).

Our recent study introduced a novel class of polymers, poly(7-oxa-2,3-diazanorbornene), characterized by synthetic accessibility and the capacity for living polymerization and degradation even under pH = 7.4 buffered conditions. In this work, our research delves into the polymer's degradation behavior, revealing a detailed mechanism of degradation under both acidic and neutral pH environments.

Double CRISPR knockout of pectin degrading enzymes improves tomato shelf‐life while ensuring fruit quality

Social Impact StatementTomato fruit is an important and popular commodity producing $95.62 billion worldwide. Tomato fruit losses in the supply chain vary between 25% and 42% depending on the production area and the availability of postharvest technologies. For many decades, conventional tomato breeding programs have focused on extending the shelf‐life of fresh‐market varieties. However, in many instances, consumer‐based quality traits were not considered a priority. Consumers are now demanding safe, nutrient‐rich, high‐flavor, and convenient fruit. Here, we demonstrate the use of gene editing to improve fruit shelf‐life and positively impact quality, which can help significantly reduce tomato fruit losses and meet consumer expectations.Summary Finding alternative ways to extend tomato fruit shelf‐life without reducing the quality is critical to ensure the accessibility and likeability of this commodity worldwide. Improving fruit firmness in tomato fresh‐market varieties directly impacts their shelf‐life potential. We simultaneously knocked out two pectin‐degrading enzymes, polygalacturonase (SlPG2a) and pectate lyase (SlPL), key for tomato fruit softening. We expected this gene‐editing approach to result in longer‐lasting fruit without negatively impacting consumer‐based quality attributes. By generating the double clustered regularly interspaced short palindromic repeats (CRISPR) knockout PGPL, we evaluated the combined functions of SlPG2a and SlPL on fruit quality, including shelf‐life attributes like firmness and water loss, fruit marketability, and disease incidence. We also assessed additional attributes impacting consumer acceptance, such as taste and aroma. We revealed that the enzymes SlPG2a and SlPL act additively, significantly impacting fruit firmness and shelf‐life, with the double CRISPR knockout PGPL outperforming the wild‐type fruit. Additionally, fruit quality traits, such as sugar: acid ratio, aroma volatiles, and skin color, were improved or not affected in the double CRISPR knockout PGPL compared to the wild‐type. The discoveries of this research provide new insights into the influence of pectin backbone degradation on fruit physiology and postharvest quality, which can be used in crop improvement programs to make fruit more resilient in the supply chain without compromising quality.

Versatile synthesis of siloxane‐based graft copolymers with tunable grafting density

AbstractA versatile synthetic platform is reported that affords high molecular weight graft copolymers containing polydimethylsiloxane (PDMS) backbones and vinyl‐based polymer side chains with excellent control over molecular weight and grafting density. The synthetic approach leverages thiol‐ene click chemistry to attach an atom‐transfer radical polymerization (ATRP) initiator to a variety of commercially available poly(dimethylsiloxane‐co‐methylvinylsiloxane) backbones (PDMS‐co‐PVMS), followed by controlled radical polymerization with a wide scope of vinyl monomers. Selective degradation of the siloxane backbone with tetrabutylammonium fluoride confirmed the controlled nature of side‐chain growth via ATRP, yielding targeted side‐chain lengths for copolymers containing up to 50% grafting density and overall molecular weights in excess of 1 MDa. In addition, by using a mixture of thiols, grafting density and functionality can be further controlled by tuning initiator loading along the backbone. For example, solid‐state fluorescence of the graft copolymers was achieved by incorporating a thiol‐containing fluorophore along the siloxane backbone during the thiol‐ene click reaction. This simple synthetic platform provides facile control over the properties of a wide variety of grafted copolymers containing flexible PDMS backbones and vinyl polymer side chains.

Insights into the borohydride reduction of dialdehyde cellulose: the dilemma of competing reduction and β-elimination reactions

Borohydride reduction of dialdehyde cellulose (DAC) is a promising strategy to generate dialcohol cellulose as bio-based alternative to petroleum-based materials. However, the degradation of the polymer backbone according to β-elimination mechanisms limits the practical applications of the reaction. Therefore, we aimed at optimizing the process to suppress degradation reactions by varying reaction time, pH, and reagent stoichiometry. The degree of oxidation (DO) of the DAC intermediates significantly impacts the yields and molecular weights of the isolated dialcohol celluloses, with a “leveling-off” effect at higher DO values. Increasing the amount of sodium borohydride can minimize—but not entirely prevent—chain scissions. Lowering the pH value during reduction slows down the degradation but results in incomplete conversion of the aldehyde functionalities. Our study provides valuable insights into the consequences of side reactions during borohydride reduction of DAC as well as into chemistry and analysis of the dialdehyde cellulose/dialcohol cellulose system.Graphical abstractAbout a dilemma in cellulose chemistry: Dialcohol cellulose derived by periodate oxidation and subsequent borohydride reduction of cellulose has received increasing attention in the development of sustainable thermoplastic materials. The present study highlights the challenge of suppressing β-elimination and favoring the reduction pathway to optimize reaction conditions and minimize chain degradation.

Toward Stable p‐Type Thiophene‐Based Organic Electrochemical Transistors

AbstractOperational stability is essential for the success of organic electrochemical transistors (OECTs) in bioelectronics. The oxygen reduction reaction (ORR) is a common electrochemical side reaction that can compromise the stability of OECTs, but the relationship between ORR and materials degradation is poorly understood. In this study, the impact of ORR on the stability and degradation mechanisms of thiophene‐based OECTs is investigated. The findings show that an increase in pH during ORR leads to the degradation of the polymer backbone. By using a protective polymer glue layer between the semiconductor channel and the aqueous electrolyte, ORR is effectively suppressed and the stability of the OECTs is significantly improved, resulting in current retention of nearly 90% for ≈2 h cycling in the saturation regime.

Preclinical evaluation of the degradation kinetics of third-generation resorbable magnesium scaffolds.

The novel sirolimus-eluting resorbable scaffold DREAMS 3G was designed as a third-generation development of its predecessor, the Magmaris scaffold. This preclinical study aimed to examine the qualitative and temporal course of the degradation of the DREAMS 3G relative to the Magmaris scaffold. Forty-nine DREAMS 3G and 24 Magmaris scaffolds were implanted into 48 mini swine for degradation kinetics analysis. Another DREAMS 3G was implanted into one mini swine for crystallinity analysis of the degradation end product after 730 days. Degradation kinetics were determined at 28, 90, 120, 180, and 365 days. Discontinuity density in DREAMS 3G was significantly lower than that in Magmaris scaffolds for the follow-up timepoints of 90 and 120 days. Planimetric analysis indicated 99.6% backbone degradation for DREAMS 3G at 12 months. Compared to the Magmaris scaffold, individual strut degradation in DREAMS 3G showed less variability and the remaining backbone core was more homogeneous. The degradation end product of DREAMS 3G manifested as calcium phosphate with a minor share of aluminium phosphate. DREAMS 3G showed almost complete degradation after one year, with amorphous calcium and aluminium phosphate as the end products of degradation. Despite its thinner struts, scaffold discontinuity was significantly lower in the DREAMS 3G than in the Magmaris scaffold, likely providing a longer scaffolding time.

Polymerization Chemistry of Vinylboronic Acid Derivatives: Boron-Based Monomer Design and Polymer Reaction through Side-Chain Replacement

In chain-growth polymerization, (co)polymerization abilities of monomers are heavily dependent on the element or functional group attaching to vinyl moiety, resulting in the limitation of accessible polymers. The replacement of the element on the polymer main chain could lead to access new class of polymers with overcoming the synthetic limitations. Herein, we describe the usability of alkenylboronic acid derivatives as the monomers for radical polymerization and post-polymerization transformation through carbon-boron bond-cleaving side-chain replacement. The key for radical polymerization ability of alkenyl boronate was vacant p-orbital of boron for moderate stabilization of chain growth radical. The alkenyl boronate monomers are usable for copolymerization with common monomers as well as for RAFT polymerization. The C-B bond transformation allows syntheses of conventionally inaccessible polymers, such as poly(α-methyl vinyl alcohol), poly(α-methyl vinyl amine), styrene-vinyl alcohol copolymer, and ethylene-acrylate copolymer. Boron on the polymer main chain was also used as the trigger for stimuli-responsive backbone degradation of methacrylate polymer through C-B bond homolysis and β-scission. Thus, alkenyl boronate monomers have an impact on not only breakthrough of the limitation in polymer synthesis but also development of novel polymer functions.

Degradation of thermoplastic cellulose acetate-based bioplastics by full-scale experimentation of industrial anaerobic digestion and composting

The ability of full-scale industrial plants to degrade bioplastics waste must be verified to exclude any negative effects on the quality of the process outputs. This study aims to assess the degradation of two thermoplastic cellulose acetate-based bioplastics, in pure and composite forms in both Anaerobic Digestion (AD) and Composting (C) industrial conditions. The main degradation occurred during AD, where a disintegration of about 36% and 50% was achieved from pure and composite thermoplastic cellulose acetate, respectively. The disintegration during C did not exceed 20% for both samples. The combined process resulted in a slightly higher degradation (58–40%) than that obtained in AD, revealing how the main alteration of samples occurred in an anaerobic environment. Despite this macroscopic degradation, the samples showed only minor superficial degradation as highlighted from SEM analysis. FT-IR spectroscopy, TGA andDSC analyses showed that the biodegradation mechanism involved mainly the plasticizer loss and deacetylation of the cellulose matrix, with only partial degradation of cellulose backbone However, both deacetylation and degradation were favored in AD and AD + C processes and from the presence of filler in anaerobic conditions. These results demonstrated how the degradation obtained on an industrial scale can differ significantly from those obtained in the laboratory scale, especially for pure thermoplastic cellulose acetate. Furthermore, current industrial AD and C process resulted not optimized for the treatment of thermoplastic cellulose acetate-based bioplastics. Hence, this works could help waste facilities managers to process emerging materials such as bioplastics in a more sustainable way.

Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers.

The therapeutic efficacy of nanomedicines is highly dependent on their access to target sites in the body, and this in turn is markedly affected by their size, shape and transport properties in tissue. Although there have been many studies in this area, the ability to design nanomaterials with optimal physicochemical properties for in vivo efficacy remains a significant challenge. In particular, it is often difficult to quantify the detailed effects of cancer drug delivery systems in vivo as tumour volume reduction, a commonly reported marker of efficacy, does not always correlate with cytotoxicity in tumour tissue. Here, we studied the behaviour in vivo of two specific poly(2-hydroxypropyl methacrylamide) (pHPMA) pro-drugs, with hyperbranched and chain-extended branched architectures, redox-responsive backbone components, and pH-sensitive linkers to the anti-cancer drug doxorubicin. Evaluation of the biodistribution of these polymers following systemic injection indicated differences in the circulation time and organ distribution of the two polymers, despite their very similar hydrodynamic radii (∼10 and 15 nm) and architectures. In addition, both polymers showed improved tumour accumulation in orthotopic triple-negative breast cancers in mice, and decreased accumulation in healthy tissue, as compared to free doxorubicin, even though neither polymer-doxorubicin pro-drug decreased overall tumour volume as much as the free drug under the dosing regimens selected. However, the results of histopathological examinations by haematoxylin and eosin, and TUNEL staining indicated a higher population of apoptotic cells in the tumours for both polymer pro-drug treatments, and in turn a lower population of apoptotic cells in the heart, liver and spleen, as compared to free doxorubicin treatment. These data suggest that the penetration of these polymer pro-drugs was enhanced in tumour tissue relative to free doxorubicin, and that the combination of size, architecture, bioresponsive backbone and drug linker degradation yielded greater efficacy for the polymers as measured by biomarkers than that of tumour volume. We suggest therefore that the effects of nanomedicines may be different at various length scales relative to small molecule free drugs, and that penetration into tumour tissue for some nanomedicines may not be as problematic as prior reports have suggested. Furthermore, the data indicate that dual-responsive crosslinked polymer-prodrugs in this study may be effective nanomedicines for breast cancer chemotherapy, and that endpoints beyond tumour volume reduction can be valuable in selecting candidates for pre-clinical trials.

Primary radiation damage in bone evolves via collagen destruction by photoelectrons and secondary emission self-absorption

X-rays are invaluable for imaging and sterilization of bones, yet the resulting ionization and primary radiation damage mechanisms are poorly understood. Here we monitor in-situ collagen backbone degradation in dry bones using second-harmonic-generation and X-ray diffraction. Collagen breaks down by cascades of photon-electron excitations, enhanced by the presence of mineral nanoparticles. We observe protein disintegration with increasing exposure, detected as residual strain relaxation in pre-stressed apatite nanocrystals. Damage rapidly grows from the onset of irradiation, suggesting that there is no minimal ‘safe’ dose that bone collagen can sustain. Ionization of calcium and phosphorous in the nanocrystals yields fluorescence and high energy electrons giving rise to structural damage that spreads beyond regions directly illuminated by the incident radiation. Our findings highlight photoelectrons as major agents of damage to bone collagen with implications to all situations where bones are irradiated by hard X-rays and in particular for small-beam mineralized collagen fiber investigations.

(Invited) Operando EPR Study on Radicals in Anion-Exchange Membrane Fuel Cells

In the rapidly developing modern society, there is an urgent need for the wide-ranging availability of advanced and eco-friendly energy sources. One of the possible alternatives is the application of anion exchange membrane fuel cells (AEMFCs) with a catalyst reducing dioxygen efficiently. These promising devices can revolutionize the energy sector since they practically produce no pollution. However, to make them more widely used, several obstacles must be overcome. As a result, vast-ranging investigations focus on improving the properties of conductive polymer membranes [1] and catalysts for the oxygen reduction reaction (ORR) [2]. The durability of the membrane electrode assembly (MEA) is one of the critical requirements for the successful commercialization of anion exchange membrane fuel cells (AEMFCs). Despite significant impacts of nucleophilic degradation on ion-exchange capability and the anionic conductivity of investigated membranes, it is believed to affect only cationic sites of membrane polymers and thus cannot explain the reported loss in the mechanical strength of degraded AEMs. Such a phenomenon might be related to polymer backbone degradation caused by free radicals. This was widely described in the literature in the case of fuel cells using proton-conducting membranes [3] but barely mentioned for AEMFCs [4]. Since the oxidative degradation of hydrocarbon polymers is very well known, we aimed to comprehensively investigate the formation of the short-lived species generated during the operation of AEMFCs as well as stable radicals present in the polymer membranes.We investigated the LDPE-base membranes with Pt black, Pd black, PdAg, and Ag as the ORR catalysts, whereas for HOR the Pt black, Pd black, and NiFe catalysts were used. The in-situ measurements are performed with a micro-AEMFC inserted into a resonator of an electron paramagnetic resonance (EPR) spectrometer, which enables separate monitoring of radicals formed on the anode and cathode sides. The creation of radicals was monitored by the EPR spin trapping technique. In Figure 1 the EPR spectra of DMPO spin adducts trapped during operation of micro-fuel cell placed in EPR spectrometer cavity are presented. In this experiment, the LDPE-base membrane with platinum catalysts on both sides was used. The main detected adducts during the operation of the micro-AEMFC were DMPO-OOH and DMPO-OH on the cathode side and DMPO-H on the anode side. Additionally, we clearly show the formation and presence of stable radicals in AEMs during and after long-term AEMFC operation [5]. Preliminary results suggest that the creation of the short-living radicals during AEMFCs operation is independent of the used membrane. However, the applied catalysts determine the number of detected radicals. The EPR investigations indicate that, in addition to the known chemical degradation mechanisms of the cationic ammonium groups of the membrane, oxidative degradation, including radical reactions, has to be taken into account when the stability of an anion conductive polymer for AEMFCs is investigated. The formation of stable radicals in AEMs was proven for the first time in this study. All short-living radicals formed during the AEMFC operation were fully identified. The presence of radicals in the AEM after AEMFC testing indicates that reactive oxygen species may play a very important role in the degradation mechanism of the anion conducting polymers. Results from this study shed light on the understanding of radical formation and presence in the membranes during AEMFC tests, which in turn may help to solve the challenge of anion exchange membrane stability. Acknowledgments. This work was supported by the Polish National Science Centre (NCN) project OPUS-14, No. 2017/27/B/ST5/01004.

Pyridine-Based NNS Tridentate Chitosan Thiosemicarbazones and Their Copper(II) Complexes: Synthesis, Characterization, and Anticancer Activity.

Chitosan-functionalized pyridine-based thiosemicarbazones and their copper(II) complexes have been found to own a substantial antiproliferative activity against the tumorigenic Madin Darby canine kidney (MDCK) and MCF-7 cancer cell lines. In the current study, chitosan oligosaccharide (CS) (87% DDA, Mw < 3000 Da) and crab shell chitosan (CCS) (67% DDA, Mw 350 kDa) were functionalized as chitosan pyridine-2-thiosemicarbazones and chitosan 2-acetyl pyridine-2-thiosemicarbazones, and their copper(II) complexes were synthesized. The formation of chitosan thiosemicarbazones and their NNS tridentate behavior to give the square planar copper(II) chitosan thiosemicarbazone complexes were established by spectroscopic studies, powder X-ray diffraction, elemental analysis, and magnetic moment measurements. The thermal study showed a marked stability of these derivatives before the outset of chitosan backbone degradation at 200 °C. The colorimetric MTT assay revealed a higher activity of CS thiosemicarbazones, viz., CSTSC series (IC50 375–381 μg mL–1 in the MDCK cell line and 281–355 μg mL–1 in the MCF-7 cell line) than that of high-molecular-weight CCS thiosemicarbazones, viz., CCSTSC series (IC50 335–400 μg mL–1 in the MDCK cell line and 365–400 μg mL–1 in the MCF-7 cell line), showing an enhanced activity with a decrease in Mw and an increase in DDA of constituent chitosan, a higher activity of both of these series of thiosemicarbazones than that of their native chitosan, viz., CS (IC50 370 μg mL–1 in the MCF-7 cell line and >400 μg mL–1 in the MDCK cell line) and CCS (IC50 > 400 μg mL–1 in both cell lines), and a higher activity of the Cu-CSTSC complexes (IC50 322–342 μg mL–1 in the MDCK cell line and 278–352 μg mL–1 in the MCF-7 cell line) and Cu-CCSTSC complexes (IC50 274–400 μg mL–1 in the MDCK cell line and 231–352 μg mL–1 in the MCF-7 cell line) than that of their respective ligands.