Neutral Anion Research Articles

Progressive Cation Triggered Anion Binding by Electron-Rich Scaffold: Case Study of a Neutral Tripodal Naphthyl Thiourea Receptor

A neutral tripodal electron-rich anion receptor L, decorated from a tren building block, has been deliberately synthesized from acetonitrile for thorough investigation of host–guest binding aptitude in the solid state especially. The naphthyl-based tris-thiourea scaffold, without the presence of any π-acidic or electron-withdrawing aryl terminals, has been established as a potential system that can efficiently bind anions of varied dimensionality consistently triggered by the size of the countercation, as regularly observed from single crystal X-ray analysis, and well supported by solution state NMR binding studies. The newness of this report is the systematic and consistent solid state anion binding within the inner tripodal receptor cleft of highly electron-rich naphthyl terminals. Although the receptor L was first synthesized in the 19th century, no solid state binding studies have been reported until now. However, numerous tren-based urea/thiourea ligands with several terminal functionalizations havin...

Placental function and structure at term is altered in broodmares fed with cereals from mid-gestation

IntroductionFeeding pregnant broodmares with cereal concentrates has been shown to increase maternal insulin resistance and affect foal metabolism in the short and long-term. These effects are likely to be mediated by the placenta. Here, we investigated feto-placental biometry and placental structure and function at term in mares fed with or without cereals concentrates. Material and methodsFrom 7 months of gestation, 22 multiparous mares were fed forage only (group F (n = 12)) or received forage and cracked barley (group B (n = 10)) until foaling. Foals and placentas were weighed and placental samples were collected above the umbilical cord insertion at birth. Placental histological structure was studied by stereology. A RNAseq analysis was performed on 9 placentas of each group. Enrichment of gene sets was analysed using the Gene Set Enrichment Analysis (GSEA) software using the KEGG and GO databases. ResultsNo difference in feto-placental biometry was observed between groups. The volume of microcotyledonary vessels was decreased in B placentas and the vascular wall of allantoic arterioles was thickened. Gene sets involved in neutral amino acids, folate and anions transport and fatty acids, cholesterol and folate degradation were down-regulated while gene sets involved in RNA expression, inflammation and vascularisation were up-regulated in B placentas. ConclusionFeeding pregnant mares with concentrates from mid-gestation alters the placental function and structure as observed in other species in cases of maternal insulin resistance.

Investigating the effects of structure on sulfate recognition by neutral dipeptide receptors

A small library of neutral peptide-based anion receptors was synthesised, where changes were made to the scaffold structure to investigate the effect these structural features have on the anion binding ability of these receptors. These changes included shortening the peptide side chain lengths, increasing the number of electron withdrawing substituents present on the squaramide phenyl substituents and increasing the length and flexibility of the peptide backbone. An effort was also made to increase the aqueous solubility of these receptors by functionalising the N-terminus of the peptide with a hydrophilic moiety. All the receptors displayed strong affinity and selectivity for sulfate in 20% v/v H2O/DMSO-d6 and a 5-fold increase in the affinity of the thiourea receptors was observed upon shortening the side chains by one methylene unit. Overall, the squaramide derivatives displayed much stronger association, in this competitive media, than the thiourea based receptors.

Selective EPR Detection of Primary Amines in Water with a Calix[6]azacryptand-Based Copper(II) Funnel Complex.

A water-soluble calix[6]arene-based azacryptand was synthesized. The corresponding tren [tris(2-aminoethyl)amine] cap grafted at the small rim coordinates strongly a copper(II) ion over a wide range of pH. The host-guest properties of the complex were explored by EPR spectroscopy. Due to second coordination sphere effects and the hydrophobic effect ascribed to the calixarene cavity, this funnel complex selectively binds neutral molecules (alcohols, nitriles, amines) versus anions in water near physiological pH. Among the coordinating guests, hydrophobic primary amines are preferentially recognized thanks to the combined effect of the better metal-ligand interaction and hydrogen bonding to the oxygen atoms present at the small rim. Hence, this Cu(II) calix[6]arene-based funnel complex behaves as a sensitive and selective EPR probe for primary amines, including biologically important molecules such as tyramine and tryptamine, in water, over a large pH window.

Bambusurils Bearing Nitro Groups and Their Further Modifications

Bambusurils are recently developed neutral anion receptors that show a high affinity towards many inorganic anions, not only in organic solvents but also in water. However, the number of water‐soluble bambusurils and also those bearing functional groups is very limited. In this paper we report the synthesis of four‐ and six‐membered bambusurils containing eight and twelve nitro groups. All the nitro groups on the bambusuril portals could be transformed into amino functions, which provided the macrocycles with water solubility and allowed their further modification. For example, we have demonstrated the conversion of amino groups on the bambusurils into the corresponding urea‐functionalized bambusuril derivatives. We also report the first example of a bambusuril bearing only two functional groups, which was prepared by the condensation of two different glycolurils.

Эволюция анионных и катионных экситонов в щелочно-галоидных кристаллах (О б з о р)

AbstractThe manifestations of the existence of free anion excitons, the processes of their self-trapping, and the coexistence of mobile and self-trapped excitons (STEs) in wide-gap alkali halide crystals are reviewed. The radiative channel of decay of anion excitons, yielding luminescence, and a particular type of nonradiative channel with the creation of elementary Frenkel defects (FDs) are considered. We analyzed the criteria for the efficiency of this channel for defect formation, possible mechanisms for the decay of self-trapped excitons with the production of neutral and charged anion Frenkel defects, and the processes of multiplication of electronic excitations in alkali halide crystals. Particular attention is paid to the decay of cation excitons, including from the point of view of the possibility of the low-temperature creation of elementary Frenkel defects in the cation sublattice of alkali halide crystals.

Design and application of a fluorogenic receptor for selective sensing of cations, small neutral molecules, and anions

An unprecedented single multi-analyte fluorogenic receptor, a sodium salt of N-(methyl-2-thiophenyl)-tyrosine (NaHTyrthio), is reported for the selective sensing of cations (Cu2+), small neutral molecules (nitrobenzene and aniline) and anions (F−) by variable spectral responses.

Chemically modified (poly)vinyl chloride with built-in neutral carrier function as a new material for ion selective electrodes

The procedure for introducing 4-(trifluoroacetyl)benzoate groups into (poly)vinyl chloride has been developed. The new material thus prepared, 4-(trifluoroacetyl)benzoate modified (poly)vinyl chloride (TFAB-PVC), contains a built-in neutral anion carrier function. It has been shown that using TFAB-PVC instead of a known anion carrier additive, 4-(trifluoroacetyl)benzoic acid heptyl ester (TFABAHE), in sulfate, hydrogen phosphate and sulfide anion selective electrodes considerably increases the electrode’s lifetime even in alkaline media, probably by preventing crystallization of TFABAHE hydrate form on the membrane surface and slowing down the hydrolysis of ester groups and dissolution of the anion carrier.

Weak M···H–C Interactions in Neutral Complexes, Anions and Cations of Palladium(II) and Rhodium(I) Containing the iso‐Quinoline Ligand – Anagostic or Preagostic?

DFT‐D calculations show that the above‐plane M···H–C separations in square‐planar complexes of PdII and RhI containing the iso‐quinoline ligand are influenced by whether the complexes are neutral, anionic or cationic, due mainly to changes in atomic charge on the metal, H and C atoms, but the nature of the cis‐ligands also plays a part because of the development of weak intramolecular interactions. The Pd···H–C separations are effected by strong σ‐withdrawing or π‐donating substituents placed at C7 of the iso‐quinoline ligand with the shortest anagostic Pd···H separation of 2.218 Å achieved using the π‐donating S– substituent in an anionic complex. The same substituent on the cationic complex leads to Pd–C covalency. Lack of flexibility of the iso‐quinoline ring system prevents the anagostic carbon approaching the metal when the electrostatics are favourable. Instead of an anagostic/preagostic divide, it is suggested that all complexes with above‐plane Pd···H–C close approaches are termed anagostic, and where some agostic covalency develops below an NBO (Natural Bond Order) E(2) value of 5 kcal mol–1 they can be regarded as having an emerging preagostic condition.

65 Placental Function at Term is Altered in Broodmares Fed with Cereals from Mid Gestation

Recent data obtained in our laboratory suggest that feeding pregnant broodmares with cereal concentrates may affect both mare and foal metabolism in the short and long term. Here, we investigated feto-placental biometry and placental function at term in mares fed with cereals and forage or forage only. Twenty-two multiparous mares inseminated with the same stallion were allocated to 1 of 2 groups from 7 months of gestation: group F (n = 10) were fed forage only, whereas group B (n = 12) received forage and cracked barley until foaling. At 3 and 9 months of gestation, a glucose tolerance test (IVGTT) was performed to evaluate the insulin resistance of pregnant mares. At birth, placentas and foals were weighed and measured. Placental samples were collected above the umbilical cord insertion and snap frozen. An RNA sequencing (RNAseq) analysis was performed on 9 placentas of each group. After normalization, gene levels were analysed using the DESEqn 2 package of R software (https://www.r-project.org/). Enrichment of gene sets was analysed using the Gene Set Enrichment Analysis (GSEA) software using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology [GO, biological processes (bp), molecular function (mf) and cellular components (cc)] databases. Gene analysis statistical results were considered significant for P-values < 0.05 after false rate discovery (fdr) correction. The IVGTT results were analysed using a type 3 ANOVA on a mixed linear model with group as fixed effect and age of the mare as random effect. At 3 months of gestation, maternal glucose metabolism was not different between groups. At 9 months, B mares had a higher insulin area under the curve (AUC) after glucose injection than F mares (P < 0.01), without any difference in glucose AUC, suggesting that B mares were more insulin resistant than F mares. At birth, no difference was observed for feto-placental biometry between groups. Gene-level analysis could not discern differences in gene expression between groups after fdr correction. The GSEA analysis, however, showed that 8 gene sets were down-regulated in C placentas (2 KEGG, 2 GObp, 3 GOmf, 1 GOcc) and 193 gene sets were up-regulated (15 KEGG, 144 GObp, 12 GOmf, 22 GOcc) in B placentas. The down-regulated gene sets were involved in neutral amino acids and anion transport, fatty acid oxidation, acetyl coA synthesis, cholesterol and folate degradation, and the up-regulated gene sets were involved in RNA expression, inflammation (activation and recruitment of immune cells, MAPK signalling, complement and coagulation cascades, pro-inflammatory cytokine production and signalling) and in vascularisation (vasculogenesis, angiogenesis and smooth muscle cells development). The results are consistent with the altered function observed in term placentas of women who suffer from gestational diabetes. In conclusion, feeding pregnant mares with cereal from mid gestation alters the placental function at term. The authors thank the GeT platform (Toulouse, France) for the sequencing of the samples.

Ion-selective electrodes based on long-chain quaternary ammonium salts with enhanced steric accessibility, and their application for determination of hydrophilic double-charged inorganic anion

The effect of long-chain quaternary ammonium salts’ exchange center steric accessibility and presence of a neutral anion carrier, 4-(trifluoroacetyl)benzoic acid heptyl ester, upon analytical characteristics of ion-selective electrodes reversible to molybdate, tungstate, sulfate, hydrogen phosphate, sulfite, carbonate and thiosulfate anions, has been studied. When the most sterically hindered quaternary ammonium salts, trinonyl octadecyl ammonium bromide, is replaced by one of the salts with the accessible exchange center, the selectivity is altered, the magnitude of the selectivity coefficient change being determined by the nature of the interfering ion. Thus, for carbonate- and sulfate-selective ISEs with hydrophobic thiocyanate ions as interference, the effect achieved is 6–8 orders of magnitude, while with nitrate ions as interference it is 3.4–5.7 orders, and for such hydrophilic interference ions as sulfate, chloride and oxalate, it is even less. Replacing trinonyl octadecyl ammonium bromide with a sterically accessible ammonium salt improves lower detection limit generally by 1–2 orders, while for sulfite and thiosulfate ISEs the effect is only 0.3–0.95 orders. The procedures for determination of sulfate, sulfite and carbonate ions in real objects (mineral water, dried fruits) have been proposed. They are simple, reasonably accurate, require only widely available equipment and can be recommended for use in chemical and food industries.

Quantum Chemical Studies on Electron-Accepting Overcrowded Ethylene with a Polarizable Skeleton.

We report the quantum chemical studies on the neutral and radical anion forms of an electron-accepting overcrowded ethylene (OCE1) featuring a highly polarizable skeleton based on the density functional theory (DFT) approach using the M06-2X hybrid functional. Calculated results indicate that OCE1 (bis{4H,8H-4-(dicyanomethylene)benzo[1,2-c:4,5-c']bis[1,2,5]thiadiazol-8-ylidene}) shows conformational behaviors and energetics similar to those of bianthrone (OCE2), a typical thermochromic overcrowded ethylene. Neutral OCE1 and its radical anion have antifolded (afOCE1) and twisted (tOCE1) isomers on their potential energy surfaces. The calculated isomerization barrier heights of OCE1 and its radical anion are considerably low, indicating that its conformation is susceptible to interactions with surrounding molecules. While two afOCE1 molecules can form a simple π-stacked dimer, tOCE1 tends to be converted to afOCE1 when the two tOCE1 molecules come close together, indicating the instability of tOCE1 in the homogeneous OCE1 solid state. The thermochromic behavior difference between OCE1 and OCE2 in solution is closely associated with the considerably small energy difference between the afOCE1 and the tOCE1 as compared with OCE2. The properties of OCE1 are also compared with other typical electron-accepting overcrowded ethylenes in terms of electronic structure, energetics, and conformational behaviors.

Guest-Responsive Metal-Organic Frameworks as Scaffolds for Separation and Sensing Applications.

Metal-organic frameworks (MOFs) have evolved to be next-generation utility materials because of their serviceability in a wide variety of applications. Built from organic ligands with multiple binding sites in conjunction with metal ions/clusters, these materials have found profound advantages over their other congeners in the domain of porous materials. The plethora of applications that these materials encompass has motivated material chemists to develop such novel materials, and the catalogue of MOFs is thus ever-escalating. One key feature that MOFs possess is their responsiveness toward incoming guest molecules, resulting in changes in their physical and chemical properties. Such uniqueness generally arises owing to the influenceable ligands and/or metal units that govern the formation of these ordered architectures. The suitable host-guest interactions play an important role in determining the specific responses of these materials and thus find important applications in sensing, catalysis, separation, conduction, etc. In this Account, we focus on the two most relevant applications based on the host-guest interactions that are carried out in our lab, viz., separation and sensing of small molecules. Separation of liquid-phase aromatic hydrocarbons by less energy-intensive adsorption processes has gained attention recently. Because of their tailored structures and functionalized pore surfaces, MOFs have become vital candidates in molecular separation. Prefunctionalization of MOFs by astute choice of ligands and/or metal centers results in targeted separation processes in which the molecular sieving effect plays a crucial role. In this view, separation of C6 and C8 liquid aromatic hydrocarbons, which are essential feedstock in various chemical industries, is one area of research that requires significant attention because of the gruesome separation techniques adopted in such industries. Also, from the environmental perspective, separation of oil/water mixtures demands significant attention because of the hazards of marine oil spillage. We have achieved successful separation of such by careful impregnation of hydrophobic moieties inside the nanochannels of MOFs, resulting in unprecedented efficiency in oil/water separation. Also, recognition of small molecules using optical methods (fluorescence, UV, etc.) has been extended to achieve sensing of various neutral species and anions that are important from environmental point of view. Incorporation of secondary functional groups has been utilized to sense nitroaromatic compounds (NACs) and other small molecules such as H2S, NO, and aromatic phenols. We have also utilized the postfunctionalization strategy via ion exchange to fabricate MOFs for sensing of environmentally toxic and perilous anionic species such as CN- and oxoanions. Our current endeavors to explore the applicability of MOFs in these two significant areas have widened the scope of research, and attempts to fabricate MOFs for real-time applications are underway.

Turn on fluorescent detection of hydrazine with a 1,8-naphthalimde derivative

It is crucial to develop highly sensitive and selective probes toward hydrazine because it is a class of highly toxic and pollutant compound. Herein, using fracture of carbon carbon double bond and dissociation of amide by hydrazine, a novel off-on fluorescent probe was developed for hydrazine. The probe can quantitatively detect hydrazine in concentration range from 0 to 20 μM with the LOD of 140 nM. Further, it displayed excellent selectivity and anti-interference ability over many neutral molecules, metal ions, anions, and biological species. The ability to target lysosome and the response of hydrazine to this probe in a living cell was successfully tracked via fluorescence imaging.

Probing the Electronic Structure of Bacteriochlorophyll Radical Ions-A Theoretical Study of the Effect of Substituents on Hyperfine Parameters.

In reaction centers (RCs) of photosynthesis, a light-induced charge separation takes place creating radical cations and anions of the participating cofactors. In photosynthetic bacteria, different bacteriochlorophylls (BChl) are involved in this process. Information about the electronic structure of the BChl radical cations and anions can be obtained by measuring the electron spin density distribution via the electron-nuclear hyperfine interaction using EPR and ENDOR techniques. In this communication, we report isotropic hyperfine coupling constants (hfcs) of the BChl b and g radical cations and anions, calculated by density functional theory, and compare them with the more common radical ions of BChl a and with available experimental data. The observed differences in the computed hyperfine data are discussed in view of a possible distinction between these species by EPR/ENDOR methods. In addition, 14 N nuclear quadrupole coupling constants (nqcs) computed for BChl a, b, g, and also for Chl a in their charge neutral, radical cation and radical anion states are presented. These nqcs are compared with experimental values obtained by ESEEM spectroscopy on several different radical ions.

Th(IV) and U(VI) removal by TODGA in ionic liquids: extraction behavior and mechanism, and radiation effect

Extraction behavior of thorium(IV) and uranium(VI) from nitric acid (HNO3) was studied using N,N,N′,N′-tetraoctyldiglycolamide (TODGA) as extractant in different ionic liquids, and isooctane as comparison. Slope analyses with varying HNO3 concentrations and diluents revealed the extraction mechanism. With increasing length of alkyl chain and HNO3 concentration, the extraction mechanism of TODGA/IL system changed from cation exchange to neutral complex and/or anion exchange, and the molar ratio between TODGA and metal ions varied gradually from 2:1 to 1:1 for Th(IV) and 3:1 to 1:1 for U(VI). The kinetics and thermodynamic studies of Th(IV) and U(VI) by the best TODGA/[C2mim][NTf2] system showed that the extraction equilibrium was reached within 2 h and extraction reactions were endothermic. Compared to TODGA/isooctane system, TODGA/[C2mim][NTf2] system presented higher radiation stability under γ-irradiation. Therefore, it would have a promising application in spent fuel reprocessing.

The extravascular penetration of tirapazamine into tumours: a predictive model of the transport and efficacy of hypoxia specific cytotoxic analogues and the potential use of cucurbiturils to facilitate delivery

A multiparameter model of the diffusion, antiproliferative assays IC50 and aerobic and hypoxic clonogenic assays for a wide range of neutral and radical anion forms of tirapazamine (TPZ) analogues has found: a) extravascular diffusion is governed by the desolvation, lipophilicity, dipole moment and molecular volume; b) hypoxic assay properties of the TPZ analogues show dependencies on the electron affinity, lipophilicity and dipole moment and desolvation; c) aerobic properties are mainly dependent on the electron affinity, involving free radicals in the extracellular matrix. The model shows that ligand water desolvation and lipophilicity are the dominant processes governing the DNA intercalation of TPZ analogues, consistent with DFT modelling of the complexes formed by TPZ analogues with neutral and N-protonated acridine moieties which intercalate with the guanine DNA nucleobases. It is shown that TPZ can form stable complexes with cucurbit[7]uril as a precursor to proof of principle of improved TPZ delivery to tumours.

The impact of ionic liquids on the coordination of anions with solvatochromic copper complexes.

Solvatochromic transition metal (TM)-complexes with weakly associating counter-anions are often used to evaluate traditional neutral solvent and anion coordination ability. However, when employed in ionic liquids (IL) many of the common assumptions made are no longer reliable. This study investigates the coordinating ability of weakly coordinating IL anions in traditional solvents and within IL solvents employing a range of solvatochromic copper complexes. Complexes of the form [Cu(acac)(tmen)][X] (acac = acetylacetonate, tmen = tetramethylethylenediamine) where [X]- = [ClO4]-, Cl-, [NO3]-, [SCN]-, [OTf]-, [NTf2]- and [PF6]- have been synthesised and characterised both experimentally and computationally. ILs based on these anions and imidazolium and pyrrolidinium cations, some of which are functionalised with hydroxyl and nitrile groups, have been examined. IL-anion coordination has been investigated and compared to typical weakly coordinating anions. We have found there is potential for competition at the Cu-centre and cases of anions traditionally assigned as weakly associating that demonstrate a stronger than expected level of coordinating ability within ILs. [Cu(acac)(tmen)][PF6] is shown to contain the least coordinating anion and is established as the most sensitive probe studied here. Using this probe, the donor numbers (DNs) of ILs have been determined. Relative donor ability is further confirmed based on the UV-Vis of a neutral complex, [Cu(sacsac)2] (sacsac = dithioacetylacetone), and DNs evaluated via23Na NMR spectroscopy. We demonstrate that ILs can span a wide donor range, similar in breadth to conventional solvents.

The extravascular penetration of tirapazamine into tumours: a predictive model of the transport and efficacy of hypoxia specific cytotoxic analogues and the potential use of cucurbiturils to facilitate delivery

A multiparameter model of the diffusion, antiproliferative assays IC50 and aerobic and hypoxic clonogenic assays for a wide range of neutral and radical anion forms of tirapazamine (TPZ) analogues has found: a) extravascular diffusion is governed by the desolvation, lipophilicity, dipole moment and molecular volume; b) hypoxic assay properties of the TPZ analogues show dependencies on the electron affinity, lipophilicity and dipole moment and desolvation; c) aerobic properties are mainly dependent on the electron affinity, involving free radicals in the extracellular matrix. The model shows that ligand water desolvation and lipophilicity are the dominant processes governing the DNA intercalation of TPZ analogues, consistent with DFT modelling of the complexes formed by TPZ analogues with neutral and N-protonated acridine moieties which intercalate with the guanine DNA nucleobases. It is shown that TPZ can form stable complexes with cucurbit[7]uril as a precursor to proof of principle of improved TPZ delivery to tumours.

Small-Molecule Uncoupling Protein Mimics: Synthetic Anion Receptors as Fatty Acid-Activated Proton Transporters.

Uncoupling proteins (UCPs) regulate energy expenditure in living cells by inducing proton leakage across the mitochondrial inner membrane, thereby uncoupling adenosine diphosphate phosphorylation from nutrient oxidation. The proton transport activity of UCP1 and UCP2 requires activation by fatty acids. We report here the first examples of synthetic neutral anion receptors performing this biologically important fatty acid-activated function in phospholipid bilayers. We have shown that a tripodal thiourea possesses poor H+/OH- transport activity without fatty acids, but in the presence of long-chain fatty acids is "switched on" as a proton transporter with an activity close to that of a commonly used protonophore. The fatty acid-enhanced proton transport was also observed for other hydrogen and halogen bond-based synthetic anion transporters. We propose that these compounds induce proton permeability by catalyzing transbilayer movement ("flip-flop") of anionic forms of fatty acids, so allowing the fatty acids to complete a proton transport cycle. Several lines of evidence have been provided to support such a fatty acid cycling mechanism. Our findings open up new applications of anion receptor chemistry and provide important clues for understanding biological activities of synthetic anion transporters and potentially the uncoupling mechanism of naturally occurring membrane proteins.