Unique Self-Phosphorylating Polybenzimidazole of the 6F Family for HT-PEM Fuel Cell Application.

High-temperature polymer-electrolyte membrane fuel cells (HT-PEMFCs) are a very important type of fuel cells since they operate at 150-200 °C, making it possible to use hydrogen contaminated with CO. However, the need to improve the stability and other properties of gas-diffusion electrodes still impedes their distribution. Self-supporting anodes based on carbon nanofibers (CNF) are prepared using the electrospinning method from a polyacrylonitrile solution containing zirconium salt, followed by pyrolysis. After the deposition of Pt nanoparticles on the CNF surface, the composite anodes are obtained. A new self-phosphorylating polybenzimidazole of the 6F family is applied to the Pt/CNF surface to improve the triple-phase boundary, gas transport, and proton conductivity of the anode. This polymer coating ensures a continuous interface between the anode and proton-conducting membrane. The polymer is investigated using CO2 adsorption, TGA, DTA, FTIR, GPC, and gas permeability measurements. The anodes are studied using SEM, HAADF STEM, and CV. The operation of the membrane-electrode assembly in the H2/air HT-PEMFC shows that the application of the new PBI of the 6F family with good gas permeability as a coating for the CNF anodes results in an enhancement of HT-PEMFC performance, reaching 500 mW/cm2 at 1.3 A/cm2 (at 180 °C), compared with the previously studied PBI-O-PhT-P polymer.

Self-Phosphorylated Polybenzimidazole: An Environmentally Friendly and Economical Approach for Hydrogen/Air High-Temperature Polymer-Electrolyte Membrane Fuel Cells.

The development of phosphorylated polybenzimidazoles (PBI) for high-temperature polymer-electrolyte membrane (HT-PEM) fuel cells is a challenge and can lead to a significant increase in the efficiency and long-term operability of fuel cells of this type. In this work, high molecular weight film-forming pre-polymers based on N1,N5-bis(3-methoxyphenyl)-1,2,4,5-benzenetetramine and [1,1'-biphenyl]-4,4'-dicarbonyl dichloride were obtained by polyamidation at room temperature for the first time. During thermal cyclization at 330-370 °C, such polyamides form N-methoxyphenyl substituted polybenzimidazoles for use as a proton-conducting membrane after doping by phosphoric acid for H2/air HT-PEM fuel cells. During operation in a membrane electrode assembly at 160-180 °C, PBI self-phosphorylation occurs due to the substitution of methoxy-groups. As a result, proton conductivity increases sharply, reaching 100 mS/cm. At the same time, the current-voltage characteristics of the fuel cell significantly exceed the power indicators of the commercial BASF Celtec® P1000 MEA. The achieved peak power is 680 mW/cm2 at 180 °C. The developed approach to the creation of effective self-phosphorylating PBI membranes can significantly reduce their cost and ensure the environmental friendliness of their production.

Proton-Conducting Polymer-Coated Carbon Nanofiber Mats for Pt-Anodes of High-Temperature Polymer-Electrolyte Membrane Fuel Cell.

High-temperature polymer-electrolyte membrane fuel cells (HT-PEM FC) are a very important type of fuel cell since they operate at 150-200 °C, allowing the use of hydrogen contaminated with CO. However, the need to improve stability and other properties of gas diffusion electrodes still hinders their distribution. Anodes based on a mat (self-supporting entire non-woven nanofiber material) of carbon nanofibers (CNF) were prepared by the electrospinning method from a polyacrylonitrile solution followed by thermal stabilization and pyrolysis of the mat. To improve their proton conductivity, Zr salt was introduced into the electrospinning solution. As a result, after subsequent deposition of Pt-nanoparticles, Zr-containing composite anodes were obtained. To improve the proton conductivity of the nanofiber surface of the composite anode and reach HT-PEMFC better performance, dilute solutions of Nafion®, a polymer of intrinsic microporosity (PIM-1) and N-ethyl phosphonated polybenzimidazole (PBI-OPhT-P) were used to coat the CNF surface for the first time. These anodes were studied by electron microscopy and tested in membrane-electrode assembly for H2/air HT-PEMFC. The use of CNF anodes coated with PBI-OPhT-P has been shown to improve the HT-PEMFC performance.

Development of High-Performance Hydrogen-Air Fuel Cell with Flourine-Free Sulfonated Co-Polynaphthoyleneimide Membrane.

This paper presents research on the technological development of hydrogen-air fuel cells with high output power characteristics using fluorine-free co-polynaphtoyleneimide (co-PNIS) membranes. It is found that the optimal operating temperature of a fuel cell based on a co-PNIS membrane with the hydrophilic/hydrophobic blocks = 70/30 composition is in the range of 60-65 °C. The maximum output power of a membrane-electrode assembly (MEA), created according to the developed technology, is 535 mW/cm2, and the working power (at the cell voltage of 0.6 V) is 415 mW/cm2. A comparison with similar characteristics of MEAs based on a commercial Nafion 212 membrane shows that the values of operating performance are almost the same, and the maximum MEA output power of a fluorine-free membrane is only ~20% lower. It was concluded that the developed technology allows one to create competitive fuel cells based on a fluorine-free, cost-effective co-polynaphthoyleneimide membrane.

Synthesis and evaluation of avermectin-imidazo[1,2-a]pyridine hybrids as potent GABAA receptor modulators.

The γ-aminobutyric acid type A (GABAA) receptors are pentameric transmembrane protein complexes. They have attracted extensive attention from the scientific community due to their significant pharmacological potential. Here we report the first synthesis of avermectin-imidazo[1,2-a]pyridine hybrids promising as GABAA receptor positive allosteric modulators (PAMs). An efficient multi-step protocol was elaborated for the installation of the 6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridine pendant to the Avermectin B1a and Ivermectin skeletons through a linker. A variety of linkers were used in order to study the effect of disturbances in the hybrid structure on the GABAA receptor affinity. In vitro experiments showed that the lead compounds exhibited high potency (IC50 = 207 and 359 nM) for binding at the benzodiazepine site of GABAA receptors. In silico studies suggest that the hybrids are able to bind at the Ivermectin binding site of the GABAA receptor. The functional properties of the highest-affinity hybrid (compound 15e) as GABAAR PAM were evaluated by patch-clamp electrophysiological recordings of GABA-mediated currents in rat cerebellar Purkinje neurons. The results obtained suggest that the potentiating effect of hybrid compound 15e is due to its interaction both with benzodiazepine- and Ivermectin-binding sites of GABAARs. Drug-induced behavioral responses in adult zebrafish for hybrids correlate with an alternative mode of action of avermectin and imidazo[1,2-a]pyridine pharmacophores. The investigation of avermectin-imidazo[1,2-a]pyridine hybrid molecules with activity as GABAA receptor modulators is important for the discovery of safe and effective drugs for the treatment of neurological disorders and pest control agents.

Cyclopropyl Substituents Transform the Viscosity-Sensitive BODIPY Molecular Rotor into a Temperature Sensor.

A quantitative fluorescent probe that responds to changes in temperature is highly desirable for studies of biological environments, particularly in cellulo. Here, we report new cell-permeable fluorescence probes based on the BODIPY moiety that respond to environmental temperature. The new probes were developed on the basis of a well-established BODIPY-based viscosity probe by functionalization with cyclopropyl substituents at α and ß positions of the BODIPY core. In contrast to the parent BODIPY fluorophore, α-cyclopropyl-substituted fluorophore displays temperature-dependent time-resolved fluorescence decays showing greatly diminished viscosity dependence, making it an attractive sensor to be used with fluorescence lifetime imaging microscopy (FLIM). We performed theoretical calculations that help rationalize the effect of the cyclopropyl substituents on the photophysical behavior of the new BODIPYs. In summary, we designed an attractive new quantitative FLIM-based temperature probe that can be used for temperature sensing in live cells.

Preparation and Study of Sulfonated Co-Polynaphthoyleneimide Proton-Exchange Membrane for a H2/Air Fuel Cell.

The sulfonated polynaphthoyleneimide polymer (co-PNIS70/30) was prepared by copolymerization of 4,4'-diaminodiphenyl ether-2,2'-disulfonic acid (ODAS) and 4,4'-methylenebisanthranilic acid (MDAC) with ODAS/MDAC molar ratio 0.7/0.3. High molecular weight co-PNIS70/30 polymers were synthesized either in phenol or in DMSO by catalytic polyheterocyclization in the presence of benzoic acid and triethylamine. The titration reveals the ion-exchange capacity of the polymer equal to 2.13 meq/g. The membrane films were prepared by casting polymer solution. Conductivities of the polymer films were determined using both in- and through-plane geometries and reached ~96 and ~60 mS/cm, respectively. The anisotropy of the conductivity is ascribed to high hydration of the surface layer compared to the bulk. SFG NMR diffusometry shows that, in the temperature range from 213 to 353 K, the 1H self-diffusion coefficient of the co-PNIS70/30 membrane is about one third of the diffusion coefficient of Nafion® at the same humidity. However, temperature dependences of proton conductivities of Nafion® and of co-PNIS70/30 membranes are nearly identical. Membrane-electrode assemblies (MEAs) based on co-PNIS70/30 were fabricated by different procedures. The optimal MEAs with co-PNIS70/30 membranes are characterized by maximum output power of ~370 mW/cm2 at 80 °C. It allows considering sulfonated co-PNIS70/30 polynaphthoyleneimides membrane attractive for practical applications.

Solubility, Rheology, and Coagulation Kinetics of Poly-(O-Aminophenylene)Naphthoylenimide Solutions.

The effect of temperature and storage time at a constant temperature on the stability of poly-(o-aminophenylene)naphthoylenimide solutions in N-methylpyrrolidone has been analyzed using rotational rheometry. A temperature-time window beyond which an irreversible change in the viscoelastic properties of solutions due to cumulative reactions of continuous polymerization and possible intramolecular cyclization has been detected. The influence of polymer concentration and its molecular weight on the rheological properties of solutions determining the choice of methods for their processing into fibers and films has been investigated. The effect of non-solvents (water and ethanol) additives on the rheological properties of solutions and the kinetics of their coagulation has been studied. Dosed addition of non-solvent into the solution promotes a significant increase in the viscoelasticity up to gelation and phase separation. Non-solvent presence in the polymer solutions reduces the activity of the solvent, accelerates the movement of the diffusion front at coagulation, and minimizes the number of macro defects. The combination of parameters under investigation renders it possible for the first time to develop new principles modifying dopes for wet spinning into aqueous or ethanol coagulation bath and finally to obtain a heat- and fire-resistant polynaphthoylenebenzimidazole fibers.

Novel d-Annulated Pentacyclic Steroids: Regioselective Synthesis and Biological Evaluation in Breast Cancer Cells.

The acid-catalyzed cyclization of benzylidenes based on 16-dehydropregnenolone acetate (16-DPA) was studied. It was found that these compounds readily undergo regioselective interrupted Nazarov cyclization with trapping chloride ion and an efficient method of the synthesis of d-annulated pentacyclic steroids based on this reaction was proposed. The structures of the synthesized pentacyclic steroids were determined by NMR and X-ray diffraction. It was found that the reaction affords a single diastereomer, but the latter can crystallize as two conformers depending on the structure. Antiproliferative activity of synthesized compounds was evaluated against two breast cancer cell lines: MCF-7 and MDA-MB-231. All tested compounds showed relatively high antiproliferative activity. The synthetic potential of the protocol developed was illustrated by the gram-scale experiment.

Fe(iii)-Catalyzed synthesis of steroidal imidazoheterocycles as potent antiproliferative agents.

An efficient and practical method has been developed for the synthesis of steroidal imidazoheterocycles via cost-effective and environmentally benign FeCl3-catalyzed oxidative amination. A library of steroidal imidazo[1,2-a]pyridines was directly synthesized from readily available 2-aminopyridines and steroidal ketones in aerobic conditions. The synthesized compounds were screened for activity on human microsomal cytochrome P450s CYP7, CYP17 and CYP21. Antiproliferative activity of two lead compounds 3ia and 3la was additionally evaluated against the human MCF-7 (breast cancer), SKOV3 (ovarian cancer), and 22Rv1 (prostate cancer) cell lines. Steroidal imidazo[1,2-a]pyridine 3la which is a substrate molecule for CYP17A1 with IC50 = 1.7 µM (MCF-7), 3.0 (SKOV3), and 6.0 µM (22Rv1) has proved to be more active than reference drug cisplatin.

Sulfur-mediated synthesis of unsymmetrically substituted N-aryl oxalamides by the cascade thioamidation/cyclocondensation and hydrolysis reaction.

A facile and straightforward synthesis of unsymmetrically substituted N-aryl oxalamides from 2,2'-biphenyldiamines, 2-chloroacetic acid derivatives, elemental sulfur, and water has been developed. This protocol is distinguished by efficiency in water under metal-free conditions for N-aryl oxalamides bearing a side-chain NH2-group; it can be adapted for scale-up synthesis. The scope and limitations of this transformation have been investigated.

Development of 1,3-thiazole analogues of imidazopyridines as potent positive allosteric modulators of GABAA receptors.

Structure-activity relationship studies were conducted in the search for 1,3-thiazole isosteric analogs of imidazopyridine drugs (Zolpidem, Alpidem). Three series of novel γ-aminobutyric acid receptor (GABAAR) ligands belonging to imidazo[2,1-b]thiazoles, imidazo[2,1-b][1,3,4]thiadiazoles, and benzo[d]imidazo[2,1-b]thiazoles were synthesized and characterized as active agents against GABAAR benzodiazepine-binding site. In each of these series, potent compounds were discovered using a radioligand competition binding assay. The functional properties of highest-affinity compounds 28 and 37 as GABAAR positive allosteric modulators (PAMs) were determined by electrophysiological measurements. In vivo studies on zebrafish demonstrated their potential for the further development of anxiolytics. Using the OECD "Fish, Acute Toxicity Test" active compounds were found safe and non-toxic. Structural bases for activity of benzo[d]imidazo[2,1-b]thiazoles were proposed using molecular docking studies. The isosteric replacement of the pyridine nuclei by 1,3-thiazole, 1,3,4-thiadiazole, or 1,3-benzothiazole in the ring-fused imidazole class of GABAAR PAMs was shown to be promising for the development of novel hypnotics, anxiolytics, anticonvulsants, and sedatives drug-candidates.

Synthesis of Dibenzo[d,f][1,3]Diazepines via Elemental Sulfur-Mediated Cyclocondensation of 2,2'-Biphenyldiamines with 2-Chloroacetic Acid Derivatives.

The three-component reaction of 2,2'-biphenyldiamines with 2-chloroacetic acid derivatives and elemental sulfur was developed for the practical synthesis of unknown 2-carboxamide-substituted dibenzo[d,f][1,3]diazepines. This protocol is distinguished by efficiency in water and good tolerance to functional groups and can be adapted to a large-scale synthesis. The chemoselective preparation of a variety of 2-S,N,O-substituted dibenzo[d,f][1,3]diazepines was accomplished using the developed method.

New Approach to Preparation of Heat-Resistant "Lola-M" Fiber.

A new approach to the synthesis of polynaphthoylenebenzimidazoles and heat resistant fiber spinning has been developed using an environmentally friendly and energy efficient method, which operates with solutions of pre-polymers based on 3,3',4,4'-tetraaminodiphenyl ether and 1,4,5,8-naphthalenetetracarboxylic acid dianhydride in N-methylpyrrolidone. Rheological properties of polymer reaction solutions and appropriate coagulant mixtures were investigated for further wet spinning process. The coagulation process was investigated through microscopic observation of solution droplets which imitate jet/fiber cross section surrounded with coagulants of different composition. For the case of the most optimal viscoelastic properties of dopes the best coagulant was found to be a ternary mixture ethanol/water/NMP (20/10/70). Fibers were prepared through the wet spinning from pre-polymers of various molecular weight characterized by intrinsic viscosity. As a result, complex yarns were spun, and their morphology was characterized and mechanical properties were measured. The strength of ~300 MPa and elastic modulus of ~2 GPa and elongation at break of ~20% were reached for the best fibers at average diameter of ~20 µm. After heat treatment "Lola-M" fibers do not burn and do not support combustion in open flame.

Novel steroidal 1,3,4-thiadiazines: Synthesis and biological evaluation in androgen receptor-positive prostate cancer 22Rv1 cells.

A flexible approach to previously unknown spirofused and linked 1,3,4-thiadiazine derivatives of steroids with selective control of heterocyclization patterns is disclosed. (N-Arylcarbamoyl)spiroandrostene-17,6' [1,3,4]thiadiazines and (N-arylcarbamoyl)17-[1',3',4']thiadiazine-substituted androstenes, novel types of heterosteroids, were prepared from 16ß,17ß-epoxypregnenolone and 21-bromopregna-5,16-dien-20-one in good to high yields by the treatment with oxamic acid thiohydrazides. The synthesized compounds were screened for antiproliferative activity against the human androgen receptor-positive prostate cancer cell line 22Rv1. Most of (N-arylcarbamoyl)17-[1',3',4']thiadiazine-substituted androstenes exhibit better antiproliferative potency (IC50 = 2.1-6.6 µM) than the antiandrogen bicalutamide. Compounds 7d with IC50 = 3.0 µM and 7j with IC50 = 2.1 µM proved to be the most active in the series under study. Lead synthesized compound 7j downregulates AR expression and activity in 22Rv1 cells. NF-κB activity is also blocked in 7j-treated 22Rv1 cells. Apoptosis is considered as a possible mechanism of 7j-induced cell death.

Steroidal N-Sulfonylimidates: Synthesis and biological evaluation in breast cancer cells.

Unique derivatives of androstene and estrane series containing N-sulfonylimidate pendants were prepared from 17α-ethynyl steroids via Cu-catalyzed azide-alkyne cycloaddition to tosyl azide in the presence of alcohols. The synthesized compounds were screened for cytotoxicity against human breast cancer cell lines and ERα agonist activity. The hit compound 3,17ß-dimethoxy-17α-[iso-propyl-2'-N-tosylacetimidate]estra-1,3,5(10)-triene (4n) had no ERα-mediated hormonal activity and was found to exhibit potent cytotoxic effect in an ERα-positive breast cancer cell line. N-Sulfonylimidate 4n displayed high antiproliferative potency against triple-negative MDA-MB-231 breast cancer cells, while it was non-toxic towards normal mammary epithelial cells. Compound 4n was found to alter activity of various signaling pathways (NF-κB, Slug, cyclin D1, ERK) supporting the growth and invasiveness of tumor cells.

Association of Endothelial Function with Parental Hypertension in Normotensive-Obese African-American Women: A Pilot Study.

Obese African-American (AA) women are at high risk of hypertension (HT) and cardiovascular disease (CVD). Flow-mediated dilation (FMD) and arterial augmentation index (AI) are measures of endothelial function and arterial stiffness. Whether endothelial function and arterial stiffness predict risk of HT or CVD in obese African-American women with, versus without, parental histories of HT and whether aerobic exercise is an effective countermeasure remain unclear. The capacity for FMD is partly heritable. Therefore, we tested the hypotheses that less FMD and greater AI may be found in normotensive-obese, young-adult (18-26 year-old) AA women with hypertensive parents (n=10) than in a matched control group with normotensive parents (n=10) and that a single bout of aerobic exercise improves both endothelial function and arterial stiffness, with less improvement in the women with hypertensive parents. We studied each subject while at rest, 20 min before and 20 min after, 30 min of aerobic exercise. The exercise-induced changes and parental hypertension-related differences in AI were not significant. The exercise increased FMD in both of the groups with no significant difference in magnitude between the women with hypertensive and normotensive parents. FMD was significantly less in the women with hypertensive parents than in the women with normotensive parents after, but not before, the exercise (mean ±95% confidence interval of 11.3 ± 4.9% vs. 15.6 ± 4.9%, P=0.05). These findings suggest that a 30-min bout of aerobic exercise may improve FMD and unmask endothelial dysfunction in normotensive-obese, young-adult AA women with parental histories of HT. Future studies should determine whether regular aerobic exercise protects obese AA women from the endothelial dysfunction associated with diabetes and prevents CVD in this high-risk population.

Unexpected Heterocyclization of Electrophilic Alkenes by Tetranitromethane in the Presence of Triethylamine. Synthesis of 5-Nitroisoxazoles.

A novel reaction of tetranitromethane with electrophilic alkenes in the presence of triethylamine affording substituted 5-nitroisoxazoles is described. Triethylamine reacts with tetranitromethane to generate N-nitrotriethylammonium and trinitromethanide. This process provides the heterocyclization of electrophilic alkenes. A variety of α,ß-unsaturated aldehydes, ketones, esters, amides, phosphonates, nitro, and sulfur compounds was involved in the heterocyclization reaction, and a wide range of functionalized 5-nitroisoxazoles was obtained in good to high yields. The scope and limitations of the reaction and the mechanistic proposal are discussed.

Synthesis and evaluation of the antiproliferative activity of benzylidenes of 16-dehydroprogesterone series.

Novel benzylidenes (chalcones) of the 16-dehydroprogesterone series have been characterized and their antitumor activity against two breast cancer cell lines was evaluated. Benzylidenes exhibit significant antiproliferative effect on cells and inhibit cell growth in hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines. Compound 3d exhibits the highest activity against two breast cancer cell lines, with the IC50 value of about 2 µM. Compounds 3e,m,n display considerable selectivity for hormone-dependent breast cancer cells, with the IC50 value lower than 6 µM. Moreover, these steroidal benzylidenes regulate ERα signaling and reveal p53-independent mechanism of pro-apoptotic action in MCF-7 cells. The new class of antitumor compounds holds promise as the basis for the design of agents for cancer therapy.