Counterintuitive solvation effect of ionic-liquid/DMSO solvents on acidic C–H dissociation and insight into respective solvation

How would acidic bond dissociation be affected by adding a small quantity of a weakly polar ionic liquid IL (the “apparent” or “measured” dielectric constant ε of the IL is around 10–15) into a strongly polar molecular solvent (e.g., ε of DMSO: 46.5), or vice versa? The answer is blurred, because no previous investigation was reported in this regard. Toward this, we, taking various IL/DMSO mixtures as representatives, have thoroughly investigated the effects of the respective solvent in ionic–molecular binary systems on self-dissociation of C–H acid phenylmalononitrile PhCH(CN)₂via pK_a determination. As disclosed, in this category of binary media, (1) no linear correspondence exists between pK_a and molar fractions of the respective solvent components; (2) only ∼1–2 mol% of weakly polar ILs in strongly polar DMSO make C–H bonds even more dissociative than in neat DMSO; (3) a small fraction of DMSO in ILs (<10 mol%) can dramatically ease acidic C–H-dissociation; and (4) while the DMSO fraction further increases, its acidifying effect becomes much attenuated. These findings, though maybe counterintuitive, have been rationalized on the basis of the precise pK_a measurement of this work in relation to the respective roles of each solvent component in solvation.

The dependence of PhCH(CN)₂ pK_a on the molar fraction of ionic liquids in ionic–molecular binary mixtures showed a nonlinear three-fragment plot, which was rationalized for the first time by the respective roles of each solvent component for solvation.     

Adsorption of N,N,N′,N′-Tetraoctyl Diglycolamide on Hypercrosslinked Polysterene from a Supercritical Carbon Dioxide Medium

The work considers for the first time the preparation of sorbents based on hypercrosslinked polysterene (HCP) and chelating agent N,N,N′,N′-tetraoctyl diglycolamide (TODGA) by impregnation in the supercritical (SC) CO₂ medium. Such sorbents can be applied for further isolation and separation of lanthanides, actinides and other metals. They are usually prepared by impregnation in toxic organic solvents (e.g., methanol, dichloromethane). Our study shows that application of SC CO₂ instead of organic solvents can significantly speed up the impregnation, perfom it in one stage and make the process more eco-friendly. At the same time, the obtained sorbents are close in their parameters to the classical ones. This article presents the results of measuring the TODGA adsorption isotherms on two HCP sorbents (MN202 and MN270) on a wide range of SC fluid parameters. Adsorption measurements were carried out using on-line supercritical fluid chromatography and gravimetry. Based on the sorption capacity parameter, MN202 sorbent was selected as the better carrier for TODGA. An impregnation temperature increase within the range 313–343 K in isochoric conditions (ρ = 0.780 g/mL) reduces the maximum of TODGA adsorption from ~0.68 mmol/g to ~0.49 mmol/g.     

The Antifungal Action Mode of N-Phenacyldibromobenzimidazoles

Our study aimed to characterise the action mode of N-phenacyldibromobenzimidazoles against C. albicans and C. neoformans. Firstly, we selected the non-cytotoxic most active benzimidazoles based on the structure–activity relationships showing that the group of 5,6-dibromobenzimidazole derivatives are less active against C. albicans vs. 4,6-dibromobenzimidazole analogues (5e–f and 5h). The substitution of chlorine atoms to the benzene ring of the N-phenacyl substituent extended the anti-C. albicans action (5e with 2,4-Cl₂ or 5f with 3,4-Cl₂). The excellent results for N-phenacyldibromobenzimidazole 5h against the C. albicans reference and clinical isolate showed IC₅₀ = 8 µg/mL and %I = 100 ± 3, respectively. Compound 5h was fungicidal against the C. neoformans isolate. Compound 5h at 160–4 µg/mL caused irreversible damage of the fungal cell membrane and accidental cell death (ACD). We reported on chitinolytic activity of 5h, in accordance with the patterns observed for the following substrates: 4-nitrophenyl-N-acetyl-β-d-glucosaminide and 4-nitrophenyl-β-d-N,N′,N″-triacetylchitothiose. Derivative 5h at 16 µg/mL: (1) it affected cell wall by inducing β-d-glucanase, (2) it caused morphological distortions and (3) osmotic instability in the C. albicans biofilm-treated. Compound 5h exerted Candida-dependent inhibition of virulence factors.     

Anti-Electrostatic Pi-Hole Bonding: How Covalency Conquers Coulombics

Intermolecular bonding attraction at π-bonded centers is often described as “electrostatically driven” and given quasi-classical rationalization in terms of a “pi hole” depletion region in the electrostatic potential. However, we demonstrate here that such bonding attraction also occurs between closed-shell ions of like charge, thereby yielding locally stable complexes that sharply violate classical electrostatic expectations. Standard DFT and MP2 computational methods are employed to investigate complexation of simple pi-bonded diatomic anions (BO⁻, CN⁻) with simple atomic anions (H⁻, F⁻) or with one another. Such “anti-electrostatic” anion–anion attractions are shown to lead to robust metastable binding wells (ranging up to 20–30 kcal/mol at DFT level, or still deeper at dynamically correlated MP2 level) that are shielded by broad predissociation barriers (ranging up to 1.5 Å width) from long-range ionic dissociation. Like-charge attraction at pi-centers thereby provides additional evidence for the dominance of 3-center/4-electron (3c/4e) n_D-π*_AX interactions that are fully analogous to the n_D-σ*_AH interactions of H-bonding. Using standard keyword options of natural bond orbital (NBO) analysis, we demonstrate that both n-σ* (sigma hole) and n-π* (pi hole) interactions represent simple variants of the essential resonance-type donor-acceptor (Bürgi–Dunitz-type) attraction that apparently underlies all intermolecular association phenomena of chemical interest. We further demonstrate that “deletion” of such π*-based donor-acceptor interaction obliterates the characteristic Bürgi–Dunitz signatures of pi-hole interactions, thereby establishing the unique cause/effect relationship to short-range covalency (“charge transfer”) rather than envisioned Coulombic properties of unperturbed monomers.     

Polycation–Polyanion Architecture of the Intermetallic Compound Mg3−xGa1+xIr

Mg_3−xGa_1+xIr (x = 0.05) was synthesized by direct reaction of the elements in welded tantalum containers at 1200 °C and subsequent annealing at 500 °C for 30 days. Its crystal structure represents a new prototype and was determined by single-crystal technique as follows: space group P6₃/mcm, Pearson symbol hP90, Z = 18, a = 14.4970(3) Å, c = 8.8638(3) Å. The composition and atomic arrangement in Mg₃GaIr do not follow the 8–N rule due to the lack of valence electrons. Based on chemical bonding analysis in positional space, it was shown that the title compound has a polycationic–polyanionic organization. In comparison with other known intermetallic substances with this kind of bonding pattern, both the polyanion and the polyanion are remarkably complex. Mg_3−xGa_1+xIr is an example of how the general organization of intermetallic substances (e.g., formation of polyanions and polycations) can be understood by extending the principles of 8–N compounds to electron-deficient materials with multi-atomic bonding.     

Chemical Characterization of Plant Extracts and Evaluation of their Nematicidal and Phytotoxic Potential

Nacobbus aberrans ranks among the “top ten” plant-parasitic nematodes of phytosanitary importance. It causes significant losses in commercial interest crops in America and is a potential risk in the European Union. The nematicidal and phytotoxic activities of seven plant extracts against N. aberrans and Solanum lycopersicum were evaluated in vitro, respectively. The chemical nature of three nematicidal extracts (EC_50,48h ≤ 113 µg mL⁻¹) was studied through NMR analysis. Plant extracts showed nematicidal activity on second-stage juveniles (J2): (≥87%) at 1000 µg mL⁻¹ after 72 h, and their EC₅₀ values were 71.4–468.1 and 31.5–299.8 µg mL⁻¹ after 24 and 48 h, respectively. Extracts with the best nematicidal potential (EC_50,48h < 113 µg mL⁻¹) were those from Adenophyllum aurantium, Alloispermum integrifolium, and Tournefortia densiflora, which inhibited L. esculentum seed growth by 100% at 20 µg mL⁻¹. Stigmasterol (1), β-sitosterol (2), and α-terthienyl (3) were identified from A. aurantium, while 1, 2, lutein (4), centaurin (5), patuletin-7-β-O-glucoside (6), pendulin (7), and penduletin (8) were identified from A. integrifolium. From T. densiflora extract, allantoin (9), 9-O-angeloyl-retronecine (10), and its N-oxide (11) were identified. The present research is the first to report the effect of T. densiflora, A. integrifolium, and A. aurantium against N. aberrans and chemically characterized nematicidal extracts that may provide alternative sources of botanical nematicides.     

Computational Studies of Coinage Metal Anion M− + CH3X (X = F,Cl, Br,I) Reactions in Gas Phase

We characterized the stationary points along the nucleophilic substitution (S_N2), oxidative insertion (OI), halogen abstraction (XA), and proton transfer (PT) product channels of M⁻ + CH₃X (M = Cu, Ag, Au; X = F, Cl, Br, I) reactions using the CCSD(T)/aug-cc-pVTZ level of theory. In general, the reaction energies follow the order of PT > XA > S_N2 > OI. The OI channel that results in oxidative insertion complex [CH₃–M–X]⁻ is most exothermic, and can be formed through a front-side attack of M on the C-X bond via a high transition state OxTS or through a S_N2-mediated halogen rearrangement path via a much lower transition state invTS. The order of OxTS > invTS is inverted when changing M⁻ to Pd, a d¹⁰ metal, because the symmetry of their HOMO orbital is different. The back-side attack S_N2 pathway proceeds via typical Walden-inversion transition state that connects to pre- and post-reaction complexes. For X = Cl/Br/I, the invS_N2-TS’s are, in general, submerged. The shape of this M⁻ + CH₃X S_N2 PES is flatter as compared to that of a main-group base like F⁻ + CH₃X, whose PES has a double-well shape. When X = Br/I, a linear halogen-bonded complex [CH₃−X∙··M]⁻ can be formed as an intermediate upon the front-side attachment of M on the halogen atom X, and it either dissociates to CH₃ + MX⁻ through halogen abstraction or bends the C-X-M angle to continue the back-side S_N2 path. Natural bond orbital analysis shows a polar covalent M−X bond is formed within oxidative insertion complex [CH₃–M–X]⁻, whereas a noncovalent M–X halogen-bond interaction exists for the [CH₃–X∙··M]⁻ complex. This work explores competing channels of the M⁻ + CH₃X reaction in the gas phase and the potential energy surface is useful in understanding the dynamic behavior of the title and analogous reactions.     

Entropy directs the self-assembly of supramolecular palladium coordination macrocycles and cages

The self-assembly of palladium-based cages is frequently rationalized via the cumulative enthalpy (ΔH) of bonds between coordination nodes (M, i.e., Pd) and ligand (L) components. This focus on enthalpic rationale limits the complete understanding of the Gibbs free energy (ΔG) for self-assembly, as entropic (ΔS) contributions are overlooked. Here, we present a study of the M₂^linL₃ intermediate species (M = dinitrato(N,N,N′,N′-tetramethylethylenediamine)palladium(ii), ^linL = 4,4′-bipyridine), formed during the synthesis of triangle-shaped (M₃^linL₃) and square-shaped (M₄^linL₄) coordination macrocycles. Thermochemical analyses by variable temperature (VT) ¹H-NMR revealed that the M₂^linL₃ intermediate exhibited an unfavorable (relative) ΔS compared to M₃^linL₃ (triangle, ΔTΔS = +5.22 kcal mol⁻¹) or M₄^linL₄ (square, ΔTΔS = +2.37 kcal mol⁻¹) macrocycles. Further analysis of these constructs with molecular dynamics (MD) identified that the self-assembly process is driven by ΔG losses facilitated by increases in solvation entropy (ΔS_solv, i.e., depletion of solvent accessible surface area) that drives the self-assembly from “open” intermediates toward “closed” macrocyclic products. Expansion of our computational approach to the analysis of self-assembly in Pd_n^benL_2n cages (^benL = 4,4''-(5-ethoxy-1,3-phenylene)dipyridine), demonstrated that ΔS_solv contributions drive the self-assembly of both thermodynamic cage products (i.e., Pd₁₂^benL₂₄) and kinetically-trapped intermediates (i.e., Pd₈^cL₁₆).

These studies demonstrate that ΔS drives the self-assembly of supramolecular palladium-based coordination macrocycles and cages. As this ΔS contribution arises from solvation, these findings broadly reflect the thermodynamic drive of self-assembly to form compact structures.     

The Removal of Time–Concentration Data Points from Progress Curves Improves the Determination of Km: The Example of Paraoxonase 1

Several approaches for determining an enzyme’s kinetic parameter K_m (Michaelis constant) from progress curves have been developed in recent decades. In the present article, we compare different approaches on a set of experimental measurements of lactonase activity of paraoxonase 1 (PON1): (1) a differential-equation-based Michaelis–Menten (MM) reaction model in the program Dynafit; (2) an integrated MM rate equation, based on an approximation of the Lambert W function, in the program GraphPad Prism; (3) various techniques based on initial rates; and (4) the novel program “iFIT”, based on a method that removes data points outside the area of maximum curvature from the progress curve, before analysis with the integrated MM rate equation. We concluded that the integrated MM rate equation alone does not determine kinetic parameters precisely enough; however, when coupled with a method that removes data points (e.g., iFIT), it is highly precise. The results of iFIT are comparable to the results of Dynafit and outperform those of the approach with initial rates or with fitting the entire progress curve in GraphPad Prism; however, iFIT is simpler to use and does not require inputting a reaction mechanism. Removing unnecessary points from progress curves and focusing on the area around the maximum curvature is highly advised for all researchers determining K_m values from progress curves.     

Structural Diversity of Silver Fluorinated β-Diketonates: Effect of the Terminal Substituent and Solvent

In order to demonstrate the role of the fluorination and some solvents in the structural organization of the Ag(I) coordination polymers with β-diketonate ligands (R¹C(O)C_αHC(O)R²)⁻ we synthesized a series of the compounds containing tfac- (R₁ = CH₃, R² = CF₃) and pfpac- (R₁ = CH₃, R² = C₂F₅) anions. Solvent-free [Ag(L)]_∞ (L = tfac 1, pfpac 2) compounds and the corresponding acetonitrile and toluene adducts have been characterized by elemental analysis and/or NMR, IR and single-crystal XRD. This series includes five new coordination polymers. Compound 1 is a 3D coordination framework based on Ag–O_{chelate/bridge}, Ag–C_α bonds, and argentophilic interactions. An increase in the fluorinated group leads to a chain coordination polymer 2 of an unusual structural organization. These chains can be represented as a “DNA-type”, where two intertwined helices based on Ag–O_chelate and Ag–C_α bonds are connected through Ag–O_bridge ones. Two structural types of chain coordination polymers, [Ag(tfac)(CH₃CN)] and [Ag₂(L)₂(solvent)], have been revealed for the adducts. The latter structural type differs significantly from the previously studied toluene and acetonitrile adducts of fluorinated Ag(I) β-diketonates of the same stoichiometry. Thermal analysis in helium showed that both 1 and 2 decompose to metallic silver with the compound of pfpac-ligand being slightly more stable.     

Highly Oxygenated Triterpenoids and Diterpenoids from Fructus Rubi (Rubus chingii Hu) and Their NF-kappa B Inhibitory Effects

During a phytochemical investigation of the unripe fruits of Rubus chingii Hu (i.e., Fructus Rubi, a traditional Chinese medicine named “Fu-Pen-Zi”), a number of highly oxygenated terpenoids were isolated and characterized. These included nine ursane-type (1, 2, and 4–10), five oleanane-type (3, 11–14), and six cucurbitane-type (15–20) triterpenoids, together with five ent-kaurane-type diterpenoids (21–25). Among them, (4R,5R,8R,9R,10R,14S,17S,18S,19R,20R)-2,19α,23-trihydroxy-3-oxo-urs-1,12-dien-28-oic acid (rubusacid A, 1), (2R*,4S*,5R*,8R*,9R*,10R*,14S*,17S*, 18S*,19R*,20R*)-2α,19α,24-trihydroxy-3-oxo-urs-12-en-28-oic acid (rubusacid B, 2), (5R,8R,9R,10R, 14S,17R,18S,19S)-2,19α-dihydroxy-olean-1,12-dien-28-oic acid (rubusacid C, 3), and (3S,5S,8S,9R, 10S,13R,16R)-3α,16α,17-trihydroxy-ent-kaur-2-one (rubusone, 21) were previously undescribed. Their chemical structures and absolute configurations were elucidated on the basis of spectroscopic data and electronic circular dichroism (ECD) analyses. Compounds 1 and 3 are rare naturally occurring pentacyclic triterpenoids featuring a special α,β-unsaturated keto-enol (diosphenol) unit in ring A. Cucurbitacin B (15), cucurbitacin D (16), and 3α,16α,20(R),25-tetrahydroxy-cucurbita-5,23- dien-2,11,22-trione (17) were found to have remarkable inhibitory effects against NF-κB, with IC₅₀ values of 0.08, 0.61, and 1.60 μM, respectively.     

Antitumor Effect of Guatteria olivacea R. E. Fr. (Annonaceae) Leaf Essential Oil in Liver Cancer

Guatteria olivacea R. E. Fries (synonym Guatteria punctata (Aubl.) R.A. Howard) is a tree of 10–27 m tall popularly known as “envira-bobó”, “envira-fofa”, “envireira”, “embira”, “embira-branca”, “embira-preta”, envira-branca”, and “envira-preta”, which can be found in the Brazilian Amazon biome. In this study, we evaluated the cytotoxic and antitumor effects of the essential oil (EO) obtained from the leaves of G. olivacea against liver cancer using HepG2 cells as a model. EO was obtained using a hydrodistillation Clevenger-type apparatus and was qualitatively and quantitatively characterized using GC–MS and GC–FID, respectively. The alamar blue assay was used to assess the cytotoxic potential of EO in a panel of human cancer cell lines and human non-cancerous cells. In HepG2 cells treated with EO, YO-PRO-1/propidium iodide staining, cell cycle distribution, and reactive oxygen species (ROS) were examined. In C.B-17 SCID mice with HepG2 cell xenografts, the efficacy of the EO (20 and 40 mg/kg) was tested in vivo. GC–MS and GC–FID analyses showed germacrene D (17.65%), 1-epi-cubenol (13.21%), caryophyllene oxide (12.03%), spathulenol (11.26%), (E)-caryophyllene (7.26%), bicyclogermacrene (5.87%), and δ-elemene (4.95%) as the major constituents of G. olivacea leaf EO. In vitro cytotoxicity of EO was observed, including anti-liver cancer action with an IC₅₀ value of 30.82 μg/mL for HepG2 cells. In HepG2 cells, EO treatment increased apoptotic cells and DNA fragmentation, without changes in ROS levels. Furthermore, the EO inhibited tumor mass in vivo by 32.8–57.9%. These findings suggest that G. olivacea leaf EO has anti-liver cancer potential.     

Supramolecular Diiodine-Bromostannate(IV) Complexes: Narrow Bandgap Semiconductors

Three supramolecular bromostannates(IV) with “trapped” diiodine molecules, Cat₂{[SnBr₆](I₂)} (Cat = Me₄N⁺ (1), 1-MePy⁺ (2) and 4-MePyH (3)), were synthesized. In all cases, I₂ linkers are connected with bromide ligands via halogen···halogen non-covalent interactions. Articles 1–3 were studied using Raman spectroscopy, thermogravimetric analysis, and diffuse reflectance spectroscopy. The latter indicates that 1–3 are narrow band gap semiconductors.     

Antimicrobial,Cytotoxic and Mutagenic Activity of Gemini QAS Derivatives of 1,4:3,6-Dianhydro-l-iditol

A series of quaternary diammonium salts derivatives of 1,4:3,6-dianhydro-l-iditol were synthesized, using isommanide (1,4:3,6-dianhydro-d-mannitol) as a starting material. Both aromatic (pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), (3-carboxamide)pyridine; N-methylimidazole) and aliphatic (trimethylamine, N,N-dimethylhexylamine, N,N-dimethyloctylamine, N,N-dimethyldecylamine) amines were used, giving eight gemini quaternary ammonium salts (QAS). All salts were tested for their antimicrobial activity against yeasts, Candida albicans and Candida glabrata, as well as bacterial Staphylococcus aureus and Escherichia coli reference strains. Moreover, antibacterial activity against 20 isolates of S. aureus collected from patients with skin and soft tissue infections (n = 8) and strains derived from subclinical bovine mastitis milk samples (n = 12) were evaluated. Two QAS with octyl and decyl residues exhibited antimicrobial activity, whereas those with two decyl residues proved to be the most active against the tested pathogens, with MIC of 16–32, 32, and 8 µg/mL for yeast, E. coli, and S. aureus reference and clinical strains, respectively. Only QAS with decyl residues proved to be cytotoxic in MTT assay against human keratinocytes (HaCaT), IC₅₀ 12.8 ± 1.2 μg/mL. Ames test was used to assess the mutagenic potential of QAS, and none of them showed mutagenic activity in the concentration range 4–2000 µg/plate.     

Activity Guided Isolation of Phenolic Compositions from Anneslea fragrans Wall. and Their Cytoprotective Effect against Hydrogen Peroxide Induced Oxidative Stress in HepG2 Cells

Anneslea fragrans Wall., commonly known as “Pangpo Tea”, is traditionally used as a folk medicine and healthy tea for the treatment of liver and intestine diseases. The aim of this study was to purify the antioxidative and cytoprotective polyphenols from A. fragrans leaves. After fractionation with polar and nonpolar organic solvents, the fractions of aqueous ethanol extract were evaluated for their total phenolic (TPC) and flavonoid contents (TFC) and antioxidant activities (DPPH, ABTS, and FRAP assays). The n-butanol fraction (BF) showed the highest TPC and TFC with the strongest antioxidant activity. The bio-guided chromatography of BF led to the purification of six flavonoids (1–6) and one benzoquinolethanoid (7). The structures of these compounds were determined by NMR and MS techniques. Compound 6 had the strongest antioxidant capacity, which was followed by 5 and 2. The protective effect of the isolated compounds on hydrogen peroxide (H₂O₂)-induced oxidative stress in HepG2 cells revealed that the compounds 5 and 6 exhibited better protective effects by inhibiting ROS productions, having no significant difference with vitamin C (p > 0.05), whereas 6 showed the best anti-apoptosis activity. The results suggest that A. fragrans could serve as a valuable antioxidant phytochemical source for developing functional food and health nutraceutical products.     

Green Strategies for the Preparation of Enantiomeric 5–8-Membered Carbocyclic β-Amino Acid Derivatives through CALB-Catalyzed Hydrolysis

Candida antarctica lipase B-catalyzed hydrolysis of carbocyclic 5–8-membered cis β-amino esters was carried out in green organic media, under solvent-free and ball-milling conditions. In accordance with the high enantioselectivity factor (E > 200) observed in organic media, the preparative-scale resolutions of β-amino esters were performed in tBuOMe at 65 °C. The unreacted β-amino ester enantiomers (1R,2S) and product β-amino acid enantiomers (1S,2R) were obtained with modest to excellent enantiomeric excess (ee) values (ee_s > 62% and ee_p > 96%) and in good chemical yields (>25%) in one or two steps. The enantiomers were easily separated by organic solvent/H₂O extraction.     

Non-metal with metal behavior: metal-free coordination-insertion ring-opening polymerization

The “coordination-insertion” ring-opening polymerization (ROP) mechanism has so far been the monopoly of metal catalysts. In this work, we present a metal-free “coordination-insertion” ROP of trimethylene carbonate (TMC) and ε-caprolactone (ε-CL), as well as their sequential block copolymerization, with N-trimethylsilyl-bis (trifluoromethanesulfonyl)imide (TMSNTf₂) as the non-metallic initiator/catalyst. TMSNTf₂ was proposed to work through an unprecedented metal-free “coordination-insertion” mechanism, which involves the coordination of monomer to the Si atom of TMSNTf₂, the nucleophilic attack of the –NTf₂ group on the coordinated monomer, and the cleavage of the acyl–oxygen bond of the monomer. The proposed metal-free “coordination-insertion” ROP was studied by NMR, SEC, and MALDI-TOF analyses. In addition, the TMSNTf₂-mediated ROP of TMC and ε-CL led to linear and cyclic polymers following two-stage first-order polymerization processes, as evidenced by structural analyses and kinetics study, which further demonstrated the metal-free “coordination-insertion” mechanism.

The first metal-free “coordination-insertion” ROP of cyclic carbonate and lactones mediated by N-trimethylsilyl-bis(trifluoromethanesulfonyl)imide (TMSNTf₂) was proposed, which in the past was exclusively the monopoly of metal complex catalysts.     

Solution and Solid State Studies of Urea Derivatives of DITIPIRAM Acting as Powerful Anion Receptors

Herein, we present the synthesis and anion binding studies of a family of homologous molecular receptors 4–7 based on a DITIPIRAM (8-propyldithieno-[3,2-b:2′,3′-e]-pyridine-3,5-di-amine) platform decorated with various urea para-phenyl substituents (NO₂, F, CF₃, and Me). Solution, X-ray, and DFT studies reveal that the presented host–guest system offers a convergent array of four urea NH hydrogen bond donors to anions allowing the formation of remarkably stable complexes with carboxylates (acetate, benzoate) and chloride anions in solution, even in competitive solvent mixtures such as DMSO-d₆/H₂O 99.5/0.5 (v/v) and DMSO-d₃/MeOH-d₃ 9:1 (v/v). The most effective derivatives among the series turned out to be receptors 5 and 6 containing electron-withdrawing F- and -CF₃ para-substituents, respectively.     

Distinct chemoselectivity in the reaction of N-(thio)phosphoryl imines with diethylzinc

This report describes the reaction of N-(thio)phosphoryl imines with diethylzinc under different conditions. An interesting and distinct chemoselectivity between hydrogen-addition and ethyl-addition to imine double bond is disclosed: in weakly polar solvent, e.g. toluene, N-(thio)phosphoryl imines were exclusively reduced in excellent yields via a β-H transfer from diethylzinc to imine double bond; in polar solvents like THF, the reduction product was competitively formed as a major product together with the minor product resulting from ethyl-addition to imine double bond; in sharp contrast, in the presence of strong coordinative additive N,N,N′,N′-tetramethylethylenediamine (TMEDA), the ethylation product was formed exclusively from the reaction of N-(thio)phosphoryl imine with diethylzinc. These results are discussed and explained in terms of the coordination interactions between the imine, solvent, and additive with diethylzinc.