Severe allergic systemic reaction to personal protective equipment during the COVID-19 pandemic.

Our case describes a hospital worker who suffered a severe reaction to personal protective equipment (PPE) during the COVID-19 pandemic. After researching the excipient list of her PPE and completing a literature review, we postulated that isocyanates used in the production of the polyurethane band of the N95 mask was the cause for her reaction. In the absence of standardised testing, we tested this hypothesis by replicating her reaction to PPE by using a commercially available isocyanate patch, identifying diphenylmethane-4, 4-diisocyanate as the culprit agent.We recommended caution in the use of polyurethane containing N95 masks- for people reporting allergic reaction- and testing for sensitivity for polyurethane. The patient was able to tolerate non-polyurethane containing standard surgical masks, providing an option for PPE in some clinical circumstances. Since avoiding N95 masks, she has not had any further reactions.

Bio-based Polyurethane Based on a Dynamic Covalent Network with Damage Tolerance for Controlled Release of Fertilizers.

Bio-based polyurethanes are promising for the controlled release of nutrients and fertilizers, but their toughness and plasticity need to be improved. We developed a smooth, dense, elastic, and indestructible bio-based polyurethane (BPU) coating with a nutrient controlled release ∼150% superior, a tensile strength ∼300% higher, and a toughness ∼1200% higher than those for the original BPU coating. Through a one-step reaction of soybean oil polyols (accounting for more than 60%), isocyanate, and benzil dioxime, the dynamic covalent network based on oxime-carbamate replaces part of irreversible covalent cross-linking. The dynamic fracture-bonding reaction in the modified coating BPU can effectively promote the hydrogen bond recombination and oxime-carbamate chain migration in the coating process, which avoids the structural defects caused by coating tear and fertilizer collision. This work provides a simple and versatile strategy for building controlled-release fertilizer coatings.

Screening of dicyanoisophorone-based probes for highly sensitive detection of viscosity changes in living cells and zebrafish.

Herein, seven viscosity-sensitive probes were developed via simple structural modification of dicyanoisophorone (DCO)-derived dyes. Among them, DCO-5 significantly enhances (180-fold) the response signal in highly viscous aqueous media while showing insensitivity to polarity changes or pH variations, and enables the successful detection of viscosity changes in nystatin-treated HepG2 cells, PC 12 cells and zebrafish.

Divergent Synthesis of γ-Amino Acid and γ-Lactam Derivatives from meso-Glutaric Anhydrides.

The first divergent synthesis of both γ-amino acid and γ-lactam derivatives from meso-glutaric anhydrides is described. The organocatalytic desymmetrisation with TMSN3 relies on controlled generation of a nucleophilic ammonium azide species mediated by a polystyrene-bound base to promote efficient silylazidation. After Curtius rearrangement of the acyl azide intermediate to access the corresponding isocyanate, hydrolysis/alcoholysis provided uniformly high yields of γ-amino acids and their N-protected counterparts. The same intermediates were shown to undergo an unprecedented decarboxylation-cyclisation cascade in situ to provide synthetically useful yields of γ-lactam derivatives without using any further activating agents. Mechanistic insights invoke the intermediacy of an unconventional γ-N-carboxyanhydride (γ-NCA) in the latter process. Among the examples prepared using this transformation are 8 APIs/molecules of considerable medicinal interest.

Successful adjunctive treatment of compartment syndrome due to acute isocyanate inhalation using hyperbaric oxygen therapy: case report.

Introduction: Isocyanates are the raw materials that make up all polyurethane products. Isocyanate is a powerful irritant to the mucosal membrane of the respiratory tract, eyes and skin. Pulmonary symptoms, especially occupational asthma, are predominant manifestations of isocyanate toxicity. Case report: We report mental changes and compartment syndrome complicated with rhabdomyolysis as an extraordinary manifestation of acute isocyanate toxicity observed in a patient during the waterproofing of a water tank. A 58-year-old man recovered consciousness after six hours in the emergency department and complained of severe pain in the lower leg. The results of his laboratory test showed that his serum creatine kinase (15,250 IU/L) level had increased. The tissue pressure in both the lower legs had increased to 180 mmHg/170 mmHg (right/left). We performed fasciotomy on the second day of hospitalization. The patient was provided hyperbaric oxygen (HBO2) therapy of 2.0 ATA for 90 minutes twice a day for seven days. His condition gradually improved over five months, and he did not require amputation. He had a mild neurological disorder in his foot and was transferred to a rehabilitation center five months after hospitalization. Conclusion: It is important to note that when working with isocyanate, non-specific complications such as a change in consciousness as well as compartment syndrome with rhabdomyolysis can occur in a confined space or high-temperature environment. In addition, we found that compartment syndrome caused by isocyanate toxicity can be effectively treated with fasciotomy and HBO2 therapy.

High-value utilization of hydroxymethylated lignin in polyurethane adhesives.

Lignin is a good candidate for the polymerization and chemical modification to prepare sustainable chemicals and materials, but a relatively low hydroxyl content becomes an obstacle for the preparation of lignin-based polyurethane (PU) adhesives. In order to improve its reactivity, the acetic acid lignin (AAL) was hydroxymethylated before copolymerized with isocyanate during the preparation of PU adhesives. The hydroxymethylation was carried out in an alkaline formaldehyde solution and it was found that 85 °C is the optimal temperature. On that condition, the free formaldehyde content of the corresponding product HL-6 was as low as 0.32%, while the hydroxymethyl was increased by 189.11% compared with original AAL and reached 2.92 mmol/g. In the polymerization of PU adhesives, the hydroxymethylated lignin with a higher aliphatic hydroxyl content formed a more compact three-dimensional urethane cross-linking network with isocyanate. The mechanical properties and thermal stability of the lignin-based PU adhesive were improved by 15-30 wt% in HL-6, and particularly the tensile strength was increased by 21-41 MPa, which indicated that the hydroxymethylation is an efficient way to enrich the hydroxyl in lignin, and the modified lignin is adequate to partially replace petroleum-based polyols for the preparation of PU adhesives with excellent properties.

New Insight on the Study of the Kinetic of Biobased Polyurethanes Synthesis Based on Oleo-Chemistry.

Nowadays, polyols are basic chemicals for the synthesis of a large range of polymers, such as polyurethane foams (PUF), which are produced with several other compounds, such as polyisocyanates. During the last decades, the oleo-chemistry has developed several routes from glycerides to polyols for the polyurethanes (PU) industry to replace mainly conventional fossil-based polyols. A large range of biobased polyols can be now obtained by epoxidation of the double bonds and ring-opening (RO) of the subsequent epoxides with different chemical moieties. In preliminary studies, the RO kinetics of an epoxidized model molecule (methyl oleate) with ethanol and acetic acid were investigated. Subsequently, polyols that were derived from unsaturated triglycerides were explored in the frame of e.g., PUF formulations. Different associations were studied with different mono-alcohols derived from epoxidized and ring-opened methyl oleate while using several ring-openers to model such systems and for comparison purposes. Kinetic studies were realized with the pseudo-first-order principle, meaning that hydroxyls are in large excess when compared to the isocyanate groups. The rate of isocyanate consumption was found to be dependent on the moiety located in ß-position of the reactive hydroxyl, following this specific order: tertiary amine >> ether > ester. The tertiary amine in ß-position of the hydroxyl tremendously increases the reactivity toward isocyanate. Consequently, a biobased reactive polyurethane catalyst was synthesized from unsaturated glycerides. These approaches offer new insights regarding the replacement of current catalysts often harmful, pungent, and volatile used in PU and PUF industry, in order to revisit this chemistry.

Effective delivery of volatile biocides employing mesoporous silicates for treating biofilms.

Nanoparticulate delivery of biocides has the potential to decrease levels of exposure to non-target organisms, and miminize long-term exposure that can promote the development of resistance. Silica nanoparticles are an ideal vehicle since they are inert, biocompatible, biodegradable, and thermally and chemically stable. Encapsulation of biocides within nanoparticulates can improve their stability and longevity and maximize the biocidal potential of hydrophobic volatile compounds. Herein, we have shown that the plant secondary metabolites allyl isothiocyanate and cinnamaldehyde demonstrated increased antimicrobial activity against Escherichia coli in planktonic form, when packaged into mesoporous silica nanoparticles. Furthermore, the biocide-loaded nanoparticles showed activity against Pseudomonas aeruginosa biofilms that have inherent resistance to antimicrobial agents. The delivery platform can also be expanded to traditional biocides and other non-conventional antimicrobial agents.

The role of nanocrystalline cellulose on the microstructure of foamed castor-oil polyurethane nanocomposites.

Nanocrystalline cellulose (CNC), obtained by sulphuric acid hydrolysis, was used to synthesize polyurethane foams (PUFs) based on a functionalized castor oil polyol and a Methylene diphenyl diisocyanate (MDI). Formulations with varying isocyanate index (FI) and NCO number were prepared. At 0.5 wt.%, SEM's of the fractured surface underlined that the CNC acted both as a nucleation agent and as a particulate surfactant with cell geometries and apparent density changing selectively. The chemical structure of the PUF (FTIR) changed after the incorporation of CNC by a relative change of the amount of urea, urethane and isocyanurate groups. A low NCO number and isocyanate index contributed to the migration of the CNC to the Hard Segment (HS), acting as reinforcement and improving substantially the compressive mechanical properties (Ec and σc improvements of 63 and 50%, respectively). For a high NCO number or isocyanate index, the CNC migrated to the Soft Segment (SS), without causing a reinforcement effect. The migration of the CNC was also detected with DSC, TGA and DMA, furtherly supporting the hypothesis that a low NCO number and index contributed both to the formation of a microstructure with a higher content of urethane groups.

Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy.

December 2014 marked the 30th year anniversary of Bhopal gas tragedy. This sudden and accidental leakage of deadly poisonous methyl isocyanate (MIC) gas instigated research efforts to understand the nature, severity of health damage and sufferings of 570 000 ailing survivors of this tragedy. In a decade-long period, our systematic laboratory investigations coupled with long-term molecular surveillance studies have comprehensively demonstrated that the risk of developing an environmental associated aberrant disease phenotype, including cancer, involves complex interplay of genomic and epigenetic reprogramming. These findings poised us to translate this knowledge into an investigative framework of "molecular biodosimetry" in a strictly selected cohort of MIC exposed individuals. A pragmatic cancer risk-assessment strategy pursued in concert with a large-scale epidemiological study might unfold molecular underpinnings of host-susceptibility and exposureresponse relationship. The challenges are enormous, but we postulate that the study will be necessary to establish a direct initiation-promotion paradigm of environmental carcinogenesis. Given that mitochondrial retrograde signaling-induced epigenetic reprogramming is apparently linked to neoplasticity, a cutting-edge tailored approach by an expert pool of biomedical researchers will be fundamental to drive these strategies from planning to execution. Validating the epigenomic signatures will hopefully result in the development of biomarkers to better protect human lives in an overburdened ecosystem, such as India, which is continuously challenged to meet population demands. Besides, delineating the mechanistic links between MIC exposure and cancer morbidity, our investigative strategy might help to formulate suitable regulatory policies and measures to reduce the overall burden of occupational and environmental carcinogenesis.

Isolation of viable type I and II methanotrophs using cell-imprinted polyurethane thin films.

Studies on methanotrophs utilizing methane as sole source of carbon and energy are meaningful for governing global warming; although, the isolation of methanotrophs from nature is challenging. Here, surface imprinted polyurethane films were fabricated to selectively capture living methanotrophs from paddy soil. Two tracks of molecularly imprinted film based on polyurethane (PU-MIF1 and PU-MIF2) were imprinted using type I or II methanotrophs as template, respectively, and then reacted with polyethylene glycol, castor oil, and hexamethylene diisocyanate. Results demonstrated these PU-MIFs hold low water absorption rate and superior biocompatibility, which was highly demanded for maintaining cell viability. Superior selectivity and affinity of PU-MIFs toward their cognate methanotroph cells was observed by fluorescent microscopy. Atomic force microscopy revealed the adhesion force of PU-MIFs with its cognate cells was much stronger in comparison with noncognate ones. Using the as-prepared PU-MIFs, within 30 min, methanotroph cells could be separated from rice paddy efficiently. Therefore, the PU-MIFs might be used as an efficient approach for cell sorting from environmental samples.

Isocyanate- and phosgene-free routes to polyfunctional cyclic carbonates and green polyurethanes by fixation of carbon dioxide.

The catalytic chemical fixation of carbon dioxide by carbonation of oxiranes, oxetanes, and polyols represents a very versatile green chemistry route to environmentally benign di- and polyfunctional cyclic carbonates as intermediates for the formation of non-isocyanate poly-urethane (NIPU). Two synthetic pathways lead to NIPU thermoplastics and thermosets: i) polycondensation of diacarbamates or acyclic dicarbonates with diols or diamines, respectively, and ii) polyaddition by ring-opening polymerization of di- and polyfunctional cyclic carbonates with di- and polyamines. The absence of hazardous and highly moisture-sensitive isocyanates as intermediates eliminates the need for special safety precautions, drying and handling procedures. Incorporated into polymer backbones and side chains, carbonate groups enable facile tailoring of a great variety of urethane-functional polymers. As compared with conventional polyurethanes, ring-opening polymerization of polyfunctional cyclic carbonates affords polyhydroxyurethanes with unconventional architectures including NIPUs containing carbohydrate segments. NIPU/epoxy hybrid coatings can be applied on wet surfaces and exhibit improved adhesion, thermal stability and wear resistance. Combining chemical with biological carbon dioxide fixation affords 100% bio-based NIPUs derived from plant oils, terpenes, carbohydrates, and bio polyols. Biocompatible and biodegradable NIPU as well as NIPU biocomposites hold great promise for biomedical applications.

Metabolomics coupled with pattern recognition and pathway analysis on potential biomarkers in liver injury and hepatoprotective effects of yinchenhao.

Metabolomics can provide an opportunity to develop the systematic analysis of the metabolites in biological samples and has been increasingly applied to discovering and identifying biomarkers and perturbed pathways. It enables us to better understand the metabolic pathways which can clarify the mechanism of traditional Chinese medicines (TCM). Yinchenhao (YCH, Artemisia annua L), a famous TCM plant, has been used clinically for more than a thousand years to relieve liver diseases in Asia, and its mechanisms are not still completely clear. Here, metabolomic techniques may provide additional insight, and our investigation was designed to assess the effects and possible mechanisms of YCH on α-naphthylisothiocyanate (ANIT)-induced liver injury. Metabolite profiling was performed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) combined with pathway analysis and pattern recognition approaches including independent component analysis (ICA) and partial least squares-discriminant analysis (PLS-DA). Biochemistry test was also performed for the liver tissue and plasma samples. The changes in metabolic profiling were restored to their baseline values after YCH treatment according to the ICA score plots. Of note, YCH has a potential pharmacological effect through regulating multiple perturbed pathways to normal state, correlating well to the assessment of biochemistry test. Five different potential biomarkers in the positive mode contributing to the treatment of YCH were discovered. Pathway analysis showed that these metabolites were associated with perturbations in pyrimidine metabolism, primary bile acid biosynthesis, and propanoate metabolism, which may be helpful to further understand the action mechanisms of YCH. It showed that changed biomarkers and pathways may provide evidence to insight into drug action mechanisms and drug discovery.

New polyurethane nanocomposites based on soya oil.

New polyurethane (PU) nanocomposites were prepared from a dispersion of 0 - 5% montmorillonite (MMT) clay with isocyanate and soya oil polyol that was synthesized via transesterification of triglycerides to reduce petroleum dependence. FT-IR spectra indicate the presence of hydrogen bonding between nanoclay and the polymer matrix, whereas the exfoliated structure of clay layers was confirmed by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Optical microscopy, mechanical and thermal analyses were done to investigate significant improvement of the nanocomposites. The results showed PU-3% nanoclay (NC) showed optimum results in mechanical properties such as tensile and flexural strength but the lowest in impact strength.

Gelatin-modified polyurethanes for soft tissue scaffold.

Recently, in the field of biomaterials for soft tissue scaffolds, the interest of their modification with natural polymersis growing. Synthetic polymers are often tough, and many of them do not possess fine biocompatibility. On the other hand, natural polymers are biocompatible but weak when used alone. The combination of natural and synthetic polymers gives the suitable properties for tissue engineering requirements. In our study, we modified gelatin synthetic polyurethanes prepared from polyester poly(ethylene-butylene adipate) (PEBA), aliphatic 1,6-hexamethylene diisocyanate (HDI), and two different chain extenders 1,4-butanediol (BDO) or 1-ethoxy-2-(2-hydroxyethoxy)ethanol (EHEE). From a chemical point of view, we replaced expensive components for building PU, such as 2,6-diisocyanato methyl caproate (LDI) and 1,4-diisocyanatobutane (BDI), with cost-effective HDI. The gelatin was added in situ (in the first step of synthesis) to polyurethane to increase biocompatibility and biodegradability of the obtained material. It appeared that the obtained gelatin-modified PU foams, in which chain extender was BDO, had enhanced interactions with media and their hydrolytic degradation profile was also improved for tissue engineering application. Furthermore, the gelatin introduction had positive impact on gelatin-modified PU foams by increasing their hemocompatibility.

Imbalance of mitochondrial-nuclear cross talk in isocyanate mediated pulmonary endothelial cell dysfunction.

Mechanistic investigations coupled with epidemiology, case-control, cohort and observational studies have increasingly linked isocyanate exposure (both chronic and acute) with pulmonary morbidity and mortality. Though ascribed for impairment in endothelial cell function, molecular mechanisms of these significant adverse pulmonary outcomes remains poorly understood. As preliminary studies conducted in past have failed to demonstrate a cause-effect relationship between isocyanate toxicity and compromised pulmonary endothelial cell function, we hypothesized that direct exposure to isocyanate may disrupt endothelial structural lining, resulting in cellular damage. Based on this premise, we comprehensively evaluated the molecular repercussions of methyl isocyanate (MIC) exposure on human pulmonary arterial endothelial cells (HPAE-26). We examined MIC-induced mitochondrial oxidative stress, pro-inflammatory cytokine response, oxidative DNA damage response and apoptotic index. Our results demonstrate that exposure to MIC, augment mitochondrial reactive oxygen species production, depletion in antioxidant defense enzymes, elevated pro-inflammatory cytokine response and induced endothelial cell apoptosis via affecting the balance of mitochondrial-nuclear cross talk. We herein delineate the first and direct molecular cascade of isocyanate-induced pulmonary endothelial cell dysfunction. The results of our study might portray a connective link between associated respiratory morbidities with isocyanate exposure, and indeed facilitate to discern the exposure-phenotype relationship in observed deficits of pulmonary endothelial cell function. Further, understanding of inter- and intra-cellular signaling pathways involved in isocyanate-induced endothelial damage would not only aid in biomarker identification but also provide potential new avenues to target specific therapeutic interventions.

Renewable non-isocyanate based thermoplastic polyurethanes via polycondensation of dimethyl carbamate monomers with diols.

1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD)-catalyzed polycondensation reactions of fatty acid derived dimethyl dicarbamates and diols are introduced as a versatile, non-isocyanate route to renewable polyurethanes. The key step for the synthesis of dimethyl carbamate monomers from plant-oil-derived dicarboxylic acids is based on a sustainable base-catalyzed Lossen rearrangement. The formed polyurethanes with molecular weights up to 25 kDa are characterized by SEC, DSC, and NMR analysis.

Isocyanate-functionalized chitin and chitosan as gelling agents of castor oil.

The main objective of this work was the incorporation of reactive isocyanate groups into chitin and chitosan in order to effectively use the products as reactive thickening agents in castor oil. The resulting gel-like dispersions could be potentially used as biodegradable lubricating greases. Three different NCO-functionalized polymers were obtained: two of them by promoting the reaction of chitosan with 1,6-hexamethylene diisocyanate (HMDI), and the other by using chitin instead of chitosan. These polymers were characterized through 1H-NMR, FTIR and thermogravimetric analysis (TGA). Thermal and rheological behaviours of the oleogels prepared by dispersing these polymers in castor oil were studied by means of TGA and small-amplitude oscillatory shear (SAOS) measurements. The evolution and values of the linear viscoelasticity functions with frequency for -NCO-functionalized chitosan- and chitin-based oleogels are quite similar to those found for standard lubricating greases. In relation to long-term stability of these oleogels, no phase separation was observed and the values of viscoelastic functions increase significantly during the first seven days of ageing, and then remain almost constant. TGA analysis showed that the degradation temperature of the resulting oleogels is higher than that found for traditional lubricating greases.

Effect of castor oil enrichment layer produced by reaction on the properties of PLA/HDI-g-starch blends.

Blends of entirely bio-sourced polymers, namely polylactide (PLA) and starch, have been melt-compounded by lab-scale co-extruder with castor oil (CO) as a plasticizer. The enrichment of castor oil on starch had great effect on the properties of the blends. If the castor oil was mainly dispersed in PLA matrix, the properties of the blends were poor, but when the hexamethylenediisocyanate (HDI) was grafted on starch granules the ready reactions between the hydroxyl on CO and the isocyante on the HDI-grafted starch (HGSTs) brought CO molecules enriched on starch particles. DSC analysis shows that the CO layer on starch has a positive effect on the crystallization of PLA in the ternary blend. The accumulation of CO on starch greatly improves the toughness and impact strength of PLA/starch blends. The grafting content of HDI on the starch granules primarily determined the compatibility and properties of the resulted blends.

Molecular simulation of fibronectin adsorption onto polyurethane surfaces.

Poly(ethylene glycol)-based polyurethanes have been widely used in biomedical applications; however, they are prone to swelling. A natural polyol, castor oil, can be incorporated into these polyurethanes to control the degree of the swelling, which alters mechanical properties and protein adsorption characteristic of the polymers. In this work, we modeled poly(ethylene glycol) and castor oil copolymers of hexamethylene diisocyanate-based polyurethanes (PEG-HDI and CO-HDI, respectively) and compared their mechanisms for fibronectin adsorption using molecular mechanics and molecular dynamics simulations. Results showed that the interplay between the hydrophobic residues concentrated at the N-terminal end of the protein, the surface roughness, and the hydrophilicity of the polymer surface determine the overall protein adsorption affinity. Incorporating explicit water molecules in the simulations results in higher affinity for fibronectin adsorption to more hydrophobic surface of CO-HDI surfaces, emphasizing the role that water molecules play during adsorption. We also observed that the strain energies that are indicative of flexibility and consequently entropy are significantly affected by the changes in the patterns of ß-sheet formation/breaking. Our study lends supports to the view that while castor oil controls the degree of swelling, it increases the adsorption of fibronectin to a limited extent due to the interplay between its hydrophobicity and its surface roughness, which needs to be taken into account during the design of polyurethane-based biomaterials.