Zwitterionic Species Research Articles

Zwitterionic dye rhodamine B (RhB) uptake on different types of clay minerals

Increased use of color dyes in textile industries resulted in great needs of treating dye-containing wastewater. As such, researches and developments for effective removal of dyes from wastewater have been conducted extensively and good progresses have already been made. However, there are still needs to understand the mechanisms of interactions between dyes and solids and to evaluate factors controlling such interactions. In this study, the interactions between different types of clay minerals and rhodamine B (RhB), a zwitterionic dye, were examined under different physic-chemical conditions. The solution pH, ionic strengths, and temperature had minimal influence of RhB uptake on these clay minerals. Uptake of RhB was limited to the external surfaces for the non-swelling clay minerals kaolinite and palygorskite. In contrast, both external and interlayer spaces are responsible for the uptake of RhB on swelling clay mineral montmorillonite. The RhB molecules intercalated into the interlayer of montmorillonite may adopt a monolayer or a bilayer configuration under low and high uptake levels. Under neutral pH condition, the RhB molecules exist as zwitterionic species in solution. The extensive uptake of RhB by the clay minerals, up to their cation exchange capacity (CEC) values, was attributed to electrostatic interactions between cationic end of the amine and the negatively charged clay minerals surfaces. The significant RhB uptake suggested that clay minerals are also good sorbents for the removal of zwitterionic dyes.

Zwitterionic Ring-Opened Oxyphosphonium Species from the Ph3P-I2 Mediated Reactions of Benzo[d]oxazol-2(3H)-ones with Secondary Amines.

Instead of the expected substituted 2-aminobenzo[d]oxazoles, relatively stable ring-opened oxyphosphonium betaines were isolated for the first time from the Ph3P-I2-mediated reactions of benzo[d]oxazol-2(3H)-ones with acyclic secondary amines. The structure of one of these compounds was unambiguously confirmed by single-crystal X-ray analysis. Thermolysis of the betaines gave rise to 2-dialkylaminobenzoxazoles with concomitant loss of triphenylphosphine oxide, suggesting their possible role as intermediates in an alternative reaction path.

Prevention of aspartimide formation during peptide synthesis using cyanosulfurylides as carboxylic acid-protecting groups

Although peptide chemistry has made great progress, the frequent occurrence of aspartimide formation during peptide synthesis remains a formidable challenge. Aspartimide formation leads to low yields in addition to costly purification or even inaccessible peptide sequences. Here, we report an alternative approach to address this longstanding challenge of peptide synthesis by utilizing cyanosulfurylides to mask carboxylic acids by a stable C–C bond. These functional groups—formally zwitterionic species—are exceptionally stable to all common manipulations and impart improved solubility during synthesis. Deprotection is readily and rapidly achieved under aqueous conditions with electrophilic halogenating agents via a highly selective C–C bond cleavage reaction. This protecting group is employed for the synthesis of a range of peptides and proteins including teduglutide, ubiquitin, and the low-density lipoprotein class A. This protecting group strategy has the potential to overcome one of the most difficult aspects of modern peptide chemistry.

Recommendations for Improving Methods and Models for Aquatic Hazard Assessment of Ionizable Organic Chemicals.

Ionizable organic chemicals (IOCs) such as organic acids and bases are an important substance class requiring aquatic hazard evaluation. Although the aquatic toxicity of IOCs is highly dependent on the water pH, many toxicity studies in the literature cannot be interpreted because pH was not reported or not kept constant during the experiment, calling for an adaptation and improvement of testing guidelines. The modulating influence of pH on toxicity is mainly caused by pH-dependent uptake and bioaccumulation of IOCs, which can be described by ion-trapping and toxicokinetic models. The internal effect concentrations of IOCs were found to be independent of the external pH because of organisms' and cells' ability to maintain a stable internal pH milieu. If the external pH is close to the internal pH, existing quantitative structure-activity relationships (QSARs) for neutral organics can be adapted by substituting the octanol-water partition coefficient by the ionization-corrected liposome-water distribution ratio as the hydrophobicity descriptor, demonstrated by modification of the target lipid model. Charged, zwitterionic and neutral species of an IOC can all contribute to observed toxicity, either through concentration-additive mixture effects or by interaction of different species, as is the case for uncoupling of mitochondrial respiration. For specifically acting IOCs, we recommend a 2-step screening procedure with ion-trapping/QSAR models used to predict the baseline toxicity, followed by adjustment using the toxic ratio derived from in vitro systems. Receptor- or plasma-binding models also show promise for elucidating IOC toxicity. The present review is intended to help demystify the ecotoxicity of IOCs and provide recommendations for their hazard and risk assessment. Environ Toxicol Chem 2020;39:269-286. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Expedient synthesis of novel antibacterial hydrazono-4-thiazolidinones under catalysis of a natural-based binary ionic liquid.

A library of pyran-2H-one-3-ylmethylidene and chromene-2H-one-3-ylmethylidene derivatives of the titled heterocyclic framework was synthesized from 3-acyl-4-hydroxypyran/chromene-2H-one via sequential reaction with thiosemicarbazide and dialkyl acetylenedicarboxylates. The syntheses were carried out under efficient catalysis of a new binary ionic liquid mixture [L-prolinium chloride][1-methylimidazolium-3-sulfonate] in one pot and solvent-free conditions. Calculations based on density functional theory displayed that the barrier energy for interconversion of the two possible diastereomeric isomers of each product is less than the thermal energy of molecules at room temperature, as only one product can be resolved from a given reaction mixture. This seems to be the case for the previously reported hydrazonothiazolidines. The binary ionic liquid mixture melts at near room temperature and can be considered as a solution of HCl in 1:1 mixture of two zwitterionic species. It proved to be more efficient than its constituents in catalyzing the above synthesis in one-pot operation. Some of the synthesized products have shown pronounced antibacterial activities. The ionic liquid is virtually stable in air and moisture, as can be retrieved several times without appreciable decrease in its catalytic activity.

Reactions of carbene-stabilized borenium cations.

In this paper we probe the reactivity of the borenium cations [C3H2(NCH2C6H4)(NCH2Ph)BH][B(C6F5)4] 2 and [C3H2(NCH2C6H4)2B][B(C6F5)4] 3. The reactions of 2 with cyclohexene or 3,3-dimethyl-1-butene gave the alkyl-aryl borenium salts [PhCH2(CHN)2CCH2C6H4BR][B(C6F5)4] (R = Cy 4, CH2CH2tBu 5) while the corresponding reactions with diphenylacetylene, 1-hexyne and 1-phenyl-1-propyne gave the aryl-alkenyl borenium cation salts [PhCH2(CHN)2CCH2C6H4BC(R1)C(H)R2][B(C6F5)4] (R1 = R2 = Ph 6, R1 = H, R2 = C4H97, R1 = Me, R2 = Ph 8a, R1 = Ph, R2 = Me 8b). In contrast, the reaction of 2 with ethynyldiphenylphosphane or 2-vinylpyridine lead to the formation of the adducts, [PhCH2(CHN)2CCH2C6H4B(H)P(Ph2)CCH][B(C6F5)4] 9, [PhCH2(CHN)2CCH2C6H4B(H)NC5H4C(H)CH2][B(C6F5)4] 10, respectively, while the more bulky donor H2C[double bond, length as m-dash]C(Ph)PMes2 gave 1,2-hydroboration of the phosphinoalkene affording [PhCH2(CHN)2CCH2C6H4BCH2CH(Ph)PMes2][B(C6F5)4] 11. In another vein of reactivity, one or two equivalents of the FLP, PtBu3/B(C6F5)3 is shown to react with 3 to give the zwitterionic borenium-borate species [C2H2(NCH(BC(CHNCH2C6H4)2)C6H4)(NCH(B(C6F5)3)C6H4)CB] 12 and the anionic bis-borate species[tBu3PH][C2H2(NCH(B(C6F5)3)2C6H4)2CB] 13. The implications of these findings are discussed.

Frontispiece: A Comprehensive Investigation of a Zwitterionic GeI Dimer with a 1,2‐Dicationic Core

The synthesis of a zwitterionic GeI dimer with a 1,2-dicationic core through reductive dehalogenation of a zwitterionic GeII species is reported herein. The stability of this compound, the molecular and electronic structures were comprehensively characterized and investigated using crystallographic, spectroscopic, and computational methods. It was determined that the Ge centers are attracted because they are both electron-rich and positively charged. A comparison to the electronic structure in triphosphenium cations revealed varying degrees of covalent bonding and that this difference can be distinguished spectroscopically. For more information see the Full Paper by P. J. Ragogna, T.-K. Sham, C. L. B. Macdonald et al. on page 14790 ff.

Kinetic and Mechanistic Studies on the Oxidation of DL-Aspartic Acid with Gold(III) in Aqueous and Micellar media

Kinetics of oxidation of DL-aspartic acid was studied at 30°C with Au(III) in sodium acetate–acetic acid buffer medium to investigate the mechanism of oxidation the presence and absence of nonionic micelle, Triton X-100. The rate of the reaction is fractional with respect to Asp and ionic strength has negligible effect. The rate of the reaction is inhibited by [Cl–] and [AuIII]. The reaction is accelerated initially by increase in pH and then showed a retardation over the value of 3.90, displaying that the rate depends on [H+]. This reaction is inhibited in the presence of Triton X-100. A mechanism involving zwitterionic species of aspartic acid and AuCl3OH– of oxidant has been proposed.

A Comprehensive Investigation of a Zwitterionic GeI Dimer with a 1,2-Dicationic Core.

The reductive dehalogenation of a zwitterionic GeII species to make a zwitterionic GeI dimer with a 1,2-dicationic core is reported herein. To the root of the stability of this compound, the molecular and electronic structures were comprehensively characterized and investigated using crystallographic, spectroscopic, and computational methods. It was determined that the Ge centers are attracted because they are both electron-rich and positively charged. A comparison to the electronic structure in triphosphenium cations revealed varying degrees of covalent bonding and that this difference can be distinguished spectroscopically.

An electron localization function analysis of the molecular mechanism and the C–O bond formation in the [3+2] cycloaddition reaction involving zwitterionic type between a nitrone and an electron deficient ethyne

The mechanistic nature of a [3+2] cycloaddition reaction involving zwitterionic species has been investigated, and the changes of electron density related to the O–C and C–C bond formation along the intrinsic reaction coordinate have been characterized. This polar [3+2] cycloaddition reaction, which takes place through a non-concerted two-stage one-step mechanism, proceeds with a moderate Gibbs free activation energy of 21 kcal mol−1. The reaction begins by the creation of a pseudoradical centre at the central carbon, first on the dimethyl acetylenedicarboxylate, and second on the nitrone framework. This immediately favours the formation of the first O–C single bond by donation of some electron density of the oxygen atom lone pairs, which represents the most attractive centre in this cycloaddition reaction.

Highly Chemo- and Diastereoselective Construction of Quaternary Stereocenters through Palladium-Catalyzed [3 + 2] Cyclization of 5-Alkenyl Thiazolones.

We report a highly chemo- and diastereoselective [3 + 2] cyclization of vinylethylene carbonates and 5-alkenyl thiazolones through palladium catalysis. The previously inert aza-thioester moiety on the thiazolone substrates is reacted selectively with the zwitterionic π-allylpalladium species. A variety of amide monothioacetals (AMTA) with two quaternary stereocenters are facilely synthesized. An additional spirocyclic quaternary stereocenter could be further installed by Rh-catalyzed metal-carbene insertion into the C-S bond on the AMTA moiety in a highly stereoselective manner.

A "Cocktail" Approach to Effective Surface Passivation of Multiple Surface Defects of Metal Halide Perovskites Using a Combination of Ligands.

Surface passivation of metal halide perovskites (MHPs) is essential for their stability and various properties as well as functionalities, including optical and electronic. Passivation is important for both stabilizing intrinsic defects and preventing extrinsic damaging species from reaching the perovskite (PVK), such as water and oxygen. Because of the ternary nature of their chemical composition, multiple surface defects exist for both bulk and nanostructured PVKs, with the latter particularly prominent because of their extremely large surface-to-volume ratio. To effectively passivate the different surface defects, a multitude of different ligands are necessary because each type of defect likely requires a different ligand for optimal passivation, as has been successfully demonstrated in a number of systems in essentially a "cocktail" approach. Characteristics of the ligands that affect effectiveness of passivation include size, shape, charge and charge distribution, orientation, conductivity, and interligand interaction. Examples of ligands for MHPs include both cationic and anionic or zwitterionic species with varied valences. The challenge is to identify the most effective ligand for each type of defect, and addressing this will require further experimental and theoretical study.

Zwitterionic forward osmosis membrane modified by fast second interfacial polymerization with enhanced antifouling and antimicrobial properties for produced water pretreatment

In this work, superfast surface modification of forward osmosis (FO) membranes was accomplished using zwitterionic species with improved antibacterial and antifouling properties. Asymmetric thin film composite (TFC) FO membranes were fabricated using superfast second interfacial polymerization (SIP). The active sides of the TFC membranes were modified with zwitterionic polyamide moieties. Subsequently, the effects of surface modification on the surface properties, morphologies, and surface charges of the TFC membranes were investigated. The TFC membranes exhibited drastically improved performance in FO processes with model and real produced water samples. The zwitterion-augmentation significantly enhanced surface hydrophilicity and shielded negative surface charge distribution on the membrane surface. Furthermore, static protein absorption and dynamic protein fouling tests with model foulant sodium alginate (SA) revealed that the antifouling characteristics of the asymmetric TFC membranes had improved remarkably. SIP with zwitterion incorporation reduced protein absorption and promoted consistent flux during permeation with the model foulant solution. The antimicrobial characteristic of these FO membranes is also demonstrated with bacterial attachment on membrane surface using Escherichiacoli. Overall, the zwitterion-augmented surface modification of these FO membranes resulted in enhanced permeability and reduction in surface structure parameter leading to improved antifouling properties with respect to organic proteins and gram-positive bacteria.

Mechanistic study on uptake and transport of pharmaceuticals in lettuce from water

The dissemination of pharmaceuticals in agroecosystems originating from land application of animal manure/sewage sludge and irrigation with treated wastewater in agricultural production has raised concern about the accumulation of pharmaceuticals in food products. The pathways of pharmaceutical entries via plant roots, transport to upper fractions, and the factors influencing these processes have yet been systematically elucidated, thus impeding the development of effective measures to mitigate pharmaceutical contamination in food crops. In this study, lettuce uptake of thirteen commonly used pharmaceuticals was investigated using a hydroponic experimental setting. Pharmaceutical sorption by lettuce roots was measured in order to evaluate the influence on pharmaceutical transport from roots to shoots. Small-sized pharmaceuticals e.g., caffeine and carbamazepine with molecular weight (MW) <300 g mol−1 and a low affinity to lettuce roots (sorption coefficient Kp < 0.05 L g−1) manifested substantial transport to shoots. Small-sized molecules lamotrigine and trimethoprim had a relatively strong affinity to lettuce roots (Kp > 12.0 L g−1) and demonstrated a reduced transport to shoots. Large-sized pharmaceuticals (e.g. MW >400 g mol−1) including lincomycin, monensin sodium, and tylosin could be excluded from cell membranes, resulting in the predominant accumulation in lettuce roots. Large-sized oxytetracycline existed as zwitterionic species that could slowly enter lettuce roots; however, the relatively strong interaction with lettuce roots limits its transport to shoots. The mass balance analysis revealed that acetaminophen, β-estradiol, carbadox, estrone and triclosan were readily metabolized in lettuce with >90% loss during 144-h exposure period. A scheme was proposed to describe pharmaceutical uptake and transport in plant, which could reasonably elucidate many literature-reported results. Molecular size, reactivity and ionic speciation of pharmaceuticals, as well as plant physiology, collectively determine their uptake, transport and accumulation in plants.

Lewis Pair Polymerization of Epoxides via Zwitterionic Species as a Route to High-Molar-Mass Polyethers.

A dual catalytic setup based on N-heterocyclic olefins (NHOs) and magnesium bis(hexamethyldisilazide) (Mg(HMDS)2 ) was used to prepare poly(propylene oxide) with a molar mass (Mn ) >500 000 g mol-1 , in some cases even >106 g mol-1 , as determined by GPC/light scattering. This is achieved by combining the rapid polymerization characteristics of a zwitterionic, Lewis pair type mechanism with the efficient epoxide activation by the MgII species. Transfer-to-monomer, traditionally frustrating attempts at synthesizing polyethers with a high degree of polymerization, is practically removed as a limiting factor by this approach. NMR and MALDI-ToF MS experiments reveal key aspects of the proposed mechanism, whereby the polymerization is initiated via nucleophilic attack by the NHO on the activated monomer, generating a zwitterionic species. This strategy can also be extended to other epoxides, including functionalized monomers.

Permeability prediction for zwitterions via chromatographic indexes and classification into 'certain' and 'uncertain'.

Background: The development of zwitterions to a drug is likely to be more challenging than compounds of other charge types. Results: Two chromatographic indexes (log k'80 PLRP-S and log KWIAM) can be successfully used as permeability classifiers of ampholytes. Moreover, a pragmatic classification into ordinary ampholytes; zwitterions 'certain' (i.e., the zwitterionic species is dominant in the physiological pH range); and zwitterions 'uncertain' (multiple species are present in the physiological pH range) enables to study the permeability of ampholytic compounds in relation to species distribution. Methodology: Potentiometry (pKa), reversed-phase (RP)-chromatography, tri-layer parallel artificial membrane permeability assays, quantitative structure-property relationships (QSPR) and block relevance (BR) analysis, receiver operating characteristic (ROC) curves. Conclusion: Structures considered as poorly permeable like zwitterions can be integrated in drug discovery programs by applying ad hoc experimental and computational tools.

Diffusion and structural behaviour of the dl-2-aminobutyric acid

dl-2-Aminobutyric acid (α-aminobutyric acid or AABA) is a non-protein amino acid with important physiological properties, and with considerable relevance in different areas, such as fundamental research and pharmaceutical industry. In this paper, the binary mutual diffusion coefficients of AABA in non-buffered aqueous solutions (0.001–0.100) mol·dm−3 at 298.15 K were measured. From these diffusion data, limiting values at infinitesimal concentration, D0, as well as those of the thermodynamic factors, FT, and activity coefficients, γ, were estimated. These data for AABA were compared with the data previously obtained for dl-4-aminobutyric acid (GABA). The difference of the behaviour of these transport properties for both amino-acids was explained based on the structural differences for the monomeric zwitterionic species of AABA and GABA. Such structural differences are supported by both 1H and 13C NMR spectroscopy and theoretical calculations, which indicate that the predominant species of AABA in these solutions is the extended zwitterionic form in contrast with the curled one of GABA.

Jammed Polyelectrolyte Microgels for 3D Cell Culture Applications: Rheological Behavior with Added Salts.

The yielding and jamming behaviors of packed granular-scale microgels enable their use as a support medium for 3D printing stable shapes made from liquid phases; under low levels of applied stress, jammed microgel packs behave like elastic solids and provide support to spatially patterned fluid structures. When swollen in cell growth media, these microgels constitute a biomaterial for bioprinting and 3D cell culture applications. However, interactions between polyelectrolytes commonly used in microgels and multivalent ions present in cell growth media may lead to drastic and adverse changes in rheological behavior or cell performance. To elucidate these interactions, we design polyelectrolyte microgels with anionic, cationic, and zwitterionic charged species and investigate their rheological behaviors in CaCl2 solutions. We find the rheological behavior of anionic and cationic microgels follow polyelectrolyte scaling laws near jamming concentrations; the rheological properties of zwitterionic microgels become independent of CaCl2 at high concentrations. We explore the potential application of these microgels as biomaterials for 3D cell culture through studies of short-term cell viability, population growth, and metabolic activity. We find that the short-term viability of cells cultured in polyelectrolytes is highly dependent on the chemical composition of the system. In addition, we find that anionic and zwitterionic microgels have minimal effects on the short-term viability and metabolic activity of cells cultured in microgel environments across a wide range of rheological properties.

Aziridination of Aromatic Aldimines Through Stabilized Ammonium Ylides: A Molecular Electron Density Theory Study

The domino reaction between ammonium salt AS 4 and aldimine AD 2, in the presence of Cs2CO3, yielding aziridine trans‐AZ 7 was studied within the Molecular Electron Density Theory at the B3LYP (PCM, DCM)/def2‐TZVP//B3LYP (PCM, DCM)/GenECP computational level. This domino reaction begins with the proton abstraction from AS 4 by Cs2CO3 yielding ammonium ylide AY 5. The subsequent nucleophilic attack of AY 5 on AD 2 furnishes the gauche betaine‐like intermediate IN‐2Tg1, which experiences a C–C single bond rotation generating the anti betaine‐like intermediate IN‐2Ta. Finally, IN‐2Ta is converted into trans‐AZ 7 by an SNi process. Analysis of the relative Gibbs free energies indicates that conversion of IN‐2Ta into trans‐AZ 7 is the rate‐determining step. Analysis of the reactivity indices allows characterizing AY 5 as a strong nucleophile and AD 2 as a strong electrophile, in clear agreement with the high polar character of the addition step, while analysis of the electrophilic Parr functions explains the regioselectivity within the C1–C2 single bond formation. A Bonding Evolution Theory study of the bonding changes along the ring‐closure step allows understanding the mechanism of the SNi reaction, which takes place through a non‐concerted two‐stage one‐step mechanism involving zwitterionic species having a carbocationic C1 center.

A comprehensive photophysical and NMR investigation on the interaction of a 4-methylumbelliferone derivative and cucurbit[7]uril

The host-guest interaction of a 7-hydroxycoumarin (3-[2-(diethylamino)ethyl]-7-hydroxy-4-methylcoumarin, 3ED4MU) with cucurbit[7]uril, CB7, was investigated in aqueous solution. From the steady-state fluorescence Job plot and 1H NMR spectroscopy the formation of a 1:1 inclusion complex, with a binding constant of 1.75 × 105 M−1 was obtained. Time-resolved fluorescence data in water, DMSO and dioxane for 3ED4MU and for umbelliferone (UM, here taken has the model compound) show that the decays are double or triple-exponentials mirroring the presence of excited neutral (N*), anionic (A*), tautomeric (T*) and zwitterionic (T*′) species (the latter only present in 3ED4MU). In the time-resolved experiments, the interaction of 3ED4MU with CB7 is mirrored by an increase of the pre-exponential factor associated to the zwitterionic species (thus giving support for the stabilization of this species when interacting with CB7) and a dramatic change in the pKa* value (from ~0.5 to ~8), associated to a displacement of the water environment probed by 3ED4MU.