Alpha-substituted 1-aryl-3-dimethylaminopropanone hydrochlorides: potent cytotoxins towards human WiDr colon cancer cells

A series of 1-aryl-2-dimethylaminomethyl-2-propenone hydrochlorides 1 were prepared which possessed IC(50) values of less than 10 microM when examined towards human WiDr colon cancer cells. The related 1-aryl-2-dimethylaminomethyl-3-hydroxypropanone hydrochlorides 2, formed by hydration of the analogs in series 1, also had IC(50) values in the low micromolar range. On the other hand, conversion of 2-dimethylaminomethyl-1-(4-nitrophenyl)-2-propenone hydrochloride 1c into the corresponding 2-mercaptoethanol of adduct 3c led to a 37-fold reduction in potency. Two thirds of the compounds prepared in this study were more potent than a reference drug cisplatin while one third of these molecules displayed greater cytotoxicity to the WiDr cells than human CRL-2522 fibroblasts. A stability study of the 4-nitrophenyl analog in each of the series 1-3 in deuterium oxide was undertaken. In the case of 1c, replacement of the dimethylamino hydrochloride group by a hydroxy function was noted while in series 2, the loss of both water and dimethylamine hydrochloride gave rise to a mixture of two enones. The mercaptoethanol adduct 3c underwent deamination. The data obtained provide guidelines for amplifying the project in the future.     

A biocatalytic approach to synthesizing optically active orthogonally protected trans-cyclopentane-1,2-diamine derivatives

A straightforward chemoenzymatic synthesis of optically active trans-N,N-dialkylcyclopentane-1,2-diamines has been efficiently developed starting out from their analogous (+/-)-trans-2-(N,N-dialkylamino)cyclopentanols. The route involves the one-pot stereospecific transformation of the racemic amino alcohols into racemic diamines and a subsequent kinetic resolution by means of lipase-B from Candida antarctica-catalyzed acylation reactions. The careful selection of both the alkyl substituents present in the diamine and the derivatization strategy applied to the enzymatic reaction enabled the easy preparation of other synthetically valuable optically active trans-cyclopentane-1,2-diamines derivatives.     

Reactivity of cyclopalladated compounds derived from biphenyl-2-ylamine towards carbon monoxide, butyl isocyanide and alkynes

The reactivity of the dimeric cyclopalladated compounds derived from biphenyl-2-ylamine (μ-X)₂[κ²-N2′,C1-1-Pd-2-{(2′-NH₂C₆H₄)C₆H₄}]₂ [X = OAc (1), X = Cl (2)] towards unsaturated organic molecules is reported. Compound 1 reacted with carbon monoxide and ^tbutyl isocyanide producing phenanthridin-6(5H)-one and N-tert-butylphenanthridin-6-amine in 63% and 88% yield, respectively. Compound 2 reacted separately with diphenylacetylene and 3-hexyne, affording the mononuclear organopalladium compounds [κ²-N2″,C1-η²-C2,C3- 1-Pd{(R-CC-R)₂-2′-(2″-NH₂C₆H₄)C₆H₄}Cl] [R = Ph (5), R = Et (6)] in 50-60% yield, which derived from the insertion of two alkyne molecules into the C-Pd σ bonds of 2. The crystal structure of compounds 5 and 6 has been determined. Compound 5 crystallized in the monoclinic space group P2₁/n with a = 13.3290(10) Å, b = 10.6610(10) Å and c = 22.3930(10) Å and β = 100.2690(10)°. Compound 6 crystallized in the triclinic space group with a = 7.271(7) Å, b = 10.038(3) Å and c = 16.012(5) Å, and α = 106.79(3)°, β = 96.25(4)° and γ = 99.62(4)°. The crystal structures of 5 and 6 have short intermolecular Pd-Cl?H-N-Pd non-conventional hydrogen bonds, which associated the molecules in chains in the first case and in dimers in the second.     

Double acylation for identification of amino-terminal peptides of proteins isolated by polyacrylamide gel electrophoresis

We report here a method for the identification of free or blocked N-terminal peptide of in-gel digested isolated proteins. The primary amino groups of the gel-entrapped protein are blocked with normal acetic or succinic anhydride, and the protein is digested with a high-specificity protease. The generated peptides are treated with an equimolar mixture of normal and deuterated acetic anhydride. Upon mass spectrometric analysis internal peptides display a complex isotopic ion distribution while the N-terminal peptide shows a normal isotopic ion distribution. The procedure was applied to the identification of the N-terminus of individual and protein mixtures isolated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE).     

A review on the electrochemical production of chlorine dioxide from chlorates and hydrogen peroxide

Chlorine dioxide is one of the most interesting oxidants because it combines a strong capacity of oxidation with low formation of hazardous byproducts such as chlorinated organics during its application. Because of that, it is widely used in disinfection of drinking water and, currently, it is aimed to be used in the disinfection of surfaces or buildings. Although it is usually produced by the chemical interaction of chlorite with hypochlorite/chlorine or hydrochloric acid, one interesting alternative for its production is the combination in strongly acidic media of chlorate and hydrogen peroxide. Both compounds are known to be efficiently manufactured with electrochemical technology, opening the possibility of a complete electrochemical process to produce this important oxidant. This review summarizes the recent progress in the electrochemical production of the two raw materials, as well as the complete electrochemical production of chlorine dioxide, not only paying attention to the scientific literature but, most importantly, to recent patents, trying to see in which technology readiness level are each of the technologies and what are the elements of the value chain required for a complete implementation of the technology.     

Analysis of curing of diglycidyl ether of bisphenol A (BADGE n = 0) with 2‐adamantylethanamine

The epoxy resin diglycidyl ether of Bisphenol A (BADGE n = 0) has been cured with a new synthesized hardener (2‐adamantylethanamine) and the crosslinking reaction was characterized by DSC. Values of 413.3 J/g and 95°C have been obtained for the enthalpy of the reaction and the glass transition temperature, respectively. The experimental results obey Kamal's model over all conversion range of temperatures (70°C‐100°C). The activation energies of the mechanisms involved in the curing reaction have been determined for both the autocatalytic and the n‐order mechanism, the values being 63.3 and 29.8 kJ/mol, respectively. The value for T_g is 23°C higher than the one for (BADGE n = 0)/amantadine, while the activation energy for the n‐order mechanism is around 13 kJ/mol lower. This is consistent with a higher steric effect of the adamantyl group in the second hardener since it will hinder the opening the oxirane ring by the nitrogen atom of the amino group. As the polymerization reaction progress, this effect will disappear as the distance adamantyl‐oxirane increase when new oxirane groups react with the hydroxyl groups (autocatalyzed reaction). Consequently, by selecting the appropriate cross‐linking agent, it is possible to simultaneously increase T_g while reducing theactivation energy, two effects which may be desirable for some industrial applications of the material.     

Physical,Chemical and Rheological Characterization of Tuber and Starch from Ceiba aesculifolia subsp. parvifolia

This work aimed to evaluate the physical, chemical and antioxidant properties of Ceiba aesculifolia subsp. parvifolia (CAP) tuber and determinate rheological, thermal, physicochemical and morphological properties of the starch extracted. The CAP tuber weight was 3.66 kg; the edible yield was 82.20%. The tuber presented a high hardness value (249 N). The content of carbohydrates (68.27%), crude fiber (15.61%) and ash (9.27%) from the isolated starch, reported in dry weight, were high. Phenolic compounds and flavonoid content of CAP tuber peel were almost 3-fold higher concerning the pulp. CAP tuber starch exhibited a pseudoplastic behavior and low viscosity at concentrations of 5–15%. Purity percentage and color parameters describe the isolated starch as high purity. Thermal characteristics indicated a higher degree of intermolecular association within the granule. Pasting properties describes starch with greater resistance to heat and shear. CAP tuber starch has X-ray diffraction patterns type A. The starch granules were observed as oval and diameters ranging from 5 to 30 µm. CAP tuber could be a good source of fiber and minerals, while its peel could be used for extracting bioactive compounds. Additionally, the starch separated from this tuber could be employed as a thickening agent in food systems requiring a low viscosity and subjected to high temperatures.     

Gossypitrin,A Naturally Occurring Flavonoid,Attenuates Iron-Induced Neuronal and Mitochondrial Damage

The disruption of iron homeostasis is an important factor in the loss of mitochondrial function in neural cells, leading to neurodegeneration. Here, we assessed the protective action of gossypitrin (Gos), a naturally occurring flavonoid, on iron-induced neuronal cell damage using mouse hippocampal HT-22 cells and mitochondria isolated from rat brains. Gos was able to rescue HT22 cells from the damage induced by 100 µM Fe(II)-citrate (EC₅₀ 8.6 µM). This protection was linked to the prevention of both iron-induced mitochondrial membrane potential dissipation and ATP depletion. In isolated mitochondria, Gos (50 µM) elicited an almost complete protection against iron-induced mitochondrial swelling, the loss of mitochondrial transmembrane potential and ATP depletion. Gos also prevented Fe(II)-citrate-induced mitochondrial lipid peroxidation with an IC₅₀ value (12.45 µM) that was about nine time lower than that for the tert-butylhydroperoxide-induced oxidation. Furthermore, the flavonoid was effective in inhibiting the degradation of both 15 and 1.5 mM 2-deoxyribose. It also decreased Fe(II) concentration with time, while increasing O₂ consumption rate, and impairing the reduction of Fe(III) by ascorbate. Gos–Fe(II) complexes were detected by UV-VIS and IR spectroscopies, with an apparent Gos-iron stoichiometry of 2:1. Results suggest that Gos does not generally act as a classical antioxidant, but it directly affects iron, by maintaining it in its ferric form after stimulating Fe(II) oxidation. Metal ions would therefore be unable to participate in a Fenton-type reaction and the lipid peroxidation propagation phase. Hence, Gos could be used to treat neuronal diseases associated with iron-induced oxidative stress and mitochondrial damage.     

Segregated Protein–Cucurbit[7]uril Crystalline Architectures via Modulatory Peptide Tectons

One approach to protein assembly involves water-soluble supramolecular receptors that act like glues. Bionanoarchitectures directed by these scaffolds are often system-specific, with few studies investigating their customization. Herein, the modulation of cucurbituril-mediated protein assemblies through the inclusion of peptide tectons is described. Three peptides of varying length and structural order were N-terminally appended to RSL, a β-propeller building block. Each fusion protein was incorporated into crystalline architectures mediated by cucurbit[7]uril ( Q7 ). A trimeric coiled-coil served as a spacer within a Q7 -directed sheet assembly of RSL, giving rise to a layered material of varying porosity. Within the spacer layers, the coiled-coils were dynamic. This result prompted consideration of intrinsically disordered peptides (IDPs) as modulatory tectons. Similar to the coiled-coil, a mussel adhesion peptide (Mefp) also acted as a spacer between protein– Q7 sheets. In contrast, the fusion of a nucleoporin peptide (Nup) to RSL did not recapitulate the sheet assembly. Instead, a Q7 -directed cage was adopted, within which disordered Nup peptides were partially “captured” by Q7 receptors. IDP capture occurred by macrocycle recognition of an intrapeptide Phe-Gly motif in which the benzyl group was encapsulated by Q7 . The modularity of these protein–cucurbituril architectures adds a new dimension to macrocycle-mediated protein assembly. Segregated protein crystals, with alternating layers of high and low porosity, could provide a basis for new types of materials.     

A Bibliometric Evaluation of the Top 100 Cited Dimethyl Fumarate Articles

Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple sclerosis. We performed a bibliometric study examining the characteristics and trends of the top 100 cited articles that include dimethyl fumarate in the title. On 21 September 2020 we carried out an electronic search in the Web of Science (WOS), seeking articles that include the following terms within the title: dimethyl fumarate, BG-12, or Tecfidera. To focus our investigation on original research, we refined the search to include only articles, early access, others, case report, and clinical trials. We obtained a total of 1115 items, which were cited 7169 times, had a citation density of 6.43 citations/item, and an h-index of 40. Around 2010, there was a jump in the number of published articles per year, rising from 5 articles/year up to 12 articles/year. We sorted all the items by the number of citations and selected the top 100 most cited (T100). The T100 had 4164 citations, with a density of 37 citations/year and contained 16 classic research articles. They were published between 1961 and 2018; the years 2010–2018 amassed nearly 80% of the T100. We noted 17 research areas with articles in the T100. Of these, the number one ranking went to neurosciences/neurology with 39 articles, and chemistry ranked second on the T100 list with 14 items. We noticed that the percentage of articles belonging to different journals changed depending on the time period. Chemistry held the highest number of papers during 1961–2000, while pharmacology andneurosciences/neurology led the 2001–2018 interval. A total of 478 authors from 145 institutions and 25 countries were included in the T100 ranking. The paper by Gold R et al. was the most successful with 14 articles, 1.823 citations and a density of 140.23 citations/year. The biotechnological company Biogen led the T100 list with 20 articles. With 59 published articles, the USA was the leading country in publications. We concluded that this study analyzed the use of and research on dimethyl fumarate from a different perspective, which will allow the readership (expert or not) to understand the relevance of classic and recent literature on this topic.