ΔpKa Values Research Articles

Designing Thermally Stable Organocatalysts for Poly(ethylene terephthalate) Synthesis: Toward a One-Pot, Closed-Loop Chemical Recycling System for PET

Organocatalysis provides robust methodology to furnish “greener” routes to polymer synthesis. However, the application toward the synthesis of aromatic polymers via step-growth polymerization is an area that justifies more investigation, as a consequence of the poor thermal stability of many organic catalysts and the high reaction temperatures commonly required. In this study, thermally stable organic salts consisting of an organic base and an organic acid were explored to understand key elements required for the bulk synthesis of poly(ethylene terephthalate) (PET) at 270 °C. The ΔpKa values of the salts played an important role in the thermal stability such that the salts with higher ΔpKa values showed higher stability because of the strong acid–base interactions. The 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) salts with high ΔpKa values (≥16.9) showed the best catalytic activity among the investigated salts in terms of both low amounts of side reactions and discoloration. The thermal and chemical stability of the salts also affected the polymer properties. Dimerization side reactions that lead to defects in the polymer backbone were found to occur more readily in salts containing strong acids as components, particularly as the ΔpKa between the acid–base components decreased. The discoloration of the PET sample was also correlated to the thermal stability of the organic salt catalyst, with a lower stability generally leading to enhanced discoloration likely due to decomposition of base components. Polymerization–depolymerization cycles were also investigated with the TBD:p-toluenesulfonic acid (TSA) salt and the feasibility of simple, closed-loop recycling of PET with the system was established.

Insights on structure and interactions of 2-amino-4-methoxy-6-methylpyrimidinium salts with 4-aminosalicylate and 5-chlorosalicylate: a combined experimental and theoretical charge-density analysis.

The proton-transfer complexes 2-amino-4-methoxy-6-methylpyrimidinium (2A4M6MP) 4-aminosalicylate (4AMSA), C6H10N3O+·C7H6NO3-, I, and 5-chlorosalicylate (5ClSA), C6H10N3O+·C7H4ClO3-, II, were synthesized by slow evaporation and crystallized. The crystal structures of both I and II were determined by single-crystal X-ray structure analysis. The crystal structures of both salts exhibit O-H...O, N-H...O, N-H...N and C-H...O interactions in their crystals. The 4AMSA and 5ClSA anions in combination with the 2A4M6MP cations form distinct synthons, which are represented by the graph-set notations R22(8), R42(8) and R22(8). Furthermore, the ΔpKa values were calculated and clearly demonstrate that 2A4M6MP is a good salt former when combined with carboxylic acids. Hirshfeld surface analysis was used to quantify the weak and strong interactions in the solid state, and energy framework calculations showed the stability of the hydrogen-bonding interactions. QTAIM (quantum theory of atoms in molecules) analysis revealed the nature of the chemical bonding in I and II, and the charge-density distribution in the intermolecular interactions in the crystal structures.

Key factor governing the physicochemical properties and extent of proton transfer in protic ionic liquids: ΔpKa or chemical structure?

In order to identify the key factor governing the transport properties and extent of proton transfer in protic ionic liquids (PILs), a series of PILs were prepared by simple neutralisation of a super-strong acid, bis(trifluoromethanesulfonyl)amide acid (H[NTf2]), with a range of amines comprising diverse structures, including secondary and tertiary amines. The bulk physicochemical properties of the resulting PILs with a wide variation in the ΔpKa values of the constituent acid and protonated bases were compared to those of previously reported PILs derived from a super-strong base, 1,8-diazabicyclo[5.4.0]-7-undecene (DBU), and different acids (M. S. Miran, H. Kinoshita, T. Yasuda, M. A. B. H. Susan and M. Watanabe, Phys. Chem. Chem. Phys., 2012, 14, 5178-5186) with emphasis on the thermal stability, vibrational spectroscopy, density, viscosity, conductivity, and ionicity characteristics. The thermal stability of all PILs, as analysed by thermogravimetric analysis (TGA), was found to linearly increase with the ΔpKa values. However, isothermal TGA measurements for an extended duration indicated that [NTf2]-based PILs exhibit higher thermal stability than [DBU]-based PILs at low ΔpKa values (<15). PILs with secondary amines showed higher viscosity and lower ionic conductivity than those with tertiary amines because of the formation of multiple hydrogen bonds. The evaluated ionicity suggested that all [NTf2]-based PILs are "good PILs", irrespective of the basicity of the amines, and have higher ionicity than [DBU]-based PILs particularly at low ΔpKa values (<15).

Can carbene decorated [FeFe]-hydrogenase model complexes catalytically produce dihydrogen? An insight from theory.

Cyclic alkyl amino carbene (CAAC) anchored [FeFe]-hydrogenase model complex featuring rotated conformation at one of the iron centers are found to be promising candidate for effective production of dihydrogen. A stepwise comparison of the complete mechanism using the CAAC stabilized model complex [1]0 has been performed with that of an experimentally isolated one ([2]0). Interestingly, the reduction events involved in the catalytic cycles are found to be more favorable than those previously reported for a similar experimentally known system. Furthermore, the computed ΔpKa values indicate that the distal iron center with a vacant coordination site is more basic compared to the amino nitrogen atom of the azadithiolate bridge. We also made an attempt to determine the oxidation states of the iron centers for the intermediates involved in the catalytic cycles on the basis of the computed Mössbauer isomer shift and Mulliken spin density values.

Critical assessment of superbase-derived protic ionic liquids as electrolytes for electrochemical applications

Non-volatile superbased-derived protic ionic liquids are thermally stable and highly conductive, thus hold great promises for electrochemical applications. However, systematic accounts of their electrochemical properties are yet to be established. In this contribution, five hydrophobic superbase-derived protic ionic liquids (PILs) have been prepared from Brønsted superbases and the salts of strong acids, and their decomposition temperature, density, conductivity and viscosity have been measured. The greatest viscosity was observed with the superbased PILs, [MTBDH][NfO] (2212 cP) and the least with [MTBDH][NTf2] (121 cP). Greatest conductivity was measured for [MTBDH][NTf2] (1.54 mS cm−1) and the least for [MTBDH][NfO] (0.089 mS cm−1). By combining density, conductivity and viscosity, a Walden plot was set up to demonstrate the degree of ionization, or ‘ionicity’ of each of the five PILs is greater than 10%. Their electrochemical characteristics were determined using cyclic voltammetry. Two IUPAC-recommended internal potential reference systems, ferrocene/ferrocenium and cobaltocenium/cobaltocene, were assessed for use in the five PILs. Potential windows of the five PILs were established at glassy carbon, gold and platinum electrodes, where the widest potential window was observed with glassy carbon electrodes with no direct correlation found between the ΔpKa values and the potential windows. The widest potential window was measured in [MTBH][beti] (4.3 ± 0.1 V) and the shortest in [HNC(dma)H][beti] (2.7 ± 0.1 V). The double layer capacitance was also investigated for potential applications in supercapacitors.

Cocrystals of indole-3-acetic acid and indole-3-butyric acid: Synthesis, structural characterization and Hirshfeld surface analysis

A series of cocrystals and a salt of the indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) (plant hormone) with 2-aminopyrimidine (2AP), 2-amino-4,6-dimethylpyrimidine (2A-4,6-DMP) and 2,4,6-triaminopyrimidine (2,4,6-TAP) were successfully prepared, with an aim to explore the robustness of acid-aminopyrimidine synthon and its behaviour, with a change in the environment at 4,6 position of the pyrimidine ring. The formation of cocrystals/salt are examined on their ΔpKa values and were characterized by powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and their structures determined by single crystal X-ray diffraction (SCXRD). Additionally, Hirshfeld surface analysis was done to investigate the strength of the interactions and the overall percentage of short contacts and their impact on the overall packing.

Transport properties of protic and aprotic guanidinium ionic liquids.

Ionic liquids (ILs) are a promising class of solvents, functional fluids and electrolytes that are of high interest for both basic as well as applied research. For further fundamental understanding of ILs and a successful implementation in technical processes, a deeper insight into transport properties and their interrelations is of particular importance. In this contribution we synthesised a series of mostly novel protic and aprotic ILs based on the tetramethylguanidinium (TMG) cation that is a derivative of the superbase guanidine. Different substitution patterns and anions from acids with broadly varied pKa values were investigated. We measured general properties, such as thermal transitions and densities of these ILs, as well as their transport quantities by means of rheology, impedance spectroscopy and NMR diffusometry. Different models for the correlation of the transport properties, namely the Nernst–Einstein, Walden and Stokes–Einstein–Sutherland relations were applied. The deviation from ideal behaviour of fully dissociated electrolytes, often termed as ionicity, was quantified by the reciprocal Haven ratio, fractional Walden rule and ionicity obtained from the Walden plot. Velocity cross-correlation coefficients were calculated to gain further insight into the correlation between ion movements. Both protic and aprotic TMG ILs show transport properties comparable to other ILs with similar molecular weight and high ionicity values especially in contrast to other protic ILs. Lowest ionicity values were found for the protic ILs with smallest ΔpKa values between constituting acid and base. This can either be explained by stronger hydrogen bonding between cation and anion or lower anti-correlations between the oppositely charged ions. These results aim to provide insight into the properties of this interesting cations class and a deeper understanding of the transport properties of ILs and their interrelations in general.

Entropy Drives the Formation of Salt Bridges in the Protein GB3

AbstractSalt bridges are very common in proteins. But what drives the formation of protein salt bridges is not clear. In this work, we determined the strength of four salt bridges in the protein GB3 by measuring the ΔpKa values of the basic residues that constitute the salt bridges with a highly accurate NMR titration method at different temperatures. The results show that the ΔpKa values increase with temperature, thus indicating that the salt bridges are stronger at higher temperatures. Fitting of ΔpKa values to the van't Hoff equation yields positive ΔH and ΔS values, thus indicating that entropy drives salt‐bridge formation. Molecular dynamics simulations show that the protein and solvent make opposite contributions to ΔH and ΔS. Specifically, the enthalpic gain contributed from the protein is more than offset by the enthalpic loss contributed from the solvent, whereas the entropic gain originates from the desolvation effect.

Entropy Drives the Formation of Salt Bridges in the Protein GB3.

Salt bridges are very common in proteins. But what drives the formation of protein salt bridges is not clear. In this work, we determined the strength of four salt bridges in the protein GB3 by measuring the ΔpKa values of the basic residues that constitute the salt bridges with a highly accurate NMR titration method at different temperatures. The results show that the ΔpKa values increase with temperature, thus indicating that the salt bridges are stronger at higher temperatures. Fitting of ΔpKa values to the van't Hoff equation yields positive ΔH and ΔS values, thus indicating that entropy drives salt-bridge formation. Molecular dynamics simulations show that the protein and solvent make opposite contributions to ΔH and ΔS. Specifically, the enthalpic gain contributed from the protein is more than offset by the enthalpic loss contributed from the solvent, whereas the entropic gain originates from the desolvation effect.

PKa values of hyodeoxycholic and cholic acids in the binary mixed micelles sodium-hyodeoxycholate–Tween 40 and sodium-cholate–Tween 40: Thermodynamic stability of the micelle and the cooperative hydrogen bond formation with the steroid skeleton

Due to a relatively small size of bile acid salts, their mixed micelles with nonionic surfactants are analysed. Of the special interests are real binary mixed micelles that are thermodynamically more stable than ideal mixed micelles. Thermodynamic stability is expressed with an excess Gibbs energy (GE) or over an interaction parameter (βij). In this paper sodium salts of cholic (C) and hyodeoxycholic acid (HD) in their mixed micelles with Tween 40 (T40) are analysed by potentiometric titration and their pKa values are determined. Examined bile acids in mixed micelles with T40 have higher pKa values than free bile acids. The increase of ΔpKa acid constant of micellary bound C and HD is in a correlation with absolute values of an interaction parameter. According to an interaction parameter and an excess Gibbs energy, mixed micelle HD–T40 are thermodynamically more stable than mixed micelles C–T40. ΔpKa values are higher for mixed micelles with Tween 40 whose second building unit is HD, related to the building unit C. In both micellar systems, ΔpKa increases with the rise of a molar fraction of Tween 40 in binary mixtures of surfactants with sodium salts of bile acids. This suggests that, ΔpKa can be a measure of a thermodynamic stabilization of analysed binary mixed micelles as well as an interaction parameter. ΔpKa values are confirmed by determination of a distribution coefficient of HD and C in systems: water phase with Tween 40 in a micellar concentration and 1-octanol, with a change of a pH value of a water phase. Conformational analyses suggests that synergistic interactions between building units of analysed binary micelles originates from formation of hydrogen bonds between steroid OH groups and polyoxyethylene groups of the T40. Relative similarity and spatial orientation of C3 and C6 OH group allows cooperative formation of hydrogen bonds between T40 and HD – excess entropy in formation of mixed micelle. If a water solution of analysed binary mixtures of surfactants contains urea in concentration of 4M significant decreases of an interaction parameter value happens which confirms the importance of hydrogen bonds in synergistic interactions (urea compete in hydrogen bonds).

Binary mixed micelles of triton X-100 and selected bile salts: Thermodynamic stabilization and pKa values of micellar bile acids

Bile acid anions are biosurfactants which form small micelles. To enhance the hydrophobic volume of the micelle, bile salts are used as mixed micelles with non-ionic surfactants. Micellar-bound bile acids (sodium-hyodeoxycholate, HD and sodium-cholate, C in binary mixed micelles with non-ionic surfactant Triton X-100) at concentration of 10cmc have higher pKa values than bile acids from the aqueous solution. Different pKa values of micellar and non-micellar bile acids (ΔpKa) are due to the excess Gibbs energy GHAE which is a function of interaction coefficient and mole fraction of Triton X-100 in the binary surfactant mixture. In the mixed micelles ΔpKa values show synergistic interactions between different building units, similarly as interaction coefficient.

Controlled Synthesis of New 5-Fluorocytosine Cocrystals Based on the pKa Rule

5-Fluorocytosine (5-FC) was investigated for the controlled synthesis of cocrystals by applying the pKa rule. Five cocrystals were designed and developed with adipic, succinic, terephtalic, benzoic, and malic acids, all exhibiting negative ΔpKa values ranging from close to zero up to roughly −1. The synthesized cocrystals were analyzed by single crystal X-ray diffraction, and the observed supramolecular synthons were compared to the reported structures containing 5-FC. In the first four cocrystals, the intermolecular interactions between adjacent 5-FC molecules form two different homodimers showing R22(8) motifs and assembled via complementary N–H···O and N–H···N hydrogen bonds, respectively. However, in the cocrystal with malic acid (ΔpKa = −0.1), an intermediate supramolecular synthon pattern between salts and cocrystals is observed. In this crystal packing, the homodimer of 5-FC molecules held by the N–H···O interactions is preserved, but a new heterodimer is formed between 5-FC and the acid molecule, ...

Influence of Water Content on Basicities in Acetonitrile

The influence of water content at impurity level (5–10,000 ppm) in acetonitrile, on the changes in relative basicity differences (ΔpK a values) of 13 pairs of bases, was studied both experimentally and computationally (COSMO-RS). The ΔpK a values involving smaller bases with localized charge in the cationic form were found to be more affected. A computational parameter, weighted average negative sigma (WANS), was proposed to quantify the charge delocalization in cations and succeeded in describing the observed changes of ΔpK a. The results validate the previously published basicity scale in acetonitrile with respect to solvent dryness and give guidelines for better experimental planning.

Accurate Method To Quantify Binding in Supramolecular Chemistry

An approach for accurate and comparable measurement of host-guest binding affinities is introduced whereby differences in binding strength (ΔlogKass values) are measured between two host molecules toward a particular guest under identical solvent conditions. Measuring differences instead of absolute values enables obtaining highly accurate results, because many of the uncertainty sources (the solvation/association state of the guest in solution, deviations in solvent composition, etc.) cancel out. As a proof of concept, this method was applied to the measurement of the binding strength of 28 synthetic anion receptors toward acetate in acetonitrile containing 0.5% water. The receptors included differently substituted indolocarbazoles, ureas, thioureas, and some others. Possible deprotonation of more acidic receptors of each compound class by acetate was checked by measuring their acidities (ΔpKa values) relative to acetic acid in the same solvent. A self-consistent (consistency standard deviation 0.04 log units) binding affinity scale ranging for around 2.7 log units was constructed from the results. Absolute logKass values were found by anchoring the scale to the absolute logKass values of two receptor molecules, determined independently by direct measurements. This new approach is expected to find use in accurate quantification of a wide range of binding processes relevant to supramolecular chemistry.

Protic Ionic Liquids Based on a Super-Strong Base: Correlation between Physicochemical Properties and ΔpKa

ABSTRACT1,8-Diazabicyclo[5,4,0]undec-7-ene (DBU) was neutralized by a range of Brønsted acids with a wide variation in the ΔpKa values of their constituent acids and base. The salts exhibited properties characteristic of an ionic liquid, such as high thermal stability and liquidity near ambient temperature. Analyses of thermal behaviors and temperature dependencies of density, viscosity (η), and ionic conductivity were made to correlate the physicochemical properties with the ΔpKa value of the obtained protic ionic liquids (PILs). Differential thermal analyses (DTA) revealed that PILs with high ΔpKa values underwent thermal decomposition resembling their aprotic counterparts; however, PILs with a low ΔpKa exhibited the evaporation of neutral species progressively generated from the shifting of the equilibrium toward neutral components during the weight loss process. The ionicity of the PILs, determined from Walden plots utilizing density, conductivity, and viscosity data, was found to decrease as temperature increased, and this effect was more pronounced for low ΔpKa values, possibly because of the shifting of the equilibrium and the imbalance between strong hydrogen bonds and Coulombic interactions. Fragility, estimated from plots of log(η) versus the scaled temperature Tg/T was found to be lower for PILs than for DBU owing to neutralization. [DBU]-based PILs exhibit intermediate fragility in nature, but this fragility becomes more prominent for PILs with low ΔpKa values

Propensity of formation of zipper architecture vs. Lincoln log arrangement in solvated molecular complexes of melamine with hydroxybenzoic acids

Molecular complexes of melamine with hydroxy and dihydroxybenzoic acids have been analyzed to assess the collective role of the hydroxyl (OH) and carboxyl (COOH) functionalities in the recognition process. In most cases, solvents of crystallization do play a major role in self-assembly and structure stabilization. Hydrated compounds generate linear chains of melamine molecules with acid molecules pendant resulting in a zipper architecture. However, anhydrous and solvated compounds generate tetrameric units consisting of melamine dimers together with acid molecules. These tetramers in turn interweave to form a Lincoln log arrangement in the crystal. The salt/co-crystal formation in these complexes cannot be predicted apriori on the basis of ΔpKa values as there exists a salt-to-co-crystal continuum.

Mapping the Landscape of Potentially Primordial Informational Oligomers: Oligo‐dipeptides Tagged with Orotic Acid Derivatives as Recognition Elements

Partner up! Base-pairing properties of oligo-dipeptides tagged with orotic acid and its 2,4-diamino counterpart (see structure) are found to be consistent with previously observed correlations between ΔpKa values and the pairing strength of complementary bases. The combined results provide a general justification for anticipating the base-pairing propensity of a recognition element based on its pKa value and the pH of the medium.

Synthon Competition and Cooperation in Molecular Salts of Hydroxybenzoic Acids and Aminopyridines

Meta- and para-substituted hydroxy-benzoic acids and amino-pyridines were cocrystallized and characterized by X-ray diffraction. Proton transfer from the COOH to pyridyl N acceptor (PyN) occurred in 11 molecular salts (1−11) leading to a PyNH+···−OOC ionic synthon in 10 structures and a PyNH+···O═C hydrogen bond in one structure. Competition and cooperation between COO−, OH, NH2, PyNH+, and H2O functional groups for the observed hydrogen bond synthons are examined in 11 structures, of which 4 are hydrates. The second and third highest occurring synthons are NH2···OH, NH2···−OOC, and OH···−OOC in nine, eight, and eight structures, respectively. Hydrogen bonding of water to/from COO−, OH, and NH2 groups is present in hydrates 1, 5, 7, and 9. There are no systematic studies on our knowledge on hydrogen bond competition and interplay when the above four common functional groups are present in the same crystal structure. Synthons in this study are compared with statistics extracted from the Cambridge Structural Database to summarize trends and predict hydrogen bonding in new cocrystal and salt structures. The term molecular salt is suggested for ionic complexes derived from organic acids and bases. Acidity constants of benzoic acids and amino-pyridines were calculated in the gas phase, MeOH, and water using the SPARC program. The ΔpKa rule is found to be inadequate for predicting neutral or ionic O−H···N/N+−H···O− hydrogen bonds when other polar functional groups are also present in the system. The persistence of PyNH+···−OOC ionic synthons is ascribed to the presence of OH and NH2 groups in the same supramolecular system. ΔpKa values are in the range 1−5 in the gas phase and water but negative in MeOH (−1 to −6), on the whole lower than the pKa difference of >3 that is generally accepted as a condition for proton transfer. Our results are at variance with a recent paper in Cryst. Growth Des. (2008, 8, 4533−4545) wherein neutral COOH···NPy heterosynthon occurs with 78% probability when competition in the presence of phenol OH group only was analyzed.

Effects of substitutions in the CXXC active-site motif of the extracytoplasmic thioredoxin ResA

The thiol-disulfide oxidoreductase ResA from Bacillus subtilis fulfils a reductive role in cytochrome c maturation. The pK(a) values for the CEPC (one-letter code) active-site cysteine residues of ResA are unusual for thioredoxin-like proteins in that they are both high (>8) and within 0.5 unit of each other. To determine the contribution of the inter-cysteine dipeptide of ResA to its redox and acid-base properties, three variants (CPPC, CEHC and CPHC) were generated representing a stepwise conversion into the active-site sequence of the high-potential DsbA protein from Escherichia coli. The substitutions resulted in large decreases in the pK(a) values of both the active-site cysteine residues: in CPHC (DsbA-type) ResA, DeltapK(a) values of -2.5 were measured for both cysteine residues. Increases in midpoint reduction potentials were also observed, although these were comparatively small: CPHC (DsbA-type) ResA exhibited an increase of +40 mV compared with the wild-type protein. Unfolding studies revealed that, despite the observed differences in the properties of the reduced proteins, changes in stability were largely confined to the oxidized state. High-resolution structures of two of the variants (CEHC and CPHC ResA) in their reduced states were determined and are discussed in terms of the observed changes in properties. Finally, the in vivo functional properties of CEHC ResA are shown to be significantly affected compared with those of the wild-type protein.

The Salt−Cocrystal Continuum: The Influence of Crystal Structure on Ionization State

Salts and cocrystals are multicomponent crystals that can be distinguished by the location of the proton between an acid and a base. At the salt end of the spectrum proton transfer is complete, and on the opposite end proton transfer is absent in cocrystals. However, for acid-base complexes with similar pK(a) values, the extent of proton transfer in the solid state is not predictable and a continuum exists between the two extremes. For these systems, both the DeltapK(a) value (pK(a) of base - pK(a) of acid) and the crystalline environment determine the extent of proton transfer. A total of 20 complexes containing theophylline and guest molecules with DeltapK(a) values less than 3 have been prepared, resulting in 13 cocrystals, five salts, and two complexes with mixed ionization states based on IR spectroscopy and single-crystal diffraction data. We propose modifications to the DeltapK(a) rule for selecting salt screen counterions that focus on the discovery of solid forms with useful physical properties rather than an arbitrary cutoff value for DeltapK(a).