Ion-pair Interactions Research Articles

Swapping the Positions in a Cross-Strand Lateral Ion-Pairing Interaction between Ammonium- and Carboxylate-Containing Residues in a β-Hairpin.

Cross-strand lateral ion-pairing interactions are important for antiparallel β-sheet stability. Statistical studies suggested that swapping the position of cross-strand lateral residues should not significantly affect the interaction. Herein, we swapped the position of ammonium- and carboxylate-containing residues with different side-chain lengths in a cross-strand lateral ion-pairing interaction in a β-hairpin. The peptides were analyzed by 2D-NMR. The fraction folded population and folding free energy were derived from the chemical shift data. The ion-pairing interaction energy was derived using double mutant cycle analysis. The general trends for the fraction folded population and interaction energetics remained similar upon swapping the position of the interacting charged residues. The most stabilizing cross-strand interactions were between short residues, similar to the unswapped study. However, the fraction folded populations for most of the swapped peptides were higher compared to the corresponding unswapped peptides. Furthermore, subtle differences in the ion-pairing interaction energy upon swapping were observed, most likely due to the “unleveled” relative positioning of the interacting residues created by the inherent right-handed twist of the structure. These results should be useful for developing functional peptides that rely on lateral ion-pairing interactions across antiparallel β-strands.

Imidazole-based ionic liquids as rheological modifiers of heavy crude oil: An experimental and theoretical study

Two series of imidazolium-based ionic liquids (ILs) were tested as rheological modifiers of heavy crude oils. ILs with the 1-butyl-3-alkylimidazolium cation optimize the effect on viscosity at low concentrations, whereas those with the 1-benzyl-3-alkylimidazolium cation are similarly effective only at higher concentrations, which is due to a stronger IL–IL interaction with respect to the IL–asphaltene interaction. The most effective ILs were [C6bim][PF6], [phetbim][PF6], and [C9bim][NTf2], with viscosity falling in the order of 44.0%, 38.2%, and 32.9%, respectively. An analysis of structural features suggests that the type of anion and the strength of the ion pair interaction play an important role in the capacity of the salts to interact with the crude oil components. In addition, computational methodologies, such as atoms in molecules and non-covalent interactions, were used to analyze the main intermolecular interactions between the most effective [C6bim][PF6] and two different substructures of an asphaltene model. According to these results, hydrogen bonding (F⋯H–C, F⋯H–N, and O⋯H–C), C–H–π, and van der Waals interactions contribute to the breaking up of the π–π stacking interactions between the complexes resulting from the self-association of the aromatic compounds; as a consequence, the crude oil viscosity decreases.

Determination of the dispersion forces in the gas phase structures of ionic liquids using exclusively thermodynamic methods.

Ionic liquids are described by a delicate balance of Coulomb interaction, hydrogen bonding and dispersion forces. Dissecting the different types of interactions from thermodynamic properties is still a challenge. Here, we show that comparison of vaporization enthalpies of tetra-alkyl-ammonium ionic liquids with bis(trifluoromethylsulfonyl)imide [NTf2]- anions and the related molecular liquids, trialkylamines, allows for determining dispersion interactions in the gas phase ion-pairs. For this purpose, we measured vapor pressures and vaporization enthalpies of these ionic and molecular liquids by using a quartz-crystal microbalance. For supporting these data, we determined the vaporization enthalpies additionally from experimental activity coefficients at infinite dilution. Characteristic alkyl chain length dependences of the vaporization enthalpies have been established and were used for quantifying the dispersion forces in the gas phase species. The dissected dispersion contributions suggest that the alkyl chains do not show star-like topologies but embrace the anion maximizing the dispersion interactions. For the longest alkyl chains with eight carbon atoms, the dispersion interaction is as strong as two and a half hydrogen bonds. The proportion of dispersion in the gas phase species depending on the number of methylene groups in the ammonium cations is strongly supported by quantum chemical calculations.

Practical considerations for generation of multi-compartment complex coacervates.

We discuss preparation of experimental models for multi-compartment membraneless organelles in which distinct compositions are maintained indefinitely for macromolecule-rich phases in contact with each other. These model systems are based on the physical chemistry phenomenon of complex coacervation. In complex coacervation, liquid-liquid phase separation occurs due to ion pairing interactions between oppositely charged polyelectrolytes. This mechanism can drive the associative phase separation of proteins and nucleic acids, the major macromolecular components of membraneless organelles. Here we provide examples, advice and practical considerations for the design, generation, and analysis of multi-compartment complex coacervates. These structures are of interest to compartmentalize the interior of artificial cells and as models for the intracellular membraneless organelles of biological cells.

Hydride Transfer Catalyzed by Glycerol Phosphate Dehydrogenase: Recruitment of an Acidic Amino Acid Side Chain to Rescue a Damaged Enzyme.

K120 of glycerol 3-phosphate dehydrogenase (GPDH) lies close to the carbonyl group of the bound dihydroxyacetone phosphate (DHAP) dianion. pH rate (pH 4.6–9.0) profiles are reported for kcat and (kcat/Km)dianion for wild type and K120A GPDH-catalyzed reduction of DHAP by NADH, and for (kcat/KdKam) for activation of the variant-catalyzed reduction by CH3CH2NH3+, where Kam and Kd are apparent dissociation constants for CH3CH2NH3+ and DHAP, respectively. These profiles provide evidence that the K120 side chain cation, which is stabilized by an ion-pairing interaction with the D260 side chain, remains protonated between pH 4.6 and 9.0. The profiles for wild type and K120A variant GPDH show downward breaks at a similar pH value (7.6) that are attributed to protonation of the K204 side chain, which also lies close to the substrate carbonyl oxygen. The pH profiles for (kcat/Km)dianion and (kcat/KdKam) for the K120A variant show that the monoprotonated form of the variant is activated for catalysis by CH3CH2NH3+ but has no detectable activity, compared to the diprotonated variant, for unactivated reduction of DHAP. The pH profile for kcat shows that the monoprotonated K120A variant is active toward reduction of enzyme-bound DHAP, because of activation by a ligand-driven conformational change. Upward breaks in the pH profiles for kcat and (kcat/Km)dianion for K120A GPDH are attributed to protonation of D260. These breaks are consistent with the functional replacement of K120 by D260, and a plasticity in the catalytic roles of the active site side chains.

Zwitterionic surface charge regulation in ionic covalent organic nanosheets: Synergistic adsorption of fluoroquinolone antibiotics

The effective removal of zwitterionic fluoroquinolone (FQ) antibiotics with high water solubility in wastewater is a key environmental challenge due to the inefficacy of conventional methods of wastewater treatment. In this work, zwitterionic covalent organic frameworks (Tp-MTABs) were synthesized through a solvothermal route using 5,5′,5″-methanetriyltris(2-aminobenzenesulfonic acid) (MTABs) as a zwitterionic linker and 1,3,5-triformylphloroglucinol (Tp) as neutral knots for efficient uptake of FQ antibiotics. Tp-MTABs compose of regular distributions of sulfonic acids and amines that produce zwitterionic binding sites, which produce complementary ion-pair interactions with zwitterionic FQ antibiotics. The charge on Tp-MTABs facilitates its initial self-exfoliation to few-layered ionic covalent organic nanosheets (iCONs) with controlled surface charge, which exposes more surface ionic sites and phenyl groups toward FQ antibiotics, improving ion-pair and π–π interactions between iCONs and FQ antibiotics. These iCONs with multiple active sites highly facilitated the process of antibiotics adsorption, boosting the adsorption kinetics and improving the selectivity towards FQ antibiotics. Tp-MTABs endows ultrafast adsorption rate (<30 s) of FQ antibiotics (average over 99%). In addition, Tp-MTABs exhibit high selectivity to the removal of FQs in complex systems containing multiple competing organic compounds and high-salinity natural seawater. This work explored the structural and functional design of iCONs for the removal of organic molecules in environmental remediation.

The Impression of a Nonexisting Catalytic Effect: The Role of CotB2 in Guiding the Complex Biosynthesis of Cyclooctat-9-en-7-ol.

Terpene synthases generate terpenes employing diversified carbocation chemistry, including highly specific ring formations, proton and hydride transfers, and methyl as well as methylene migrations, followed by reaction quenching. In this enzyme family, the main catalytic challenge is not rate enhancement, but rather structural and reactive control of intrinsically unstable carbocations in order to guide the resulting product distribution. Here we employ multiscale modeling within classical and quantum dynamics frameworks to investigate the reaction mechanism in the diterpene synthase CotB2, commencing with the substrate geranyl geranyl diphosphate and terminating with the carbocation precursor to the final product cyclooctat-9-en-7-ol. The 11-step in-enzyme carbocation cascade is compared with the same reaction in the absence of the enzyme. Remarkably, the free energy profiles in gas phase and in CotB2 are surprisingly similar. This similarity contrasts the multitude of strong π-cation, dipole-cation, and ion-pair interactions between all intermediates in the reaction cascade and the enzyme, suggesting a remarkable balance of interactions in CotB2. We ascribe this balance to the similar magnitude of the interactions between the carbocations along the reaction coordinate and the enzyme environment. The effect of CotB2 mutations is studied using multiscale mechanistic docking, machine learning, and X-ray crystallography, pointing the way for future terpene synthase design.

Association Constant And Free Energy Change Properties Of Sodium Salt Of 1-Butane Sulphonic Acid In Aqueous Meoh And Aqueous Dmso Composition

Various elements similar to density, viscosity, medium dielectric constant, ion-solvent relationships, and measurements of solvent-solvent, form properties of ion-conductance and ion solvation related to different solvent electrolytes. In solving it, ion-solvent relations pacify the ion. In the analysis of ion solvent associations and ion solvation activities, conductance data and association constant figures of distant electrolytes are used. Conductance and ion solving properties of 1-butane sulphonic acid sodium salt measured in aqueous methanol and aqueous DMSO of varying composition in the 298 K to 318 K-temperature range. Limiting molar conductance, ion pair interaction constants, KA using Shedlovsky limiting law to work out. With the percentage of water in the solvent mixture, ∧0 increases. In 80% aqueous-methanol mixture, KAvalue and free energy changes are maximum, indicating that ion-solvent interactions are maximum in this composition of solvent blend and ion conductance properties as a purpose of clear ion-solvent links, including structural influence.

Ionic liquids to remove toxic metal pollution

Pollution by toxic, non-degradable metals is a rising health concern in the context of increasing industrialization and metal demand. Diseases may include brain damage, cardiovascular problems, gastrointestinal disorders and cancer, calling for advanced methods to clean soil, water, wastewater and air. Here, we review the use of ionic liquids, which are considered as eco-friendly solvents, to remove metals. Ionic liquids have unique properties such as no vapor emission, good solvation ability, higher thermal stability and tunability. Ionic liquids separate efficiently metal ions from aqueous solutions by electrostatic, Van der Waals and ion–pair interactions. Ionic liquids can be recovered by stripping, then reused several times for liquid–liquid extraction, adsorption and membrane separation. Ionic liquids improve membrane stability in membrane separation, and they act as surfactant for adsorption.

Catalytic Asymmetric Intermolecular Radical Aminotrifluoromethylation of Alkenes with Hydrazines by Cu(I)/CPA Cooperative Catalysis

AbstractA first catalytic enantioselective intermolecular radical aminotrifluoromethylation of alkene with hydrazine and Togni's reagent by Cu(I)/CPA cooperative catalysis has been reported, accessing diversely substituted CF3‐containing enantioenriched diarylmethylamines bearing an α‐tertiary stereocenter with high enantioselectivity and excellent chemoselectivity. The highly asymmetric induction of C−N bond formation between hydrazine and the carbocation intermediate was achieved by using a CPA catalyst via hydrogen‐bonding and ion pair interaction.

Charge-Inverted Hydrogen-Bridged Bond in HCa(μ-H)3E (E = Si, Ge, and Sn): Matrix Isolation Infrared Spectroscopic and Theoretical Studies

Matrix isolation infrared spectroscopy combined with quantum-chemical calculations were employed to study the reactions of calcium atoms with silane, germane, and stannane in a 4 K argon matrix. The ion pairs [HCa]+ and [EH3]- (E = Si, Ge, and Sn) in both the classical structure HCaEH3 and the bridged structure HCa(μ-H)3E were identified based on the H/D isotopic substitution experiments and quantum-chemical calculations. The results show that the reaction between ground-state Ca and EH4 proceeds inefficiently, and only after the photolytic activation of Ca atoms to the Ca(1P:4s4p) state does insertion occur to give HCaEH3, which rearranges to HCa(μ-H)3E upon photolysis. Topological analysis of the electronic structure suggests that the nonclassical structure HCa(μ-H)3E is formed by the electrostatic interaction with charge-inverted hydrogen bridge bond, while HCaEH3 is dominated by (HCa)+(EH3)- ion pair interactions.

Asymmetric Spirocyclization Enabled by Iridium and Brønsted Acid-Catalyzed Formal Reductive Cycloaddition

A catalytic, enantioselective spirocyclization of formanilides or formylindolines and enamides has been developed herein. The reaction proceeds through a sequential iridium-catalyzed hydrosilylatio...

Molecular recognizable ion-paired complex formation between diclofenac/indomethacin and famotidine/cimetidine regulates their aqueous solubility

This study focused on the physicochemical interactions between acidic and basic drugs in aqueous solutions. Their ion pair interactions were evaluated in an in vitro study. The model non-steroid anti-inflammatory drugs (NSAIDs), indomethacin (INM) and diclofenac (DIC), were used as acidic and hydrophobic drugs, whereas cimetidine (CIM), famotidine (FAM), and imidazole (IMD) were used as basic additives with heterocyclic moieties. The drug mixtures were evaluated by thermal analysis, dissolution test, nuclear magnetic resonance (NMR) spectroscopy, and mass spectroscopy. The fusion enthalpy of DIC-CIM, INM-CIM, and INM-arginine (ARG) sample was calculated based on melting temperature transformation. The DIC mixture with CIM, IMD, antipyrine (ANT), and ARG showed enhanced solubility, whereas the DIC-FAM mixture sample showed a decreased solubility. Electrospray ionization mass spectroscopy was carried out to detect binary mixtures. The interactions in DIC-FAM mixture sample were found between the carboxyl group of DIC and the amine groups of FAM by NMR. These findings were suggested that DIC-FAM mixture samples construct ion pair complexes based on the theory of Bjerrum. Moreover, the acid model drug and basic model drug also can be constructed 1:1 complexes that affects their solubility in the solvent of water type.

Properties and stability of quaternary ammonium-biphosphate ion-pair poly(sulfone)s high temperature proton exchange membranes for H2/O2 fuel cells

Quaternized poly(sulfone)s based on trimethylamine (PSf-TMA-x) and triethylamine (PSf-TEA-x) are developed to form quaternary ammonium (QA)-biphosphate ion pairs as promising high temperature proton exchange membrane (HT-PEM) in H2/O2 fuel cells. The strong QA-biphosphate ion-pair interaction results in high acid absorption and thus high proton conductivity of 78.1 mS cm−1 for PSf-TEA-110/PA membrane at 160 °C in spite of its lower degree of functionalization. Thus, the peak power density of more than 400 mW cm−2 is achieved at 160 °C for the quaternized PSf membranes in H2/O2 fuel cell, which is higher than that of the poly(benzeimidazole) (m-PBI) membrane (370 mW cm−2). Subsequently, the degradation mechanism of the PSf membranes is demonstrated using NMR technique to be occurred in both the polymer backbone and the QA groups. The stability investigation of model compounds further confirms that the degradation of the membranes resulted from the scission of ether linkage and isopropylidene group and the SN2 nucleophilic substitution of QA at operating conditions. Therefore, the significant performance decrease is observed and the lifetime is only less than 30 h at 200 mA cm−2 which is much lower than that of m-PBI membrane (>40 h).

Noncovalent Interaction-Assisted Ferrocenyl Phosphine Ligands in Asymmetric Catalysis.

Noncovalent interactions are ubiquitous in nature and are responsible for the precision control in enzyme catalysis via the cooperation of multiple active sites. Inspired by this principle, noncovalent interaction-assisted transition metal catalysis has emerged recently as a powerful tool and has attracted intense interest. However, it is still highly desirable to develop efficient and operationally convenient ligands along this line with new structural motifs. Based on the specific nature of hydrogen bonding and ion pairing interactions, we developed a series of noncovalent interaction-assisted chiral ferrocenyl phosphine ligands, including Zhaophos, Wudaphos, and miscellaneous SPO-Wudaphos. Due to the assistance of noncovalent interactions, this catalytic mode is capable of achieving transition metal catalyzed asymmetric hydrogenation and other transformations with remarkable improvement of reactivity and selectivity. In some specific challenging cases, this probably represents one of the most productive methods. Moreover, these ligands are easily prepared, air stable, and highly tunable, meeting the requirements of industrial application.In this Account, we give a concise review of recent advances in asymmetric catalysis. By means of hydrogen bonding interactions, Rh- and Ir-Zhaophos complexes exhibited excellent activities and enantioselectivities in asymmetric hydrogenation of a wide range of substrates: C═C bonds of substituted conjugate alkenes with neutral hydrogen bond acceptors, including nitro groups, carbonyl groups (ketones, esters, amides, maleinimides, and anhydrides), ethers, and sulfones; C═N bonds of substituted iminium salts with chloride as an anionic hydrogen bond acceptor, including N-H imines and cyclic imines; N-heteroaromatic compounds with HCl as an additive, including unprotected quinolines, isoquinolines, and indoles; carbocation of substituted oxocarbenium ions. By means of ion pairing interactions, Rh-Wudaphos complexes enabled the catalytic asymmetric hydrogenation of α-substituted unsaturated carboxylic acids, carboxy-directed α,α-disubstituted terminal olefins, and sodium α-arylethenylsulfonates. Rh-SPO-Wudaphos utilized both hydrogen bonding and ion pairing interactions in asymmetric hydrogenation of α-substituted unsaturated carboxylic acids and phosphonic acids. In addition, Zhaophos has achieved highly selective intramolecular reductive amination and inter- and intramolecular asymmetric decarboxylative allylation. Investigations into mechanism implied that noncovalent interactions were involved in the catalytic cycle and played a critical role for both high reactivity and selectivity. Notably, a rare ionic hydrogenation pathway has been proposed in some cases. Furthermore, these catalytic systems have been used in the gram-scale synthesis of natural products and pharmaceuticals.

A highly sensitive fluorescence “turn on” detection of perrhenate Anion, a non-radioactive surrogate of hazardous pertechnetate anion

Perrhenate oxoanion is a non-radioactive surrogate of the radioactive and hazardous pertechnetate oxoanion. The efficient sensor systems for perrhenate anion in aqueous medium is barely reported and still remains challenging due to low charge density and large size of the anion. In this regard, we have identified a cyanine based molecular rotor probe, pseudoisocyanine, which produces an appreciably larger emission enhancement of ∼60 fold in response to perrhenate anion, which is highest reported, till date, for any turn-on sensor for perrhenate anion leading to a significant improvement in the detection limit (0.17 μM) over existing sensors for perrhenate. Our sensing scheme operates through the ion pairing interaction between perrhenate and pseudoisocyanine which induces the formation of J-aggregates of pseudoisocyanine that yield dramatic changes in its fluorescence properties. The J-aggregate formation of pseudoisocyanine, in the presence of perrhenate anion, also yields significant changes in the absorption properties providing an opportunity of dual sensing of perrhenate, i.e. via fluorimetry and colorimetry. Apart from being sensitive and selective, our probe molecule exhibits a desirable feature of emission and excitation wavelength lying in the red region of the visible specrum which is advantageous for operation of a probe molecule in complex sensing matrix.

Ion-Pair Interaction and Hydrogen Bonds as Main Features of Protein Thermostability in Mutated T1 Recombinant Lipase Originating from Geobacillus zalihae.

A comparative structure analysis between space- and an Earth-grown T1 recombinant lipase from Geobacillus zalihae had shown changes in the formation of hydrogen bonds and ion-pair interactions. Using the space-grown T1 lipase validated structure having incorporated said interactions, the recombinant T1 lipase was re-engineered to determine the changes brought by these interactions to the structure and stability of lipase. To understand the effects of mutation on T1 recombinant lipase, five mutants were developed from the structure of space-grown T1 lipase and biochemically characterized. The results demonstrate an increase in melting temperature up to 77.4 °C and 76.0 °C in E226D and D43E, respectively. Moreover, the mutated lipases D43E and E226D had additional hydrogen bonds and ion-pair interactions in their structures due to the improvement of stability, as observed in a longer half-life and an increased melting temperature. The biophysical study revealed differences in β-Sheet percentage between less stable (T118N) and other mutants. As a conclusion, the comparative analysis of the tertiary structure and specific residues associated with ion-pair interactions and hydrogen bonds could be significant in revealing the thermostability of an enzyme with industrial importance.

Modulating Electrostatic Interactions in Ion Pair Intermediates To Alter Site Selectivity in the C-O Deoxygenation of Sugars.

Controlling which products one can access from the predefined biomass-derived sugars is challenging. Changing from CH2 Cl2 to the greener alternative toluene alters which C-O bonds in a sugar are cleaved by the tris(pentafluorophenyl)borane/HSiR3 catalyst system. This increases the diversity of high-value products that can be obtained through one-step, high-yielding, catalytic transformations of the mono-, di-, and oligosaccharides. Computational methods helped identify this non-intuitive outcome in low dielectric solvents to non-isotropic electrostatic enhancements in the key ion pair intermediates, which influence the reaction coordinate in the reactivity-/selectivity-determining step. Molecular-level models for these effects have far-reaching consequences in stereoselective ion pair catalysis.

Modulating Electrostatic Interactions in Ion Pair Intermediates To Alter Site Selectivity in the C−O Deoxygenation of Sugars

AbstractControlling which products one can access from the predefined biomass‐derived sugars is challenging. Changing from CH2Cl2 to the greener alternative toluene alters which C−O bonds in a sugar are cleaved by the tris(pentafluorophenyl)borane/HSiR3 catalyst system. This increases the diversity of high‐value products that can be obtained through one‐step, high‐yielding, catalytic transformations of the mono‐, di‐, and oligosaccharides. Computational methods helped identify this non‐intuitive outcome in low dielectric solvents to non‐isotropic electrostatic enhancements in the key ion pair intermediates, which influence the reaction coordinate in the reactivity‐/selectivity‐determining step. Molecular‐level models for these effects have far‐reaching consequences in stereoselective ion pair catalysis.

Activation Loop Dynamics Are Coupled to Core Motions in Extracellular Signal-Regulated Kinase-2.

The activation loop segment in protein kinases is a common site for regulatory phosphorylation. In extracellular signal-regulated kinase 2 (ERK2), dual phosphorylation and conformational rearrangement of the activation loop accompany enzyme activation. X-ray structures show the active conformation to be stabilized by multiple ion pair interactions between phosphorylated threonine and tyrosine residues in the loop and six arginine residues in the kinase core. Despite the extensive salt bridge network, nuclear magnetic resonance Carr-Purcell-Meiboom-Gill relaxation dispersion experiments show that the phosphorylated activation loop is conformationally mobile on a microsecond to millisecond time scale. The dynamics of the loop match those of previously reported global exchange within the kinase core region and surrounding the catalytic site that have been found to facilitate productive nucleotide binding. Mutations in the core region that alter these global motions also alter the dynamics of the activation loop. Conversely, mutations in the activation loop perturb the global exchange within the kinase core. Together, these findings provide evidence for coupling between motions in the activation loop and those surrounding the catalytic site in the active state of the kinase. Thus, the activation loop segment in dual-phosphorylated ERK2 is not held statically in the active X-ray conformation but instead undergoes exchange between conformers separated by a small energetic barrier, serving as part of a dynamic allosteric network controlling nucleotide binding and catalytic function.