Examinations of Dimethyl Sulfoxide-Phase Equilibrium Acidities of Selected Polycyclic Aromatic Compounds

Comparisons of dimethyl sulibxide (DMSO)-phase pK _a's (in parentheses) for 10-cyano-9-methoxymethy-lanthracene (17.35), 10-cyano-9-phenoxymethylanthracene (14.9), 9-cyanomethoxymethylanthracene (20.4), and (α-methoxy) phenylacetonitrile (23.0) with literature DMSO-phase pK _a's for 9-methylanth-racene, 9-methoxymethylanthracene, 9-phenoxymethylanthracene, 9-cyanomethylanthracene, 10-cyano-9-methylanthracene, and phenylacetonitrile (31.1, 30.6, 30.2, 19.7, 20.0, and 21.9, respectively), indicate that: (a) α-methoxy and α-phenoxy substituents acidify 10-cyano-9-methylanthracene; (b) an α-methoxy moiety deacidifies 9-cyanomethylanthracene and phenylacetonitrile; and (c) 10-cyano substituents acidify 9-methylanthracene, 9-methoxymethylanthracene, and 9-phenoxymethylanthracene by 11.1, 13.25, and 15.3 pK _a units, respectively. These data are indicative of steric inhibition of resonance, resonance saturation, and effects due to cross conjugation, in carbanions derived from variously substituted 9-methylanthracenes. DMSO-phase pK _a for phenalene (18.2) and benzanthrene (20.2) have also been determined. In DMSO, phenalene is therefore 4.4 pK units more acidic than its isomeric analogue fluorene (22.6), while benzanthrene is 0.5 pK units less acidic than its isomeric analogue 1,2-benzofluorene (19.7). Specific solvation of the allylic-like phenalenide anion is a likely reason for its enhanced acidity, relative to benzanthrene.     

Cucurbit[n]uril Host-Guest Complexes of Acids,Photoacids, and Super Photoacids

The supramolecular chemistry of host-guest complexes of cucurbit[n]urils (CB[n]) with acidic guests in the ground (HG⁺) and excited states (HG⁺*) are reviewed. The effects of CB[n] complexation on the guests’ pK_a and/or pK_a* values are related to relative binding constants and host-guest structures of the acid form of the guest and its conjugate base. Included are carbon acids, guests of biological and medicinal interest, dyes and related polyaromatic guests, and other organic and organometallic guests. The applications of the pK_a shifts to the solubility, stability, and bioavailabilty of drug molecules, the stability and enhanced spectral properties of dyes, and in pH-induced self-sorting, micelle formation, host-guest shuttling, and controlled guest release, are discussed.     

The Dynamic Range of Acidity: Tracking Rules for the Unidirectional Penetration of Cellular Compartments

Labeled ammonium cations with pK_a∼7.4 accumulate in acidic organelles because they can be neutralized transiently to cross the membrane at cytosolic pH 7.2 but not at their internal pH<5.5. Retention in early endosomes with less acidic internal pH was achieved recently using weaker acids of up to pK_a 9.8. We report here that primary ammonium cations with higher pK_a 10.6, label early endosomes more efficiently. This maximized early endosome tracking coincides with increasing labeling of Golgi networks with similarly weak internal acidity. Guanidinium cations with pK_a 13.5 cannot cross the plasma membrane in monomeric form and label the plasma membrane with selectivity for vesicles embarking into endocytosis. Self-assembled into micelles, guanidinium cations enter cells like arginine-rich cell-penetrating peptides and, driven by their membrane potential, penetrate mitochondria unidirectionally despite their high inner pH. The resulting tracking rules with an approximated dynamic range of pK_a change ∼3.5 are expected to be generally valid, thus enabling the design of chemistry tools for biology research in the broadest sense. From a practical point of view, most relevant are two complementary fluorescent flipper probes that can be used to image the mechanics at the very beginning of endocytosis.     

Zur physikalisch‐chemischen Charakterisierung von 5‐Amino‐1‐aryl‐1H‐tetrazolen: Elektronische Molekülparameter aus der thermischen Isomerisierung zu 5‐Arylamino‐1H‐tetrazolen

The known thermal isomerization of 5‐amino‐1‐aryl‐1H‐tetrazoles ( A ) into corresponding 5‐arylamino‐1H‐tetrazoles ( HB ) was used to derive physicochemical parameters characterizing the electronic substituent effect on isomerism and dissociation equilibria. For a series of 26 tetrazoles A as starting materials the equilibrium constants (pK_i) of isomerization in boiling ethylene glycol at 197 °C and the dissociation constants (pK_a) of the NH‐acidic tetrazoles HB were determined by potentiometric titration of rapidly cooled equilibrium mixtures in water and ethanol/water with KOH at 25 °C. The pK values are closely correlated with Hammett′s electronic substituent constants σ and can be used as electronic molecule parameters in QSAR or QSPR (QSAR = quantitative structure‐activity relationship; QSPR = quantitative structure‐property relationship) studies.     

Pyridine-catalyzed depolymerization of cellulose during carbanilation with phenylisocyanate in dimethylsulfoxide

Carbanilation reactions of cellulose samples (bleached cotton linters and Avicel) with phenylisocyanate in dimethylsulfoxide (DMSO) were carried out at 60°C in the presence of various pyridine derivatives. The molecular weight distributions of the resulting cellulose tricarbanilates (CTCs) were measured by high-performance size exclusion chromatography. When pyridine or its derivatives were included in the reactions, the CTCs had reduced degree of polymerization (DP) values compared to those of CTCs prepared without the additives. The cellulose depolymerization was promoted by pyridines with electron-donating substituents and was not favored by pyridines with electron-withdrawing substituents nor with groups at positions ortho to the pyridine ring nitrogen atom. For the 3-, 4-, and 3,4- substituted pyridines, there was a linear relationship between log (weight-average CTC DP) and the pK_a (in water) of the pyridine derivative. For 2- and 2,6-substituted pyridines, the DP–pK_a relationships were different, probably because of steric effects of the different substituents ortho to the pyridine nitrogen atom. The optimum DMSO : pyridine solvent ratio for cellulose depolymerization during carbanilation in DMSO : pyridine mixtures was 3 : 1. All three components, phenylisocyanate, pyridine or its derivatives, and DMSO, are required for the depolymerization reaction. It is suggested that the depolymerization may be a consequence of cellulose oxidation by DMSO and/or cleavage of glucosidic bonds of partially carbanilated cellulose by reactions promoted by an enhanced solvent effect of DMSO.     

Surface reactivity of fuel shales from the Baltic basin

The distribution and content of acid–base centers at the surface of fuel shales and shale ash are determined. The results indicate that they may be used as fillers in polymer composites, filter materials, and sorbents. The surface of fuel shales is characterized by the presence of centers with pK_a = +1.5, pK_a = +3.5, pK_a = +6.4, pK_a = +9.5, and pK_a = +14. At the surface of shale ash, we find centers with pK_a = +1.5, pK_a = +4.1, pK_a = +6.4, pK_a = +9.5, and pK_a = +14.2. The presence of acidic and basic Bronsted centers indicates sorptional activity with respect to organic pollutants (petroleum and its products, for example) and ionic heavy metals.     

Cathodic reduction of acids in dimethylformamide on platinum

A linear correlation was shown to exist between the acidity and the cyclic voltammetric half-potential of the reduction of acids in DMF for carboxylic and N-acids in the pK_a range of 6-16. Chlorophenols are reduced at slightly lower potentials giving a separate parallel line. Applying the obtained equation and employing the same method to literature data in DMSO, the pK_a values for conjugate aids of DMF and DMSO can be calculated, showing DMSO·H⁺ to be more acidic (pK_a = 2.9) than DMF·H⁺ (pK_a = 5.7). The analysis of cyclovoltammetric data demonstrated that a CE mechanism operates in the reduction of strong acids, including the conjugate acid of DMF. Weaker acids are reduced by direct discharge or a mixed mechanism.     

Two reduction waves of oximes and imine formation in acidic media

The separation of the two two-electron waves in acidic media in solutions of some aromatic aldoximes and ketoximes is attributed to differences between the pK_a-values of oximes (which are smaller than about 1.0) and those of protonated forms of corresponding imines. Dependences of half-wave potentials on pH show that the lower limit pK_a of imine varies from −0.25 for p-formylbenzaldehyde oxime to 2.2 for p-fluorobenzaldehyde oxime. For the benzaldehyde and acetophenone oximes bearing substituents, which have pK_a higher than −1.50, a good agreement was observed for pK_a-values obtained spectrophotometrically and pK_ox values obtained from the change in the slope of plots. Past misrepresentations of the electroreduction mechanism of protonated forms of imines is attributed to insufficiently controlled compositions of supporting electrolytes. The reduction potential of protonated forms of oximes in the more positive wave i₁ is affected by the concentration of halides in the supporting electrolyte. This is attributed to an ion-pair formation, between these anions and protonated forms of oximes. The reduction of the protonated form of imines at acidity, where in the bulk predominates the same protonated form that is reduced, is independent of the nature and concentration of anions of the supporting electrolyte.     

Electrochemical behavior of o-chloranil in aqueous solution at an activated glassy carbon electrode

A study has been conducted on the effect of specific adsorption of o-chloranil, OCA, at an activated glassy carbon electrode, AGCE, surface on its electrochemical behavior in an aqueous solution. The voltammetric responses of OCA at an AGCE show an anodic prepeak and a cathodic postpeak other than the diffusion main couple in weak acidic and neutral pHs. The anodic prepeak and the cathodic postpeak are ascribed to specific adsorption of OCA. The pK_a value of the adsorbed redox couple of OCA at an AGCE is at least by 4 and 2 pK_a units higher than those of the free redox couple in solution at bare and activated glassy carbon electrodes, respectively. The slop of (I_p)_ads/(I_p)_diff ratio versus ν^1/2 for the cathodic and anodic peaks indicates a stronger adsorption of OCA at AGCE in comparison with OCAH₂. The effects of OCA concentration on its adsorption behavior and applied potential on anodic adsorption of OCA at AGCE have been studied and the surface coverage of OCA (Γ_OCA) has been calculated.     

Experimental pKa Value Determination of All Ionizable Groups of a Hyperstable Protein

Electrostatic interactions significantly contribute to the stability and function of proteins. The stabilizing or destabilizing effect of local charge is reflected in the perturbation of the pK_a value of an ionizable group from the intrinsic pK_a value. Herein, the charge network of a hyperstable dimeric protein (ribbon–helix–helix (rhh) protein from plasmid pRN1 from Sulfolobus islandicus) is studied through experimental determination of the pK_a values of all ionizable groups. Transitions were monitored by multiple NMR signals per ionizable group between pH 0 and 12.5, prior to a global analysis, which accounted for the effects of neighboring residues. It is found that for several residues involved in salt bridges (four Asp and one Lys) the pK_a values are shifted in favor of the charged state. Furthermore, the pK_a values of residues C40 and Y47, both located in the hydrophobic dimer interface, are shifted beyond 13.7. The necessary energy for such a shift is about two-thirds of the total stability of the protein, which confirms the importance of the hydrophobic core to the overall stability of the rhh protein.     

Ionic end‐capping of (semi)telechelic polymers by mesogens

Two methods have been used to end‐cap linear polymer chains at one end or at both ends by a mesogen through ionic bonding. These polymers are designated as liquid‐crystalline halato(semi)telechelic polymers (LC H(S)TPs). The first method relies on the ion exchange reaction between the metal counterion of halato(semi)telechelic polymers and an ionic mesogen. The second method is based on the proton transfer from a sulfonic or carboxylic acid end‐group to a tertiary aliphatic amine, this approach being controlled by the relative pK_a values of the acidic and basic groups. If the pK_a difference is not large enough, strong hydrogen‐bonding is observed by Fourier‐transform infrared (FTIR) spectroscopy rather than proton transfer. The resulting materials have been characterized by differential scanning calorimetry (DSC), polarized optical microscopy (POM) and small‐angle X‐ray scattering (SAXS). © 2000 Society of Chemical Industry     

Dissociation constants of long chain fatty acids in methanol-water and ethanol-water mixtures

The pK_a values of lauric acid, myristic acid, palmitic acid and stearic acid in methanol-water and ethanol-water mixtures of different compositions at 303 K and ionic strength, I=0.1M(KNO₃) have been determined. The pK_a values of the fatty acids have been found to increase with the alcohol content of the solvent. It has also been found that, in general, the pK_a values in the ethanolic solvent are greater than those in the methanolic solvent. In a given solvent mixture the observed pK_a value decreases in the order of stearic acid > palmitic acid > myristic acid > lauric acid. Departure from the predicted linearity of the plots of pK_a against the inverse of the dielectric constant, 1/D indicates that the electrostatic effects taken into account by the Born theory are not adequate enough to represent the total medium effects on pK_a.     

Struktur und Reaktivität heterosubstituierter Nitrile. XVII [1]. Kinetik und Mechanismus der Phenol-Addition an Arylcyanate in Gegenwart tertiärer Amine

Structure and Reactivity of Heterosubstituted Nitriles. XVII. Kinetics and Mechanism of the Addition of Phenols to Aryl Cyanates in Presence of Tertiary Amines The rate of carbonic acid diaryl ester imides formation by the addition of phenols to aryl cyanates in the presence of tertiary amines was determined by IR-spektroscopy. The rate constants are first order in aryl cyanates and correlate linear with [ArOH] [ArO⁻ ∥ R₃NH⁺]. The third order rate constants depend linear on the (σ + σ⁻)-values of the phenol substituents, the σ⁰-values of the aryl cyanate substituents, and the pK_a of the tertiary ammonium salts. These results support a transition state formed by the nucleophilic attack of a phenoxide trialkyl ammonium ion pair to an aryl cyanate phenol associate.     

Phase transfer methodology for the synthesis of substituted stilbenes under Knoevenagel condensation condition

This work describes the use of phase transfer catalyst (PTC) for the Knoevenagel condensation in the synthesis of several substituted stilbenes derived from weak acidic substrates such as p-nitro toluene (pK_a = 20.4) and phenylacetonitrile (pK_a = 21.9) with benzaldehyde using TBAB (tetrabutylammonium bromide) or 18-crown-6 as PTCs, respectively. Reaction of p-nitro toluene with benzaldehyde suffered from the competitive Cannizzaro reaction along with Knoevenagel condensation. Nevertheless, the problem has been solved and the novel procedure yielded >90% of isolated p-nitro stilbene. Utilizing a solid potassium carbonate as base and crown-ether as PTC proved to be the best reaction conditions for phenylacetonitrile and benzaldehyde, which showed 100% conversion of phenylacetonitrile to the corresponding stilbene (1,2-diphenyl-1′-nitrile ethene). To explore the role of PTC, we carried out a thorough kinetic investigation of these reactions. This includes modifying the catalyst nature and structure, the stirring rate, temperature effect and varying the concentration of the reactants and catalysts. Here, we prove for the first time that the PTC extraction mechanism taking place in a solid–liquid system for the carbonate anion. We conclude that it behaves as a typical second order reaction.     

Effects of the Protonation State of Titratable Residues and the Presence of Water Molecules on Nocodazole Binding to β‐Tubulin

Regulation of microtubule assembly by antimitotic agents is a potential therapeutic strategy for the treatment of cancer, parasite infections, and neurodegenerative diseases. One of these agents is nocodazole (NZ), which inhibits microtubule polymerization by binding to β‐tubulin. NZ was recently co‐crystallized in Gallus gallus tubulin, providing new information about the features of interaction for ligand recognition and stability. In this work, we used state‐of‐the‐art computational approaches to evaluate the protonation effects of titratable residues and the presence of water molecules in the binding of NZ. Analysis of protonation states showed that residue E198 has the largest modification in its pK_a value. The resulting E198 pK_a value, calculated with pH‐REMD methodology (pK_a=6.21), was higher than the isolated E amino acid (pK_a=4.25), thus being more likely to be found in its protonated state at the binding site. Moreover, we identified an interaction between a water molecule and C239 and G235 as essential for NZ binding. Our results suggest that the protonation state of E198 and the structural water molecules play key roles in the binding of NZ to β‐tubulin.     

Dissociation ability of humic acids: Spectroscopic determination of pKa and comparison with multi-step mechanism

Humic acids are operationally defined as the fraction of humic substances which is not soluble under acidic conditions. This, does not mean, however, that their solid particles easily dissolve in water. Experimental results suggest that the dissolving of solid humic acids in an aqueous environment is more complex than the conventional solubility behaviour of sparingly soluble solids. The multi-step mechanism of their interaction with water includes partial equilibrium dissolution as well as direct equilibrium dissociation from the solid state. In this work, the pK_a value of the dissolved humic acid fraction was determined on the basis of changes in the shape and intensity of their UV/VIS spectra measured in media with various values of pH. The shape of the spectra depends on the pH value, because acidic and alkaline media, in which these compounds are dissolved, shift their dissociation equilibrium towards non-dissociated molecules or to completely dissociated species. The aim of this work was to characterize the dissociation behaviour of selected humic samples by means of dissociation constants using this method. It was shown that the obtained values of pK_a characterize the real dissociation behaviour of humic acids in an aqueous environment and can be used as the mean or effective value of pK_a corresponding with the multi-step mechanism of dissociation of humic acids.     

Determination of the pKa of the Aci-Nitro Intermediate in o-Nitrobenzyl Systems

The structural volume changes following photoexcitation of o-nitrobenzyl systems are used to estimate the excited state pK_a of the aci-nitro intermediate in aqueous solutions. The rather large contractions induced in solution by UV excitation are due to the rapid deprotonation of the short-lived aci-nitro intermediate, which leads to the formation of two charged species. The magnitude of the measured contraction as a function of the pH in acidic solutions follows a sigmoidal curve, from which it is possible to extract the pK_a of the aci-nitro intermediate. This method is generally applicable to short-lived intermediates with stronger acid character than the parent compound, provided they undergo irreversible chemical transformations to a product that cannot rebind the photodetached proton. The reaction volume for water formation from its ionic constituents at basic pH allows the determination of the deprotonation quantum yields.     

Non‐native N‐Aroyl L‐Homoserine Lactones Are Potent Modulators of the Quorum Sensing Receptor RpaR in Rhodopseudomonas palustris

Quorum sensing (QS) is a process by which bacteria use low‐molecular‐weight signaling molecules (or autoinducers) to assess their local population densities and alter gene expression levels at high cell numbers. Many Gram‐negative bacteria use N‐acyl L ‐homoserine lactones (AHLs) with aliphatic acyl groups as signaling molecules for QS. However, bacteria that utilize AHLs with aroyl acyl groups have been recently discovered; they include the metabolically versatile soil bacterium Rhodopseudomonas palustris, which uses p‐coumaroyl HL (p‐cAHL) as its QS signal. This autoinducer is especially unusual because its acyl group is believed to originate from a monolignol (i.e., p‐coumarate) produced exogenously by plants in the R. palustris environment, rather than through the endogenous fatty acid biosynthesis pathway like other native AHLs. As such, p‐cAHL could signal not only bacterial density, but also the availability of an exogenous plant‐derived substrate and might even constitute an interkingdom signal. Like other Gram‐negative bacteria, QS in R. palustris is controlled by the p‐cAHL signal binding its cognate LuxR‐type receptor, RpaR. We sought to determine if non‐native aroyl HLs (ArHLs) could potentially activate or inhibit RpaR in R. palustris, and thereby modulate QS in this bacterium. Herein, we report the testing of a set of synthetic ArHLs for RpaR agonism and antagonism by using a R. palustris reporter strain. Several potent non‐native RpaR agonists and antagonists were identified. Additionally, the screening data revealed that lower concentrations of ArHL are required to strongly agonize RpaR than to antagonize it. Structure–activity relationship analyses of the active ArHLs indicated that potent RpaR agonists tend to have sterically small substituents on their aryl groups, most notably in the ortho position. In turn, the most potent RpaR antagonists were based on either the phenylpropionyl HL (PPHL) or the phenoxyacetyl HL (POHL) scaffold, and many contained an electron‐withdrawing group at either the meta or para positions of the aryl ring. To our knowledge, the compounds reported herein represent the first abiotic chemical modulators of RpaR, and more generally, the first abiotic ligands capable of intercepting QS in bacteria that utilize native ArHL signals. In view of the origins of the p‐cAHL signal in R. palustris, the largely unknown role of QS in this bacterium, and R. palustris' unique environmental lifestyles, we anticipate that these compounds could be valuable as chemical probes to study QS in R. palustris in a range of fundamental and applied contexts.     

Stability of multi-walled carbon nanotubes in commonly used acidic media

Multi-walled carbon nanotubes (MWCNT) were treated in five commonly used acidic media with different pK_a values. The stability of the MWCNT was evaluated by using various characterization techniques. The results indicated that oxidative damage of MWCNT was not closely related to acid strength, and that the MWCNT was more sensitive to the oxidizing nature of the acid. As a result, the MWCNT treated with the strongest acid, trifluoromethanesulfonic acid (pK_a = ?15.9), only reached oxygen content of 1.8%, while nitric acid (pK_a = ?1.5)/sulfuric acid (pK_a = ?3.0) treated MWCNT showed oxygen content as high as 19% after 24 h treatment. The remaining acidic media did not noticeably increase the oxygen content of the MWCNT up to 24 h treatment.     

Thermally crosslinked anionic hydrogels composed of poly(vinyl alcohol) and poly(γ‐glutamic acid): Preparation,characterization, and drug permeation behavior

pH‐sensitive anionic hydrogels composed of poly(vinyl alcohol) (PVA) and poly(γ‐glutamic acid) (γ‐PGA) were prepared by the freeze drying method and thermally crosslinked to suppress hydrogel deformation in water. The physical properties, swelling, and drug‐diffusion behaviors were characterized for the hydrogels. In the equilibrium swelling study, PVA/γ‐PGA hydrogels shrunk in pH regions below the pK_a (2.27) of γ‐PGA, whereas they swelled above the pK_a. In the drug‐diffusion study, the drug permeation rates of the PVA/γ‐PGA hydrogels were directly proportional to their swelling behaviors. The cytocompatibility test showed no cytotoxicity of the PVA/γ‐PGA hydrogels for the 3T3 fibroblast cell lines. The results of these studies suggest that hydrogels prepared from PVA and γ‐PGA could be used as orally administrable drug‐delivery systems. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008