Protonation Equilibria Research Articles

A fresh look at dense hydrogen under pressure. II. Chemical and physical models aiding our understanding of evolving H–H separations

In order to explain the intricate dance of intramolecular (intra-proton-pair) H-H separations observed in a numerical laboratory of calculationally preferred static hydrogen structures under pressure, we examine two effects through discrete molecular models. The first effect, we call it physical, is of simple confinement. We review a salient model already in the literature, that of LeSar and Herschbach, of a hydrogen molecule in a spheroidal cavity. As a complement, we also study a hydrogen molecule confined along a line between two helium atoms. As the size of the cavity/confining distance decreases (a surrogate for increasing pressure), in both models the equilibrium proton separation decreases and the force constant of the stretching vibration increases. The second effect, which is an orbital or chemical factor, emerges from the electronic structure of the known molecular transition metal complexes of dihydrogen. In these the H-H bond is significantly elongated (and the vibron much decreased in frequency) as a result of depopulation of the σ(g) bonding molecular orbital of H(2), and population of the antibonding σ(u)∗ MO. The general phenomenon, long known in chemistry, is analyzed through a specific molecular model of three hydrogen molecules interacting in a ring, a motif found in some candidate structures for dense hydrogen.

Influence of 2′‐Deoxy Sugar Moiety on Excited‐State Protonation Equilibrium of Adenine and Adenosine with Acridine inside SDS Micelles: A Time‐Resolved Study with Quantum Chemical Calculations

The protonation dynamics of the DNA base adenine (Ade) and its nucleoside 2'-deoxyadenosine (d-Ade) are investigated by monitoring the deprotonation kinetics of an N-heterocyclic DNA intercalator, acridine (Acr), in the confined environment of sodium dodecyl sulfate (SDS) micelles. Protonation of acridine (AcrH(+)) occurs at the hydrophilic interface and this species remains in dynamic equilibrium with its deprotonated counterpart (Acr) inside the hydrophobic core of SDS micelles. Quenching of the fluorescence of AcrH(+)* at 478 nm is observed after addition of Ade and d-Ade with Stern-Volmer constant (K(SV)) 298 and 75 M(-1), respectively, with a concomitant increment in Acr* at 425 nm. Time-resolved fluorescence studies reveal quenching in the lifetime of AcrH(+)*. The relative amplitude of AcrH(+)* decreases from 0.97 to 0.51 and 0.97 to 0.89 with equimolar addition of Ade and d-Ade, respectively. These observations are explained by excited-state proton transfer (ESPT) from AcrH(+)* to the bases. The reduced K(SV) value and negligible change in the relative amplitudes of AcrH(+)* with d-Ade infer that ESPT is hindered substantially by the presence of a 2'-deoxy sugar unit. Transient time-resolved absorption spectra of Acr reflect that Ade reduces the absorbance of (3)AcrH(+)*; however, d-Ade keeps it unaltered for more than a time delay of 2 μs. The optimized geometries calculated by quantum chemical methods reflect deprotonation of AcrH(+)* with protonation at the N1 position of Ade, while it remains protonated with d-Ade. The hindered ESPT between AcrH(+)* and d-Ade singles out the significance of the 2'-deoxy sugar moiety in controlling the deprotonation kinetics.

On the evolution of one-electron-oxidized deoxyguanosine in damaged DNA under physiological conditions: a DFT and ONIOM study on proton transfer and equilibrium

Different deprotonation paths of the radical cation formed by one-electron oxidation of 2'-deoxyguanosine (2dG) sites in DNA have been studied using Density Functional Theory (M05-2X/6-31+G(d,p)) and ONIOM methodology (M05-2X/6-31+G(d,p):PM6) in conjunction with the SMD model to include the solvent effects. Models of increased complexity have been used ranging from the isolated nucleoside to a three unit double-stranded oligomer including the sugar units, the base pairing with cytidine, and the phosphate linkage. The reported results correspond to aqueous solution, at room temperature, and pH = 7.4. Under such conditions it was found that the proton transfer (PT) within the base pair is a minor path compared to the PT between the base pair and the surrounding water. It was also found that the deprotonation of ground-state 2dG˙(+) sites mainly yields C centered radicals in the sugar unit, with the largest populations corresponding to C4'˙ and C5'˙, followed by C3'˙. The different aspects of the presented theoretical study have been validated with experimental results.

Effect of Solvent on Protonation Equilibria ofL-Proline andL-Valine in 1, 2-Propanediol-Water Mixtures

Protonation equilibria ofL-proline and L-valine in varying compositions (0.0-60.0% v/v) of 1, 2-Propanediol-water mixtures were investigated pH-metrically. Titrations were performed at 303.0 K and the ionic strength of the medium was maintained at 0.16 mol L-1using sodium chloride. The best fit chemical models of the protonation equilibria were based on crystallographic R-factor, Χ2, skewness, and kurtosis. All the protonation constants of proline and valine increased with increasing propanediol content. This is attributed to the dielectric constant of the medium.

Protonation Equilibriums of Porphin, 5,10,15,20-Tetraphenylporphin, 5,10,15,20-Tetrakis(4’-sulfonatophenyl)­porphin in Methanol

The comparative investigation of substituent effects and media effects in relation to protonation equilibriums of porphyrinic platform (H2P) in series of porphin, 5,10,15,20-tetraphenylporphin and 5,10,15,20-tetrakis(4'-sulfonatophenyl)porphin was carried out by spectropotentiometric and computer chemistry (PM3) methods in methanol at 298 K. It was shown, that the receptor Н4Р forms methanol solvatocomplexes [Н4Р](CH3OH) like “roost” and [Н4Р](CH3OH)2 like “double roost”, but the equilibriums of the second protonation step of porphyrins practically are totally shifted to [Н4Р](CH3OH)2. The appropriate step protonation and complexation constants were determined. It was determined, that media effects are the reason of the leveling of the step protonation constants of porphyrins, measured by spectrophotometric method, which “doesn’t distinguish” the light-absorbing centers H4P, [Н4Р](CH3OH) and [Н4Р] (CH3OH)2.

Effect of dielectric constant on protonation equilibria of 2, 3-dihydroxybenzoic acid and malonic acid in 1, 2-propanediol-water mixtures

The protonation constants of 2,3-diydroxybenzoic acid (2, 3-DHBA) and malonic acid (MA) at 303.0 ± 0.1 K and 0.16 mol L-1 ionic strength in various concentrations (0–60% v/v) of 1,2-propanediol–water-mixtures were determined by pH-metric method. The protonation constants were calculated with MINIQUAD75 computer program. Selection of the best fit chemical models of the acid–base equilibria was based on statistical parameters. The log K values were found to increase with the increase in percentage of 1,2-propanediol and vary linearly with the reciprocal of the dielectric constant of the medium. This has been attributed to the dominance of electrostatic forces. Distributions of species and effect of influential parameters on the protonation constants are also presented.

Ion Exchange Behaviors of Ca(II) and Mg(II) on Lewatit MonoPlus TP 207 and TP 208 Chelating Resins

The protonation process, the adsorption equilibrium process, the adsorption isotherms and the adsorption kinetics of adsorbing Ca(II) and Mg(II) onto Lewatit MonoPlus TP 207 and TP 208 chelating resins were studied using the pH titration method and batch experimental method. By omitting the ionic charges, first protonation constants, second protonation constants and equilibrium constants were determined. The adsorption behaviors were found to be dependent on contact time, pH, temperature and initial concentrations. The experimental adsorption isotherms were fitted using both the Freundlich and Langmuir models. The adsorption kinetics was described by means of the pseudo-first-order and pseudo-second-order kinetic models. The adsorption mechanism was found to involve intra-particle diffusion and film diffusion, where both were found to be the rate control steps.

The Cu(II)-fluconazole complex revisited. Part I: Structural characteristics of the system

Protonation equilibria and Cu(II) binding processes by an antifungal agent fluconazole, α-(2,4-difluorophenyl)-α-(1H-1,2,4-triazol-1-yl-methyl)-1H-1,2,4-triazole-1-ethanol, were studied using the UV–Vis, EPR and NMR spectroscopic techniques. The protonation constant of fluconazole was determined from NMR titration and attributed to N4′ nitrogen atoms using the DFT methods. The spectroscopic data suggest that at pH as low as 0.4 the first complex is formed, in which one or two Cu(II) ions are bound to one of the nitrogen atoms (N4′) from triazole rings. Above pH 1.5 each Cu(II) ion is surrounded by two nitrogen atoms (also N4′) from two different ligand molecules, forming primary monomeric complexes and above pH = 5, both dimeric or oligomeric species occur, which is well registered by the EPR technique. The mixture of Cu(NO 3) 2 with fluconazole in a 1:1 molar ratio in a water (pH = 4.5)/ethanol solution gave crystals of [Cu 2(H 2O){(C 6H 3-2,4-F 2)(CH 2N 3C 2H 2) 2C-OH}{(C 6H 3-2,4-F 2)(CH 2N 3C 2H 2) 2C-O}(NO 3)](NO 3) 2·9(H 2O). This complex is the first example of a cupric 3D polymeric structure with a fluconazole ligand coordinated via both N2′ and N4′ atoms from the same triazole rings. At higher pH values, we obtained a binuclear complex [Cu 2(L) 2(H 2O) 2(NO 3) 2], in which the copper(II) atoms were bridged by the oxygen atoms of the deprotonated OH group of fluconazole. The hypothetical oxidative properties of this system were also examined, however it failed to generate either reactive oxygen species or DNA scission products.

NMR, potentiometric and ESI-MS combined studies on the zinc(II) magnesium(II) and calcium(II) complexation by (morpholin-1-yl)methane-1,1-diphosphonic acid and its thio-analog

The crystal structures of the two derivatives of aminomethane-1,1-diphosphonic acid with morpholinyl- ( 1) and thiomorpholinyl- ( 2) side chains were determined by single crystal X-ray diffraction and discussed with respect to molecular geometry and solid state organization. The protonation equilibria, solution behavior and complex-formation equilibria in solutions of 1 and 2 with the Zn(II), Mg(II) and Ca(II) ions were studied by means of NMR, pH-potentiometry and ESI-MS methods. As the p K ( NH + ) protonation constants of 1 and 2 are high (11.65 and 11.91, respectively) two different approaches were used to evaluate the pH-potentiometric data. The first approach disregarded the proton-dissociation from the NH + group. In the second one, all the p K a values were considered in the M(II):ligand formation equilibria. For 1, the accuracy of the p K ( NH + ) determination was shown to be sufficient to calculate reliable stability constants of metal complexes with the use of both approaches. For 2, only approach neglecting the p K ( NH + ) protonation constant was shown to be correct. The studied acids form dinuclear, [M 2L 3H x ], [M 2L 2H x ] and mononuclear MLH x and ML 2H x complexes with different degree of ligand protonation. Tendency to undergo some oligomerization with the increase in the metal and ligand concentration was demonstrated for the [CaLH] complex of 1 and 2. As far as 1 and 2 remain protonated, the Zn(II), Mg(II) and Ca(II) ions are coordinated exclusively through oxygen atoms of the phosphonate groups. The metal promoted proton dissociation from the NH + ring atom takes place in alkaline pH.

N to the Rescue

Chemistry In the war against infectious disease, bacteria are in the process of scoring a frightening tactical victory. Vancomycin is often used as the antibiotic to treat strains that have evolved resistance to other drugs, but it too is falling prey to resistant strains. A simple swap of oxygen for protonated nitrogen (more specifically, lactate for alanine) by the bacteria at vancomycin's binding site is remarkably effective at disarming the drug's mechanism of action. Xie et al. fight back by introducing a compensatory swap of their own—NH for O at the complementary site on the vancomycin framework. This modification leads not only to high-affinity binding with a model of the resistant target, it also conserves impressive binding affinity with a model of the native target (just a factor of 2 shy of vancomycin itself). In other words, the NH-substituted drug derivative appears to have the capacity to bind either to the lactate site or to the alanine site, which the authors rationalize by a flexible protonation equilibrium that would render the drug's nitrogen center an effective H-bond donor or acceptor. The authors furthermore observe promising results with the modified drug against vancomycin-resistant bacteria in culture. J. Am. Chem. Soc. 133 , 10.1021/ja207142h (2011).

Spectroscopic studies with fluorescein dye—Protonation, aggregation and interaction with nanoparticles

The interesting protonation reaction between the well-known xanthene dye, fluorescein and Vitamin C (ascorbic acid) has been followed by UV–visible absorption and fluorescence spectroscopy. Ascorbic acid has been observed to exert a profound effect on fluorescein. At high dye concentration, ascorbic acid leads to very efficient deaggregation while at low dye concentration it affects the protonation equilibrium of the dye. In addition to this, stable silver nanoparticles have been incorporated into the above system and interesting results have been noted. While no strong action of the nanoparticles has been observed at low dye concentration, at high dye concentrations, the nanoparticles lead to a more profound effect on the protonation equilibrium of the dye and better deaggregation of dye aggregates. The results are rationalized in terms of the surface effects exerted by the nanoparticles.

Reactive ZrIV and HfIV Butterfly Peroxides on Polyoxometalate Surfaces: Bridging the Gap between Homogeneous and Heterogeneous Catalysis

At variance with previously known coordination compounds, the polyoxometalate (POM)-embedded Zr(IV) and Hf(IV) peroxides with formula: [M(2)(O(2))(2)(α-XW(11)O(39))(2)](12-) (M=Zr(IV), X=Si (1), Ge (2); M=Hf(IV), X=Si (3)) and [M(6)(O(2))(6)(OH)(6)(γ-SiW(10)O(36))(3)](18-) (M=Zr(IV) (4) or Hf(IV) (5)) are capable of oxygen transfer to suitable acceptors including sulfides and sulfoxides in water. Combined (1)H NMR and electrochemical studies allow monitoring of the reaction under both stoichiometric and catalytic conditions. The reactivity of peroxo-POMs 1-5 is compared on the basis of substrate conversion and kinetic. The results show that the reactivity of POMs 1-3 outperforms that of the trimeric derivatives 4 and 5 by two orders of magnitude. Reversible peroxidation of 1-3 occurs by H(2)O(2) addition to the spent catalysts, restoring oxidation rates and performance of the pristine system. The stability of 1-3 under catalytic regime has been confirmed by FT-IR, UV/Vis, and resonance Raman spectroscopy. The reaction scope has been extended to alcohols, leading to the corresponding carbonyl compounds with yields up to 99% under microwave (MW) irradiation. DFT calculations revealed that polyanions 1-3 have high-energy peroxo HOMOs, and a remarkable electron density localized on the peroxo sites as indicated by the calculated map of the electrostatic potential (MEP). This evidence suggests that the overall description of the oxygen-transfer mechanism should include possible protonation equilibria in water, favored for peroxo-POMs 1-3.

Impact of Micelle Ionic Electrical Double Layer Structure on the Excited State Protolytic Reaction in the Fluorescent Probe Bound to the Colloidal Nanoparticles

The fluorescent probe, 2-hydroxynaphthalene(dodecylo)-6-sulfonamide (NSDA) bound selectively to shear plane of various electrostatic charges was synthesized and its photophysical properties have been investigated by means of steady state fluorescence and nanosecond time-resolved spectroscopy. Our experimental data allowed us to determine the excited state proton transfer (ESPT) rate and equilibrium constants of NSDA bound to micelles and to estimate the electric potential value (Ψ) at the particle surface. The spatial dependence of proton movement velocity through electric double layer (EDL) of micelles has been thoroughly analyzed. In this article, a new approach of estimating the values of the micelle potential (Ψ(R)) from the excited state proton transfer rate constant of the fluorescent probe bound at a certain distance (R) to a micellar surface has been proposed. The Ψ(R) values, obtained in this way, are compared with electrophoretic values of the particle potential (ζ). Our results on electrophoretic potentials and the reaction course of the ESPT in colloidal environment may contribute to a deeper understanding of micellar interactions and behavior of the living cells in contact with various diluted substances such as pharmacological drugs, hormones, proteins, and other colloidal particles.

Theoretical Analysis of Proton Relays in Electrochemical Proton-Coupled Electron Transfer

The coupling of long-range electron transfer to proton transport over multiple sites plays a vital role in many biological and chemical processes. Recently the concerted proton-coupled electron transfer (PCET) reaction in a molecule with a hydrogen-bond relay inserted between the proton donor and acceptor sites was studied electrochemically. The standard rate constants and kinetic isotope effects (KIEs) were measured experimentally for this double proton transfer system and a related single proton transfer system. In the present paper, these systems are studied theoretically using vibronically nonadiabatic rate constant expressions for electrochemical PCET. Application of this approach to proton relays requires the calculation of multidimensional proton vibrational wave functions and the incorporation of multiple proton donor-acceptor motions. The decrease in proton donor-acceptor distances due to thermal fluctuations and the contributions from excited electron-proton vibronic states play important roles in these systems. The calculated KIEs and the ratio of the standard rate constants for the single and double proton transfer systems are in agreement with the experimental data. The calculations indicate that the standard PCET rate constant is lower for the double proton transfer system because of the smaller overlap integral between the ground state reduced and oxidized proton vibrational wave functions, resulting in greater contributions from excited electron-proton vibronic states with higher free energy barriers. The theory predicts that this rate constant may be increased by modifying the molecule in a manner that decreases the equilibrium proton donor-acceptor distances or alters the molecular thermal motions to facilitate the concurrent decrease of these distances. These insights may guide the design of more efficient catalysts for energy conversion devices.

π-Electron Manipulation of the 5,6-Dihydroxyindole/Quinone System by 3-Alkynylation: Mild Acid-Mediated Entry to (Cross)-Conjugated Scaffolds and Paradigms for Medium-Tunable Chromophores

5,6-Dihydroxyindole-based systems engender increasing interest for the design and implementation of new functional aromatic scaffolds and eumelanin-like materials with tailored absorption and electronic properties. However, studies aimed at elucidating the influence of external π-conjugating groups on the redox properties and acid-induced reactivity of these highly oxidizable indolic platforms are lacking. We report herein the synthesis (as acetyl derivatives) and chemical/quantum chemical characterization of the first π-extended 5,6-dihydroxyindole derivatives, 3-ethynyl-5,6-dihydroxyindole (1) and 3,3'-(1,2-ethynediyl)bis-5,6-dihydroxyindole (2), in order to understand whether and how β extension of the enamine-like pyrrole sector affects the absorption properties, redox behavior, and protonation equilibria at both the o-diphenol and quinone levels. Oxidation of 1 and 2 proceeded smoothly to generate dark insoluble materials with eumelanin-like UV properties. On exposure to phosphate buffer at pH 3, 1 was rapidly converted to 3-acetyl-5,6-dihydroxyindole (5) and, in the presence of 5,6-dihydroxyindole, to the cross-conjugated 3,3'-ethenylidenebis-5,6-dihydroxyindole (6). DFT calculations on 1 and 2 and their quinones in their pristine states and after protonation provided a mechanistic frame to rationalize the unusual acid-mediated chemistry of 1 and disclosed 2-quinone as the prototype of a novel class of medium-dependent chromophores. The ethynyl(ene) structural motif is thus proposed as the key to new tunable π-electron extended 5,6-dihydroxyindole/5,6-indolequinone paradigms for the rational design of alkyne-containing hybrid eumelanin-type polymers.

Human serum albumin conformational changes as induced by tenoxicam and modified by simultaneous diazepam binding.

The binding of tenoxicam to human serum albumin has been shown by affinity chromatography proton titration and equilibrium dialysis to be dependent on the neutral to basic conformational change of the protein. The influence of diazepam on the interaction was also investigated using the same techniques, suggesting that diazepam increases the association of tenoxicam to albumin. Affinity chromatography revealed that the reciprocal effect also occurs. Displacement studies indicated that diazepam causes a significant increase in the affinity of tenoxicam to its main binding site, albumin site I, which is different from the diazepam site (site II). Tenoxicam seemed to cause an allosteric change in the conformation of the protein during its own binding, as did warfarin. The mechanism of this effect was a pH-dependent conformational change of albumin induced by electrostatic forces within the protein. Diazepam induced a distant accommodation of the protein, an effect accompanied by an enhanced inhibition of the release of protons from albumin.

A Partial Proton Transfer in Hydrogen Bond O−H···O in Crystals of Anhydrous Potassium and Rubidium Complex Chloranilates

Hydrogen bonding and proton transfer in the solid state are studied on the crystals of isostructural anhydrous potassium and rubidium complex chloranilates by variable-temperature single crystal X-ray diffraction, solid state (1)H NMR and IR spectroscopies, and periodic DFT calculations of equilibrium geometries, proton potentials, and NMR chemical shifts. Their crystal structures reveal neutral molecules of chloranilic acid and its dianions connected into a chain by O-H···O hydrogen bond. A strong hydrogen bond with a large-amplitude movement of the proton with NMR shift of 13-17 ppm and a broad continuum in IR spectra between 1000 and 500 cm(-1) were observed. Periodic DFT calculations suggest that proton transfer is energetically more favorable if it occurs within a single pair of chloranilate dianion and chloranilic acid molecule but not continuously along the chains of long periodicity. The calculated chemical shifts confirm the assumption that the weak resonance signals observed at lower magnetic fields pertain to the case when the proton migrates to the acceptor side of the hydrogen bond. The detected situation can be described by a partial proton transfer.

Protonation Equilibria and Stepwise Hydrolysis Behavior of a Series of Thiomonophosphate Anions

The stepwise protonation constants of a series of thiomonophosphate anions, i.e., monothiomonophosphate, dithiomonophosphate, trithiomonophosphate, and tetrathiomonophosphate anions, were determined by (31)P NMR chemical shift measurements in aqueous solution. Despite the remarkably fast hydrolysis rates of these anions, the protonation processes of all thiomonophosphate anions may be evaluated accurately without any previous purification, because the NMR signals corresponding to thiomonophosphate anions and hydrolyzed residues are well resolved. The stepwise protonation constants decrease with an increase in the number of sulfur atoms bound to the central phosphorus atom. It was revealed that the logarithms of the stabilities of the proton complexes of the series of thiomonophosphate anions decrease "linearly" with an increase in the number of sulfur atoms in the anions. The intrinsic (31)P NMR chemical shifts due to orthophosphate and tetrathiomonophosphate anions show upfield shifts upon successive protonations of the anions, whereas the shifts of mono-, di-, and trithiomonophosphate anions move downfield relative to the anions upon protonation. Furthermore, more asymmetric molecular structures experience greater changes in their X-P-Y bond angles upon protonation or complex formation, leading to drastic changes in the nuclear screening. The symmetry of the molecular structure is related to the direction of the (31)P NMR chemical shift change upon successive protonation of thiomonophosphate anions.

Associated electron and proton transfer between Acridine and Triethylamine in AOT reverse micelles probed by laser flash photolysis with magnetic field

Laser flash photolysis with magnetic field (MF ∼0.08 T) has been used to study interaction between Acridine (Acr) and Triethylamine (TEA) in reverse micelles with w 0 = 2.5–40. Dynamic protonation equilibrium exists between 3Acr and 3AcrH +. The intermediates indicate excited-state proton transfer (PT) between 3AcrH + and TEA. However, application of MF highlights the formation of geminate radical ion pairs (RIPs) with triplet spin-correlation, a signature of latent photoinduced electron transfer between 3AcrH + and TEA co-exists with PT. Magnetic field effect (MFE) is prominent for smaller w 0 showing importance of optimum separation between RIP to maximize MFE, whereas PT remains unaltered.

Spectroscopic and Electronic Structure Studies of Copper(II) Binding to His111 in the Human Prion Protein Fragment 106−115: Evaluating the Role of Protons and Methionine Residues

The prion protein (PrP(C)) is implicated in the spongiform encephalopathies in mammals, and it is known to bind Cu(II) at the N-terminal region. The region around His111 has been proposed to be key for the conversion of normal PrP(C) to its infectious isoform PrP(Sc). The principal aim of this study is to understand the role of protons and methionine residues 109 and 112 in the coordination of Cu(II) to the peptide fragment 106-115 of human PrP, using different spectroscopic techniques (UV-vis absorption, circular dichroism, and electron paramagnetic resonance) in combination with detailed electronic structure calculations. Our study has identified a proton equilibrium with a pK(a) of 7.5 associated with the Cu(II)-PrP(106-115) complex, which is ascribed to the deprotonation of the Met109 amide group, and it converts the site from a 3NO to a 4N equatorial coordination mode. These findings have important implications as they imply that the coordination environment of this Cu binding site at physiological pH is a mixture of two species. This study also establishes that Met109 and Met112 do not participate as equatorial ligands for Cu, and that Met112 is not an essential ligand, while Met109 plays a more important role as a weak axial ligand, particularly for the 3NO coordination mode. A role for Met109 as a highly conserved residue that is important to regulate the protonation state and redox activity of this Cu binding site, which in turn would be important for the aggregation and amyloidogenic properties of the protein, is proposed.