“Texas-Sized” Molecular Boxes: From Chemistry to Applications

The design and synthesis of novel macrocyclic host molecules continues to attract attention because such species play important roles in supramolecular chemistry. However, the discovery of new classes of macrocycles presents a considerable challenge due to the need to embody by design effective molecular recognition features, as well as ideally the development of synthetic routes that permit further functionalization. In 2010, we reported a new class of macrocyclic hosts: a set of tetracationic imidazolium macrocycles, which we termed “Texas-sized” molecular boxes (TxSBs) in homage to Stoddart’s classic “blue box” (CBPQT⁴⁺). Compared with the rigid blue box, the first generation TxSB displayed considerably greater conformational flexibility and a relatively large central cavity, making it a good host for a variety of electron-rich guests. In this review, we provide a comprehensive summary of TxSB chemistry, detailing our recent progress in the area of anion-responsive supramolecular self-assembly and applications of the underlying chemistry to water purification, information storage, and controlled drug release. Our objective is to provide not only a review of the fundamental findings, but also to outline future research directions where TxSBs and their constructs may have a role to play.     

Design,Synthesis and Biological Evaluation of New Carbohydrate-Based Coumarin Derivatives as Selective Carbonic Anhydrase IX Inhibitors via “Click” Reaction

In this work, we designed a series of new carbohydrate-based coumarin carbonic anhydrase IX inhibitors by using 1,2,3-triazoles as linker. Next, these designed compounds were synthesized by the optimized one-pot click chemistry reaction condition. Subsequently, these target compounds were assayed for the inhibition of three carbonic anhydrase isoforms (CA I, CA II and CA IX). Intriguingly, all the compounds showed better CA IX inhibitory activity than initial coumarin fragments. Among them, compound 10a (IC₅₀: 11 nM) possessed the most potent CA IX inhibitory activity, which was more potent than the reference drug acetazolamide (IC₅₀: 30 nM). Notably, compound 10a showed 3018-fold, 1955-fold selectivity relative to CA I and CA II, respectively. Meanwhile, representative compounds could reduce tumor cell viability and the extracellular acidification in HT-29 and MDA-MB-231 cancer cell lines. Even more interestingly, our target compounds had no apparent cytotoxicity toward MCF-10A cell line. In addition, the in vitro stability assays also indicated our developed compounds possessed good liver microsomal metabolic stabilities and plasma stability. Furthermore, representative compounds revealed relatively low hERG cardiac toxicity and acute toxicity. Furthermore, docking studies were carried out to understand the interactions of our target compounds with the protein target CA IX. Collectively, our results suggest that compound 10a, as a selective CA IX inhibitor, could be an important lead compound for further optimization and development as an anticancer agent.     

Carbocatalysis: The State of “Metal‐Free” Catalysis

The rise in global demand for crucial chemical compounds has driven immense research in the fundamental science of catalysis. Graphene and its derivatives (chemically modified graphene, CMGs) have recently emerged as a new class of heterogeneous catalyst that promises economically viable and greener routes to these compounds. Although CMGs possess unique catalytic properties, the actual active sites are often points of discussion. Current minimal understanding on the possible effects of metallic impurities on the electrocatalytic performances of these CMGs calls forth the need to raise awareness on possible metallic impurities misrepresenting the actual chemical catalytic performances of the CMGs. This Minireview highlights the latest advances in the application of CMGs as catalysts, with an emphasis on the possible effects of metallic impurities on CMG catalysis.     

A Chewable Cure “Kanna”: Biological and Pharmaceutical Properties of Sceletium tortuosum

Sceletium tortuosum (L.) N.E.Br. (Mesembryanthemaceae), commonly known as kanna or kougoed, is an effective indigenous medicinal plant in South Africa, specifically to the native San and Khoikhoi tribes. Today, the plant has gained strong global attraction and reputation due to its capabilities to promote a sense of well-being by relieving stress with calming effects. Historically, the plant was used by native San hunter-gatherers and Khoi people to quench their thirst, fight fatigue and for healing, social, and spiritual purposes. Various studies have revealed that extracts of the plant have numerous biological properties and isolated alkaloids of Sceletium tortuosum are currently being used as dietary supplements for medicinal purposes and food. Furthermore, current research has focused on the commercialization of the plant because of its treatment in clinical anxiety and depression, psychological and psychiatric disorders, improving mood, promoting relaxation and happiness. In addition, several studies have focused on the isolation and characterization of various beneficial bioactive compounds including alkaloids from the Sceletium tortuosum plant. Sceletium was reviewed more than a decade ago and new evidence has been published since 2008, substantiating an update on this South African botanical asset. Thus, this review provides an extensive overview of the biological and pharmaceutical properties of Sceletium tortuosum as well as the bioactive compounds with an emphasis on antimicrobial, anti-inflammatory, anti-oxidant, antidepressant, anxiolytic, and other significant biological effects. There is a need to critically evaluate the bioactivities and responsible bioactive compounds, which might assist in reinforcing and confirming the significant role of kanna in the promotion of healthy well-being in these stressful times.     

Design of Conjugates Based on Sesquiterpene Lactones with Polyalkoxybenzenes by “Click” Chemistry to Create Potential Anticancer Agents

Using the methodology of “click” chemistry, a singular method has been developed for the synthesis of unique conjugates based on sesquiterpene lactones: dehydrocostuslactone and alantolactone with polyalkoxybenzenes. To expand the structural range of the resulting conjugates, the length of the 1,2,3-triazole spacer was varied. For all synthesized compounds, the cytotoxic profile was determined on the cell lines of tumor origin (SH-SY5Y, HeLa, Hep-2, A549) and normal Hek 293 cells. It was found that the compounds based on alantolactone 7a–d with a long spacer and substances containing dehydrocostuslactone 10a–d with a short spacer have the greatest toxic effect. The decrease in cell survival under the action of these conjugates may be due to their ability to cause dissipation of the transmembrane potential of mitochondria and inhibit the process of glycolysis, leading to cell death. The obtained results confirm the assumption that the development of conjugates based on sesquiterpene lactones and polyalkoxybenzenes can be considered as a promising strategy for the search for potential antitumor agents.     

Asymmetric Phase‐Transfer‐Catalyzed Intramolecular N‐Alkylation of Indoles and Pyrroles: A Combined Experimental and Theoretical Investigation

Asymmetric phase‐transfer catalysis (PTC) has risen to prominence over the last decade as a straightforward synthetic methodology for the preparation of pharmacologically active compounds in enantiomerically pure form. However, the complex interplay of weak nonbonded interactions (between catalyst and substrate) that could account for the stereoselection in these processes is still unclear, with tentative pictorial mechanistic representations usually proposed. Here we present a full account dealing with the enantioselective phase‐transfer‐catalyzed intramolecular aza‐Michael reaction (IMAMR) of indolyl esters, as a valuable synthetic tool to obtain added‐value compounds, such as dihydro‐pyrazinoindolinones. A combined computational and experimental investigation has been carried out to elucidate the key mechanistic aspects of this process.     

Microwaves as “Co-Catalysts” or as Substitute for Catalysts in Organophosphorus Chemistry

The purpose of this review is to summarize the importance of microwave (MW) irradiation as a kind of catalyst in organophosphorus chemistry. Slow or reluctant reactions, such as the Diels-Alder cycloaddition or an inverse-Wittig type reaction, may be performed efficiently under MW irradiation. The direct esterification of phosphinic and phosphonic acids, which is practically impossible on conventional heating, may be realized under MW conditions. Ionic liquid additives may promote further esterifications. The opposite reaction, the hydrolysis of P-esters, has also relevance among the MW-assisted transformations. A typical case is when the catalysts are substituted by MWs, which is exemplified by the reduction of phosphine oxides, and by the Kabachnik–Fields condensation affording α-aminophosphonic derivatives. Finally, the Hirao P–C coupling reaction may serve as an example, when the catalyst may be simplified under MW conditions. All of the examples discussed fulfill the expectations of green chemistry.     

Direct Synthesis of an α,ω‐Diester from 2,7‐Octadienol as Bulk Feedstock in Three Tandem Catalytic Steps

A new tandem catalytic process was designed and developed as a tool for the direct conversion of the widely available feedstock 2,7‐octadienol into an α,ω‐diester. This innovative auto‐tandem catalysis is atom efficient and consists of three consecutive palladium‐catalysed reactions: ether formation, ether carbonylation and alkoxycarbonylation. By using the design of experiments (DoE) approach, significant parameters were determined and the yield of the desired α,ω‐diester was optimised. Model substrates allowed deeper insight into the progress of the reaction to be gained and, as a result, the reaction sequence was uncovered. Furthermore, by simply applying other ligands, a different reaction path was followed, allowing other, new tandem catalytic sequences to be explored and enabling new compounds to be obtained.     

Metal‐Free Boron‐Containing Heterogeneous Catalysts

Metal‐free catalysts have distinct advantages over metal and metal oxide catalysts, such as lower cost as well as higher reliability and sustainability. Among the nonmetal compounds used in catalysis, boron‐containing compounds with a few unique properties have been developed. In this Minireview, the recent advances in the field of boron‐containing metal‐free catalysts are presented, including binary and ternary boron‐containing catalytic materials. Additionally, the three main applications in catalysis are considered, namely, electrocatalysis, thermal catalysis, and photocatalysis, with the role of boron discussed in depth for each specific catalytic application. Boron‐containing compounds could have a substantial impact on the field of metal‐free catalysts in the future.     

Practical approaches to the ESI‐MS analysis of catalytic reactions

Electrospray ionization mass spectrometry (ESI‐MS) is a soft ionization technique commonly coupled with liquid or gas chromatography for the identification of compounds in a one‐time view of a mixture (for example, the resulting mixture generated by a synthesis). Over the past decade, Scott McIndoe and his research group at the University of Victoria have developed various methodologies to enhance the ability of ESI‐MS to continuously monitor catalytic reactions as they proceed. The power, sensitivity and large dynamic range of ESI‐MS have allowed for the refinement of several homogenous catalytic mechanisms and could potentially be applied to a wide range of reactions (catalytic or otherwise) for the determination of their mechanistic pathways. In this special feature article, some of the key challenges encountered and the adaptations employed to counter them are briefly reviewed. Copyright © 2014 John Wiley & Sons, Ltd.     

Combinatorial Chemistry—Challenge and Chance for the Development of New Catalysts and Materials

One should not underestimate the capability of the combinatorial method in solid-state chemistry; this is the opinion of the author. Combinatorial chemistry can provide a large number of new compounds, but once the components that are interesting for a certain application have been successfully selected, the techniques of conventional catalysis and materials research are required. The strengths of conventional chemistry lie in the optimization, systematic modification, and improvement of new lead structures. In contrast, discovery is the potential strength of combinatorial chemistry. Careful design is most important for the synthesis of useful libraries, since the diversity of the periodic table is much too large to be accessed comprehensively or systematically by such large libraries.     

Triazolyl‐Based Molecular Gels as Ligands for Autocatalytic ‘Click’ Reactions

The catalytic performance of triazolyl‐based molecular gels was investigated in the Huisgen 1,3‐dipolar cycloaddition of alkynes and azides. Low‐molecular‐weight gelators derived from l ‐valine were synthesized and functionalized with a triazole fragment. The resultant compounds formed gels either with or without copper, in a variety of solvents of different polarity. The gelators coordinated Cu^I and exhibited a high catalytic activity in the gel phase for the model reaction between phenylacetylene and benzylazide. Additionally, the gels were able to participate in autocatalytic synthesis and the influence of small structural changes on their performance was observed.     

Continuous‐Flow Suzuki‐Miyaura and Mizoroki‐Heck Reactions under Microwave Heating Conditions

Microwave‐assisted continuous‐flow reactions have attracted significant interest from synthetic organic chemists, especially process chemists from practical points of view, due to a less complicated shift to large‐scale synthesis based on simple and continuous access to products with low energy requirements. In this personal account, we focused on the Suzuki‐Miyaura and Mizoroki‐Heck reactions, both of which are significantly important cross‐coupling reactions for the synthesis of various functional materials. Microwave power is effective for heating. Typical homogeneous palladium catalysts, such as PdCl₂(PPh₃)₂, Pd(PPh₃)₄, and Pd(OAc)₂, as well as heterogeneous palladium catalysts, such as Pd‐film, Pd/Al₂O₃, Pd/SiO₂, and Pd supported on polymers, can be used for these reactions.     

“For Asia Market Only”: A Green Tattoo Ink between Safety and Regulations

Due to the increasing tattoo practicing in Eastern countries and general concern on tattoo ink composition and safety, the green tattoo inks Green Concentrate by Eternal, for European and “for Asia Market Only” were analyzed, under the premise that only the former falls under a composition regulation. A separation of the additives from the pigment was carried out by successive extraction in solvents of different polarities, i.e., water, acetone and dichloromethane. The solid residues were analyzed by IR and Raman spectroscopies, the liquid fractions by GC/mass spectrometry. The relative pigment load and element traces were also estimated. We found that the European and the Asian inks are based on the same pigment, PG7, restricted in Europe, though at different loads. They have a similar content of harmful impurities, such as Ni, As, Cd and Sb and both contain siloxanes, including harmful D4. Furthermore, they have different physical-chemical properties, the European ink being more hydrophilic, the Asian more hydrophobic. Additionally, the Asian ink contains harmful additives for the solubilization of hydrophobic matrices and by-products of the phthalocyanine synthesis. Teratogenic phthalates are present as well as chlorinated teratogenic and carcinogenic compounds usually associated to the laser treatment for removal purposes, to a larger extent in the European ink. The composition of the inks does not seem to reflect regulatory restrictions, where issued.     

Organometallic Homogeneous Catalysis—Quo vadis?

Homogeneous catalysis is the success story of organometallic chemistry. Otto Roelen's initial discovery of hydroformylation in 1938 not only entailed large-capacity production plants but was later followed by systematic research into the catalytic chemistry of the ever-growing class of organometallic compounds. Further developments in industrial chemistry towards clean, low-temperature, low-pressure, and economic processes—in feedstock or in the fine chemicals and polymer area—clearly depend on improved catalysts. Molecularly defined, tailor-made structures are the safest prerequisites for chemical selectivity; hence, organometallic compounds with their overwhelming variety of compositions and structures offer the most promising approach. Wilkinson's catalysts [HRh(CO){P(C₆H₅)₃] and [ClRh{P(C₆H₅)}₃}₃] are outstanding examples. On the other hand, process technology has to be considered also (for example catalyst-product separation and hear-exchange problems). The following review attempts to critically assess the future trends and present demands in the applied area of orgnometallic catalysis–a “gentle art” that is far from being a mature field.     

Stanna‐closo‐dodecaborate: A New Ligand in Coordination Chemistry

Most of the divalent compounds of tin have a lone pair and hence can act as donors. In tin‐transition metal chemistry neutral molecules as well as anions have been studied as ligands. This research report summarizes recent research on coordination compounds with a closo‐heteroborate cage compound stanna‐closo‐dodecaborate [SnB₁₁H₁₁]^2?. The syntheses of the first coordination compounds and studies on the ligand abilities of this tin borate are discussed in this article.     

Catalytic Enantioselective Flow Processes with Solid‐Supported Chiral Catalysts

Sustainability concerns are the wind in the sails for the development of novel, more selective catalytic processes. Hence, chiral catalysts play a crucial role in the green production of enantioenriched compounds. To further increase the green profile of this approach, the use of solid‐supported catalytic species is appealing due to the reduced generation of waste, as well as the possibility of reusing the precious catalyst. Even more attractive is the implementation of flow processes based on these immobilized catalysts, a flexible strategy that allows to generate from milli‐ to multi‐gram amounts of chiral product with a reduced footprint set‐up. Herein, we will present the efforts devoted in our laboratory towards the immobilization of chiral catalysts and their use in single‐pass, highly enantioselective, flow processes. Proline, diarylprolinols, other aminocatalysts, squaramides, thioureas, phosphoric acids and even chiral ligands and metal‐based catalysts constitute our current toolkit of supported species for enantioselective catalysis.     

Physico-Chemical and Phytochemical Characterization of Moroccan Wild Jujube “Zizyphus lotus (L.)” Fruit Crude Extract and Fractions

Wild jujube “Ziziphus lotus (L.) Desf.” belongs to the Rhamnaceae family and is a traditionally herbaceous medicinal plant. It is very common in arid and semi-arid regions and is currently used for its antidiabetic, sedative, analgesic, anti-inflammatory and hypoglycemic activities. The aim of the present work was to characterize the physico-chemical properties and the phytochemical profile of wild jujube sample collected from the Guercif region, in order to determine the polyphenolic compounds and the antioxidant ability Analyses were carried out directly after the harvest for the determination of pH, refractive index, total soluble solid (°Brix), dry matter, sugar/acidity, total sugars, reducing sugars, as well as lipid and protein content. Results showed that the investigated fruit is acidic (pH 4.9 ± 0.23) and rich in sugars (80.2 g/100 g ± 3.81). The GC-MS analysis of the fruit revealed a number of volatile compounds, as many as 97, belonging to different chemical classes. The HPLC-DAD-ESI/MS analysis showed the presence of a total of 20 polyphenolic compounds in both EtOAc and MeOH-water extracts. Among them, p-Hydroxybenzoic acid was the most abundant in the EtOAc extract (185.68 µg/100 mg ± 0.5) whereas Quercetin 3-O-rhamnoside-7-O-glucoside was found in higher amounts in the MeOH-water extract (25.40 µg/100 mg ± 0.5). These components have medical interest, notably for human nutrition, as well as health benefits and therapeutic effects. Therefore, Moroccan jujube “Zizyphus lotus (L.)” fruit may have potential industrial applications for food formulations.     

Highly Efficient Microwave‐Assisted Substitution of β‐Dicarbonyl Compounds with Secondary Alcohols Using Fluoroboric Acid as the Catalyst

The microwave‐assisted substitution of β‐dicarbonyl compounds with secondary alcohols has been achieved efficiently, using very cheap fluoroboric acid (HBF₄) as the catalyst. For various β‐dicarbonyl compounds and a series of secondary alcohols, the direct substitution gives high yields after only 5 min of microwave irradiation.     

Resin‐supported palladium nanoparticles as recyclable catalyst for the hydrodechlorination of chloroarenes and polychlorinated biphenyls

This study focuses on the hydrodechlorination of chlorinated arenes as well as polychlorinated biphenyls (PCBs) utilizing a resin‐supported Pd(0) catalyst. Bearing in mind the dangers associated with toxic PCBs, treatment of the remnants of industrial wastes containing PCB congeners is indispensable. One such method is reductive hydrodechlorination. Instead of utilizing traditional sources of hydrogen, ammonium formate is used for in situ hydrogen generation. Moreover, palladium nanoparticles are supported on an anionic exchange resin which makes the process recyclable with a negligible change of yield after recycling experiments. The catalyst is demonstrated in the hydrodechlorination of a wide range of chlorinated compounds and PCB congeners including aroclors 1242, 1248 and 1254. Copyright © 2016 John Wiley & Sons, Ltd.