Solvent effect modelling of isocyanuric products synthesis by chemometric methods

Chemometric tools were used to generate the modelling of solvent e inverted exclamation markects on the N-alkylation of an isocyanuric acid salt. The method proceeded from a central composite design applied on the Carlson solvent classification using principal components analysis. The selectivity of the reaction was studied from the production of different substituted isocyanuric derivatives. Response graphs were obtained for each compound and used to devise a strategy for solvent selection. The prediction models were validated and used to search for the best selectivity for the reaction system. The solvent most often selected as the best for the reaction is the N,N-dimethylformamide.     

Oxidative catabolism of α-tocopherol in rat liver microsomes

The goal of this study was to clarify the mechanism responsible for the catabolism of α-tocopherol. The vitamin, bound to albumin, was incubated with rat liver microsomes and appeared to be broken down. Optimal production of the metabolite was obtained when 1 mg of microsomal protein was incubated with 36 μM of α-tocopherol in the presence of 1.5 mM of NADPH. Chromatographic and mass spectrometric analyses of the metabolite led to the conclusion that it consists of an ω-acid with an opened chroman ring, although we could not perform nuclear magnetic resonance analysis to confirm this. Our data show that α-tocopherol is ω-oxidized to a carboxylic acid and that this process can occur in rat liver microsomes in the presence of NADPH and O₂. The oxidation to the quinone structure appears to be a subsequent event that may be artifactual and/or catalyzed by a microsomal enzyme(s).     

Biodegradability Study of the Biosurfactant Contained in a Crude Extract from Corn Steep Water

Over the last few years, the global biosurfactant market has raised due to the increasing awareness among consumers, for the use of biological or bio-based products. Because of their composition, it can be speculated that these are more biocompatible and more biodegradable than their chemical homologous. However, at the moment, no studies exist in the literature about the biodegradability of biosurfactants. In this work, a biosurfactant contained in a crude extract, obtained from a corn wet-milling industry stream that ferments spontaneously in the presence of lactic acid bacteria, was subjected to a biodegradation study, without addition of external microbial biomass, under different conditions of temperature (5–45 °C), biodegradation time (15–55 days), and pH (5–7). For that, a Box–Behnken factorial design was applied, which allowed to predict the percentage of biodegradation for the biosurfactant contained in the crude extract, between the range of the independent variables selected in the study, obtaining biodegradation values between 3 and 80%. The percentage of biodegradation for the biosurfactant was calculated based on the increase in the surface tension of samples of the crude extract. Furthermore, it was also possible to predict the variation in t_1/2 for the biosurfactant (time to achieve the 50% of biodegradation) under different conditions.     

Synthesis of new polyester polyols from epoxidized vegetable oils and biobased acids

Biobased polyols were synthesized from reaction between epoxidized soybean oil and lactic, glycolic, or acetic acids. Polyols were characterized by NMR, alcohol and acid titration, and SEC. These analyses allowed to determine an average hydroxyl functionality between 4 and 5, with an oligomer content close to 50 wt%. Synthesized polyols were formulated with isocyanate to yield polyurethanes (PUs). Thermal and mechanical properties of obtained materials showed that synthesized polyols lead to rigid and brittle material with Young moduli higher than 900 N/mm² at RT and with T_g values around 50°C. Practical application: The products of the chemistry described in this contribution, i.e.: polyol from vegetable oils and lactic, glycolic, or acetic acids, provide biobased building blocks for further PUs syntheses by reaction with diisocyanates. The obtained PUs are partially biobased and may be applied as binders and coatings.     

A Simple Bioconjugate Attachment Protocol for Use in Single Molecule Force Spectroscopy Experiments Based on Mixed Self-Assembled Monolayers

Single molecule force spectroscopy is a technique that can be used to probe the interaction force between individual biomolecular species. We focus our attention on the tip and sample coupling chemistry, which is crucial to these experiments. We utilised a novel approach of mixed self-assembled monolayers of alkanethiols in conjunction with a heterobifunctional crosslinker. The effectiveness of the protocol is demonstrated by probing the biotin-avidin interaction. We measured unbinding forces comparable to previously reported values measured at similar loading rates. Specificity tests also demonstrated a significant decrease in recognition after blocking with free avidin.     

Influence of various process conditions on surface finishes induced by the direct metal deposition laser technique on a Ti–6Al–4V alloy

The direct metal deposition (DMD) with laser is a free-form metal deposition process for manufacturing dense pieces, which allows generating a prototype or small series of near net-shape structures. One of the most critical issues is that produced pieces have a deleterious surface finish which systematically requires post machining steps. This problem has never been fully addressed before.The present work describes investigations on the DMD process, using an Yb-YAG disk laser, and a widely used titanium alloy (Ti–6Al–4V) to understand the influence of the main process parameters on the surface finish quality. The focus of our work was: (1) to understand the physical mechanisms responsible for deleterious surface finishes, (2) to propose different experimental solutions for improving surface finish.In order to understand the physical mechanisms responsible for deleterious surface finishes, we have carried out: (1) a precise characterization of the laser beam and the powder stream; (2) a large number of multi-layered walls using different process parameters (P(W), V(m/min), D_m (g/min), Gaussian or uniform beam distribution); (3) a real time fast camera analysis of melt pool dynamics and melt-pool – powder stream coupling; (4) a characterization of wall morphologies versus process parameters using 2D and 3D profilometry.The results confirm that surface degradation depends on two distinct aspects: the sticking of non-melted or partially melted particles on the free surfaces, and the formation of menisci with more or less pronounced curvature radii. Among other aspects, a reduction of layer thickness and an increase of melt-pool volumes to favor re-melting processes are shown to have a beneficial effect on roughness parameters. Last, a simple analytical model was proposed to correlate melt-pool geometries to resulting surface finishes.     

Rheological properties of sMBR sludge under unsteady state conditions

The aim of this work is to investigate the rheological behaviour of MBR sludge for prolonged sludge retention time and during unsteady state conditions. The role of the total suspended solids and of the soluble organic matter is specifically studied through two running periods characterized by different organic loads and/or solid retention times. Diverse rheological parameters are examined. They are obtained from flow measurements carried out for an extent range of shear stress values.The obtained results show clearly that operating conditions capable of changing the total suspended solid (TSS) and soluble organic compound (COD) concentrations modify the rheological behaviour of the sludge.In comparison with the TSS concentration, the soluble organic compounds greatly affect the cohesion and the rigidity of the sludge three dimensional network. On the other hand, the COD concentration and the TSS content have equivalent quantitative influence on the rheological parameters characterizing the flow of the sludge.The results obtained are of great importance because operating conditions leading to the modification of the soluble microbial product concentration, and of the sludge rheological characteristics in the reactor, can strongly modify not only the mixing and aeration performances but also the membrane fouling of the MBR unit.     

Epoxidized natural rubber/dicarboxylic acid self-vulcanized blends

Curing behaviour as well as mechanical properties of binary blends of epoxidized natural rubber (ENR) and dodecanedioic acid (DA) were investigated for development of self-vulcanizable elastomer blends. Cross-linking reaction at 180 °C of reactive functional rubber containing 25 and 10 mol% epoxide groups was followed by rheology. The properties of the cured materials were studied by dynamic mechanical analysis, stress-strain experiments, and DSC measurements. It was shown that a specific ratio ENR/DA gave rise to optimum mechanical properties. This ratio decreases together with the epoxidation level of the rubber. DSC measurements revealed that the glass transition temperature of the cured material increases nonlinearly at high concentrations of cross-linking agent. By comparing cross-linking with DA and reaction with monofunctional lauric acid, this behaviour was attributed to polar interactions due to free carboxylic groups of pending diacid grafts.     

Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.     

TP53 Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation

Circulating cell-free DNA (cfDNA) is emerging as a potential tumor biomarker. CfDNA-based biomarkers may be applicable in tumors without an available non-invasive screening method among at-risk populations. Esophageal squamous cell carcinoma (ESCC) and residents of the Asian cancer belt are examples of those malignancies and populations. Previous epidemiological studies using cfDNA have pointed to the need for high volumes of good quality plasma (i.e., >1 mL plasma with 0 or 1 cycles of freeze-thaw) rather than archival serum, which is often the main available source of cfDNA in retrospective studies. Here, we have investigated the concordance of TP53 mutations in tumor tissue and cfDNA extracted from archival serum left-over from 42 cases and 39 matched controls (age, gender, residence) in a high-risk area of Northern Iran (Golestan). Deep sequencing of TP53 coding regions was complemented with a specialized variant caller (Needlestack). Overall, 23% to 31% of mutations were concordantly detected in tumor and serum cfDNA (based on two false discovery rate thresholds). Concordance was positively correlated with high cfDNA concentration, smoking history (p-value = 0.02) and mutations with a high potential of neoantigen formation (OR; 95%CI = 1.9 (1.11–3.29)), suggesting that tumor DNA release in the bloodstream might reflect the effects of immune and inflammatory context on tumor cell turnover. We identified TP53 mutations in five controls, one of whom was subsequently diagnosed with ESCC. Overall, the results showed that cfDNA mutations can be reliably identified by deep sequencing of archival serum, with a rate of success comparable to plasma. Nonetheless, 70% non-identifiable mutations among cancer patients and 12% mutation detection in controls are the main challenges in applying cfDNA to detect tumor-related variants when blindly targeting whole coding regions of the TP53 gene in ESCC.