Sustainable and Safe N-alkylation of N-heterocycles by Propylene Carbonate under Neat Reaction Conditions.

A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform N-alkylation of N-, O- and/or S-containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl halides were required. No auxiliary was necessary when using anhydrous PC. Product formation includes nucleophilic substitution with the concomitant loss of water and carbon dioxide. Substrates prepared, including the newly invented PROTAC drugs, are widely used.

Ultramicroporous Hydrogen-Bonded Organic Framework Material with a Thermoregulatory Gating Effect for Record Propylene Separation.

Propane/propylene separation is one of the most challenging and energy-consuming but most important tasks in the petrochemical industry. Herein, a stable hydrogen-bonded organic framework (HOF-FJU-1) was tailor-made for highly efficient propylene separation from binary C3H6/C3H8 and even seven component CH4/C2H4/C2H6/C3H6/C3H8/CO2/H2 mixtures. The temperature-controllable diffusion channels in HOF-FJU-1 have enabled the porous material to completely exclude propane to reach high-performance propylene purification under energy-efficient operation conditions. Single-crystal structural analysis revealed that the well-matched pore aperture of HOF-FJU-1 can exactly accommodate propylene molecules via multiple intermolecular interactions, exhibiting a very high propylene/propane selectivity of 616 at 333 K. The propylene purity and productivity are over 99.5% and 30.2 L kg-1 from the binary C3H6/C3H8 (50/50) mixture at 333 K. Through a follow-up column separation of C3H6/C2H4 at 353 K, not only high-purity propylene (99.5%) but also ethylene (98.3%) can be readily collected from the seven component CH4/C2H4/C2H6/C3H6/C3H8/CO2/H2 (31/10/25/10/10/1/13) cracking gas mixtures. The great potential of HOF-FJU-1 for the industrial propylene separation process has been further supported by the high stability of this porous material under different environments and straightforward processibility and regeneration feasibility.

An Atomistic Picture of Boron Oxide Catalysts for Oxidative Dehydrogenation Revealed by Ultrahigh Field 11B-17O Solid-State NMR Spectroscopy.

Boron oxide/hydroxide supported on oxidized activated carbon (B/OAC) was shown to be an inexpensive catalyst for the oxidative dehydrogenation (ODH) of propane that offers activity and selectivity comparable to boron nitride. Here, we obtain an atomistic picture of the boron oxide/hydroxide layer in B/OAC by using 35.2 T 11B and 17O solid-state NMR experiments. NMR spectra measured at 35.2 T resolve the boron and oxygen sites due to narrowing of the central-transition powder patterns. A 35.2 T 2D 11B{17O} dipolar heteronuclear correlation NMR spectrum revealed the structural connectivity between boron and oxygen atoms. The approach outlined here should be generally applicable to determine atomistic structures of heterogeneous catalysts containing quadrupolar nuclei.

Modulation of ODH Propane Selectivity by Zeolite Support Desilication: Vanadium Species Anchored to Al-Rich Shell as Crucial Active Sites.

The commercially available zeolite HY and its desilicated analogue were subjected to a classical wet impregnation procedure with NH4VO3 to produce catalysts differentiated in acidic and redox properties. Various spectroscopic techniques (in situ probe molecules adsorption and time-resolved propane transformation FT-IR studies, XAS, 51V MAS NMR, and 2D COS UV-vis) were employed to study speciation, local coordination, and reducibility of the vanadium species introduced into the hierarchical faujasite zeolite. The acid-based redox properties of V centres were linked to catalytic activity in the oxidative dehydrogenation of propane. The modification of zeolite via caustic treatment is an effective method of adjusting its basicity-a parameter that plays an important role in the ODH process. The developed mesopore surface ensured the attachment of vanadium species to silanol groups and formation of isolated (SiO)2(HO)V=O and (SiO)3V=O sites or polymeric, highly dispersed forms located in the zeolite micropores. The higher basicity of HYdeSi, due to the presence of the Al-rich shell, aided the activation of the C-H bond leading to a higher selectivity to propene. Its polymerisation and coke formation were inhibited by the lower acid strength of the protonic sites in desilicated zeolite. The Al-rich shell was also beneficial for anchoring V species and thus their reducibility. The operando UV-vis experiments revealed higher reactivity of the bridging oxygens V-O-V over the oxo-group V=O. The (SiO)3V=O species were found to be ineffective in propane oxidation when temperature does not exceed 400 °C.

Dendritic Mesoporous Silica Nanoparticle Supported PtSn Catalysts for Propane Dehydrogenation.

PtSn catalysts were synthesized by incipient-wetness impregnation using a dendritic mesoporous silica nanoparticle support. The catalysts were characterized by XRD, N2 adsorption-desorption, TEM, XPS and Raman, and their catalytic performance for propane dehydrogenation was tested. The influences of Pt/Sn ratios were investigated. Changing the Pt/Sn ratios influences the interaction between Pt and Sn. The catalyst with a Pt/Sn ratio of 1:2 possesses the highest interaction between Pt and Sn. The best catalytic performance was obtained for the Pt1Sn2/DMSN catalyst with an initial propane conversion of 34.9%. The good catalytic performance of this catalyst is ascribed to the small nanoparticle size of PtSn and the favorable chemical state and dispersion degree of Pt and Sn species.

Exploring the copper binding ability of Mets7 hCtr-1 protein domain and His7 derivative: An insight in Michael addition catalysis.

Mets7 is a methionine-rich motif present in hCtr-1 transporter that is involved in copper cellular trafficking. Its ability to bind Cu(I) was recently exploited to develop metallopeptide catalysts for Henry condensation. Here, the catalytic activity of Mets7-Cu(I) complex in Michael addition reactions has been evaluated. Furthermore, His7 peptide, in which Met residues have been substituted with His ones, was also prepared. This substitution allowed His7 to coordinate Cu (II), with the obtainment of a stable turn conformation as evicted by CD experiments. His7-Cu (II) proved also to be a better catalyst than Mets7-Cu(I) in the addition reaction. In particular, when the substrate was the (E)-1-phenyl-3-(pyridin-2-yl)prop-2-en-1-one, a conversion of 71% and a significative 58% of e.e. was observed.

Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates.

The advent of transition-metal catalysed strategies for forming new carbon-carbon bonds has revolutionized the field of organic chemistry, enabling the efficient synthesis of ligands, materials, and biologically active molecules. In cases where a single metal fails to promote a selective or efficient transformation, the synergistic cooperation of two distinct catalysts--multimetallic catalysis--can be used instead. Many important reactions rely on multimetallic catalysis, such as the Wacker oxidation of olefins and the Sonogashira coupling of alkynes with aryl halides, but this approach has largely been limited to the use of metals with distinct reactivities, with only one metal catalyst undergoing oxidative addition. Here, we demonstrate that cooperativity between two group 10 metal catalysts--(bipyridine)nickel and (1,3-bis(diphenylphosphino)propane)palladium--enables a general cross-Ullmann reaction (the cross-coupling of two different aryl electrophiles). Our method couples aryl bromides with aryl triflates directly, eliminating the use of arylmetal reagents and avoiding the challenge of differentiating between multiple carbon-hydrogen bonds that is required for direct arylation methods. Selectivity can be achieved without an excess of either substrate and originates from the orthogonal reactivity of the two catalysts and the relative stability of the two arylmetal intermediates. While (1,3-bis(diphenylphosphino)propane)palladium reacts preferentially with aryl triflates to afford a persistent intermediate, (bipyridine)nickel reacts preferentially with aryl bromides to form a transient, reactive intermediate. Although each catalyst forms less than 5 per cent cross-coupled product in isolation, together they are able to achieve a yield of up to 94 per cent. Our results reveal a new method for the synthesis of biaryls, heteroaryls, and dienes, as well as a general mechanism for the selective transfer of ligands between two metal catalysts. We anticipate that this reaction will simplify the synthesis of pharmaceuticals, many of which are currently made with pre-formed organometallic reagents, and lead to the discovery of new multimetallic reactions.

3-Hydroxypropionic acid contributes to the antibacterial activity of glycerol metabolism by the food microbe Limosilactobacillus reuteri.

Strains of Limosilactobacillus reuteri are used as starter and bioprotective cultures and contribute to the preservation of food through the production of fermentation metabolites lactic and acetic acid, and of the antimicrobial reuterin. Reuterin consists of acrolein and 3-hydroxypropionaldehyde (3-HPA), which can be further metabolized to 1,3-propanediol and 3-hydroxypropionic acid (3-HP). While reuterin has been the focus of many investigations, the contribution of 3-HP to the antimicrobial activity of food related reuterin-producers is unknown. We show that the antibacterial activity of 3-HP was stronger at pH 4.8 compared to pH 5.5 and 6.6. Gram-positive bacteria were in general more resistant against 3-HP and propionic acid than Gram-negative indicator strains including common food pathogens, while spoilage yeast and molds were not inhibited by ≤ 640 mM 3-HP. The presence of acrolein decreased the minimal inhibitory activity of 3-HP against E. coli indicating synergistic antibacterial activity. 3-HP was formed during the growth of the reuterin-producers, and by resting cells of L. reuteri DSM 20016. Taken together, this study shows that food-related reuterin producers strains synthesize a second antibacterial compound, which might be of relevance when strains are added as starter or bioprotective cultures to food products.

Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives.

Deoxyribonuclease I (DNase I) inhibitory properties of two 1-(pyrrolidin-2-yl)propan-2-one derivatives were examined in vitro. Determined IC50 values of 1-[1-(4-methoxyphenyl)pyrrolidin-2-yl]propan-2-one (1) (192.13±16.95 µM) and 1-[1-(3,4,5-trimethoxyphenyl)pyrrolidin-2-yl]propan-2-one (2) (132.62±9.92 µM) exceed IC50 value of crystal violet, used as a positive control, 1.89- and 2.73-times, respectively. Compounds are predicted to be nontoxic and to have favorable pharmacokinetic profiles, with high gastrointestinal absorption and blood-brain barrier permeability. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, Glu 78, Arg 111, Pro 137, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Determined inhibitory properties along with predicted ADMET profiles and observed interactions would be beneficial for the discovery of new active 1-(pyrrolidin-2-yl)propan-2-one-based inhibitors of DNase I.

The New Salicylaldehyde S,S-Propanedithioacetal Ester Enables N-to-C Sequential Native Chemical Ligation and Ser/Thr Ligation for Chemical Protein Synthesis.

The combination of distinct peptide ligation techniques to facilitate chemical protein synthesis represents one of the long-standing goals in the field. A new combination ligation method of N-to-C sequential native chemical ligation and Ser/Thr ligation (NCL-STL) is described for the first time. This method relies on the peptide salicylaldehyde S,S-propanedithioacetal (SALPDT)-ester prepared by a new 1,3-propanedithiol-mediated reaction. The peptide SALPDT-ester, which is compatible with NCL, can be fully activated by N-chlorosuccinimide (NCS)/AgNO3 in aqueous solution to afford peptide SAL-ester for use in the subsequent STL. The practicality of the combined NCL-STL method is illustrated by the synthesis of S-palmitoylated matrix-2 (S-palm M2) ion channel from Influenza A virus and S-palmitoylated interferon-induced transmembrane protein 3 (S-palm IFITM3). This approach expands the multiple-segments peptide ligation toolkit for producing important and complex custom-made protein samples by chemical protein synthesis.

Discovery of Diphenoxy Derivatives with Flexible Linkers as Ligands for ß-Amyloid Plaques.

The highly rigid and planar scaffolds with π-conjugated systems have been widely considered to be indispensable for ß-amyloid (Aß) binding ligands. In this study, a library of diphenoxy compounds with different types of more flexible linkers as Aß ligands were synthesized and evaluated. Most of them displayed good affinity (Ki < 100 nM) for Aß1-42 aggregates, and some ligands even showed values of Ki less than 10 nM. Structure-activity relationship analysis revealed that modification on the linkers or substituents tolerated great flexibility, which challenged the long-held belief that rigid and planar structures are exclusively favored for Aß binding. Three ligands were labeled by iodine-125, and they exhibited good properties in vitro and in vivo, which further supported that this flexible scaffold was potential and promising for the development of Aß imaging agents.

The synthesis of trifluoromethylated N-nitroaryl-2-amino-1,3-dichloropropane derivatives and their evaluation as potential anti-cancer agents.

Six N-nitroaryl-2-amino-1,3-dichloropropane derivatives have been prepared and evaluated against 18 cancer cell lines and two non-cancerous cell lines. Analysis of cell viability data and IC50 values indicated that the presence of a trifluoromethyl group in the nitroaryl moiety is an important structural feature associated with the compounds' cytotoxicities.

Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3-bis(3,4-dichlorophenoxy)propan-2-aminium chloride.

BACKGROUND: Fungal infections are highly prevalent and are responsible for high rates of morbidity and mortality. In this context, the search for new treatment alternatives is very relevant. OBJECTIVES: Analyse chemical compounds for antifungal potential against dermatomycosis fungi. METHODS: The antifungal activity of 121 compounds, intermediates or derivatives of 1,3-bis(aryloxy)propane substituted at C-2 (111 compounds) and isothiouronium derivatives (10 compounds) was investigated through susceptibility tests, mechanism of action, toxicity and hydrogel incorporation. RESULTS: The compound 1,3-bis(3,4-dichlorophenoxy)propan-2-aminium chloride (2j) was the most active fungicide against dermatophytes and Candida spp., at very low concentrations (0.39-3.12 µg/mL), including action on resistant and multidrug-resistant clinical strains. Compound 2j has presented a promising toxicity profile, showing selectivity index >10, relative to human lymphocytes. The compound was classified as non-irritant by the HET-CAM test and did not cause histopathological alterations in pig ear skin, thus presenting an excellent perspective for topical application. 2j targets the fungal cell wall, which was confirmed by scanning electron microscopy, which also indicated the additional ability of 2j to inhibit the Candida albicans pseudohyphae formation and biofilm of Microsporum canis. Compound 2j was incorporated in a hydrogel with bioadhesive potential. The results of the human skin permeation showed that 2j remained significantly in the epidermis, ideally for the dermatomycosis treatment. CONCLUSIONS: Therefore, the compound 2j demonstrated the potential for antifungal drug development, with a action mechanism elucidated and already applied in a semisolid formulation as a new therapeutic option for fungal skin infections.

Oxidative Dehydrogenation of Propane over Vanadium-Containing Faujasite Zeolite.

Oxidative dehydrogenation (ODH) of light alkanes to olefins-in particular, using vanadium-based catalysts-is a promising alternative to the dehydrogenation process. Here, we investigate how the activity of the vanadium phase in ODH is related to its dispersion in porous matrices. An attempt was made to synthesize catalysts in which vanadium was deposited on a microporous faujasite zeolite (FAU) with the hierarchical (desilicated) FAU as supports. These yielded different catalysts with varying amounts and types of vanadium phase and the porosity of the support. The phase composition of the catalysts was confirmed by X-ray diffraction (XRD); low temperature nitrogen sorption experiments resulted in their surface area and pore volumes, and reducibility was measured with a temperature-programmed reduction with a hydrogen (H2-TPR) method. The character of vanadium was studied by UV-VIS spectroscopy. The obtained samples were subjected to catalytic tests in the oxidative dehydrogenation of propane in a fixed-bed gas flow reactor with a gas chromatograph to detect subtract and reaction products at a temperature range from 400-500 °C, with varying contact times. The sample containing 6 wt% of vanadium deposited on the desilicated FAU appeared the most active. The activity was ascribed to the presence of the dispersed vanadium ions in the tetragonal coordination environment and support mesoporosity.

Conversion of the Propane-Butane Fraction into Arenes on MFI Zeolites Modified by Zinc Oxide and Activated by Low-Temperature Plasma.

The effect of modification of MFI zeolite 1-5 wt.% ZnO activated by plasma on acid and catalytic properties in the conversion of the propane-butane fraction into arenes was investigated. The high-silica zeolites with silicate module 45 were synthesized from alkaline alumina-silica gels in the presence of an 'X-oil' organic structure-forming additive. The modification of the zeolite with zinc was carried out by impregnating the zeolite granules in the H-form with an aqueous solution of Zn(NO3)2. The obtained zeolites were characterized by X-ray phase analysis and IR spectroscopy. It is shown that the synthesized zeolites belong to the high-silica MFI zeolites. The study of microporous zeolite-containing catalysts during the conversion of C3-C4 alkanes to aromatic hydrocarbons made it possible to establish that the highest yield of aromatic hydrocarbons is observed on zeolite catalysts modified with 1 and 3% ZnO and amount to 63.7 and 64.4% at 600 °C, respectively, which is 7.7-8.4% more than on the original zeolite. The preliminary activation of microporous zeolites modified with 1-5% ZnO and plasma leads to an increase in the yield of aromatic hydrocarbons from the propane-butane fraction; the maximum yield of arenes is observed in zeolite catalysts modified with 1 and 3% ZnO and activated by plasma, amounting to 64.9 and 65.5% at 600 °C, respectively, which is 8.9-9.5% more than on the initial zeolite. The activity of the zeolite catalysts modified by ZnO and activated by plasma show good agreement with their acid properties. Activation of the zeolites modified by 1 and 3% ZnO and plasma leads to an increase in the concentration of the weak acid sites of the catalyst to 707 and 764 mmol/g in comparison with plasma-inactivated 1 and 3% ZnO/ZKE-XM catalysts at 626 and 572 mmol/g, respectively.

Chemical Additives Enable Native Mass Spectrometry Measurement of Membrane Protein Oligomeric State within Intact Nanodiscs.

Membrane proteins play critical biochemical roles but remain challenging to study. Recently, native or nondenaturing mass spectrometry (MS) has made great strides in characterizing membrane protein interactions. However, conventional native MS relies on detergent micelles, which may disrupt natural interactions. Lipoprotein nanodiscs provide a platform to present membrane proteins for native MS within a lipid bilayer environment, but previous native MS of membrane proteins in nanodiscs has been limited by the intermediate stability of nanodiscs. It is difficult to eject membrane proteins from nanodiscs for native MS but also difficult to retain intact nanodisc complexes with membrane proteins inside. Here, we employed chemical reagents that modulate the charge acquired during electrospray ionization (ESI). By modulating ESI conditions, we could either eject the membrane protein complex with few bound lipids or capture the intact membrane protein nanodisc complex-allowing measurement of the membrane protein oligomeric state within an intact lipid bilayer environment. The dramatic differences in the stability of nanodiscs under different ESI conditions opens new applications for native MS of nanodiscs.

Liposome-Mediated Chemotherapeutic Delivery Is Synergistically Enhanced by Ternary Lipid Compositions and Cationic Lipids.

Most small molecule chemotherapeutics must cross one or more cellular membrane barriers to reach their biochemical targets. Owing to the relatively low solubility of chemotherapeutics in the lipid membrane environment, high doses are often required to achieve a therapeutic effect. The resulting systemic toxicity has motivated efforts to improve the efficiency of chemotherapeutic delivery to the cellular interior. Toward this end, liposomes containing lipids with cationic head groups have been shown to permeabilize cellular membranes, resulting in the more efficient release of encapsulated drugs into the cytoplasm. However, the high concentrations of cationic lipids required to achieve efficient delivery remain a key limitation, frequently resulting in toxicity. Toward overcoming this limitation, here, we investigate the ability of ternary lipid mixtures to enhance liposomal delivery. Specifically, we investigate the delivery of the chemotherapeutic, doxorubicin, using ternary liposomes that are homogeneous at physiological temperature but have the potential to undergo membrane phase separation upon contact with the cell surface. This approach, which relies upon the ability of membrane phase boundaries to promote drug release, provides a novel method for reducing the overall concentration of cationic lipids required for efficient delivery. Our results show that this approach improves the performance of doxorubicin by up to 5-fold in comparison to the delivery of the same drug by conventional liposomes. These data demonstrate that ternary lipid compositions and cationic lipids can be combined synergistically to substantially improve the efficiency of chemotherapeutic delivery in vitro.

Biological conversion of propane to 2-propanol using group I and II methanotrophs as biocatalysts.

Propane is the main component of liquefied petroleum gas and is derived from crude oil processing. Methanotrophic bacteria can convert various alkanes using methane monooxygenase enzyme to primary alcohols. These are further oxidized to various aldehydes by alcohol dehydrogenases or methanol dehydrogenases. In this study, 2-propanol was produced from propane using the whole cells of Methylosinus trichosporium OB3b, Methylomicrobium alcaliphilum 20Z, and Methylomonas sp. DH-1 as the biocatalysts. The biocatalytic process of converting propane to 2-propanol was optimized by the use of several inhibitors and additives, such as EDTA, sodium phosphate, and sodium formate to prevent oxidation of 2-propanol to acetone and to enhance conversion of propane to propanol. The maximum titer of 2-propanol was 0.424 g/L, 0.311 g/L, and 0.610 g/L for Methylomonas sp. DH-1, M. alcaliphilum 20Z, and M. trichosporium OB3b whole cells, respectively. These results showed that type I and type II methanotrophs could be used as the potent biocatalyst for conversion of propane to propanol.

Partial propane extraction of aromatic compounds from dehydrated basils (Ocimum Lamiaceae).

BACKGROUND: Many conventional extraction methods for basils (Ocimum sp. Lamiaceae) produce only the extract as a usable product and leave the extracted herb as a waste product. We demonstrate partial extraction of chemically and morphologically diverse basil cultivars using propane at low temperature (20-27 °C) and pressure (950-1200 kPa) and evaluate the process for production of dual products, the extracted herb (raffinate) and the herb extract in terms of aromatic content and color. RESULTS: The extracts contained aromatic compounds that were characteristic of but not always identical in terms of relative abundance to the dehydrated herb. Extraction decreased total aromatics in the raffinate by 12-43% but the individual aromatic proportions remained essentially the same, preserving flavor characteristics of the raffinate. Color was mostly unchanged by the extraction process. CONCLUSION: Partial propane extraction resulted in two useful basil products (an extract and extraction raffinate). Aromatic extractability was tissue and cultivar dependent for basils. Therefore, partial extraction protocols should be optimized according to cultivar/plant tissue abundance to provide consistent aromatic intensity of these potential food products. © 2019 Society of Chemical Industry.

Computational Tale of Two Enzymes: Glycerol Dehydration With or Without B12.

We present a series of QM/MM calculations aimed at understanding the mechanism of the biological dehydration of glycerol. Strikingly and unusually, this process is catalyzed by two different radical enzymes, one of which is a coenzyme-B12-dependent enzyme and the other which is a coenzyme-B12-independent enzyme. We show that glycerol dehydration in the presence of the coenzyme-B12-dependent enzyme proceeds via a 1,2-OH shift, which benefits from a significant catalytic reduction in the barrier. In contrast, the same reaction in the presence of the coenzyme-B12-independent enzyme is unlikely to involve the 1,2-OH shift; instead, a strong preference for direct loss of water from a radical intermediate is indicated. We show that this preference, and ultimately the evolution of such enzymes, is strongly linked with the reactivities of the species responsible for abstracting a hydrogen atom from the substrate. It appears that the hydrogen-reabstraction step involving the product-related radical is fundamental to the mechanistic preference. The unconventional 1,2-OH shift seems to be required to generate a product-related radical of sufficient reactivity to cleave the relatively inactive C-H bond arising from the B12 cofactor. In the absence of B12, it is the relatively weak S-H bond of a cysteine residue that must be homolyzed. Such a transformation is much less demanding, and its inclusion apparently enables a simpler overall dehydration mechanism.