Zwitterionic Species Research Articles

Behavior of uncharged oximes compared to HI6 and 2-PAM in the human AChE-tabun conjugate: a molecular modeling approach

Tabun is one of the most dangerous nerve agents because it has deleterious effects like inhibition of the essential enzymes acetylcholinesterase (AChE) and butyrylcholinesterase. Some oximes such HI6 as 2-PAM are nucleophiles that are capable to reactivate inhibited human AChE under some conditions. Zwitterionic and cationic species have the best chance of productive action on inhibited AChE. However uncharged oximes can give important interaction information. In order to investigate the interaction and behavior of cationic and uncharged oximes, we performed molecular docking simulations and molecular dynamics and calculated binding energies of complexes of these compounds with human AChE. The uncharged oximes of larger structure were more susceptible to the influence of the substituents on the phosphorus atom and presented low binding energies. In contrast, HI 6 and 2-PAM showed high binding energy values with great contribution of the amino acid Asp74, demonstrating the importance of the quaternary nitrogen to the affinity and interaction of the oximes/AChE tabun-inhibited complexes.

Outer-Sphere Reactivity Shift of Secondary Phosphine Oxide-Based Nickel Complexes: From Ethylene Hydrophosphinylation to Oligomerization.

A new dimension for secondary phosphine oxide (SPOs) ligands is described in this article. Demonstrated on original π-allylic nickel structures, these self-assembled complexes trigger catalytic hydrophosphinylation reactions. Addition of a Lewis acid B(C6 F5 )3 switches the reactivity towards migratory insertion and thus ethylene oligomerization through an unprecedented outer-sphere interaction with the coordinated SPO ligand. NMR experiments and X-ray analyses allowed for the observation of the formation of zwitterionic active species as well as their degradation pathway.

Deproteinization assessment using isotopically enriched compounds to trace the coprecipitation of low-molecular-weight selenium species with proteins

Studies have shown that information related to the presence of low-molecular-weight metabolites is frequently lost after deproteinization of complex matrices, such as blood and plasma, during sample preparation. Therefore, the effect of several deproteinization reagents on low-molecular-weight selenium species has been compared by species-specific isotope labeling. Two isotopically enriched selenium tracers were used to mimic models of small inorganic anionic (77Se-selenite) and organic zwitterionic (76Se-selenomethionine) species. The results presented here show that the use of a methanol-acetonitrile-acetone (1:1:1 v/v/v) mixture provided approximately two times less tracer loss from plasma samples in comparison with the classic procedure using acetonitrile, which may not be optimal as it leads to important losses of low-molecular-weight selenium species. In addition, the possible interactions between selenium tracers and proteins were investigated, revealing that both coprecipitation phenomena and association with proteins were potentially responsible for selenite tracer losses during protein precipitation in blood samples. However, coprecipitation phenomena were found to be fully responsible for losses of both tracers observed in plasma samples and of the selenomethionine tracer in blood samples. This successfully applied strategy is anticipated to be useful for more extensive future studies in selenometabolomics.

Carbanion Translocations via Intramolecular Proton Transfers: AQuantum Chemical Study.

Intramolecular proton transfers are important processes in chemical reactions and biological transformations. In particular, the translocation of reactive carbanion centers can be achieved through 1,n-proton transfer in either a direct or an assisted manner (via the protonation/deprotonation mechanism). Despite some mechanistic investigations on proton transfers within zwitterionic species, no guiding principles have been summarized for carbanion-induced intramolecular proton transfers. Herein, we report our quantum chemical study on the carbanion translocations via intramolecular proton transfers. Our calculations indicated that the reaction barriers generally decrease with longer tether lengths and more π-withdrawing substituents. The physical bases behind these effects were revealed according to the charge and bond energy decomposition analysis, showing that the destabilizing closed-shell Pauli repulsions play important roles in determining the relative ease of intramolecular proton transfers. We also found that the thermodynamic driving force may affect the regiochemistry. This study may help chemists to understand whether a carbanion translocation occurs via an intramolecular proton transfer or with the assistance of proton shuttles, such as water and alcohols.

Structural diversities and preliminary antimicrobial studies of 1-((E)-(pentylimino)methyl)naphthalen-2-ol and its metal complexes

Schiff bases and their metal complexes have a number of biological activities such as antidepressant, analgesic, antimicrobial, antiviral, and antitumor. In the present studies, the 1-((E)-(pentylimino)methyl)naphthalen-2-ol ligand is prepared by the reaction of 2-hydroxynaphthaldehyde with n-amyl amine. The ligand results in CoL3, NiL2 and CuL2 complexes when reacted with the cobalt acetate, nickel acetate, and copper acetate salts respectively. The complexes along with their ligand are fully characterized by X-ray diffraction studies and biologically screened. The ligand structure reveals that it is a zwitterion species where the iminic nitrogen atom is protonated and the C–O bond shows a high double bond character. The cobalt complex has an octahedral geometry around the metal center and each nitrogen atom is in the trans position to the oxygen donor site. On the other hand, the copper complex shows a centrosymmetric square planar coordination, and in this case, the nitrogen sites are trans to each other. The complexes and the ligand are found to be more potent than the standard drugs used against some microbes in their preliminary biological studies.

Resonance Raman and UV–VIS spectroscopic investigation of the reaction of tetracyanoethylene and N‐methyldiphenylamine

Tetracyanoethylene is an archetypal electron acceptor and in the presence of aromatic amines forms charge transfer π‐complexes, which subsequently leads to the formation of a tricyanovinylation product by the electrophilic aromatic substitution at para position of tertiary amine ring. Factors as amine concentration and solvent polarity influence both the rate and extension of reaction. In contrast to the aromatic amines containing only one phenyl ring, in the case of N‐methyldiphenylamine, the rate of reaction is much slower in particular conditions allowing the spectroscopic characterization (ultraviolet–visible and Raman) of all the species involved, including the neutral adduct and zwitterionic intermediate species. The stabilities of such intermediate species in solution can be controlled by both the concentration of amine and solvent polarity. The results illustrate the dual role played by the amine as a reactant and as a catalyst in the proton abstraction, the rate determining step. The comparison of the reactions in dichloromethane and acetonitrile shows that the neutral adduct and zwitterionic intermediate species are stabilized in nonpolar medium, revealing the role played by the solvent in defining the mechanistic pathways of this model charge transfer initiated reaction. Quantum chemical calculations based on density functional theory and time‐dependent density functional theory were used to obtain the theoretical vibrational and electronic spectra and showed fair agreement with experimental data. Copyright © 2017 John Wiley & Sons, Ltd.

Coordination behavior of bis-phenolate saturated and unsaturated N-heterocyclic carbene ligands to zirconium: reactivity and activity in the copolymerization of cyclohexene oxide with CO2.

Tetravalent zirconium complexes supported by tridentate bis-phenolate imidazolidin-2-ylidene (L1), imidazol-2-ylidene (L2) and benzimidazol-2-ylidene (L3) NHC ligands were synthesized and evaluated as precursors for the copolymerization of cyclohexene oxide (CHO) with CO2. While the reactivity of the imidazolidinium [H3L1] chloride salt with Zr(OiPr)4(HOiPr), and subsequent ligand exchanges with either (CH3)3SiCl or LiOiPr lead to a series of heteroleptic compounds (κ3-O,C,O-L1)Zr(X)2(THF) (X = Cl, OiPr), both imidazolium [H3L2] and benzimidazolium [H3L3] chloride salts give a mixture of homoleptic (κ3-O,C,O-NHC)2Zr and zwitterionic (κ2-O,O-HL)ZrCl2(OiPr) compounds along with traces or the absence of the heteroleptic intermediate (κ3-O,C,O-NHC)Zr(Cl)(OiPr)(THF). Such dissimilar reactivity between the unsaturated and saturated NHC ligands is predominantly ascribed to the increased acidity of azolium salts along with the π-donor strength of the Ccarbene in L2 and L3-Zr moieties. The reactivity with the more acidic azolium salts (H3L2/3) and the destabilized Zr-Xtrans to NHCcarbene bond results in a significant increase in the amount of homoleptic compounds generating HCl. The released HCl reacts preferentially with the heteroleptic intermediates having non-planar NHC ligands (i.e. L2/3) promoting the formation of zwitterionic complexes. The in situ deprotonation of the isolated zwitterionic (κ2-O,O-HL3)ZrCl2(OiPr) compound by using Ag2O gives the homoleptic complex as the major component along with a bimetallic hydroxo-bridged [(κ3-O,C,O-L3)Zr(μ-OH)(OiPr)]2 compound. Of particular interest is that only the heteroleptic NHC-Zr(iv) complexes were identified to be active and highly selective towards the copolymerization of CHO with CO2 independently of the co-catalysts used (both anionic and neutral) under mild conditions (PCO2 < 1 bar, T = 60 °C), and gave atactic and completely alternating copolymers in a controlled manner (Mw/Mn ≈ 1.3-1.8). In contrast, the isolated homoleptic, zwitterionic and bimetallic zirconium species were found to be inactive under similar reaction conditions. Although the activity found for NHC-Zr(iv) complexes is nearly of the same order of magnitude as that of the NHC-Ti(iv) analogues, these results are the first examples of tetravalent zirconium complexes achieving high selectivity (99% in PCHC) in the catalyzed copolymerization of CHO with CO2.

Living Ring-Opening Polymerization of Lactones by N-Heterocyclic Olefin/Al(C6F5)3 Lewis Pairs: Structures of Intermediates, Kinetics, and Mechanism

The strong Lewis acid Al(C6F5)3, in combination with a strong Lewis base N-heterocyclic olefin (NHO), cooperatively promotes the living ring-opening (co)polymerization of lactones, represented by δ-valerolactone (δ-VL) and e-caprolactone (e-CL) in this study. Medium to high molecular weight linear (co)polyesters (Mw up to 855 kg/mol) are achieved, and most of them exhibit narrow molecular weight distributions (Đ as low as 1.02). Detailed investigations into the structures of key reaction intermediates, kinetics, and polymer structures have led to a polymerization mechanism, in that initiation involves nucleophilic attack of the Al(C6F5)3-activated monomer by NHO to form a structurally characterized zwitterionic, tetrahedral intermediate, followed by its ring-opening to generate active zwitterionic species. In the propagation cycle, this ring-opened zwitterionic species and its homologues attack the incoming monomer activated by Al(C6F5)3 to generate the tetrahedral intermediate, followed by the rate-deter...

Characterization of polyaniline-coated stationary phases by using the linear solvation energy relationship in the hydrophilic interaction liquid chromatography mode using capillary liquid chromatography.

A polyaniline coating was used to modify the surface of bare silica gel and octadecyl silica stationary phases to characterize the properties of altered materials. It was assumed that the mixed-mode retention was established on the basis of the polyaniline chemical structure and its combination with the original sorbents. Polyaniline was deposited onto the original surfaces during the chemical polymerization of aniline hydrochloride. The prepared materials were slurry packed into capillary columns and systematic chromatographic characterization was performed using the linear solvation energy relationship, also employing descriptors that allow inclusion of ionic interactions in the proposed retention mechanism. The retention times of 80 solutes with various chemical structures were measured in the hydrophilic interaction liquid chromatography mode. The obtained results demonstrated the significant contribution of the polyaniline coating to the retention mechanism under the given conditions; the assumed mixed-mode retention was confirmed. The dominant retention interaction for both modified stationary phases was based on the protonation of nitrogen atoms in the polyaniline structure, leading to suitable retention and selectivity for the hydrophilic analytes, especially anionic and zwitterionic species. Thus, especially, the polyaniline-coated bare silica gel sorbent seems to be promising for potential applications related to the separation of polar compounds.

Aquatic photolysis of β2-agonist salbutamol: kinetics and mechanism studies.

Salbutamol (SAL) has been widely used as medicine both in treating asthma and in animal primary production; an increasing number of reports have detected SAL in natural waters. The photolysis kinetic and pathway of SAL in aquatic system were studied, as well as the effect of several natural water constituents, such as nitrate, dissolved oxygen (DO) and ferric ions. According to our research, the direct photolysis of SAL followed pseudo-first-order reaction kinetics. Alkaline condition could promote the degradation of SAL; the increase of solution pH would simultaneously increase the fraction of the deprotonated forms of SAL (including the deprotonated and zwitterionic species), which were easier to be excited, and result in the bathochromic shift of the UV-Vis spectrum and, finally, accelerate the degradation rate of SAL. The presence of nitrate could enhance the removal rate of SAL via generation hydroxyl radical (·OH) under irradiation. In addition, the absence of oxygen in the reaction solution could decrease the photolysis. Moreover, Fe(III) was able to chelate with SAL to form an octahedral complex, which was photochemically reactive. The octahedral complex could generate ·OH to oxidize SAL itself in turn. The pathways of SAL photolysis were also investigated by means of the solid phase extraction (SPE)-LC-MS method. The major pathways of SAL photodegradation included oxidation and side-chain cleavage.

Activation of an Au-Cl Bond by a Pendent SbIII Lewis Acid: Impact on Structure and Catalytic Activity.

With the objective of identifying new coordination modes of ambiphilic ligands, we have investigated the bidentate Sb/P ligands (o-(Ph2 P)C6 H4 )SbCl2 (LCl ) and (o-(Ph2 P)C6 H4 )SbPh2 (LPh ). Reaction of these ligands with (tht)AuCl affords the monoligated species LCl AuCl (1) and LPh AuCl (2), respectively, in which the antimony centers are only weakly engaged with the coordinated gold atom. Treatment of 1 with PPh3 induces an intramolecular transfer of a chloride ligand from gold to antimony to form the zwitterionic species o-(Cl3 Sb)C6 H4 (Ph2 P)Au(PPh3 ) (3). Natural bond orbital (NBO) calculations show that the antimony and gold centers are involved in weak Sb→Au and Au→Sb interactions, the latter reflecting the Lewis acidity of the pendent antimony group. Finally, we demonstrate that the ability of the antimony center in 1 to abstract a gold-bound chloride in the presence of a Lewis basic substrate may be utilized to activate the gold center for the electrophilic cycloisomerization of propargylic amides.

Unique Sensing Interface That Allows the Development of an Electrochemical Immunosensor for the Detection of Tumor Necrosis Factor α in Whole Blood

Electrochemical affinity biosensors that can operate in whole blood are a rarity because biofouling of electrode surfaces compromises the performance of the final device. The common anti-biofouling layers that can be applied to electrodes, poly(ethylene glycol) (PEG) or oligo(ethylene glycol) (OEG) layers, form a high impedance layer on the electrode, effectively passivating the electrode. In response to this issue, we have developed effective anti-biofouling chemistry, that employs short chain zwitterionic species, derived from aryl diazonium salts, that give low impedance layers compatible with amperometry. Herein, we demonstrate the application of this surface chemistry to mixed layers of phenyl phosphorylcholine (PPC) and phenyl butyric acid (PBA), to develop immunosensors that can be used in whole blood. The capability of these new modification layers is demonstrated with an immunosensor for detecting tumor necrosis factor α in whole blood. The immunosensor is shown to specifically and precisely dete...

Control of CO2 Adsorption and Desorption Using Polyethylene Glycol in a Tetraethylenepentamine Thin Film: An In Situ ATR and Theoretical Study

The reversible adsorption of CO2 on tetraethylenepentamine (TEPA) and the polyethylene glycol (PEG)-modified amine sites were investigated using attenuated total reflection infrared (ATR-IR) spectroscopy, mass spectrometry (MS), and density functional theory (DFT). The presence of PEG at the amine site increased the rate of formation of adsorbed CO2, enhanced the formation of weakly adsorbed CO2 which can be removed from flowing inert gas at room temperature, and decreased CO2 desorption peak (i.e., sorbent regeneration) temperature. The calculated CO2 binding energy (BE) and optimized structures suggest CO2 adsorbed on TEPA primarily in the form of ammonium carbamate. The presence of PEG promoted the formation of a species which exhibited an experimental IR spectrum resembling the simulated spectrum of a low BE zwitterion species. The observation suggests PEG controlled the formation of the adsorbed intermediate species. Modeling of the transient CO2 adsorption profiles further showed PEG accelerated the...

Experimental and theoretical studies on electropolymerization of polar amino acids on platinum electrode

The anodic oxidation of polar amino acids (l-serine, l-threonine, l-asparagine, and l-glutamine) in aqueous electrolyte on smooth platinum electrode was carried out by cyclic voltammetry coupled to electrochemical quartz crystal microbalance (EQCM). pH (zwitterion, acidic and alkaline) effects on their electrochemical behavior were examined. The maximum current values are measured for zwitterion species. In addition, the current increases with increasing of concentration and scan rate, and decreases with increasing pH. The resulting passivation was studied by spectroscopic analysis such as attenuated total reflection FT infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and mass spectroscopy (MALDI-TOF). From thin film coatings observed on the electrode surface, peptide bonds are found, and are in favor of electropolymerization of these polar amino acids into poly-l-amino acids in an irreversible way. Scanning electronic microscopy was also used to study the morphology of these electrodeposited l-amino acids. The electrodeposited poly-l-amino acids on Pt electrode were tested as bioinspired transducer for pH sensing purposes.

A Frustrated Lewis Pair Catalyzed Asymmetric Transfer Hydrogenation of Imines Using Ammonia Borane.

Inspired by the zwitterion species generated from the splitting of H2 by frustrated Lewis pairs, we put forward a novel frustrated Lewis pair by the combination of Hδ- and Hδ+ incorporated Lewis acid and base together. Piers' borane and chiral tert-butylsulfinamide were chosen as the FLP, and a metal-free asymmetric transfer hydrogenation of imines was realized with high enantioselectivities. Significantly, with ammonia borane as hydrogen source, a catalytic asymmetric reaction using 10 mol % of Piers' borane, chiral tert-butylsulfinamide, and pyridine additive, has been successfully achieved to furnish optically active amines in 78-99% yields with 84-95% ee's. Experimental and theoretical mechanistic studies reveal an interesting 8-membered ring hydrogen transfer transition state and an expected regeneration of reactive species with ammonia borane. Accordingly, a plausible catalytic pathway for this reaction is depicted.

Preliminary Oligomerization in a Glycolic Acid-Glycine Mixture: A Free Energy Map.

Glycolic acid and glycine can potentially self-oligomerize or co-oligomerize in solution by forming ester and amide bonds. Using density functional theory with implicit solvent, we have mapped a baseline free energy landscape to compare the relative stabilities of monomers, dimers, and trimers in solution. We find that amide bond formation is favored over ester bond formation both kinetically and thermodynamically, although the differences decrease when zwitterionic species are taken into account. The replacement of ester linkages by amide bonds is favored over lengthening the oligomer, suggesting that one route to oligopeptide formation is utilizing oligoesters as a starting point. We also find that diketopiperazine, the cyclic dimer of glycine, is favored over the linear dimer; however, the linear trimers are favored over their cyclic counterparts. Because glycolic acid and glycine are dominant products from a Strecker synthesis starting from formaldehyde and HCN, this study sheds light on potential pathways to prebiotic formation of oligopeptides via oligoesters.

The structure and diffusion behaviour of the neurotransmitter γ-aminobutyric acid (GABA) in neutral aqueous solutions

GABA (γ-aminobutyric acid) is a non-protein amino acid with important physiological properties, and with considerable relevance to the food and pharmaceutical industries. Particular interest has focused on its role as an inhibitory neurotransmitter in the mammalian cerebral cortex. In this paper, we report density and mutual diffusion coefficients of GABA in non-buffered aqueous solutions (0.001–0.100)mol·dm−3 at 298.15K. Under these conditions, 1H and 13C NMR spectroscopy and pH measurements show that it is present predominantly as a monomeric zwitterionic species. Diffusion coefficients have been computed assuming that this behaves as the binary system GABA/water. From density and intermolecular diffusion coefficients measurements, the molar volume, hydrodynamic radii, Rh, diffusion coefficients at infinitesimal concentration, D0, activity coefficients and the thermodynamic factors, FT, have been estimated. Within experimental error, the hydrodynamic volume calculated from this is identical to the molar volume obtained from density measurements. From the NMR spectra and literature data, it is suggested that this amino acid diffuses in aqueous solution as a curved, coil-like hydrated zwitterionic entity.

ChemInform Abstract: Amino Acid‐Derived Bifunctional Phosphines for Enantioselective Transformations

AbstractReview: 52 refs.

1000-fold enhancement in proton conductivity of a MOF using post-synthetically anchored proton transporters.

Pyridinol, a coordinating zwitter-ionic species serves as stoichiometrically loadable and non-leachable proton carrier. The partial replacement of the pyridinol by stronger hydrogen bonding, coordinating guest, ethylene glycol (EG), offers 1000-fold enhancement in conductivity (10−6 to 10−3 Scm−1) with record low activation energy (0.11 eV). Atomic modeling coupled with 13C-SSNMR provides insights into the potential proton conduction pathway functionalized with post-synthetically anchored dynamic proton transporting EG moieties.

Fluoroquinolones: A micro-species equilibrium in the protonation of amphoteric compounds

The knowledge of the speciation of fluoroquinolones is of great actuality for the implications on the activity, bioavailability and pharmacokinetics. Literature reports a number of contrasting evaluations on the existence of tautomeric forms of mono-protonated species, described by a set of protonation micro-constants. Here the protonation sequence and the related protonation constants of four representative molecules are evaluated by a combined potentiometric-spectrophotometric method. The experimental observations necessary to differentiate between a protonation scheme represented by macro-constants alone, and the one that requires the introduction of a micro-protonation scheme, are clearly delineated based on a careful analysis of experimental data and of simulated models. The role of the medium was investigated and UV–vis spectra in water- methanol solution were analyzed. The existence of the zwitterionic species alone at physiological pH in water, and an increase of the relative amount of the neutral species with the lipophilicity of the medium were remarked. This surely affects the bioavailability of FQs, with the increase of the neutral species when the molecules approach the local lipophilic environment close to the cellular membranes. NMR studies allowed the attribution of the protonation sites of the different forms. Quantum chemical evaluation of all the possible existent forms with different protonation degrees and in different sites strongly substantiates the experimental results. The study of the relevant frontier molecular orbitals completed the detailed theoretical characterization of the species.