Protonation-deprotonation Reactions Research Articles

Determining obstructive or promoting effects of anions and DOM on phosphate transport combining with Donnan dialysis and selective electrodialysis

In recent, nutrient recovery from wastewater by selective electrodialysis has been getting more attention, especially for non-renewable elements like phosphorus. However, phosphates usually possess a slow transfer flux in the electrodialysis process. This study aimed to decipher the influence of competing anions and dissolved organic matters (DOM) on phosphate migration with and without electric field. Anions that do and do not participate in protonation-deprotonation reactions showed discrepant effects on competitive phosphate transport. Carbonates enhance the sorption of phosphates in the anion exchange membrane and their diffusion through the membrane. However, this advantage gradually reduced with the increasing voltage during the selective electrodialysis, caused by the development of water splitting and an increase of the carbonate charge in the membrane. DOM substances, especially humic and fulvic acids, delay the phosphate transfer by the formation of fouling and biofouling and substantially intensify water splitting. With the increase of electric field, fouling of humic and fulvic acids were enhanced, while the presence of DOM has little effect on phosphate in Donnan dialysis. These findings help the understanding of phosphorus transfer in the electrodialysis process, and providing insights into the underlying mechanisms of membrane selectivity in competitive ion transport.

On Analogies in Proton-Transfers for Pyrimidine Bases in the Gas Phase (Apolar Environment)—Cytosine Versus Isocytosine

Inter- and intra-molecular proton-transfers between functional groups in nucleobases play a principal role in their interactions (pairing) in nucleic acids. Although prototropic rearrangements (intramolecular proton-transfers) for neutral pyrimidine bases are well documented, they have not always been considered for their protonated and deprotonated forms. The complete isomeric mixtures in acid-base equilibria and in acidity–basicity parameters have not yet been examined. Taking into account the lack of literature and data, research into the question of prototropy for the ionic (protonated and deprotonated) forms has been undertaken in this work. For the purposes of this investigation, two isomeric pyrimidine bases (C—cytosine and iC—isocytosine) were chosen. They exhibit analogous (symmetrical) general acid-base equilibria (intermolecular proton-transfers). Being similar polyfunctional tautomeric systems, C and iC possess two labile protons and five conjugated tautomeric sites. However, positions of exo groups are different. Consequently, structural conversions such as prototropy, rotational, and geometrical isomerism of exo groups (=O/−OH and =NH/−NH2) and their intramolecular interactions with endo groups (=N−/>NH) possible in neutral C and iC and in their ionic forms lead to some differences in compositions of isomeric mixtures. By application of quantum–chemical methods to the isolated (in vacuo) species, stability of all possible neutral and ionic isomers has been examined and the candidate isomers selected. The complete isomeric mixtures have been considered for the first time for di-deprotonated, mono-deprotonated, mono-protonated, and di-protonated forms. Protonation–deprotonation reactions have been analyzed in the gas phase that models non-polar environment. The gas-phase microscopic (kinetic) and macroscopic (thermodynamic) acidity–basicity parameters have been estimated for each step of acid-base equilibria. When proceeding from di-anion to di-cation in four steps of protonation–deprotonation reaction, the macroscopic proton affinities for C and iC differ by less than 10 kcal mol−1. Their DFT-calculated values are as follows: 451 and 457, 340 and 339, 228 and 224, and 100 and 104 kcal mol−1, respectively. Differences between the microscopic proton affinities for analogous isomers of C and iC seem to be larger for the exo than endo groups. Owing to variations of relative stabilities for neutral and ionic isomers, in some cases they are even larger than 10 kcal mol−1.

Voltage Mediated Control of Fluorescence Protein Emissions at the Metal-Solution Interface

The fluorescence protein technologies have made remarkable contributions to the advancement of life science. Accordingly, the physicochemical properties of fluorescence proteins have been deeply investigated in the bulk solution that mimics the cellular environment, but those at the less common environment such as surface and interface have not been deeply investigated. We recently found the phenomenon that the fluorescence protein immobilized at the metal-solution interface exhibits voltage-dependent photoluminescence. Upon the blue light photoexcitation of Venus, a yellow-emitting variant of green fluorescence protein, immobilized on the gold electrode surface, robust enhancement or decrease of fluorescence was induced by applying negative or positive bias, respectively. This previously unappreciated phenomenon was then implemented as a protein-based microdisplay. We then sought to solve the mechanism for the cathodic enhancement utilizing the characteristic optical properties in the three different fluorescence proteins. From the simultaneous electrochemical and fluorescence measurements in Venus, we found a strong correlation between the fluorescence modulation and the current reflecting cathodic hydrogen evolution, which led to a hypothesis that shift in the protonation-deprotonation equilibrium of the chromophore driven by hydrogen evolution at the metal surface underlies the phenomena. The hypothesis predicted that voltage dependency should be also found in the green-to-red photoconversion of fluorescence protein which is known as a protonation-dependent process. The hypothesis was verified by observing clear voltage dependency for the photoconversion in KikGR, an engineered photoconvertible fluorescence protein, at the interface. We then addressed how the shift in protonation equilibrium is driven by hydrogen evolution. The analysis using iR-phuruolin, a fluorescence protein variant with the inverse pH-sensitivity revealed the existence of an interface-specific mode of protonation-deprotonation reactions, where the protonation equilibrium is directly coupled to the cathodic hydrogen evolution. The interface-specific mode is distinct from that conventionally seen in protein in the bulk solution where the protonation patterns of the constituent titratable residues are determined through the local environmental acid-base equilibrium. The potential applications based on this interface-specific mechanism are then discussed, including the spatially resolved monitoring of hydrogen evolution reactions at the near-neutral condition. Fluorescent Protein The original Green Fluorescent Protein (GFP) was discovered by the researchers back in the early 1960s when studying the bioluminescent properties of a blue light emitting bioluminescent protein called aequorin together with another protein isolated from Aequorea victoria jellyfish and that another protein was eventually named the Green Fluorescent Protein [1]. GFP like fluorescent proteins have been discovered in other organisms including corals, copepods, sea anemones, lancelets, zoanithids [2]. GFP can be modified because the genetic code and amino acid code is well known [3]. Modifications allow for GFP to fluoresce with different colors such as blue (BFP), yellow (YFP), cyan (CFP), red (RFP) [4]. Their physiochemical phenomena can be used for various biological and medical research [5,6]. Advances such as, Förster resonance energy transfer (FRET), a fluorescence microscopy application was developed with GFP and permitting the researchers to use even more specific and powerful applications of fluorescence for their imaging [7]. last ten years, many new RSFPs (Reversibly photoswitchable fluorescent proteins) have been developed and novel applications in cell imaging discovered that rely on their photoswitching properties [8,9].

Synthesis, molecular structure and fluxional behavior of the elusive [HRu4(CO)12]3- carbonyl anion.

The elusive mono-hydride tri-anion [HRu4(CO)12]3- (4) has been isolated and fully characterized for the first time. Cluster 4 can be obtained by the deprotonation of [H3Ru4(CO)12]- (2) with NaOH in DMSO. A more convenient synthesis is represented by the reaction of [HRu3(CO)11]- (6) with an excess of NaOH in DMSO. The molecular structure of 4 has been determined by single-crystal X-ray diffraction (SC-XRD) as the [NEt4]3[4] salt. It displays a tetrahedral structure of pseudo C3v symmetry with the unique hydride ligand capping a triangular Ru3 face. Variable temperature (VT) 1H and 13C{1H} NMR experiments indicate that 4 is fluxional in solution and reveal an equilibrium between the C3v isomer found in the solid state and a second isomer with Cs symmetry. Protonation-deprotonation reactions inter-converting H4Ru4(CO)12 (1), [H3Ru4(CO)12]- (2), [H2Ru4(CO)12]2- (3), [HRu4(CO)12]3- (4) and the purported [Ru4(CO)12]4- (5) have been monitored by IR and 1H NMR spectroscopy. Whilst attempting the optimization of the synthesis of 4, crystals of [NEt4]2[Ru3(CO)9(CO3)] ([NEt4]2[7]) were obtained. Anion 7 contains an unprecedented CO32- ion bonded to a zero-valent Ru3(CO)9 fragment. Finally, the reaction of 6 as the [N(PPh3)2]+ ([PPN]+) salt with NaOH in DMSO affords [Ru3(CO)9(NPPh3)]- (9) instead of 4. Computational DFT studies have been carried out in order to support experimental evidence and the location of the hydride ligands as well as to shed light on possible isomers.

Influence of Protonation–Deprotonation Reactions on the Diffusion of Ammonium Chloride through Anion-Exchange Membrane

Influence of Protonation–Deprotonation Reactions on the Diffusion of Ammonium Chloride through Anion-Exchange Membrane

Interface-specific mode of protonation–deprotonation reactions underlies the cathodic modulation of fluorescence protein emission

While fluorescence protein immobilized at the metal–solution interface has been known to exhibit voltage-dependent fluorescence, the underlying mechanism has remained unresolved. Here, we addressed the cathodic mechanism employing the characteristic properties of three different fluorescence proteins showing conventional pH-sensitivity, inverse pH-sensitivity, and green-to-red photo-convertibility. Through the analysis, we found that the interface-specific mode of protonation–deprotonation reactions underlies the cathodic effect, where the protonation state is directly coupled to hydrogen evolution at the interface rather than to the environmental acid-base equilibrium. The potential applications based on the interface effect are then discussed, including the spatially-resolved monitoring of hydrogen evolution reactions.

A comprehensive mathematical model of water splitting in bipolar membranes: Impact of the spatial distribution of fixed charges and catalyst at bipolar junction

Bipolar ion-exchange membranes (BPM) have a long history and many uses. Still, the number of applications continues to grow every year, as does the interest in a better understanding of the mechanisms of ion transport and water splitting. We reconsider the existing theoretical background for the BPMs and propose a one-dimensional stationary model. For the first time, the Nernst-Planck-Poisson equations are coupled with the equations, which locally describe the water splitting kinetics. The catalytic effects exerted by the functional groups and the catalyst (if present), the protonation-deprotonation reactions of these groups as well as the effect of strong electric field (the second Wien effect) are taken into account when describing the reverse-bias mode. The effective rate constant of water splitting occurring in the absence of electric field is determined from the acid dissociation constants (Ka). The concentration profiles, the thickness of the reaction zone and space charge region (SCR) are simulated and analyzed. The results of numerical computation are compared with the known analytical estimations. Thus, the basic assumptions of the theory of BPMs are examined, and the conditions under which these assumptions are valid or not are found. Current-voltage curves and partial currents are calculated and compared with experimental data. The occurrence of two limiting currents at pKa close to 7 is predicted due to current-induced membrane discharge. According to simulations, any increase in the SCR thickness leads to a decrease of the water spitting rate at a fixed voltage due to a decrease in the second Wien effect. A very thin (about 4 nm) catalytic layer within the bipolar junction is sufficient to obtain 100 mA cm−2 current density at 1 V even when the anion-exchange and cation-exchange membrane layers do not contain catalytically active functional groups.

Identification of montmorillonite particle edge orientations by atomic-force microscopy

Statistical information on the edge surface area and edge crystallographic orientation of clay nanoparticle surfaces is essential for proper accounting of the protonation-deprotonation reactions as a part of mechanistic surface complexation models. A combination of atomic-force microscopy (AFM) measurements and molecular dynamics computer simulations made it possible to quantify the relative contributions of the most frequently occurring montmorillonite edge surfaces to the total edge surface area. Edge surfaces normal to the [110] and [010] crystallographic directions are found to be the most abundant (~60% and ~20%, respectively), in agreement with previous estimations.

Transport of uranium(VI) in red soil in South China: influence of initial pH and carbonate concentration.

Uranium-contaminated wastewater associated with uranium (U) mining and processing inevitably releases into soil environment. In order to assess the risk of U wastewater contamination to groundwater through percolation, U adsorption and transport behavior in a typical red soil in South China was investigated through batch adsorption and column experiments, and initial pH and carbonate concentration were considered of the high-sulfate background electrolyte solution. Results demonstrated that U adsorption isotherms followed the Freundlich model. The adsorption of U to red soil significantly decreased with the decrease of the initial pH from 7 to 3 in the absence of carbonate, protonation-deprotonation reactions controlled the adsorption capacity, and lnCs had a linear relationship with the equilibrium pH (pHeq). In the presence of carbonate, the adsorption was much greater than that in the absence of carbonate owing to the pHeq values buffered by carbonate, but the adsorption decreased with the increase of the carbonate concentration from 3.5 to 6.5 mM. Additionally, the breakthrough curves (BTCs) obtained by column experiments showed that large numbers of H+ and CO32- competed with the U species for adsorption sites, which resulted in BTC overshoot (C/C0 > 1). Numerical simulation results indicated that the BTCs at initial pH 4 and 5 could be well simulated by two-site chemical non-equilibrium model (CNEM), whereas the BTCs of varying initial carbonate concentrations were suitable for one-site CNEM. The fractions of equilibrium adsorption sites (f) seemed to correlate with the fractions of positively charged complexes of U species in solution. The values of partition coefficients (kd') were lower than those measured in batch adsorption experiments, but they had the same variation trend. The values of first-order rate coefficient (ω) for all BTCs were low, representing a relatively slow equilibrium between U in the liquid and solid phases. In conclusion, the mobility of U in the red soil increased with the decrease of the initial pH and with the increase of the initial carbonate concentrations.

Protonation–Deprotonation Treatment Modulating the Aggregate Structure and Fluorescence Property of (9-Anthryl)vinyl(4-pyridyl)vinylbenzene Position Isomers

The solid-state fluorescence property of organic materials is sensitive to molecule arrangement. Herein, solid-state protonation–deprotonation reactions are used as a tool to tune the molecular pac...

A stimuli-responsive and chemically tunable organic microcrystal laser switch.

We demonstrated a stimuli-responsive and chemically switchable organic microbelt laser through reversible protonation-deprotonation reactions. The parent microbelt cavity together with the optically allowed 0-1 transition of H-aggregates enables a microlaser to operate at 585 nm. Upon HCl vapor treatment, the protonation of surface molecules shifts the lasing wavelength to 560 nm, generating an intensity contrast ratio >105, accompanied by a sharp color change from orange (deprotonated) to green (protonated). When treated with HCl-NH3 vapor, the protonation-deprotonation reactions lead to a reversible microlaser switch between 585 nm and 560 nm with good reproducibility and photostablity, making them attractive in high-throughput chemical and biological sensing applications.

Intrinsic Thermodynamics of Protein-Ligand Binding by Isothermal Titration Calorimetry as Aid to Drug Design.

Isothermal titration calorimetry (ITC) is one of the main techniques to determine specific interactions between molecules dissolved in aqueous solution. This technique is commonly used in drug development programs when low-molecular-weight molecules are sought that bind tightly and specifically to a protein (disease target) molecule. The method allows a complete thermodynamic characterization of an interaction, i.e., ITC enables direct determination of the model-independent observed interaction change in enthalpy (ΔH) and a model-dependent observed interaction affinity (change in Gibbs free energy, ΔG) in a single experiment. The product of temperature and change in entropy (TΔS) can be obtained by the subtraction of ΔG from ΔH, and the change in heat capacity (ΔCp) can be determined as a slope of the temperature dependence of the binding ΔH.Despite the apparent value of ITC in characterization of interactions, it is often forgotten that many protein-ligand binding reactions are linked to protonation-deprotonation reactions or various conformational changes. In such cases, it is important to determine the linked-reaction contributions and obtain the intrinsic values of the changes in Gibbs energy (affinity), enthalpy, and entropy. These energy values can then be used in various SAR-type structure-thermodynamics and combined with structure-kinetics correlations in drug design, when searching for small molecules that would bind the protein target molecule. This manuscript provides a detailed protocol on how to determine the intrinsic values of protein-ligand binding thermodynamics by ITC.

Carborane derivatives of 1,2,3-triazole depolarize mitochondria by transferring protons through the lipid part of membranes

Boron containing polyhedra (carboranes) are three-dimensional delocalized aromatic systems. These structures have been shown to transport protons through lipid membranes and mitochondria. Conjugation of carboranes to various organic moieties is aimed at obtaining biologically active compounds with novel properties. Taking advantage of 1,2,3-triazoles as the scaffolds valuable in medicinal chemistry, we synthesized 1-(o-carboranylmethyl)-4-pentyl-1,2,3-triazole (c-triazole) and 1-(o-carboranylmethyl)-4-pentyl-1,2,3-triazolium iodide (c-triazolium). Both compounds interacted with model lipid membranes and exhibited a proton carrying activity in planar bilayers and liposomes in a concentration- and pH-dependent manner. Importantly, mechanisms of the protonophoric activity differed; namely, protonation-deprotonation reactions of the triazole and the o-carborane moieties were involved in the transport cycles of c-triazole and c-triazolium, respectively. At micromolar concentrations, c-triazole and c-triazolium stimulated respiration of isolated rat liver mitochondria and depolarized their membrane potential, with c-triazole being more potent. In living K562 (human chronic myelogenous leukemia) cells, both c-triazolium and c-triazole altered the mitochondrial membrane potential as determined by a decreased intracellular accumulation of the potential-dependent dye tetramethylrhodamine ethyl ester. Finally, cell viability testing demonstrated a cytotoxic potency of c-triazolium and, to a lesser extent, of c-triazole against K562 cells, whereas non-malignant fibroblasts were much less sensitive. In all tests, the reference boron-free benzyl-4-pentyl-1,2,3-triazole showed little-to-no effects. These results demonstrated that carboranyltriazoles carry protons across biological membranes, a property potentially important in anticancer drug design.

Mechanistic Studies of the Protonation-Deprotonation Reactions for Type 1 and Type 2 Isopentenyl Diphosphate:Dimethylallyl Diphosphate Isomerase.

Type 1 and type 2 isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-1 and IDI-2) catalyze the interconversion of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the fundamental building blocks for biosynthesis of isoprenoid compounds. Previous studies indicate that both isoforms of IDI catalyze isomerization by a protonation-deprotonation mechanism. IDI-1 and IDI-2 are "sluggish" enzymes with turnover times of ∼10 s-1 and ∼1 s-1, respectively. We measured incorporation of deuterium into IPP and DMAPP in D2O buffer for IDI-1 and IDI-2 under conditions where newly synthesized DMAPP is immediately and irreversibly removed by coupling its release to condensation with l-tryptophan catalyzed by dimethylallyltrytophan synthase. During the course of the reactions, we detected formation of d1, d2, and d3 isotopologues of IPP and DMAPP, which were formed during up to five isomerizations between IPP and DMAPP during each turnover. The patterns for deuterium incorporation into IPP show that d2-IPP is formed in preference to d1-IPP for both enzymes. Analysis of the patterns of deuterium incorporation are consistent with a mechanism involving addition and removal of protons by a concerted asynchronous process, where addition substantially precedes removal, or a stepwise process through a short-lived (<3 ps) tertiary carbocationic intermediate. Previous work with mechanism-based inhibitors and related model studies supports a concerted asynchronous mechanism for the enzyme-catalyzed isomerizations.

Reactive Porphyrin Adsorption on TiO2 Anatase Particles: Solvent Assistance and the Effect of Water Addition.

The surface functionalization of metal oxide nanoparticles with complex organic molecules can lead to optoelectronically very different material properties, depending on whether adsorption occurs at the solid-gas or solid-liquid interface. Here, we report on two different approaches to decorate anatase TiO2 nanoparticle powders with 2 H-tetraphenylporphyrin (2HTPP) molecules: (i) porphyrin adsorption in dispersions of organic liquids and (ii) gas-phase functionalization where evaporated porphyrin molecules attach to dehydrated particle surfaces in the absence of solvent molecules. In the latter case, a bottom-up approach is pursued to explore both the impact of organic solvent molecules and the impact of spurious water on the surface chemistry of porphyrin-sensitized TiO2 nanoparticles. Vis diffuse reflectance and photoluminescence emission spectroscopy provide clear evidence for the promotion of interfacial reorganization processes of the adsorbate species by coadsorbed solvent molecules in liquids. Moreover, traces of spurious water were found to induce protonation-deprotonation reactions on the adsorbed porphyrins with a strong impact on the optical properties of the resulting hybrid materials.

Influence of β-octabromination on free-base triarylcorroles: Electrochemistry and protonation-deprotonation reactions in nonaqueous media

Electrochemical and acid-base properties of four free-base triarylcorroles were examined in nonaqueous media. These compounds are represented here as (tdcc)H[Formula: see text], (tpfc)H[Formula: see text], (Br[Formula: see text]tdcc)H[Formula: see text] and (Br[Formula: see text]tpfc)H[Formula: see text], where tdcc and tpfc are the trianions of tris(2,6-dichlorophenyl)corrole and tris(pentafluorophenyl)corrole, respectively. Different spectroscopic and electrochemical properties were observed for the [Formula: see text]-brominated corroles as compared to the non-brominated derivatives, due in part to the corrole ring distortion and in part to the strong electron-withdrawing properties of the Br groups. The brominated free-base corroles are easier to deprotonate than the non-brominated corroles in solution, which was confirmed by electrochemistry and spectroelectrochemistry as well as protonation/deprotonation reactions of the compounds with acid or base in PhCN. The electrochemistry of the protonated and deprotonated corroles is presented and comparisons made with previously published data for other protonated and deprotonated free-base corroles under the same solution conditions.

A pOH Jump Driven by N═N Out-of-Plane Motion in the Photoisomerization of Water-Solvated Triazabutadiene.

Utilization of photoinitiated isomerization reaction has recently emerged as a very promising platform to modulate the basicity of compounds; however, theoretical insight into its regulatory mechanism remains largely unknown and needs to be addressed. For the first time, an unexpected trans-cis photoisomerization via the N═N out of plane (NOOP) motion triggered by an in-plane inversion of N-N═N moiety was computationally demonstrated to regulate the pOH jump of water-solvated triazabutadiene by using the multiconfigurational perturbation theory together with the calculation of rate constants of protonation-deprotonation reactions. Kinetic analyses show that the dramatic pOH change can be attributed to the reinforced intramolecular hydrogen bonding resulting from water cluster reorientation and the enhanced coupling between the rotated π orbital and N lone pair of triazabutadiene in the remarkable trans-cis photoisomerization.

On the complex •OH/•O−-induced free radical chemistry of arylalkylamines with special emphasis on the contribution of the alkylamine side chain

A full account of the •OH-induced free radical chemistry of an arylalkylamine is given taking all the possible reaction pathways quantitatively into consideration. Such knowledge is indispensable when the alkylamine side chain plays a crucial role in biological activity. The fundamental reactions are investigated on the model compound N-methyl-3-phenypropylamine (MPPA), and extended to its biologically active analog, to the antidepressant fluoxetine (FLX). Pulse radiolysis techniques were applied including redox titration and transient spectral analysis supplemented with DFT calculations. The contribution of the amine moiety to the free radical-induced oxidation mechanism appeared to be appreciable. •O− was used to observe hydrogen atom abstraction events at pH 14 giving rise to the strongly reducing α-aminoalkyl radicals (∼38% of the radical yield) and to benzyl (∼4%), β-aminoalkyl (∼24%), and aminyl radicals (∼31%) of MPPA. One-electron transfer was also observed yielding aminium radicals with low efficiency (∼3%). In the •OH-induced oxidation protonated α-aminoalkyl (∼49%), β-aminoalkyl (∼27%), benzyl radicals (∼4%), and aminium radicals (∼5%) are initially generated on the side chain of MPPA at pH 6, whereas hydroxycyclohexadienyl radicals (∼15%) were also produced. These initial events are followed by complex protonation–deprotonation reactions establishing acid–base equilibria; however, these processes are limited by the transient nature of the radicals and the kinetics of the ongoing reactions. The contribution of the radicals from the side chain alkylamine substituent of FLX totals up to ∼54% of the initially available oxidant yield.

Kinetic modeling of pH-dependent antimony (V) sorption and transport in iron oxide-coated sand

Understanding the mechanisms and kinetics controlling the retention and transport of antimony (Sb) is prerequisite for evaluating the risk of groundwater contamination by the toxic element. In this study, kinetic batch and saturated miscible displacement experiments were performed to investigate effects of protonation–deprotonation reactions on sorption–desorption and transport of Sb(V) in iron oxide-coated sand (IOCS). Results clearly demonstrated that Sb(V) sorption was highly nonlinear and time dependent, where both sorption capacity and kinetic rates decreased with increasing solution pH. Breakthrough curves (BTCs) obtained at different solution pH exhibited that mobility of Sb(V) were higher under neutral to alkaline condition than under acidic condition. Because of the nonlinear and non-equilibrium nature of Sb(V) retention and transport, multi-reaction models (MRM) with equilibrium and kinetic sorption expressions were utilized successfully to simulate the experiment data. Equilibrium distribution coefficient (Ke) and reversible kinetic retention parameters (k1 and k2) of both kinetic sorption and transport experiment showed marked decrease as pH increased from 4.0 to 7.5. Surface complexation is suggested as the dominant mechanism for the observed pH-dependent phenomena, which need to be incorporated into the kinetic models to accurately simulate the reactive transport of Sb(V) in vadose zone and aquifers.

Intrinsic Thermodynamics - Structure Correlation of Carbonic Anhydrase Inhibitors

For the design of selective inhibitors towards 12 active human carbonic anhydrase (CA) isoforms, a map correlating thermodynamics of inhibitor binding with cocrystal structures was created. A series of over 600 inhibitors were chemically synthesized. Their binding to CA isoforms was measured by three biophysical and biochemical techniques, namely, isothermal titration calorimetry (ITC), fluorescent thermal shift assay (FTSA), and enzymatic inhibition methods. A database of over 3000 binding reactions, including the intrinsic Gibbs free energies and sometimes the enthalpies, entropies and heat capacities, was assembled. Intrinsic energetics of binding was determined by accounting for the linked protonation-deprotonation reactions of both protein and ligand. Together with over 80 cocrystal structures, this database provided insight into some general issues of protein-ligand interactions, especially the enthalpy - entropy compensation and isoform-selective ligand design. Parts of some ligands contained flexible tailgroups that correlated with increased intrinsic entropy of binding. All designed ligands exhibited enthalpy-driven binding with minor but important entropic contributions. The method is useful for the design of ligands with appropriate affinities and selectivities.