Short Side Chains Research Articles

Dapsone is not a Pharmacodynamic Lead Compound for its Aryl Derivatives.

The relatedness between the linear equations of thermodynamics and QSAR was studied thanks to the recently elucidated crystal structure complexes between sulfonamide pterin conjugates and dihydropteroate synthase (DHPS) together with a published set of thirty- six synthetic dapsone derivatives with their reported entropy-driven activity data. Only a few congeners were slightly better than dapsone. Our study aimed at demonstrating the applicability of thermodynamic QSAR and to shed light on the mechanistic aspects of sulfone binding to DHPS. To this end ligand docking to DHPS, quantum mechanical properties, 2D- and 3D-QSAR as well as Principle Component Analysis (PCA) were carried out. The short aryl substituents of the docked pterin-sulfa conjugates were outward oriented into the solvent space without interacting with target residues which explains why binding enthalpy (ΔH) did not correlate with potency. PCA revealed how chemically informative descriptors are evenly loaded on the first three PCs (interpreted as ΔG, ΔH and ΔS), while chemically cryptic ones reflected higher dimensional (complex) loadings. It is safe to utter that synthesis efforts to introduce short side chains for aryl derivatization of the dapsone scaffold have failed in the past. On theoretical grounds we provide computed evidence why dapsone is not a pharmacodynamic lead for drug profiling because enthalpic terms do not change significantly at the moment of ligand binding to target.

Radiation resistance evaluation of HCP with superplasticizers using DSC

Today, when constructing new nuclear power plants, they most often start from the data of studies conducted more than 50 years ago. At the same time, the modern achievements of construction science, such as high-tech concrete compositions using highly effective admixtures, are applied either without preliminary studies with irradiation, or are not applied at all. In this paper, we consider the mechanism of radiation-thermal changes in concrete under the influence of neutron irradiation, as the most dangerous factor in the external impact on the design of modern nuclear power plants. The methodology for assessing the radiation resistance of concrete developed by domestic specialists, as well as the possibility of using the differential scanning calorimetry method as part of a comprehensive assessment of the effect of modern admixtures (using the example of superplasticizers) on the radiation resistance of concrete, is considered. It was proved that when analyzing the effect of admixtures on the radiation resistance of concrete, it is sufficient to conduct studies on the HCP rather than using concrete. To analytically establish the effect of superplasticizers on the radiation resistance of HCP, polycarboxylate superplasticizers of well-known brands with short side chains and insignificant steric effect, as well as long side chains and high steric effect. The general behaviour of HCP with superplasticizers was observed using DSC.

The effect of hydrophobic alkyl sidechains on size and solution behaviors of nanodiscs formed by alternating styrene maleamic copolymer

The development of amphipathic polymers, including various formulations of styrene-maleic acid (SMA) copolymers, has allowed the purification of increasing sizes and complexities of biological membrane protein assemblies in native nanodiscs. However, the factors determining the sizes and shapes of the resulting bio-nano particles remain unclear. Here, we show how grafting on short alkyl amine sidechains onto the polar residues leads to a broad set of nanoparticle sizes with improved solution behavior. The solubilization of lipid vesicles occurs over a wide range of pH levels and calcium concentrations, providing utility across the physiologically relevant range of solution conditions.Furthermore, the active SMA derivatives can contain strictly alternating monomers, which have inherently lower sequence polydispersity. Pronounced differences in the shapes of native nanoparticles were formed from Escherichia coli bacterial outer membrane containing PagP protein using methyl, ethyl and propylamine derivatives of styrene-maleic anhydride. In particular, the methylamine-substituted polymer forms smaller, monodispersed nanodiscs, while the longer alkyl derivatives form worm-like nanostructures. Thus the introduction of hydrophobicity onto the polar sidechains of amphipathic polymers has profound effects on morphology of native nanodisc, with shorter methyl moieties offering more uniformity and utility for structural biology studies.

Antiproliferative activity of side-chain truncated vitamin D analogs (PRI-1203 and PRI-1204) against human malignant melanoma cell lines

Vitamin D compounds are versatile molecules widely considered as promising agents in cancer prevention and treatment, including melanoma. Previously we investigated series of double point modified vitamin D2 analogs as well as non-calcemic 20S-hydroxyvitamin D3 and 21-hydroxypregnacalciferol as to their anti-melanoma activity. Surprisingly, short side-chain vitamin D analogs were found to be biologically active compounds. Thus, here we tested novel derivatives of pregnacalciferol with an additional hydroxyl at the end of the truncated side chain, PRI-1203 and PRI-1204, as to their potency against human melanoma A375 and RPMI7951 cell lines. Tested compounds are geometric isomers, with 19-methylene positioned in PRI-1203 like in a calcitriol molecule, but reversed in the PRI-1204 analog to the (5E,7E) geometry (5,6-trans). We noticed a decrease in cells viability exerted by PRI-1203. The antiproliferative effect of PRI-1204 was very low, emphasizing the importance of the natural 19-methylene geometry in the PRI-1203. PRI-1203 was also effective in inhibition of A375 melanoma cells migration. PRI-1203, but not PRI-1204, increased the percentage of A375 and RPMI7951 melanoma cells in the G0/G1 phase of cell cycle, possibly in a p21 and p27 independent manner. Both, analogs have very low effect on the level of CYP24A1 mRNA, in comparison to active form of vitamin D – 1.25(OH)2D3. In addition, both tested compounds failed to elicit VDR translocation to the nucleus. Thus, it could be postulated that side chain shortening strongly affects binding of analogs to VDR and activation of genomic responses, however do not impair their antiproliferative activities.

Effect of Functional Superplasticizers on Concrete Strength and Pore Structure

The current work investigates the fluidity and the loss of the flow rate of cement paste and mortar over time, as well as the pore structure and compressive strength of concrete and mortar in the presence of functional polycarboxylic acid high-performance water-reducing agents. The hydration rate, hydration products, and pore structure of the concrete containing different functional polycarboxylic acid superplasticizers were analyzed by means of mercury intrusion test, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results show that water-reducing agent Z significantly improves the pore structure of concrete and further compacts the structure of concrete and mortar, thereby improving the compressive strength of concrete. Moreover, the shorter side chains and ester functional groups in the structure of water-reducing agent H can slow down cement hydration rate, which lowers the early strength of mortar; nevertheless, at later stages, the pore structure of the concrete and mortar including superplasticizer H is less different from that of the concrete and mortar containing polycarboxylic acid water-reducing agents. Water-reducing agent J performs best but has a weaker effect on the pore structure of concrete and mortar compared to superplasticizer Z; it is also better than naphthalene-based water-reducing agents.

Linear Viscoelastic Response of Unentangled Polystyrene Bottlebrushes

We investigated the linear viscoelasticity of bottlebrush polystyrenes (PSs) with total molar masses ranging from 132 to 769 kg/mol, bearing short side chains (with molar masses of 5 and 7 kg/mol, ...

Structure and properties of soft rice starch

Pasting and rheological properties of starch from soft rice and two traditional rice varieties were analyzed. Soft rice starch was found to have a low pasting temperature of 67.2 °C, with a high system viscosity, including peak and trough viscosity. The storage modulus and loss modulus of soft rice starch were high and showed good viscoelasticity. The amylose content of soft rice starch was found to be 11.3%, classifying it was low amylose content type. Compared with japonica rice starch, soft rice starch had lower solubility but higher swelling power, gel consistency, and water binding capacity. The medium particle size and volume mean particle size of soft rice starch were the highest. The average molecular weight of soft rice starch was 5.4 × 107. The molecular density and proportion of short amylopectin side chains, with a range of 6–12, were the highest among all varieties tested. These findings provide a theoretical basis for the processing of soft rice starch and breeding of high-quality rice.

A scaled-up proton exchange membrane fuel cell with enhanced performance and durability

A proton exchange membrane fuel cell with enhanced performance and durability has been developed by using graphene for the microporous layer on the cathode side, and short-side-chain ionomer in the catalyst layers and electrolyte membrane layer. The cell components are analyzed for their detailed morphological, microstructural, physical, and electrochemical characteristics, and the performance and durability are investigated following the established protocol of accelerated stress tests for a scaled-up cell with an active area of 45 cm2 at 75 °C and 35 kPag, and a range of reactant flow rate and relative humidity conditions. The results indicate that the graphene flakes are arranged in the in-plane direction of the cell, and coupled with the improved proton conductivity and water retention of the short-side chain ionomer and membrane, the cell exhibits excellent performance and durability, and is highly tolerant to the variations in the operating conditions. Before and after 30,000 cycles of the accelerated stress tests, the maximum power densities are around 1.13 W/cm2 and 0.75 W/cm2 for the high-flow fully humidified reactants, and about 0.77 W/cm2 and 0.50 W/cm2 for the low-flow and low-humidity conditions, respectively. The excellent performance and durability at low relative humidity operation are significantly important for practical applications.

Galactose-derived poly(amide-triazole)s. Degradation, deprotection and derivatization studies

A family of stereoregular poly(amide-triazole)s derived from D-galactose was obtained following several principles of Green Chemistry, namely bio-based starting materials, high yields, benign reaction conditions, energy efficiency, catalysis, atom economy, and chemical degradation. The monomer precursors, the α-azido-ω-N-alkynylamide derivatives, were prepared from D-galactose, which was oxidized to D-galactono-1,4-lactone and the secondary hydroxyl groups were protected as isopropylidene acetals. The AB-type azide-alkyne click polymerization led to poly(amide-triazole)s. The Cu(I)-catalyzed polymerization led regioselectively to 1,4-disubstituted triazole ring, and hence to a stereoregular polymer. In contrast, the thermal polymerization produced also 1,5-disubstituted triazole units. The stereoregular polymer underwent acid-promoted chemical degradation, and the degradation products were identified. Moreover, selective removal of theacid labile acetonide moieties led to a partially protected poly(amide-triazole). This polymer was further modified using the “grafting from” approach. Thus, the ROP of caprolactone initiated from the free hydroxyl groups of the polymer led to a linear poly(amide-triazole) grafted with short biodegradable polycaprolactone side-chains. On the other hand, complete HO-deprotection of the monomer gave, after click polymerization, the fully unprotected polymer. The protected poly(amide-triazole)s showed a higher thermal stability compared to the hydroxylated derivatives, which could undergo dehydration processes at lower temperatures. Similarly, the partially protected polymer gave a lower Tg value, in agreement with an increasing degree of structural disorder (non-stereoregular materials) and/or lower molecular weight.

Fast, Light-Responsive, Metal-Like Polymer Actuators Generating High Stresses at Low Strain

Summary Producing lightweight polymeric actuators able to generate high stresses typical of hard metals and/or ceramics remains challenging. The photo-mechanical responses of ultra-drawn ultra-high molecular weight polyethylene (UHMWPE) actuators containing azobenzene photo-switches with symmetrically attached polyethylene (PE) side chains are reported. Long PE side chains promote dispersion within the apolar UHMWPE matrix, and the ultra-drawn films are highly aligned. The ultra-drawn azobenzene-doped UHMWPE films have high Young's moduli (∼100 GPa) and are viscoelastic at room temperature at strains below 1%. The photo-mechanical response of the films is fast ( 6 × 104 Pa (kg m−3)−1) to UV or visible light at a low strain (∼0.06%). The actuator responds to rotating linearly polarized light, causing a photo-induced stress wave response. Such rapid, high-stress, low-strain, photo-mechanical responses are unique in soft polymer systems with physical values approaching hard metals/ceramics.

Chemical structure changes of lacustrine Type-II kerogen under semi-open pyrolysis as investigated by solid-state 13C NMR and FT-IR spectroscopy

At present, there is a lack of research on the structural changes of lacustrine Type-II kerogen, which is regionally distributed but has significant potential for hydrocarbon resources. In our previous work, a series of non-hydrous, temperature-based semi-open pyrolysis experiments have been performed on the Chang 7 oil shale to simulate the thermal maturation (from 0.53 %Ro to 1.68 %Ro) of lacustrine Type-II kerogen. In that work, the parallel reaction pathway for kerogen decomposition was supported. The aim of this work is to reveal the structural changes of the post-pyrolysis kerogen. Integrated analysis including elemental analysis, programmed pyrolysis (Rock-Eval), Fourier transform infrared (FT-IR) spectroscopy, and solid-state 13 C nuclear magnetic resonance ( 13 C NMR) spectroscopy were conducted on the native unheated and post-pyrolysis rocks and kerogens. Based on the compositional features of the hydrocarbon products, structural changes of the post-pyrolysis kerogen were investigated, and insights on the initial chemical structure of the kerogen were also obtained. Before the peak hydrocarbon-generating stage ( R o < 0.6%), defunctionalization of oxygen-containing functional groups, which leads to the generation of water, CO 2 and NSOs, occurs simultaneously with the detachment of short aliphatic side chains and small aromatic rings, which leads to the generation of volatile fractions (C 6 –C 14 , C 15+ sat and C 15+ aro). This process suggests that the Chang7 kerogen is highly branched. During the peak hydrocarbon-generating stage (0.6–1.09 % R o ), the concurrent breakage of weak cross-link bonds and long aliphatic chains lead to the simultaneous peak generation of liquid hydrocarbons and NSOs. This reflects the highly cross-linked features of the Chang7 kerogen. After the peak hydrocarbon-generating stage ( R o > 1.09%), the reactions in the previous two stages produce a highly aromatic kerogen. The increased aromaticity of the highly matured kerogen is most likely to be caused by aromatization or dehydrogenation of hydroaromatics and coking of aromatic bitumen, not by fusing or condensation of aromatic rings. • Chemical structural evolution of Chang7 lacustrine Type-II kerogen was characterized for the first time. • Kerogen reached artificial maturation under non-hydrous, temperature-based semi-open pyrolysis experiments. • Parallel bond breaking mechanism of unusual lacustrine Type-II kerogen was supported from chemical structure changes.

Biological Activities and Molecular Docking of Brassinosteroids 24-Norcholane Type Analogs.

The quest and design of new brassinosteroids analogs is a matter of current interest. Herein, the effect of short alkyl side chains and the configuration at C22 on the growth-promoting activity of a series of new brassinosteroid 24-norcholan-type analogs have been evaluated by the rice leaf inclination test using brassinolide as positive control. The highest activities were found for triol 3 with a C22(S) configuration and monobenzoylated derivatives. A docking study of these compounds into the active site of the Brassinosteroid Insensitive 1(BRI1)–ligand–BRI1-Associated Receptor Kinase 1 (BAK1) complex was performed using AutoDock Vina, and protein–ligand contacts were analyzed using LigPlot+. The results suggest that the hydrophobic interactions of ligands with the receptor BRI1LRR and hydrogen bonding with BAK1 in the complex are important for ligand recognition. For monobenzoylated derivatives, the absence of the hydrophobic end in the alkyl chain seems to be compensated by the benzoyl group. Thus, it would be interesting to determine if this result depends on the nature of the substituent group. Finally, mixtures of S/R triols 3/4 exhibit activities that are comparable or even better than those found for brassinolide. Thus, these compounds are potential candidates for application in agriculture to improve the growth and yield of plants against various types of biotic and abiotic stress.

Dispersion performances and adsorption behavior of novel block polycarboxylate with hybrid side chains in coal-water slurry

A serial of novel block polycarboxylate dispersants (PCDs) with hybrid side chains employing long-short composite side chains for making coal-water slurry (CWS) were synthesized and applied to a low rank coal in the north of China to make slurry. The relationship of the fine structure of side chains and properties of the CWS were investigated. The results show that the apparent viscosity, zeta potential and stability of the CWS are impacted by the molar ratio of short side chain to long side chain of the PCD. Meanwhile, the viscosity reduction, stability property and zeta potentials of the CWSs are increased in accord with the order of adsorption amount of PCD on coal. These facts confirm that the PCD with a molar ratio of the short side chain to long side chain of just over unity more easily forms a larger adsorption amount on the coal surface and has optimal dispersion and stability characteristics. It is helpful to regulate the adsorption behavior of polycarboxylate dispersant to improve its dispersion property. It provides a good pathway to design and prepare a highly effective dispersant for low rank coal.

Effect of side chain length change of polycarboxylate-ether based high range water reducing admixture on properties of self-compacting concrete

In this study, the effect of side chain length, molecular weights changes and adsorption amount of polycarboxylate ether-based high range water reducing admixtures having constant main chain length, free non-ionic amount and anionic/non-ionic ratio on fresh properties, early and advanced age compressive strength, water absorption capacity and ultrasonic pulse velocity value of self-compacting concretes (SCC) were investigated. FTIR (Fourier transform infrared) and GPC (Gel Permeation Chromatography) analyzes were carried out to characterize admixtures. According to the test results, all SCC mixtures produced within the scope of the study provided EFNARC criteria. If the admixture side chain length is higher or shorter than a certain value, the admixture requirement is increased for providing the desired target slump-flow value in SCC mixtures. This negative effect is thought to be due to the weakness of the steric hindrance effect for admixture with short side chain, the low adsorption amount and interlacing risk of side chains for admixture with the long side chain. On the other hand, the increase in the side chain length of the admixtures had a positive effect on the time-dependent fresh state performance of the mixtures. This positive effect is thought to be due to the low adsorption amount of the admixture, the increase in the side chain length and the increase of the non-adsorbed free polymer content in the mixture. While side chain length change of the water reducing admixture affected the 1 and 2-day compressive strength values of SCC mixtures, the 3, 7 and 28-day compressive strengths and the 28-day water absorption, ultrasound and dynamic elasticity modulus values did not significantly affect.

Deconstructing poloxamer and poloxamine block copolymers to access poly(ethylene glycol) and poly(propylene oxide)-based thermoresponsive polymers

Poloxamer (Pluronic®) and poloxamine (Tetronic®) are commercially important block copolymers composed of polypropylene oxide (PPO) and polyethylene glycol (PEG) segments. Due to the difference in chemical polarity of the two blocks, the copolymers exhibit amphiphilicity and thermally induced aggregation behavior in aqueous solutions. The present work shows that block copolymer architecture is not necessary to achieve an amphiphilic character in PPO and PEG-based polymers. Instead a simple molecular tweaking by adding a very short hydrophilic or hydrophobic side-chain allows for attaining amphiphilicity and consequential thermoresponsiveness in PEG and PPO-rich polymers.

An amendment to the fine structure of galactoxyloglucan from Tamarind (Tamarindus indica L.) seed

A polysaccharide from tamarind seeds (TSP) was characterized in terms of backbone and side chain structural features, as well as conformational property using methylation and GC–MS analysis, 2D NMR, MALDI-TOF MS, and high performance size exclusion chromatography (HPSEC). Results showed that TSP was a galactoxyloglucan (GXG) consisting of glucose, xylose, and galactose in a molar ratio of 3.1: 1.7: 1.0. The Mw was determined to be 524.0 kDa with radius of gyration (Rg) of 55.6 nm. The chemical structure was confirmed as a classical β-(1 → 4)-glucan with short side chains of T-β-Galp-(1 → 2)-α-Xylp-(1 → and T-α-Xylp-(1 → attached to O-6 position of glucose. MALDI-TOF MS analysis indicated that TSP mainly composed of nonasaccharide (XLLG) and octasaccharide (XLXG or XXLG) blocks in periodic or interrupted sequence in a ratio of 3: 2, occasionally interrupted by heptasaccharide (XXXG), hexasaccharide (XLG or XXGG), or even hendesaccharide blocks. Conformational study indicated that TSP was in a random-coil shape with relative extended stiff chain in aqueous solution. This study provided more evidences to make an amendment to the fine structure of tamarind GXG.

Micellization, surface activities and thermodynamics study of dialkylpyridinium [C16pymCn][Br] (n = 1–4) in aqueous solutions

The pyridinium-base ionic liquids surfactants: N-hexadecyl-3-alkylpyridinium bromide [C16pymCn][Br] (n: the carbon numbers of short alkyl side chain, n = 1, 2, 3, 4) were synthesized and characterized by NMR(1H, 13C) and FTIR. The thermal properties of the [C16pymCn][Br] showed a same transition from a crystalline phase to a thermotropic liquid-crystalline phase and then to an isotropic liquid phase, and were thermally stable in the desired temperature range. The critical micelle concentration (CMC) values and surface tension of [C16pymCn][Br] gradually decreases with the increasing length of the side chain from 1 to 4. The temperature dependence of CMC shows typical U-shaped. The surface chemical parameters of all the synthesized surfactants showed moderate surface activity. The calculated thermodynamic parameters showed that the micellization processes of [C16pymCn][Br] are spontaneous, endothermic at low temperatures and exothermic at high temperatures. For the micellization process of [C16pymCn][Br] (n = 1–3) were entropy-driven in the investigated temperature range. The micellization process of [C16pymC4][Br] changes from entropy-driven to enthalpy-driven at high temperature. The standard heat capacity were further discussed. It can be concluded that propyl- and butyl-chain of meta-position can be folded and thus at least partially removed from contact with water.

Photochemical fluoro-amino etherification reactions of aryldiazoacetates with NFSI under stoichiometric conditions.

Herein, we report on a photochemical three-component reaction of aryldiazoacetates with NFSI and cyclic ethers. This method allows the introduction of both fluorine and a short ether sidechain using 1,4-dioxane as solvent in high yields via an ylide pathway as demonstrated by DFT calculations (26 examples, up to 99% yield).

Perfluorinated Proton-Conducting Membrane Composites with Functionalized Nanodiamonds

Composite proton-conducting membranes based on perfluorinated short side chain polymers modified with nanodiamonds having a hydrophilic surface owing to grafted carboxyl groups have been produced. Membrane films are prepared by precipitating the polymer from a dimethylformamide solution with introduced nanodiamonds. The proposed method for synthesizing the composites provides a high mechanical strength and an increase in the proton conductivity of the material with an increase in temperature in a 20–50°С range at rather low diamond concentrations (0.25–1 wt %). These features are important for using the composites in fuel cells at high temperatures.

Synthesis and Structural Determination of New Brassinosteroid 24-Nor-5α-Cholane Type Analogs.

Natural brassinosteroids possess a 22R, 23R configuration that appears essential for biological activity. It is, therefore, interesting to elucidate if the activity of brassinosteroids with a short side chain depends on the C22 configuration. Herein, we describe the synthesis of new brassinosteroids analogs with 24-norcholane type of side chain and R configuration at C22. The initial reaction is the dihydroxylation of a terminal olefin that leads to S/R epimers. Three different methods were tested in order to evaluate the obtained S/R ratio and the reaction yields. The results indicate that Upjohn dihydroxylation is the most selective reaction giving a 1.0:0.24 S/R ratio, whereas a Sharpless reaction leads to a mixture of 1.0:0.90 S/R with 95% yield. Using the latter mixture and following a previous reported method, benzoylated derivatives and both S and R brassinosteroids analogs were synthesized. All synthesized compounds were completely characterized by NMR spectroscopy, and HRMS of new compounds are also given. In conclusion, a synthetic route for preparation of new analogs of brassinosteroids of 24-norcholane type and R configuration at C22 were described. It is expected that this will help to elucidate if a configuration at C22 is a structural requirement for hormonal growth activity in plants.