Monoprotic Acids Research Articles

Investigating the phase diagram-ionic conductivity isotherm relationship in aqueous solutions of common acids: hydrochloric, nitric, sulfuric and phosphoric acid

The relationship between phase diagram features around the solid–liquid equilibrium region and ionic conductivity in aqueous solutions is not well understood over the whole concentration range as is the case for acidic aqueous solutions. In this work, we have studied the ionic conductivity (κ) as a function of molar fraction (x) and temperature (T) for four acid/water solutions namely, monoprotic hydrochloric acid (HCl) and nitric acid (HNO3), diprotic sulfuric acid (H2SO4) and triprotic phosphoric acid (H3PO4) along with their binary phase diagrams. The connection between the main features of the phase diagrams and the trends in the ionic conductivity isotherms is established with a new insight on the two pertinent dominant conductivity mechanisms (hopping and vehicular). Ionic conductivity at different temperatures were collected from literature and fitted to reported isothermal (κ vs. x) and iso-compositional (κ vs. T) equations along with a novel semi-empirical equation (κ = f (x, T)) for diprotic and triprotic acids. This equation not only has the best fit for acids with different valency; but also contains four parameters, less than any other similar equation in literature. This work is one of few that advances the understanding of the intricate relationship between structure and ionic transport in various acidic aqueous solutions.

A sustainable approach exploiting Chrysanthemum Coronarium flowers distillation waste as a corrosion suppressor for low carbon steel in monoprotic acid medium through electrochemical and computational evaluations

This study focuses on evaluating a biowaste generated amid the hydrodistillation process of Chrysanthemum Coronarium Flower compounds as a sustainable inhibitor for the corrosion of carbon steel in the hydrochloric medium. Total phenolic and flavonoid contents, phytochemical screening protocols as well as Fourier Transform Infrared (FT-IR) analysis were implemented to examine the phytochemical diversity of the Chrysanthemum Coronarium flowers extract (CCFE). Electrochemical impedance spectroscopy (EIS) as well as Tafel extrapolation techniques were adopted for examining the corrosion suppression efficiency of the liquid waste as a corrosion inhibitor at 293 K. The findings indicated that the CCFE displayed strong corrosion suppression properties on the metal, achieving an impressive efficiency of 82 %. Following a mixed-type inhibition mechanism. Temperature influence in the presence of the CCFE was assessed at a 293–313 K domain, and the combined impact of KI and the CCFE inhibitor was investigated to determine their synergistic effects. Furthermore, an in-depth analysis of the surface morphology of metal was carried out using SEM-EDX analysis to investigate the electrochemical behavior and comprehend alterations occurring on the surface as a result of the CCFE introduction. Moreover, computational analysis through Density Functional Theory (DFT) and Molecular Dynamic simulations (MD) were performed to gain a more comprehensive understanding of the mechanism of electronic adsorption occurring at specific active sites in the presence of the Chrysanthemum Coronarium Flowers compounds.

High-throughput and reliable assessments of the ionization constant of monoprotic organic acids through an arginine based mixed mode HPLC

The charge state of a molecule is the single most prominent attribute ruling out its interactions with the surrounding environment. In a previous study, the retention of acids on the new Celeris™ Arginine (ARG) column was found to be predominantly driven by electrostatics and, specifically, their charge state. Therefore, we analysed 41 compounds in liquid chromatography with ultraviolet detection to study possible relationships between the analytical retention on this phase and the pKa of the acidic solutes. Highly significant relationships were observed indicating either a linear (r2 = 0.86) or a quadratic (r2= 0.89) trend. To improve the throughput of the method, this was transferred to LC mass spectrometry, allowing the analysis of a molecule every 3 mins. The developed method was found to be fast, reliable, accurate, easily automatable and simple to set up. Finally, the analytical column’s being industrially manufactured and commercially available offers broad applicability.

Phenomenological description of the acidity of the citric acid and its deprotonated species: informational-theoretical study.

In spite of the fact that molecular acidity is a fundamental physicochemical property of molecular systems, the vast majority of theoretical studies have focused attention on monoprotic acids and on the prediction of pKa's. Polyprotic acids, represent a challenge for electronic structure calculations since the multiple acidic sites result in a vast group of species with different conformations and reactivities. In this work, Information-theoretic (IT) concepts of localizability, order and uniformity are applied to the Citric Acid and its deprotonated species through the one-electron density functionals: Shannon entropy (S), Fisher information (I) and Disequilibrium (D), respectively. We pursue the goal of characterizing the acidity of the aforementioned species with the aim to associate the IT concepts to chemical features such as the polarizability of the protonated/deprotonated species, the liability of the acidic sites, atomic electrostatic potentials, covalent bonding. IT analyses looks very promising for future studies on the acidity of specific deprotonation-sites of polyprotic acids. Density functional theory (DFT) calculations were performed with Gaussian 09 program. A sensitivity analysis of the IT-measures was performed for the citric acid and the citrate using B3LYP, B3PW91, BPW91, M05-2X, M06-2X and PBEPBE functionals with the 6-311++g(3df,2p), 6-311++g(d,p), 6.311+g(d,p) and aug-cc-pVDZ basis sets. The rest of the analysis was performed with the M05-2X/6-311+G(d,p) level of theory. Additionally, aqueous media was considered by use of the SMD solvent model. The IT-measures were calculated using a suite of programs developed in our laboratory jointly with the DGRID software package.

Closed-form expressions for monoprotic weak acid aqueous solutions

A general closed-form expression for {[textrm{H}_{3}textrm{O}^+]} of solutions of a weak acid and a weak acid buffer, as well as their titration with a strong base, has been obtained and mathematically analyzed with the aid of computer algebra systems. This expression is used to evaluate, without the use of numerical approximations, the precision and accuracy of different approximations commonly employed in general chemistry and chemical analysis courses. The closed-form expression for {{[textrm{H}_{3}textrm{O}^+]}} of a buffer solution is used to obtain an analytical expression for the pH stability when a strong base is added. Finally, it is shown that the {[textrm{H}_{3}textrm{O}^+]} expressions for all the systems under study can be obtained from a general closed-form expression in terms of an effective weak acid constant and an effective acid concentration. The formulas found in this work do not display numerical rounding errors and do not require the use of numerical or graphical methods for their evaluation.Graphical abstractGraphical TOC: A closed-form expression for the weak acid and weak acid buffersolutions and their titrations with a strong base

Buffer Solutions of known Ionic Strength

pH buffer solutions are those in which minimal pH variations occur when moderate amounts of strong acids or bases are added or diluted. The most common buffers are those used in the intermediate pH zone and are made up of an acid-base conjugate pair (HA/A-), with Ca and Cb as analytical concentrations of acid and base respectively. The buffer capacity of a solution is the measure of its effectiveness in preserving the pH value when adding an acid or a base. Three new programs working under the Windows 10 environment have been developed. The first one, the BUFFER program, allows to prepare buffers of known ionic strength without the need of adding an inert electrolyte, calculating the pH and buffering capacity. On the other hand, the BRÖMSTED method allows calculating the pH of conjugated acid-base systems applying the Newton-Raphson method. In this work two more programs are described, one applying the Brömsted method to monoprotic acids and another new one to diprotic acids.

The challenges of using treatment solution properties to determine concentrations for the inhibition of seedling processes by monoprotic phenolic acids

The challenges of using treatment solution properties to determine concentrations for the inhibition of seedling processes by monoprotic phenolic acids

PH-Dependent Partitioning of Ionizable Organic Chemicals between the Silicone Polymer Polydimethylsiloxane (PDMS) and Water.

The silicone polymer polydimethysiloxane (PDMS) is a popular passive sampler for in situ and ex situ sampling of hydrophobic organic chemicals. Despite its limited sorptive capacity for polar and ionizable organic chemicals (IOC), IOCs have been found in PDMS when extracting sediment and suspended particulate matter. The pH-dependent partitioning of 190 organics and IOCs covering a range of octanol-water partition constants log K ow from -0.3 to 7.7 was evaluated with a 10-day shaking method using mixtures composed of all chemicals at varying ratios of mass of PDMS to volume of water. This method reproduced the PDMS-water partition constant K PDMS/w of neutral chemicals from the literature and extended the dataset by 93 neutral chemicals. The existing quantitative structure-activity relationship between the log K ow and K PDMS/w could be extended with the measured K PDMS/w linearly to a log K ow of -0.3. Fully charged organics were not taken up into PDMS. Thirty-eight monoprotic organic acids and 42 bases showed negligible uptake of the charged species, and the pH dependence of the apparent D PDMS/w(pH) could be explained by the fraction of neutral species multiplied by the K PDMS/w of the neutral species of these IOCs. Seventeen multiprotic chemicals with up to three acidity constants pK a also showed a pH dependence of D PDMS/w(pH) with the tendency that the neutral and zwitterionic forms showed the highest D PDMS/w(pH). D PDMS/w(pH) of charged species of more hydrophobic multiprotic chemicals such as tetrabromobisphenol A and telmisartan was smaller but not negligible. Since these chemicals show high bioactivity, their contribution to mixture effects has to be considered when testing passive sampling extracts with in vitro bioassays. This work has further implications for understanding the role of microplastic as a vector for organic micropollutants.

Studies on the aggregation behavior of mineral acid and Zr(IV) loaded Tris(2-methylbutyl) phosphate and tri-n-alkyl phosphate systems using small angle neutron scattering

ABSTRACT The third-phase phenomenon has been observed during the extraction of certain metal ions and mineral acids by 30% (v/v) tri-n-butyl phosphate (TBP) in n-dodecane in the solvent extraction stage of spent nuclear fuel reprocessing. At molecular scale, it has been predicted that the self-organization of the extracted polar species to form reverse micelle-like structure is primarily responsible for third-phase formation. In this regard, the aggregation behavior of solutions of three different trialkyl phosphates in n-alkanes loaded with monoprotic mineral acids (HClO4, HCl and HNO3) as well as tetravalent Th and Zr has been evaluated using Small Angle Neutron Scattering (SANS). The aggregation of TBP has been compared with two of its five carbon analogues i.e. tri-n-amyl phosphate (TAP) and tris(2-methylbutyl) phosphate (T2MBP), which have gained its attention in the course of development of an alternate extractant for the reprocessing process. The effects of trialkyl phosphate structure, diluent chain length and extractant concentration on the aggregation have been emphasized. The contribution of the polar (anionic and cationic component) as well as the apolar part of the reverse micelle toward the phase splitting behavior has been analyzed. The SANS results are in agreement with the earlier reported solvent extraction data.

Copigmentation of anthocyanins with copigments possessing an acid-base equilibrium in moderately acidic solutions

The fact that many copigments such as cinnamic acids exhibit an acid-base equilibrium at moderately acidic pH values have not been taken in consideration in the copigmentation models and respective equations. In this work, the copigmentation constants of malvidin-3-O-glucoside and sinapic acid (pKa = 4.5) is reported. The flavylium cation (AH+) in moderately acid medium (pH ≤ 6) can be considered a monoprotic acid in equilibrium with its conjugated base (CB) equal to the sum of the concentrations of quinoidal base (A), hemiketal (B), cis and trans chalcones (Cc and Ct), with equilibrium constant K'a. Based on this behavior a new mathematical expression to account for the copigmentation of AH+ and CB was deduced. The system was also studied by a series of reverse pH jumps monitored by stopped flow and a previously reported procedure was extended to consider the acid-base equilibrium of the copigment. The copigmentation constant of the flavylium cation with the acidic form of the copigment, CP, is 243 M−1, and no copigmentation with the basic form of the copigment, CP(−), was observed. This was explained by the very small superposition of these two species in the pH domain. The copigmentation constants of CB with the acidic and basic forms of the copigment, calculated from the UV–Vis measurements are respectively KCBCP = 53 M−1 and KCBCP(−) = 78 M−1. The reverse pH jumps monitored by stopped flow allowed the calculation of the copigmentation constants of the acidic form of the copigment (CP) with quinoidal base (A), hemiketal (B) and cis-chalcone (Cc), respectively KACP = 531 M−1, KBCP = 17, KCcCP = 41 M−1 as well as with the basic form of the copigment KACP(−) = 196 M−1, KBCP(−) = 79, KCcCP(−) = 94 M−1. The reverse pH jumps followed by a standard spectrophotometer allows for determination of KCtCP = 55 M−1 and KCcCP(−) = 80 M−1 and KCBCP = 54 M−1 and KCBCP(−)=89 M−1. The estimated error for all copigmentation constants is circa 10%.

On the Accuracy of the Direct Method to Calculate pKa from Electronic Structure Calculations.

The direct method (HA(soln) ⇌ A(soln)– + H(soln)+) for calculating pKa of monoprotic acids is as efficient as thermodynamic cycles. A selective adjustment of proton free energy in solution was used with experimental pKa data. The procedure was analyzed at different levels of theory. The solvent was described by the solvation model density (SMD) model, including or not explicit water molecules, and three training sets were tested. The best performance under any condition was obtained by the G4CEP method with a mean absolute error close to 0.5 units of pKa and an uncertainty around ±1 unit of pKa for any training set including or excluding explicit solvent molecules. PM6 and AM1 performed very well with average absolute errors below 0.75 units of pKa but with uncertainties up to ±2 units of pKa, using only the SMD solvent model. Density functional theory (DFT) results were highly dependent on the basis functions and explicit water molecules. The best performance was observed for the local spin density approximation (LSDA) functional in almost all calculations and under certain conditions, as high as those obtained by G4CEP. Basis set complexity and explicit solvent molecules were important factors to control DFT calculations. The training set molecules should consider the diversity of compounds.

Alternative Kinetic Model of the Iodide–Iodate Reaction for Its Use in Micromixing Investigations

The Villermaux–Dushman method, one of the most extensively used test reaction systems for micromixing characterization, has been widely criticized for years due to uncertainties regarding the incomplete dissociation of sulfuric acid and the proposed kinetic study by Guichardon et al. In this work, a renewed study of the kinetics of the iodide–iodate reaction is presented, using perchloric acid to avoid issues concerning incomplete acid dissociation. The experimental results are in good agreement with the fifth-order rate law for the iodide–iodate reaction. The reaction rate coefficient strongly depends on the ionic strength and can be modeled with a Davies-like equation. When implemented in the incorporation model, the kinetic model presented in this study can be used to estimate micromixing times that are in line with the theoretical engulfment time. This is observed in two different reactors with low and high intensities of mixing: an unbaffled stirred vessel and a rotor–stator spinning disk reactor. The results from the latter are also compared with the second Bourne reaction, giving very similar micromixing times. The kinetic model presented in this study in combination with strong monoprotic acids is suggested as an alternative to characterize micromixing behavior.

A Mechanistic Physiologically Based Pharmacokinetic (PBPK) Drug Interaction Model for the Mouse Double Minute 2 (MDM2) Inhibitor KRT-232

Background: KRT-232 is a potent, selective, orally available, targeted inhibitor of human MDM2 homolog interactions with tumor suppressor protein 53 (p53). KRT-232 is under development for treatment of myeloproliferative neoplasms, acute myeloid leukemia and Merkel cell carcinoma. KRT-232 is a highly permeable 568.6 g/mol, monoprotic carboxylic acid (pKa 4.35); elimination involves primarily biliary-fecal excretion of an acyl glucuronide metabolite (M1) and enteric glucuronide hydrolysis with enterohepatic recirculation of parent drug. M1 is a 744.7 g/mol monoprotic acid with pKa 3.32 and 1/5th the MDM2 inhibitory potency of KRT-232. Plasma protein binding (fup) of KRT-232 and M1 were ~0.026 and ~0.006, respectively. Static model drug-drug interaction (DDI) calculations (FDA-CDER. 2020) indicated a potential minor DDI with substrates of cytochrome P450s (CYP) CYP3A4 and CYP2C8, UGT1A1, P-glycoprotein 1 (P-gp) and OATP1B1/3. Here, a 'fit-for-purpose' PBPK model for KRT-232 was developed using physicochemical, preclinical (in vitroandin vivo) and clinical pharmacokinetic (PK) data (KartosData on file; Ye et al.Xenobiotica. 2015; Gluck et al.Invest New Drugs. 2020 [Study A]). Methods:Simcyp Simulator V17 (release 1; 27/11/2017; 17.0.90.0) was used. In vitro kinetic parameters: In vitroKi for competitive inhibition of CYP2C8 was 3.8 and 0.17 µM for KRT-232 and M1, respectively.In vitroKI and kinact for mechanism-based inhibition of CYP3A4 by KRT-232 were 28 µM and 4.14 h-1, respectively. Estimatedin vitroKi values for KRT-232-mediated inhibition of UGT1A1, P-gp, OATP1B1 and OATP1B3, were 1.9, 14.8, 4.9 and 6.9 µM. For M1-mediated inhibition of UGT1A1, OATP1B1 and OATP1B3, values were 2.3, 0.393 and 0.606 µM. Model development and verification:KRT-232 absorption was described by a first-order process; fraction absorbed was assumed to be 100% and the absorption rate constant was manually optimized using observed mean plasma concentration data from Part 1 of Study A. KRT-232 clearance was based onin vitroformation clearance of M1 in human liver microsomes, scaled up 4-fold based on observed oral clearance of KRT-232 (Wood et al.Drug Metab Dispos. 2017). KRT-232 distribution volume was described by a minimal PBPK model. KRT-232 and M1 DDI parameters were based onin vitrodata. M1 clearance was manually optimized using mean observed data from Study A (Part 1, 240 mg dose), and distribution volume was predicted by the Simulator using Method 1 and a full PBPK model. PBPK simulated data were compared with patient PK data collected during Part 2 of Study A. Model application:The model predicted potential DDI after steady state (SS) 240 mg once daily KRT-232 administration with substrates of CYP3A4, CYP2C8, UGT1A1, P-gp and OATP1B1/3. DDI simulations included 100 virtual subjects assigned to 10 virtual trials (N=10 each). Population estimates of geometric mean and median Cmax and AUC0-∞ ratios were generated. A "worst case" sensitivity analysis was performed by using a 10-fold increase inin vitroCYP3A4 interaction potency (KI, EC50) relative to the measuredin vitrovalue. Results:Figure 1shows simulated SS mean and individual observed KRT-232 and M1 concentration data from Part 2 of Study A. SS KRT-232 Cmax, AUC0-24h and t1/2 were predicted within 0.80-1.25-fold of observed PK data and tmax was under-predicted (0.36-fold) by the model (Table 1). M1 Cmax and AUC0-24h were within 0.80-1.25-fold of observed PK data on Day 1 (not shown). M1 Cmax on Day 7 was within 0.80-1.25-fold of observed PK data and SS AUC0-24h, t1/2, and tmax were underpredicted (0.72, 0.79 and 0.61-fold) relative to observed PK data. In all simulated DDIs, no clinically significant interaction was predicted for SS 240 mg doses of KRT-232 since predicted Cmax and AUC0-∞ geometric mean ratio (GMR) changes were less than 1.25-fold (Table 2). The CYP3A4 DDI simulation gave a population GMR (90% CI) for Cmax and AUC0-∞ of 1.07 (1.06, 1.09) and 1.15 (1.12, 1.17), respectively. In a sensitivity check, predicted midazolam Cmax and AUC0-∞ after a 10-fold reduction ofin vitroKI and EC50 were 1.44-fold and 2.18-fold, respectively. Although unlikely, a weak CYP3A4 DDI could not be definitively excluded. Conclusions: Mean plasma exposure of KRT-232 and M1 and inter-individual variability were adequately described by the PBPK model. No clinically significant DDI were predicted based on Cmax and AUC0-∞ GMR changes of less than 1.25-fold. Disclosures Templeton: Certara UK, LTD.:Current Employment.Podoll:IV/PO, LLC:Consultancy.Krejsa:Kartos Therapeutics:Current Employment;AstraZeneca:Current equity holder in publicly-traded company;Seattle Genetics:Current equity holder in publicly-traded company;Acerta Pharma:Current equity holder in private company.Slatter:Kartos Therapeutics:Current Employment;AstraZeneca:Current equity holder in publicly-traded company;Amgen:Divested equity in a private or publicly-traded company in the past 24 months.

The definitive challenge of forming uncommon pseudo‐π···H–F and C···H–F hydrogen bonds on cyclic and cubic nonpolar hydrocarbons

AbstractDue to the high symmetry and low polarity of the cyclopropane (C3H6), cyclobutane (C4H8), prismane (C6H6), and cubane (C8H8), it is widely known that these structures unlikely act as proton receptors to form intermolecular interactions with monoprotic acids, such as the hydrogen fluoride. Although the C3H6···HF, C4H8···HF, C6H6···HF, and C8H8···HF are weakly bound complexes, in this current work, all of them were definitively certified on the basis of a theoretical analysis. In according with the structural parameters and spectroscopy modes appraised through the density‐functional theory calculations, the more accentuated perturbations are manifested in the hydrogen fluoride. The new hydrogen bond forms framed as pseudo‐π···H and C···H were unveiled through the calculations of the quantum theory of atoms in molecules and natural bond orbital. In this context, the knowledge about the nature of these hydrogen bonds is necessary, wherein it used the symmetry‐adapted perturbation theory for computing the contributions of the electrostatic, polarization, exchange, dispersion, and charge transfer terms. Lastly, the practical behavior of these hydrocarbons under the condition to form intermolecular interactions was examined by taking into account the solvent effect with calculations of the polarizable continuum model.

In-Situ Combination of Bipolar Membrane Electrodialysis with Monovalent Selective Anion-Exchange Membrane for the Valorization of Mixed Salts into Relatively High-Purity Monoprotic and Diprotic Acids.

The crystalized mixed salts from the zero liquid discharge process are a hazardous threat to the environment. In this study, we developed a novel electrodialysis (SBMED) method by assembling the monovalent selective anion-exchange membrane (MSAEM) into the bipolar membrane electrodialysis (BMED) stack. By taking the advantages of water splitting in the bipolar membrane and high perm-selectivity of MSAEM for the Cl− ions against the SO42− ions, this combination allows the concurrent separation of Cl−/SO42− and conversion of mixed salts into relatively high-purity monoprotic and diprotic acids. The current density has a significant impact on the acid purity. Both the monoprotic and diprotic acid purities were higher than 80% at a low current density of 10 mA/cm2. The purities of the monoprotic acids decreased with an increase in the current density, indicating that the perm-selectivity of MSAEM decreases with increasing current density. An increase in the ratio of monovalent to divalent anions in the feed was beneficial to increase the purity of monoprotic acids. High-purity monoprotic acids in the range of 93.9–96.1% were obtained using this novel SBMED stack for treating simulated seawater. Therefore, it is feasible for SBMED to valorize the mixed salts into relatively high-purity monoprotic and diprotic acids in one step.

Modeling buffer capacity and pH in acid and acidified foods.

Standard ionic equilibria equations may be used for calculating pH of weak acid and base solutions. These calculations are difficult or impossible to solve analytically for foods that include many unknown buffering components, making pH prediction in these systems impractical. We combined buffer capacity (BC) models with a pH prediction algorithm to allow pH prediction in complex food matrices from BC data. Numerical models were developed using Matlab software to estimate the pH and buffering components for mixtures of weak acid and base solutions. The pH model was validated with laboratory solutions of acetic or citric acids with ammonia, in combinations with varying salts using Latin hypercube designs. Linear regressions of observed versus predicted pH values based on the concentration and pK values of the solution components resulted in estimated slopes between 0.96 and 1.01 with and without added salts. BC models were generated from titration curves for 0.6 M acetic acid or 12.4mM citric acid resulting in acid concentration and pK estimates. Predicted pH values from these estimates were within 0.11pH units of the measured pH. Acetic acid concentration measurements based on the model were within 6% accuracy compared to high-performance liquid chromatography measurements for concentrations less than 400mM, although they were underestimated above that. The models may have application for use in determining the BC of food ingredients with unknown buffering components. Predicting pH changes for food ingredients using these models may be useful for regulatory purposes with acid or acidified foods and for product development. PRACTICAL APPLICATION: Buffer capacity models may benefit regulatory agencies and manufacturers of acid and acidified foods to determine pH stability (below pH 4.6) and how low-acid food ingredients may affect the safety of these foods. Predicting pH for solutions with known or unknown buffering components was based on titration data and models that use only monoprotic weak acids and bases. These models may be useful for product development and food safety by estimating pH and buffering capacity.

Weak acids as an alternative anti-microbial therapy

Weak acids such as acetic acid and N-acetyl cysteine (NAC) at pH less than their pKa can effectively eradicate biofilms due to their ability to penetrate the biofilm matrix and the cell membrane. However, the optimum conditions for their activity against drug resistant strains, and safety, need to be understood for their application to treat infections or to inactivate biofilms on hard surfaces. Here, we investigate the efficacy and optimum conditions at which weak acids can eradicate biofilms. We compared the efficacy of various mono and triprotic weak acids such as N-acetyl cysteine (NAC), acetic acid, formic acid and citric acid, in eradicating biofilms. We found that monoprotic weak acids/acid drugs can kill mucoid P. aeruginosa mucA biofilm bacteria provided the pH is less than their pKa, demonstrating that the extracellular biofilm matrix does not protect the bacteria from the activity of the weak acids. Triprotic acids, such as citric acid, kill biofilm bacteria at pH ​< ​pKa1. However, at a pH between pKa1 and pKa2, citric acid is effective in killing the bacteria at the core of biofilm microcolonies but does not kill the bacteria on the periphery. The efficacy of a monoprotic weak acid (NAC) and triprotic weak acid (citric acid) were tested on biofilms formed by Klebsiella pneumoniae KP1, Pseudomonas putida OUS82, Staphylococcus aureus 15981, P. aeruginosa DK1-NH57388A, a mucoid cystic fibrosis isolate and P. aeruginosa PA_D25, an antibiotic resistant strain. We showed that weak acids have a broad spectrum of activity against a wide range of bacteria, including antibiotic resistant bacteria. Further, we showed that a weak acid drug, NAC, can kill bacteria without being toxic to human cells, if its pH is maintained close to its pKa. Thus weak acids/weak acid drugs target antibiotic resistant bacteria and eradicate the persister cells in biofilms which are tolerant to other conventional methods of biofilm eradication.

Properties of Pertechnic Acid.

Dilute aqueous pertechnic acid has long been known as strong monoprotic acid that behaves as a simple pertechnetate ion in aqueous solution. As pertechnic acid concentrates by evaporation, it becomes yellow and then dark red, and dark-red crystalline material may ultimately be obtained. We show that as pertechnic acid concentrates, at least three compounds are formed: a yellow viscous liquid, a colorless (not red) crystalline solid, and a small amount of an intensely colored red-purple compound. The colorless crystalline compound melts at 118 °C and can be melted and recrystallized several times with little decomposition. The red-purple compound is apparently not stable at room temperature and quickly decomposes if it is isolated. UV-vis spectra show that Beer's law does not hold as pertechnic acid concentrates by evaporation. We report densities,99Tc nuclear magnetic resonance spectra, and ultraviolet-visible absorption spectra for highly pure aqueous pertechnic acid (accompanied by the other technetium compounds that form) ranging from 1 to 14 M in technetium concentration.

Assessment of pKa Determination for Monocarboxylic Acids with an Accurate Theoretical Composite Method: G4CEP.

For 22 monoprotic acids, pKa values were calculated using the G4CEP composite theory. The solvation effect was included considering the continuous SMD solvation model; SMD and one explicit water molecule; and SMD, one water molecule, and linear correction with respect to the experimental pKa values. The three tests provided mean absolute errors equal to 0.83, 0.51, and 0.30 pKa units, respectively, indicating excellent performance of the G4CEP method. Comparison with density functional theory at the B3LYP and BMK levels showed that these results are quickly obtained but with a significant error. The best performance of the functionals was obtained from the combination of SMD, one explicit water molecule, linear regression correction, and basis set including diffuse functions. However, the dispersion of the results with DFT can lead to deviations of up to two pKa units, whereas for G4CEP the largest deviations seldom exceed one pKa unit.

Química analítica básica

A maioria dos estudantes de Química sempre foi induzida a pensar e a trabalhar os equilíbrios iônicos em solução aquosa usando o tratamento algébrico tradicional, como nos exemplos mostrados recentemente para equilíbrios ácido-base [1-3]. Entretanto, a solução algébrica exata deste tipo de problema frequentemente requer a resolução de polinômios de mais altos graus. Por exemplo, o cálculo exato do pH de uma simples solução aquosa de um ácido monoprótico fraco requer a solução de uma equação cúbica e no caso de um ácido triprótico (ex.: ácido fosfórico), a solução de um polinômio de quinto grau [1,2]. Isto induz o uso de aproximações para simplificar o trabalho, o que sempre leva a resultados aproximados. Um outro procedimento proposto por Birk [4], que emprega uma formulação matricial baseada na extensão de reação, também pode ser utilizada para este propósito, mas é um método que exige conhecimentos mais aprofundados de química e de álgebra linear, razão pela qual não é apresentado em livros textos e também não será discutido neste trabalho. Uma abordagem alternativa, mais fácil, é a utilização de cálculos numéricos e a apresentação gráfica dos resultados, procedimento bastante facilitado pelo uso de planilhas eletrônicas. Isto permite uma visão geral do sistema ácido-base, reforça princípios importantes e permite o tratamento de uma ampla gama de sistemas químicos.