Interaction of aromatic isocyanates with n-acetyl-lcysteine under physiological conditions

Isocyanates are of toxicological relevance since they are considered to cause occupational asthma. The majority of polyurethanes is based on aromatic diisocyanates (e.g., TDI and MDI), they are used for foams, elastomers, adhesives and coatings. Therefore we studied reactions of p-tolylisocyanate (pTI), 2,4-toluene diisocyanate (TDI) and 4,4- methylenediphenyl diisocyanate (MDI) with N-acetyl-L-cysteine (AcCys) with different molar ratios in aqueous buffer solutions of pH 5.0 - 7.4. Type and amounts of products formed in these reactions were identified and quantified. Conjugates of AcCys and the aromatic isocyanates have been synthesized and characterized as reference materials. Conjugates and ureas were found to be the main products. The ratio of these two compounds varied with the ratio of AcCys to isocyanate. Approximately 90 % of pTI conjugate were found for the 10 : 1 ratio, approximately 40 % conjugate for the 10 : 5 and around 15 % for the 10 : 15 ratio. For TDI yields of conjugate were comparable. Ureas, apart from minor amounts of TDA-urea could not be determined quantitatively due to formation of oligomeric ureas with different end groups. Minor amounts of MDI-conjugates were found apart from high amounts of insoluble material, which proved to be unreacted MDI encapsulated by oligomeric ureas. The reaction of the -SH group with the isocyanate moiety is independent of the pH of the solution in the range studied. No diamine, i.e. 2,4-TDA or 4,4-MDA, could be detected in reactions of the diisocyanates 2,4-TDI or 4,4-MDI. Small amounts of p-toluidine (pTA) were found in the reaction of the mono isocyanate pTI when it was in excess with respect to AcCys. Reactions of the isocyanates with an aqueous buffer solution of pH 6.5 in the absence of AcCys gave ureas as main products, while significant amounts of unreacted diisocyanates remained encapsulated in the mixture. No 2,4-TDA or 4,4-MDA was detected under these conditions. Again small amounts of pTA were formed from the reaction of pTI with water

Reactions of N-acetylcysteine adducts of aromatic (di)isocyanates with functional groups of organic molecules

Glutathione thiocarbamate conjugates of isocyanates play a key role in transport and final reactions of isocyanates in the human body by transcarbamoylation. N-acetylcysteine is the simplest model for thiocarbamate reactions. Therefore, transcarbamoylation of Nacetylcysteine adducts of p-tolylisocyanate (pTI-AcCys) and 4,4’-diisocyanatodiphenyl- methane (MDI(AcCys)2) with N-acetylcysteine methyl ester (thiolysis), morpholine (aminolysis), methoxyethanol (alcoholysis), and water (hydrolysis) has been studied in aqueous phosphate buffer solution and in dimethylacetamide (DMAc). Expected reaction products have been synthesised as reference compounds for HPLC-analysis. Concentrations of adducts and of reaction products were monitored by HPLC. Reaction rates and activation energies were determined for pTI in both media, reactions of MDI(AcCys)2 were run at one temperature only. Formation of insoluble reaction products and side reactions due to hydrolysis prevented in depth kinetic analysis of the reactions. Two regimes of reaction rate were observed in aqueous buffer, clear second order kinetics resulted in DMAc. In aqueous buffer (pH 7.4) a reactivity thiolysis > aminolysis > hydrolysis was found, while in DMAc aminolysis was faster than thiolysis. This can be explained by formation of thiolate at pH 7.4, which is not possible in anhydrous DMAc. Reactions of (MDI(AcCys)2) are by a factor of 2 to 4 faster than those of pTI-AcCys. p-Toluidine (pTA) was found in the aqueous system due to hydrolysis, while no 4,4’-methylene dianiline (MDA) could be detected. Under physiological conditions hydrolysis should compete with thiolysis under homogeneous conditions while ureas and carbamates should be much more stable against hydrolysis. No free isocyanate groups could be detected in any of the reactions. In conclusion the isocyanate moiety in thiocarbamates is readily transferred to sulfhydryl- and amino groups but not to aliphatic hydroxy groups. Under physiological conditions hydrolysis competes with these transcarbamoylation reactions. Formation of free isocyanate groups in analytical quantities was shown to be highly unlikely

Terminology of polymers and polymerization processes in dispersed systems (IUPAC Recommendations 2011)

A large group of industrially important polymerization processes is carried out in dispersed systems. These processes differ with respect to their physical nature, mechanism of particle formation, particle morphology, size, charge, types of interparticle interactions, and many other aspects. Polymer dispersions, and polymers derived from polymerization in dispersed systems, are used in diverse areas such as paints, adhesives, microelectronics, medicine, cosmetics, biotechnology, and others. Frequently, the same names are used for different processes and products or different names are used for the same processes and products. The document contains a list of recommended terms and definitions necessary for the unambiguous description of processes, products, parameters, and characteristic features relevant to polymers in dispersed systems

Source-based nomenclature for single-strand homopolymers and copolymers (IUPAC Recommendations 2016)

IUPAC recommendations on source-based nomenclature for single-strand polymers have so far addressed its application mainly to copolymers, non-linear polymers and polymer assemblies, and within generic source-based nomenclature of polymers. In this document, rules are formulated for devising a satisfactory source-based name for a polymer, whether homopolymer or copolymer, which are as clear and rigorous as possible. Thus, the source-based system for naming polymers is presented in a totality that serves as a user-friendly alternative to the structure-based system of polymer nomenclature. In addition, because of their widespread and established use, recommendations for the use of traditional names of polymers are also elaborated

Decomposing multifractal crossovers

Physiological processes-such as, the brain's resting-state electrical activity or hemodynamic fluctuations-exhibit scale-free temporal structuring. However, impacts common in biological systems such as, noise, multiple signal generators, or filtering by transport function, result in multimodal scaling that cannot be reliably assessed by standard analytical tools that assume unimodal scaling. Here, we present two methods to identify breakpoints or crossovers in multimodal multifractal scaling functions. These methods incorporate the robust iterative fitting approach of the focus-based multifractal formalism (FMF). The first approach (moment-wise scaling range adaptivity) allows for a breakpoint-based adaptive treatment that analyzes segregated scale-invariant ranges. The second method (scaling function decomposition method, SFD) is a crossover-based design aimed at decomposing signal constituents from multimodal scaling functions resulting from signal addition or co-sampling, such as, contamination by uncorrelated fractals. We demonstrated that these methods could handle multimodal, mono- or multifractal, and exact or empirical signals alike. Their precision was numerically characterized on ideal signals, and a robust performance was demonstrated on exemplary empirical signals capturing resting-state brain dynamics by near infrared spectroscopy (NIRS), electroencephalography (EEG), and blood oxygen level-dependent functional magnetic resonance imaging (fMRI-BOLD). The NIRS and fMRI-BOLD low-frequency fluctuations were dominated by a multifractal component over an underlying biologically relevant random noise, thus forming a bimodal signal. The crossover between the EEG signal components was found at the boundary between the δ and θ bands, suggesting an independent generator for the multifractal d rhythm. The robust implementation of the SFD method should be regarded as essential in the seamless processing of large volumes of bimodal fMRI-BOLD imaging data for the topology of multifractal metrics free of the masking effect of the underlying random noise. © 2017 Nagy, Mukli, Herman and Eke