Red-Shifting the Excitation Energy of Carbonic Acid Clusters Via Nonminimum Structures.

Nonminimum carbonic acid clusters provide excitation energies and oscillator strengths in line with observed ice-phase UV absorptions better than traditional optimized minima. This equation-of-motion coupled cluster quantum chemical analysis on carbonic acid monomers and dimers shows that shifts to the dihedral angle for the internal heavy atoms in the monomer produce UV electronic excitations close to 200 nm with oscillator strengths that would produce observable features. This τ(OCOO) dihedral is actually a relatively floppy motion unlike what is often expected for sp2 carbons and can be distorted by 30° away from equilibrium for an energy cost of only 11 kcal/mol. As this dihedral decreases beyond 30°, the excitation energies decrease further. The oscillator strengths do, as well, but only to a point. Hence, the lower-energy distortions of τ(OCOO) are sufficient to produce structures that exhibit excitation energies and oscillator strengths that would red-shift observed spectra of carbonic acid ices away from the highest UV absorption feature at 139 nm. Such data imply that colder temperatures (20 K) in the experimental treatment of carbonic acid ices are freezing these structures out after annealing, whereas the warmer temperature experiments (80 K) are not.

Green approach for fabrication of bacterial cellulose-chitosan composites in the solutions of carbonic acid under high pressure CO2.

The functionalization of the bacterial cellulose (BC) surface with a chitosan biopolymer to expand the areas of possible applications of the modified BC is an important scientific task. The creation of such composites in the carbonic acid solutions that were performed in this work has several advantages in terms of being biocompatible and eco-friendly. Quantitative analysis of chitosan content in the composite was conducted by tritium-labeled chitosan radioactivity detection method and this showed three times increased chitosan loading. Different physicochemical methods showed successful incorporation of chitosan into the BC matrix and interaction with it through hydrogen bonds. Microscopy results showed that the chitosan coating with a thickness of around 10 nm was formed in the bulk of BC, covering each microfibril. It was found that the inner specific surface area increased 1.5 times on deposition of chitosan from the solutions in carbonic acid.

Potent Inhibition of Mandelate Racemase by Boronic Acids: Boron as a Mimic of a Carbon Acid Center.

Boronic acids have been successfully employed as inhibitors of hydrolytic enzymes. Typically, an enzymatic nucleophile catalyzing hydrolysis adds to the electrophilic boron atom forming a tetrahedral species that mimics the intermediate(s)/transition state(s) for the hydrolysis reaction. We show that para-substituted phenylboronic acids (PBAs) are potent competitive inhibitors of mandelate racemase (MR), an enzyme that catalyzes a 1,1-proton transfer rather than a hydrolysis reaction. The Ki value for PBA was 1.8 ± 0.1 µM, and p-Cl-PBA exhibited the most potent inhibition (Ki = 81 ± 4 nM), exceeding the binding affinity of the substrate by ∼4 orders of magnitude. Isothermal titration calorimetric studies with the wild-type, K166M, and H297N MR variants indicated that, of the two Brønsted acid-base catalysts Lys 166 and His 297, the former made the greater contribution to inhibitor binding. The X-ray crystal structure of the MR·PBA complex revealed the presence of multiple H-bonds between the boronic acid hydroxyl groups and the side chains of active site residues, as well as formation of a His 297 Nε2-B dative bond. The dramatic upfield change in chemical shift of 27.2 ppm in the solution-phase 11B nuclear magnetic resonance spectrum accompanying binding of PBA by MR was consistent with an sp3-hybridized boron, which was also supported by density-functional theory calculations. These unprecedented findings suggest that, beyond substituting boron at carbon centers participating in hydrolysis reactions, substitution of boron at the acidic carbon center of a substrate furnishes a new approach for generating inhibitors of enzymes catalyzing the deprotonation of carbon acid substrates.

Small Molecules, Non-Covalent Interactions, and Confinement.

This review gives an overview of current trends in the investigation of small guest molecules, confined in neat and functionalized mesoporous silica materials by a combination of solid-state NMR and relaxometry with other physico-chemical techniques. The reported guest molecules are water, small alcohols, and carbonic acids, small aromatic and heteroaromatic molecules, ionic liquids, and surfactants. They are taken as characteristic role-models, which are representatives for the typical classes of organic molecules. It is shown that this combination delivers unique insights into the structure, arrangement, dynamics, guest-host interactions, and the binding sites in these confined systems, and is probably the most powerful analytical technique to probe these systems.

Intact carbonic acid is a viable protonating agent for biological bases.

Carbonic acid H2CO3 (CA) is a key constituent of the universal CA/bicarbonate/CO2 buffer maintaining the pH of both blood and the oceans. Here we demonstrate the ability of intact CA to quantitatively protonate bases with biologically-relevant pKas and argue that CA has a previously unappreciated function as a major source of protons in blood plasma. We determine with high precision the temperature dependence of pKa(CA), pKa(T) = -373.604 + 16,500/T + 56.478 ln T. At physiological-like conditions pKa(CA) = 3.45 (I = 0.15 M, 37 °C), making CA stronger than lactic acid. We further demonstrate experimentally that CA decomposition to H2O and CO2 does not impair its ability to act as an ordinary carboxylic acid and to efficiently protonate physiological-like bases. The consequences of this conclusion are far reaching for human physiology and marine biology. While CA is somewhat less reactive than (H+)aq, it is more than 1 order of magnitude more abundant than (H+)aq in the blood plasma and in the oceans. In particular, CA is about 70× more abundant than (H+)aq in the blood plasma, where we argue that its overall protonation efficiency is 10 to 20× greater than that of (H+)aq, often considered to be the major protonating agent there. CA should thus function as a major source for fast in vivo acid-base reactivity in the blood plasma, possibly penetrating intact into membranes and significantly helping to compensate for (H+)aq's kinetic deficiency in sustaining the large proton fluxes that are vital for metabolic processes and rapid enzymatic reactions.

Mass Transport Analysis of Bicarbonate Buffer: Effect of the CO2-H2CO3 Hydration-Dehydration Kinetics in the Fluid Boundary Layer and the Apparent Effective p Ka Controlling Dissolution of Acids and Bases.

The main buffering system influencing ionizable drug dissolution in the human intestinal fluid is bicarbonate-based; however, it is rarely used in routine pharmaceutical practice due to the volatility of dissolved CO2. The typical pharmaceutical buffers used fail to capture the unique aspects of the hydration-dehydration kinetics of the bicarbonate-CO2 system. In particular, CO2 is involved in a reversible interconversion with carbonic acid (H2CO3), which is the actual conjugate acid of the system, as follows CO2 + H2O ⇌ H2CO3. In contrast to ionization reactions, this interconversion does not equilibrate very rapidly compared to the diffusional processes through a typical fluid diffusion boundary layer at a solid-liquid interface. In this report, a mathematical mass transport analysis was developed for ionizable drug dissolution in bicarbonate using the rules of conservation of mass and electric charge in addition to accounting for the diffusional times and reaction rate constants of the CO2-H2CO3 interconversion. This model, which includes both the hydration reaction rate and dehydration reaction rate, we called the "reversible non-equilibrium" (RNE) model. The predictions made by this RNE approach for ionizable drug dissolution rates were compared to the experimental data generated by an intrinsic dissolution method for three ionizable drugs, indomethacin, ibuprofen, and haloperidol. The results demonstrate the superiority of predictions for the RNE approach compared to the predictions of a model assuming equilibrium between CO2 and H2CO3, as well as models ignoring reactions. The analysis also shows that bicarbonate buffer can be viewed as having an effective p Ka in the boundary layer that is different from that in bulk and is hydrodynamics-dependent.

Characterization of a trans-trans Carbonic Acid-Fluoride Complex by Infrared Action Spectroscopy in Helium Nanodroplets.

The high Lewis basicity and small ionic radius of fluoride promote the formation of strong ionic hydrogen bonds in the complexation of fluoride with protic molecules. Herein, we report that carbonic acid, a thermodynamically disfavored species that is challenging to investigate experimentally, forms a complex with fluoride in the gas phase. Intriguingly, this complex is highly stable and is observed in abundance upon nanoelectrospray ionization of an aqueous sodium fluoride solution in the presence of gas-phase carbon dioxide. We characterize the structure and properties of the carbonic acid-fluoride complex, F-(H2CO3), and its deuterated isotopologue, F-(D2CO3), by helium nanodroplet infrared action spectroscopy in the photon energy range of 390-2800 cm-1. The complex adopts a C2 v symmetry structure with the carbonic acid in a planar trans-trans conformation and both OH groups forming ionic hydrogen bonds with the fluoride. Substantial vibrational anharmonic effects are observed in the infrared spectra, most notably a strong blue shift of the symmetric hydrogen stretching fundamental relative to predictions from the harmonic approximation or vibrational second-order perturbation theory. Ab initio thermostated ring-polymer molecular dynamics simulations indicate that this blue shift originates from strong coupling between the hydrogen stretching and bending vibrations, resulting in an effective weakening of the OH···F- ionic hydrogen bonds.

Synthesis of an allyl carbonate monomer as alternative to TEGDMA in the formulation of dental composite resins.

Over the past years, significant effort has been dedicated to synthesizing low-shrinking formulations, however, development of dental composites with low volumetric shrinkage continues to be challenging. The purpose of this study was to synthesize a bisphenol allylic derivate (BPhADAC) and evaluate its inclusion in the formulation of a photopolymerizable dental composite resin, as a BisGMA diluent. Experimental (BisGMA/BPhADAC) and control (BisGMA/TEGDMA) photopolymerizable composites were prepared. Double bond conversion, polymerization kinetics, volumetric shrinkage, water sorption, solubility, and flexural properties were investigated. The experimental composite showed higher degree of conversion values, less volumetric shrinkage and less water sorption than the control composite (p < 0.05). In addition, flexural strength between the materials was found to be similar. The overall properties prove that the allylic monomer BPhADAC could be potentially useful in the formulation of low-shrinking dental composite resins.

Coccolithophore community response along a natural CO2 gradient off Methana (SW Saronikos Gulf, Greece, NE Mediterranean).

A natural pH gradient caused by marine CO2 seeps off the Methana peninsula (Saronikos Gulf, eastern Peloponnese peninsula) was used as a natural laboratory to assess potential effects of ocean acidification on coccolithophores. Coccolithophore communities were therefore investigated in plankton samples collected during September 2011, September 2016 and March 2017. The recorded cell concentrations were up to ~50 x103 cells/l, with a high Shannon index of up to 2.8, along a pH gradient from 7.61 to 8.18, with values being occasionally <7. Numerous holococcolithophore species represented 60-90% of the surface water assemblages in most samples during September samplings. Emiliania huxleyi was present only in low relative abundances in September samples, but it dominated in March assemblages. Neither malformed nor corroded coccolithophores were documented. Changes in the community structure can possibly be related to increased temperatures, while the overall trend associates low pH values with high cell densities. Our preliminary results indicate that in long-termed acidified, warm and stratified conditions, the study of the total coccolithophore assemblage may prove useful to recognize the intercommunity variability, which favors the increment of lightly calcified species such as holococcolithophores.

Assuring precision and calibration linearity in ultrasensitive suppressed ion chromatography by using deliberately contaminated hydroxide eluent.

EXPERIMENTAL: and theoretical studies were conducted to investigate low and non-linear responses in sub-micro molar-level suppressed ion chromatography with a hydroxide eluent. A calculated response was derived using experimentally determined detector effluent ion composition data and compared with measured experimental responses. The calibration curve was non-linear, and its slope varied considerably with different instrumental setups and operating conditions. The non-linearity of the solution conductivity response was determined by two acid-base equilibria of water and carbonic acid, and fluoride ion. By using eluent contaminated with para-toluene sulfonate at micro molar level, the non-linear response was greatly alleviated.

Developing cellulosic waste products as platform chemicals: protecting group chemistry of α-glucoisosaccharinic acid.

Alpha and beta-glucoisosaccharinic acids ((2S,4S)-2,4,5-trihydroxy-2-(hydroxymethyl)pentanoic acid and (2R,4S)-2,4,5-trihydroxy-2-(hydroxymethyl)pentanoic acid) which are produced when cellulosic materials are treated with aqueous alkali are potentially valuable platform chemicals. Their highly functionalised carbon skeleton, with fixed chirality at C-2 and C-4, makes them ideal starting materials for use in synthesis. In order to assess the potential of these saccharinic acids as platform chemicals we have explored the protecting group chemistry of the lactone form of alpha-glucoisosaccharinic acid (α-GISAL). We report here the use of single and multiple step reaction pathways leading to the regioselective protection of the three different hydroxyl groups of α-GISAL. We report strategies for protecting the three different hydroxyl groups individually or in pairs. We also report the synthesis of a range of tri-O-protected α-GISAL derivatives where a number of the products contain orthogonal protecting groups.

Impact of CO2-solvent separators on the degradation of benzyl-2,3-dihydroxypiperidine-1-carboxylate during preparative supercritical fluid chromatographic (SFC) purification.

During a preparative separation of the cis enantiomeric pair of benzyl-2,3-dihydroxypiperidine-1-carboxylate using supercritical-fluid chromatography (SFC) with methanol modifier, significant degradation of the products in the collected fractions was observed when a Waters SFC-350® (Milford, MA, USA) was used, but same was not observed when a Waters SFC-80q® (Milford, MA, USA) was used. Through a systematic investigation, we discovered that the compound degraded over time under an acidic condition created by the formation of methyl carbonic acid from methanol and CO2. The extent of the product degradation was dependent on the time and the concentration of CO2 remained in the product fraction, which was governed by the efficiency of CO2-methanol separation during the fraction collection. Hence, we demonstrated that the different designs of CO2-solvent separator (high pressurized cyclone in Waters SFC-350® and low-pressurized vortexing separator in Waters SFC-80q®®) had a significant impact on the degradation of an acid-sensitive compound. The acidity caused by CO2 in methanol was supported by diminished degradation after a nitrogen purging or after neutralizing the collected fractions with a base. Three different solutions to overcome the degradation problem of the acid sensitive compounds using SFC-350® with the high pressurized separator were investigated and demonstrated. The degraded products were isolated as four enantiomers and their relative stereochemistry were established based on 2D NMR data along with the plausible mechanism of degradation.

Automated programmable pressurized carbonic acid eluent ion exclusion chromatography of organic acids.

Conductometric ion exclusion chromatography of weak acids does not enjoy the same degree of success as its counterpart in suppressed conductometric anion exchange chromatography. Compared to the latter, eluent preparation is not automated. Commonly, a strong acid is used as the eluent leading to a relatively high-detector background and poorer limits of detection. In addition, generally applicable gradient elution has not been possible. We introduce the automated preparation of carbonic acid eluents at concentrations exceeding 0.15M by introducing CO2 into a flowing water stream through the walls of a Teflon AF® capillary tube under pressure; the resulting eluent concentration is controlled by varying the CO2 pressure in a programmed manner. The acidic carbonic acid solution functions as the eluent and can be almost completely removed (detector background 1.2-1.6µS/cm) by an improved carbon dioxide removal device before detection. Theoretical and practical considerations are discussed and illustrative isocratic and gradient ion exclusion chromatography is demonstrated.

Modeling of formation and prevention of a pure water zone in capillary isoelectric focusing with narrow pH range carrier ampholytes.

This paper comprises a continuation of computer simulation studies dealing with carrier ampholyte based CIEF in presence of narrow pH gradients. With this technique, amphoteric sample components with pI values outside the pH gradient are migrating isotachophoretically toward the cathode or anode whereas components with pI values within the gradient become focused. In order to understand the processes occurring in presence of the electric field, the behavior of both carrier ampholytes and amphoteric sample components is investigated by computer modeling. Characteristics of two pH unit gradients with end components having pI values at or around 7.00 and conditions that lead to the formation of a water zone at neutrality were investigated. Data obtained reveal that a zone of water is formed in focusing with carrier ampholytes when the applied pH range does not cover the neutral region, ends at pH 7.00 or begins at pH 7.00. The presence of additional amphoteric components that cover the neutrality region prevent water zone formation under current flow. This situation is met in experiments with narrow pH gradients that end or begin around neutrality. Simulation data reveal that no water zone evolves when atmospheric carbon dioxide dissolved in the catholyte causes the migration of carbonic acid (in the form of carbonate and/or hydrogen carbonate ions) from the catholyte through the focusing structure. An electrolyte change in the electrode solution does not have an impact on the focusing part but does change the isotachophoretic pattern migrating behind the leading ion.

In vitro Evaluation of the Efficacy of 2% Carbonic Acid and 2% Acetic Acid on Retrieval of Mineral Trioxide Aggregate and their Effect on Microhardness of Dentin.

INTRODUCTION: In this in vitro study, the efficacy of 2% carbonic acid and 2% acetic acid on the surface, microhardness of white mineral trioxide aggregate (MTA) and dentin after 1 day of setting and 21 days of setting of MTA is measured. MATERIALS AND METHODS: Tooth molds were made using 60 single-rooted premolars by slicing them to 4 mm in the mid-root region. White MTA (Angelus) was mixed and packed in the molds. Three experimental groups were formed and exposed to 2% carbonic acid, 2% acetic acid, and saline for 10 minutes on 1 and 21 days of setting respectively. Vickers hardness test of white MTA and dentin was done before and after exposure. Data were subjected to analysis of variance (ANOVA) and post hoc tests. RESULTS: The results show that 2% acetic acid was significantly effective in reducing the microhardness of white MTA compared to 2% carbonic acid and saline on exposure for 10 minutes. CONCLUSION: The results of the present study indicate that 2% acetic acid has maximum efficacy in reducing the surface microhardness of partial and completely set MTA, followed by 2% carbonic acid. CLINICAL SIGNIFICANCE: The following study will help find an adjunct for retrieval of MTA, which was found difficult with the existing methods.

Effect of Different Concentrations of Chlorhexidine in Glass-ionomer Cements on In Vivo Biocompatibility.

PURPOSE: To examine whether a difference exists between the in vivo biocompatibility of glass-ionomer cements (GICs) containing chlorhexidine (CHX) in different concentrations. MATERIALS AND METHODS: Eighty-four male Wistar rats were distributed into 7 groups (n = 12) and received subcutaneous implants of small tubes containing different materials, as follows: Ketac control (K), Ketac-CHX 10% (K10), Ketac-CHX 18% (K18), Resilience control (R), Resilience-CHX 10% (R10), Resilience-CHX 18% (R18), Control (polyethylene). The animals were then sacrificed on post-insertion days 7, 15 and 30, and tissues were examined under an optical microscope for inflammatory infiltrate, edema, necrosis, granulation tissue, multinucleated giant cells, and collagen fibers. The results were statistically analyzed using Kruskal-Wallis and Dunn's tests (p < 0.05). RESULTS: Groups K18 and R18 showed larger areas of intense inflammatory infiltrate, with significant differences between group C and groups K18 and R18 (p = 0.007) at 7 days, and between groups C and K18 (p = 0.017) at 15 days. In terms of tissue repair, groups K18 and R18 demonstrated a lower quantity of collagen fibers with significant differences from group C (p = 0.019) at 7 days, and between group K18 and group C (p = 0.021) at 15 days. CONCLUSION: The 18% concentration of CHX was shown to have a toxic effect. The 10% concentration of CHX was shown to be suitable for tissue contact. The addition of CHX to the glass-ionomer cements is a highly promising method for obtaining of an antibacterial GIC for use in clinical practice.

Formation of isomers of anionic hemiesters of sugars and carbonic acid in aqueous medium.

Hemiesters of carbonic acid can be freely formed in aqueous media containing HCO3(-)/CO2 and mono- or poly-hydroxy compounds. Herein, (13)C NMR spectroscopy was used to identify isomers formed in aqueous solutions of glycerol (a prototype compound) and seven carbohydrates, as well as to estimate the equilibrium constant of formation (Keq). Although both isomers are formed, glycerol 1-carbonate corresponds to 90% of the product. While fructose and ribose form an indistinct mixture of isomers, the anomers of d-glucopyranose 6-carbonate correspond to 74% of the eight isomers of glucose carbonate that were detected. The values of Keq for the disaccharides sucrose (4.3) and maltose (4.2) are about twice the values for the monosaccharides glucose (2.0) and fructose (2.3). Ribose (Keq = 0.89)-the only sugar without a significant concentration of a species containing a -CH2OH group in an aqueous solution-resulted in the smallest Keq. On the basis of the Keq value and the concentrations of HCO3(-) and glucose in blood, one can anticipate a concentration of 2-4 µmol L(-1) for glucose 6-carbonate, which corresponds to ca. of 10% of its phosphate counterpart (glucose 6-phosphate).

Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution I: Acid and Base Coordinate and Charge Dynamics.

Protonation by carbonic acid H2CO3 of the strong base methylamine CH3NH2 in a neutral contact pair in aqueous solution is followed via Car-Parrinello molecular dynamics simulations. Proton transfer (PT) occurs to form an aqueous solvent-stabilized contact ion pair within 100 fs, a fast time scale associated with the compression of the acid-base hydrogen-bond (H-bond), a key reaction coordinate. This rapid barrierless PT is consistent with the carbonic acid-protonated base pKa difference that considerably favors the PT, and supports the view of intact carbonic acid as potentially important proton donor in assorted biological and environmental contexts. The charge redistribution within the H-bonded complex during PT supports a Mulliken picture of charge transfer from the nitrogen base to carbonic acid without altering the transferring hydrogen's charge from approximately midway between that of a hydrogen atom and that of a proton.

Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution II: Solvent Coordinate-Dependent Reaction Path.

The protonation of methylamine base CH3NH2 by carbonic acid H2CO3 within a hydrogen (H)-bonded complex in aqueous solution was studied via Car-Parrinello dynamics in the preceding paper (Daschakraborty, S.; Kiefer, P. M.; Miller, Y.; Motro, Y.; Pines, D.; Pines, E.; Hynes, J. T. J. Phys. Chem. B 2016, DOI: 10.1021/acs.jpcb.5b12742). Here some important further details of the reaction path are presented, with specific emphasis on the water solvent's role. The overall reaction is barrierless and very rapid, on an ∼100 fs time scale, with the proton transfer (PT) event itself being very sudden (<10 fs). This transfer is preceded by the acid-base H-bond's compression, while the water solvent changes little until the actual PT occurrence; this results from the very strong driving force for the reaction, as indicated by the very favorable acid-protonated base ΔpKa difference. Further solvent rearrangement follows immediately the sudden PT's production of an incipient contact ion pair, stabilizing it by establishment of equilibrium solvation. The solvent water's short time scale ∼120 fs response to the incipient ion pair formation is primarily associated with librational modes and H-bond compression of water molecules around the carboxylate anion and the protonated base. This is consistent with this stabilization involving significant increase in H-bonding of hydration shell waters to the negatively charged carboxylate group oxygens' (especially the former H2CO3 donor oxygen) and the nitrogen of the positively charged protonated base's NH3(+).

How Acidic Is Carbonic Acid?

Carbonic, lactic, and pyruvic acids have been generated in aqueous solution by the transient protonation of their corresponding conjugate bases by a tailor-made photoacid, the 6-hydroxy-1-sulfonate pyrene sodium salt molecule. A particular goal is to establish the pK(a) of carbonic acid H2CO3. The on-contact proton transfer (PT) reaction rate from the optically excited photoacid to the carboxylic bases was derived, with unprecedented precision, from time-correlated single-photon-counting measurements of the fluorescence lifetime of the photoacid in the presence of the proton acceptors. The time-dependent diffusion-assisted PT rate was analyzed using the Szabo-Collins-Kimball equation with a radiation boundary condition. The on-contact PT rates were found to follow the acidity order of the carboxylic acids: the stronger was the acid, the slower was the PT reaction to its conjugate base. The pK(a) of carbonic acid was found to be 3.49 ± 0.05 using both the Marcus and Kiefer-Hynes free energy correlations. This establishes H2CO3 as being 0.37 pK(a) units stronger and about 1 pK(a) unit weaker, respectively, than the physiologically important lactic and pyruvic acids. The considerable acid strength of intact carbonic acid indicates that it is an important protonation agent under physiological conditions.