Zwitterionic State Research Articles

Prediction of the tautomer stability and acidity of phenacylpyridines in aqueous solution

In this work, the aqueous acidity and tautomeric equilibrium constants are predicted in a systematic manner for the family of 2-, 3- and 4-phenacylpyridines which exhibit simultaneous keto–enol and imine–enamine tautomerism. The computational approach is based on electronic structure methods rooted in density functional theory, on an implicit SMD solvation model, and on thermodynamic cycles. In some instances, the high-quality hybrid CBS-QB3 method is used to obtain accurate gas-phase Gibbs free energies. The cationic, neutral, anionic and zwitterionic states of phenacylpyridines are considered, subject to a careful conformational analysis. Provided that a flexible enough basis set is used, estimated aqueous $${\text{p}}K_{{\mathrm{a}}}$$ and $${\text{p}}K_{{\mathrm{t}}}$$ values based on direct thermodynamic cycle correlate well with experimental data and show a reasonable quantitative agreement. On the other hand, it is found that the proton exchange scheme does not improve the accuracy of the predictions and different reference compounds are needed for each different type of the acidic site. Therefore, the errors herein are beyond systematic control. We use our results to present a brief discussion of the factors influencing the accuracy for the prediction of $${\text{p}}K_{{\mathrm{a}}}$$ and $${\text{p}}K_{{\mathrm{t}}}$$ for phenacylpyridines and presumably for other tautomeric compounds with multiple acidic centers.

A Many-Faced Alkaloid: Polymorphism of (-)-Monophyllidin.

The synthesis of the alkaloid (–)-monophyllidin is described. The molecule is a hybrid of xanthoxyline and (S)-proline, accessible in one-step through a Mannich reaction. In the solid-state, defined structural arrangements with different physical properties are formed. Single crystal X-ray diffraction revealed structures of six distinct polymorphs. In the crystalline state, the alkaloid can host small polar molecules (preferably water), while the (S)-proline moiety is present in the zwitterionic state. Combined with the chelate, which is already present in the xanthoxyline substructure, an ideal disposition for multiple hydrogen bond networks evolve. Therefore, highly water-soluble polymorphs of monophyllidin can form. This structural flexibility explains the many faces of the molecule in terms of structure as well as analytical data. Furthermore, speculations about the biological role of the molecule, with regard to the manifold interactions with water, are presented.

Understanding the nature of quinoidal and zwitterionic states in carbazole-based diradicals.

We report two carbazole-based diradicals, out of which the m-isomer shows a large diradical character y0 (0.89) and a small singlet-triplet energy gap ΔES-T (-0.98 kcal mol-1), whereas the p-isomer exhibits smaller y0 (0.79) but a much larger ΔES-T (-6.16 kcal mol-1). DFT calculations reveal that this tendency is also suitable for nitrogen and carbon-centered diradicals.

Спектры комбинационного рассеяния света глицина и их моделирование в дискретно-континуальной модели сольватной оболочки воды

Annotation. The Raman spectra of glycine in crystalline form and in aqueous solution were obtained. The model of stabilization of the zwitterion state of glycine with a single water molecule connected by hydrogen bonds with the –COO- and –NH3+ groups is proposed. It is shown that quantum chemical calculations at the level of B3LYP/6-311++G(3df,2p) using the discrete-continuum model of water environment of glycine complexes Gly + n H2O (n = 1–3) provide a good description of the Raman spectra of glycine.

Small anion-assisted electrochemical potential splitting in a new series of bistriarylamine derivatives: organic mixed valency across a urea bridge and zwitterionization.

We report the synthesis of a new bistriarylamine series having a urea bridge and investigate its mixed-valence (MV) states by electrochemical and spectroelectrochemical methods. We found that the supporting electrolytes had unusual effects on potential splitting during electrochemical behavior, in which a smaller counteranion thermodynamically stabilized a MV cation more substantially than did a bulky one. The effects contrary to those reported in conventional MV systems were explained by zwitterionization through hydrogen bonding between the urea bridge and the counteranions, increasing the electronic interactions between two triarylamino units. Furthermore, we clarified the intervalence charge transfer characteristics of the zwitterionic MV state.

Self-assembly of l-tryptophan on Cu(111) studied by low-temperature scanning tunneling microscopy

The self-assembly of l-tryptophan on Cu(111) is investigated by an ultrahigh vacuum scanning tunneling microscope (STM) at 4.4 K. When deposited onto the substrate at around 120 K with a coverage of 0.1 monolayer, molecular trimers, tetramers, hexamers, and chains coexist on Cu(111). Then almost all molecules self-assemble into chiral hexamers after being annealed at room temperature. When increasing molecular coverage to the full layer, a new type of chain is observed on the surface. Based on the high-resolution STM images at sub-molecular level, we suggest that the l-tryptophan molecules are present in neutral, zwitterionic or anionic states in these structures.

Facile crystallization of 2-phenyl benzimidazole-5-sulfonic acid: Characterization of lattice water dependent zwitterionic supramolecular forms, with modulation in proton conductivities

A facile aqueous medium crystallization strategy has been found for this water insoluble title compound. Two crystalline forms, differing in the number of lattice water molecules (mono hydrated; form I & di-hydrated; form II), have been obtained, depending on the duration of crystallization. X-ray structural studies reveal that the compound crystallizes in the zwitterionic state in both the forms, due to the protonation of one imidazole nitrogen by – $$\hbox {SO}_{3}\hbox {H}$$ group, are engaged in hydrogen bonded interactions, involving lattice water molecule(s), and thus the supramolecular arrangements of the forms are influenced by lattice waters. Additional water molecules in the form II make it more hydrophilic, as confirmed using contact angle measurements. Procedures were optimized for better crystalline yields, and the bulk purity were ascertained by TGA, elemental and PXRD analysis. AC impedance measurements prove that both the crystalline forms are indeed proton conducting electrolytes, with magnitudes of $$1 \times 10^{-5}\,\hbox {S cm}^{-1}$$ and $$5 \times 10^{-5}\,\hbox {S cm}^{-1}$$ for form I & II, respectively under humidified conditions at $$25\,^{\circ }\hbox {C}$$ . Proton conducting performance of II has been found to be greater than I and could be correlated with its higher hydrophilicity and enriched hydrogen bonds for Grotthuss mechanism. Two lattice water dependent supramolecular forms and their influence in the spectroscopic and proton conductivity results of the materials are discussed. SYNOPSIS Simple crystallization strategies for this water-insoluble title compound were identified. X-ray studies show occurrences of two lattice water dependent forms. Crystalline forms are distinguishable using spectroscopic techniques. Form II has been shown to be a better humidity based proton electrolyte than I.

Preservation of Protein Zwitterionic States in the Transition from Solution to Gas Phase Revealed by Sodium Adduction Mass Spectrometry.

The structural characterization of proteins and their interaction network mapping in the gas phase highlights the need to preserve their most nativelike conformers in the transition from the solution to gas phase. Zwitterionic interactions in a protein are weak bonds between oppositely charged residues, which make an important contribution to protein stability. However, it is still not clear whether the native zwitterionic states of proteins can be retained or not when it is transferred from the solution to gas phase. Using the nonspecific Na+ adduction as a novel signature, here we show that the zwitterionic states of proteins can be preserved when a moderated droplet desolvation condition (temperature <30 °C) is used in native electrospray ionization mass spectrometry. The very low-level nonspecific metal adduction to proteins under such conditions also enables rapid and direct determination of the binding states of metal-binding proteins and sensitive detection of proteins from solutions containing highly concentrated involatile salts (e.g., 50 mM NaCl). We believe that our findings can be instructive for performing mass spectrometric analysis of proteins and useful for protein ions desalting which simply involves altering the temperature and flow rate of drying gas in the desolvation region.

A generalized vibronic-coupling Hamiltonian for molecules without symmetry: Application to the photoisomerization of benzopyran.

We present a model for the lowest two potential energy surfaces (PESs) that describe the photoinduced ring-opening reaction of benzopyran taken as a model compound to study the photochromic ring-opening reaction of indolinobenzospiropyran and its evolution toward its open-chain analog. The PESs are expressed in terms of three effective rectilinear coordinates. One corresponds to the direction between the equilibrium geometry in the electronic ground state, referred to as the Franck-Condon geometry, and the minimum of conical intersection (CI), while the other two span the two-dimensional branching space at the CI. The model correctly reproduces the topography of the PESs. The ab initio calculations are performed with the extended multiconfiguration quasidegenerate perturbation theory at second order method. We demonstrate that accounting for electron dynamic correlation drastically changes the global energy landscape since some zwitterionic states become strongly stabilized. Quantum dynamics calculations using this PES model produce an absorption spectrum that matches the experimental one to a good accuracy.

High performance of electrochemical and fluorescent probe by interaction of cell and bacteria with pH-sensitive polymer dots coated surfaces

Using pH-switchable fluorescent polymer dots (PD) by means of fluorescent, colorimetric, and electrochemical signals generated from surfaces coated with PD of zwitterionic structure provided a fast and easy method to assess their performance in mammalian cell and bacterial interactions. The PD-coated surfaces showed high sensitivity over a broad range of pH levels by switching reversibly zwitterionic states, which led to an excellent cellular resistance effect by inhibiting the attachment of nearly 95% of mammalian cells. Similarly, they exhibited a strong interaction with the negatively charged surfaces of bacteria, as observed in the fluorescence ON/OFF system. In addition, PD were employed to detect the attachment of mammalian and bacterial cells: we deposited PD on a screen-printed carbon electrode for cyclic voltammetry analysis. Notably, the presence of cells remarkably interfered with the current flow between the PD and the screen-printed carbon electrode surface by causing an impressive decline in both reduction-oxidation signals, implying the high sensitivity of the PD-coated surfaces to cells and bacteria in different pH environments. Therefore, as smart materials with high sensitivity, biocompatibility, selectivity, and accuracy, PD-coated surfaces represent a promising approach to visualizing and controlling biological cell attachment, thereby helping to avoid contamination in biomedical applications.

Synthesis, Assembled Structures, and DNA Complexation of Thermoresponsive Lysine-Based Zwitterionic and Cationic Block Copolymers.

A series of anionic, zwitterionic, and cationic lysine-based block copolymers with a thermoresponsive segment were synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization of N-acryloyl- N-carbobenzoxy-l-lysine [A-Lys(Cbz)-OH], which contains a carboxylic acid and a protected amine-functionality in the monomer unit. Carboxylic acid-containing homopolymers, poly(A-Lys(Cbz)-OH), with predetermined molecular weights with relatively low polydispersities were initially synthesized by RAFT polymerization of A-Lys(Cbz)-OH. The chain extension of the dithiocarbamate-terminated poly(A-Lys(Cbz)-OH) to N-isopropylacrylamide (NIPAM) via the RAFT process and subsequent deprotection afforded the zwitterionic block copolymer composed of thermoresponsive poly(NIPAM) and poly(A-Lys-OH), which exhibited switchability among the zwitterionic, anionic, and cationic states by pH change. The assembled structures and thermoresponsive and chiroptical properties of these block copolymers were evaluated by dynamic light scattering, circular dichroism, and turbidity measurements. Finally, the cationic block copolymer, poly(A-Lys-OMe)- b-poly(NIPAM), was obtained by the methylation of the carboxylic acid group in the zwitterionic poly(A-Lys-OH) segment. Selective interactions of DNA with the cationic poly(A-Lys-OMe) segment in the lysine-based block copolymer were further evaluated by agarose gel electrophoresis and atomic force microscopy measurements, which revealed characteristic assembled structures and temperature-responsive properties of the polyplexes.

Variation of Donor and Acceptor Strength in Analogues of Brooker's Merocyanine and Generalization to Various Classes of Charge Transfer Compounds.

Derivatives of Brooker's merocyanine (BM) have been investigated, which possess different donors and acceptors and therefore vary their donor-acceptor strength SDA. The 00 energies have been extracted from the spectra and compared. Under basic conditions, where the neutral (merocyanine) form is present, the absorption energies for all compounds are similar, whereas there is a large difference for acidic conditions where the cationic (cyanine) form is present. This behavior could be explained by a simple theoretical model involving the dependence of the excitation energy Δ E01 on SDA. This model can be generalized to describe in a consistent way two different well-known classes of neutral chromophores with a certain degree of charge separation, namely merocyanine I (TICT) and merocyanine II (often betainic) compounds. Merocyanines I are characterized by a medium polar aromatic ground state and a zwitterionic quinoid excited state and hence positive solvatochromism, whereas merocyanines II are formally characterized by a zwitterionic aromatic ground state and a less polar quinoid excited state and, accordingly, by negative solvatochromism. On increasing the donor-acceptor strength SDA sufficiently, merocyanines II can, however, move to the so-called overcritical region with the excited state dominated by the zwitterionic valence bond structure. For many of the merocyanine II molecules investigated here, a weakly positive solvatochromic behavior is observed indicating that the ground state contains less of the zwitterionic valence bond wave function than the excited state and that these compounds belong to the overcritical region. The fluorescence spectra have been analyzed in terms of the Franck-Condon model and confirm these conclusions.

Water enables an asymmetric cross reaction of α-keto acids with α-keto esters for the synthesis of quaternary isotetronic acids.

A water promoted asymmetric aldol/lactonization/enolization cascade reaction of α-keto acids and α-keto esters was developed, affording the first general protocol for the construction of chiral quaternary isotetronic acids with excellent enantioselectivity. Theoretical results indicate that intramolecular ionized enamine intermediates stabilized by water generate zwitterionic transition states in a lower activation energy and higher face selectivity, resulting in high activity and chemo- and enantioselectivity.

Self-assembly of l-phenylalanine amino acid: electrostatic induced hindrance of fibril formation.

Nanostructure morphology originating from the self-assembly of molecules has attracted substantial attention due to its role in toxic amyloid fibril formation and immense potential in the design and fabrication of novel biomaterials. This study presents the role of intermolecular electrostatic interaction on the self-assembly process of l-phenylalanine (L-Phe) amino acid. We have employed attenuated total reflection Fourier transform infrared spectroscopy to probe the existence of different ionization states of the amino acid in various pH aqueous solutions. The self-assembly process of L-Phe in the aqueous phase is explored by using circular dichroism absorption and nuclear magnetic resonance spectroscopic tools. The observed spectral features have shown the signature of higher order structures and possible perturbation in the π–π stacking aromatic interactions for the cationic and anionic states of the amino acid. Scanning electron microscopy is used to probe the self-assembled morphology of the L-Phe amino acid dried samples prepared from the same pH aqueous solutions. We find that for the case of zwitterionic states the self-assembly nanostructures are dominated by the presence of fibrillar morphology, however interestingly for cationic and anionic states the morphology is dominated by the presence of flakes. Our finding demonstrates the potential influence of intermolecular electrostatic interaction over the aromatic π–π stacking interaction in hindering the fibril formation.

Biodegradable phosphorylcholine-based zwitterionic polymer nanogels with smart charge-conversion ability for efficient inhibition of tumor cells

Zwitterionic polymer nanocarriers have attracted much attention in recent years due to their desirable biocompatibility and anti-fouling properties. However, the super-hydrophilic and neutral charge of zwitterionic polymer results in weak interactions with negatively charged cell membranes, which leads to suboptimal uptake by tumor cells. Herein, a series of biodegradable poly(2-methacryloyloxyethyl phosphorylcholine-s-s-vinylimidazole) (PMV) nanogels with uniform spherical shape was fabricated by one-step reflux precipitation polymerization, which was clean and efficient. The PMV nanogels remained in zwitterionic state at physiological pH (pH 7.4) and were converted rapidly to positive charged state at tumor extracellular pH (pH 6.5). Proton nuclear magnetic resonance spectra and acid-base titration experiment proved that the charge-conversion ability of PMV nanogels was attributed to protonation of the imidazole ring in an acidic environment. Protein stability experiment showed that PMV nanogels exhibited a protein-adsorption resistance at pH 7.4 for as long as 7 days while adsorbed protein rapidly at pH 6.5. Moreover, PMV nanogels showed a reducing-labile property, which was able to degrade into short linear polymer chains in the presence of reduction agents. Therefore, the doxorubicin (DOX) release profile was controlled finely with a low DOX leakage under physiological conditions (7.8% in 48 h) and a rapid DOX release in 10 mM glutathione at pH 7.4 (78.9% in 48 h). Confocal laser scanning microscope and flow cytometry showed that the PMV nanogels exhibit an enhanced cellular uptake by tumor cells at pH 6.5 compared with pH 7.4, which allows for a severe cytotoxic effect of DOX-loaded PMV nanogels against tumor cells.

Stepwise versus Concerted Reductive Elimination Mechanisms in the Carbon–Iodide Bond Formation of (DPEphos)RhMeI2 Complex

Reductive elimination is the key bond formation process of organometallic reactions. Goldberg and co-workers recently revealed an unprecedented competition of parallel stepwise reductive elimination pathways for the carbon–iodide bond formation of (DPEphos)RhMeI2 complex. To understand the controlling factors that differentiate the concerted and stepwise pathways, we performed density functional theory (DFT) calculations to elucidate the mechanistic details. The competing stepwise pathways were identified as the anionic and zwitterionic stepwise pathways. The anionic pathway involves the direct SN2 attack of the external iodide anion to the methyl group, leading to the observed carbon–iodide bond formation. Alternatively, heterolytic Rh–I bond cleavage generates the cationic (DPEphos)RhMeI+ intermediate, and the subsequent SN2 attack of the iodide anion to the methyl group occurs via the zwitterionic transition state. In comparison with the stepwise reductive elimination pathways, the classic concerted pa...

Density Functional Theory and ab Initio Computational Evidence for Nitrosamine Photoperoxides: Hammett Substituent Effects in the Photogeneration of the Nitrooxide Intermediate.

Little attention has been focused on diradical and zwitterionic photoperoxides formed from nitrosamine compounds. Here, an attempt is made to probe the electronic character of the nitrooxide intermediate formed in photochemical reactions with triplet oxygen (3 O2 ). Theoretical studies have been conducted to screen para-substituted phenyl nitrosamines. In particular, we find that electron-withdrawing substituents produce low-lying triplet nitrooxide diradicals. A clear electronic dependence in the S0 - T1 and S0 - S1 energy gaps of nitrooxides was found using Hammett plots. Computed geometries show a twisted diradical triplet nitrooxide moiety, which contrasts to the nearly flat singlet zwitterionic ground state nitrooxide moiety; analyses of charges (natural bond order), molecular orbitals (HOMO/LUMO) and spin densities enable these assignments. Calculations predict the former triplet species is photogenerated initially from nitrosamine with O2 . The conversion of the triplet nitrooxide diradical to the singlet ground state is an example where longer-lived zwitterionic nitrooxide structures become possible. The reaction mechanism is consistent with a zwitterionic ground state nitrooxide playing an important role in the bimolecular oxygen-transfer reaction with phosphine and phosphite trapping agents as has been observed experimentally.

Surface enhanced Raman scattering of neutral and zwitterionic α- and β-Proline monomers adsorbed on Au3 cluster: A DFT study

Density functional theory (DFT) based energetics and surface enhanced Raman spectra of Au3 tagged neutral and zwitterionic states of both α and β-Proline monomers are investigated to gain molecular level understanding in detection of the amino acids. Raman enhancement of vibrational modes is significant when the cluster interacts with the Proline systems through energetically less preferential orientation of the monomers. While methylene stretching, NH rocking and stretching modes of CO and OH bonds are important for recognition of the neutral systems, methylene stretching, the asymmetric stretching, wagging and scissoring modes of vibrations of NH2+ and asymmetric stretching of OCO− play prominent role in detection of zwitterionic systems. Justification for observed trends comes from the molecular polarizability, depolarization ratio of the vibrational modes, enhancement factors of the modes calculated based on the static Raman intensities and NBO analysis of stabilizing interactions.

DFT Studies on the Reactions of Boroles with Alkynes.

DFT calculations were performed to investigate the reactions of boroles with alkynes, in which boranorbornadiene, borepin and/or boracyclohexadiene can be formed depending on the substituents on the borole and alkyne. Our computational results indicated that formation of boranorbornadiene and borepin is generally kinetically favoured and that the products can interconvert. Formation of boracyclohexadiene is kinetically unfavourable in most reactions. However, certain substituents can promote the formation of boracyclohexadiene by stabilizing an energetically high-lying zwitterionic transition state that leads to boracyclohexadiene. Borafluorene reacted with most alkynes to give borepin exclusively due to its propensity to maintain its aromaticity. However, when it reacted with silyl-substituted alkyne(s), a novel product, different from boranorbornadiene, borepin and boracyclohexadiene was generated, which can be attributed to the well-known ability of silyl groups to migrate.

Glycine Oligomerization by Pulsed Discharge Plasma over Aqueous Solution under Atmospheric Pressure

Chemical reactions of amino acids induced by discharge plasma are important for understanding the mechanism of biological effects of discharge plasma in biomedical applications. In this study, we generated a nano-second pulsed discharge plasma under atmospheric pressure over an aqueous solution containing glycine. The reaction products after the pulsed discharge plasma treatments were analyzed by high-performance liquid chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. The oligomerization reaction of glycine was induced in aqueous solution and produced glycine oligomers at the beginning of the discharge plasma. However, the glycine oligomers were decomposed into products with low molecular weight by excessive pulsed discharge plasma. According to comparative experiments, physical force of the plasma is believed to induce the glycine reaction. Moreover, the reactions depended on the pH, but not the conductivity, of the glycine solution. Glycine in aqueous solution was reacted by the discharge plasma only at neutral pH because the reaction proceeded only when glycine ions were in the zwitterionic state. Anions and cations of glycine reacted very little under the discharge plasma.