pKa Values Research Articles

Tunable protic ionic liquid catalysts for the efficient one-step synthesis of isosorbide-based polycarbonates

Using CO2-derived dimethyl carbonate (DMC) instead of diphenyl carbonate (DPC) as a carbonyl source for synthesizing bio-based polycarbonates is a green and cost-effective route. However, the synthesis of high-performance polycarbonates via the DMC route remains challenging due to the poor reactivity and selectivity of DMC compared to DPC. Herein, we designed a series of highly active protic ionic liquid (PIL) catalysts for the synthesis of poly(isosorbide carbonate) (PIC) from DMC with ISB. The influences of the structures of anion and cation on the catalytic activity of PILs were systematically studied. Compared with the reported aprotic IL catalysts, the unique reactive hydrogen of the cation in PILs could form a strong hydrogen bond interaction with the carbonyl group of DMC, resulting in higher reactivity of the carbonyl carbon of DMC. Moreover, the nucleophilicity of the anion could be easily tuned by adjusting the pKa value, which effectively realized the balance of the reactivity difference between exo-OH and endo-OH in ISB. Among them, [DBUH][Im] showed the highest catalytic activity, and the weight-average molecular weight (Mw) and glass transition temperature of PIC reached 55,700 g/mol and 160 °C, respectively. Combined with NMR analyses and DFT calculations, the mechanism that exhibited the synergetic catalytic effect of anion-cation for the polymerization of DMC and ISB was presented.

The pKa of Water and the Fundamental Laws Describing Solution Equilibria: An Appeal for a Consistent Thermodynamic Pedagogy

AbstractA recurring misconception in some textbooks and research papers has led to an abandonment of fundamental physical laws when describing a subset of acid‐base equilibria, especially regarding the role of the solvent. In the specific case of the autoprotolysis of water, experiments and theoretical calculations prove that the Kw of water at 25 °C, 1.00×10−14, is identical to its acid ionization constant, Ka. Nevertheless, several articles have been published erroneously purporting to give theoretical proof that the Ka of water is 10−15.743 (1.81×10−16) and that the Ka of the aqueous proton (hydronium ion) is 55.3 rather than 1.00. Here we argue that using the incorrect numbers has pedagogical implications beyond those of a simple error. Arguments for the incorrect Ka and pKa values require a misapplication of Henry's law and violate long‐standing methods that use Raoult's law and the conservation of matter to describe the behavior of solutions. As a result, chemistry students may be asked to accept one set of physical principles in one course and another set in another course. Here we argue for adherence to fundamental physical laws governing solution equilibria as applied to the autoprotolysis of water and all aqueous acid base equilibria.

Chitosan-Based Electronics: The Importance of Acid Strength and Plasticizing Additives on Device Performance.

A rise in demand for disposable consumer electronics such as smart packaging, wearable electronics, and single-use point-of-source sensors requires the development of eco-friendly and compostable electronic materials. Chitosan is derived from crustacean waste and offers high dielectric constant values without requiring rigorous purification, making it sustainable for large-scale electronic device manufacturing. When processed in acidic media, the protonated backbone of chitosan pairs with counterions from the acid dissociation to form chitosan thin films with electrical double layers (EDLs) and tunable capacitive properties. We report the importance of the choice of acid when processing chitosan by surveying a series of halogenated and biosourced acids with varying pKa values and solutions with different pH values. Oxalic acid outperforms other acids, with a maximum areal capacitance of 161 nF·mm-2. Tartaric acid and citric acid, despite lower capacitance values, showed promising results with a stable EDL capacitance and high reproducibility, making them optimal for large-area manufacturing. The incorporation of sorbitol as a plasticizer boosts the EDL formation onset of all chitosan-acid combinations to 1 × 103-105 Hz and improves reproducibility. High-performing single-walled carbon nanotube thin film transistors were made using chitosan-based dielectrics treated with different acids with and without sorbitol, leading to transconductance as high as ≈5.2 μS and Ion/Ioff of 105. The capacitors and transistors remain functional after one year of storage in ambient conditions. Overall, this study demonstrates durable high-performance electronics based on chitosan and stresses the importance of processing acid and the use of plasticizing additives, such as sorbitol.

S‐Aryl Substitution Enhances Acidity of the 1,2,4‐Triazolium Scaffold

AbstractThe 1,2,4‐triazolium scaffold in asymmetric organocatalysis results in remarkable rate accelerations, with reactions typically occurring via N‐heterocyclic carbene (NHC) intermediates. Although the most acidic NHC pre‐catalyst class, there remains scope for further increases in acidity particularly for aqueous organocatalysis applications. The acidity‐enhancing effects of thio‐substituents on carbon acidity are well‐documented but not explored in the 1,2,4‐triazolium scaffold. Herein, we report the synthesis of a large series of N, N‐dialkyl‐C(3)‐S‐aryltriazolium ions and quantitative kinetic evaluation of C(5)‐H acidity. The direct attachment of S‐aryl substituents to the triazolium heterocycle results in substantial increases in protofugalities (kinetic acidities) with second order rate constants (kDO) for C(5)‐H deprotonation by DO− base that are 2.9–60.3 fold higher than for reference 1,4‐dimethyl‐1,2,4‐triazolium iodide in D2O solution. Protofugalities for the N, N‐dialkyl‐C(3)‐S‐aryltriazolium series are similar to commonly used bicyclic N‐aryl‐1,2,4‐triazolium organocatalysts despite having two electron donating N‐alkyl substituents. This highlights the future potential of this NHC design which could enable the introduction of two chiral alkyl substituents close to the C(5) carbenic position with pre‐catalyst acidity controlled by distal C(3)‐S‐aryl substitution. Detailed X‐ray structural data‐protofugality correlations enabled evaluation of the S‐aryl substituent effect origins. C(5)‐H pKa values (16.9–18.6) were calculated by utilisation of experimental protofugalities.

Water-Induced Switching in Selectivity and Steric Control of Activity in Photochemical CO2 Reduction Catalyzed by RhCp*(bpy) Derivatives.

Photocatalytic reduction of CO2 to formic acid (HCOOH) was investigated in either organic or aqueous/organic media by employing three water-soluble [RhIIICp*(LH2)Cl]+ (LH2 = n,n'-dihydroxy-2,2'-bipyridine; n = 4, 5, or 6) in the presence of [Ru(bpy)3]2+, 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole (BIH) and triethanolamine (TEOA). Through studying the electron-donating effects of two hydroxyl groups introduced into the bipyridyl ligand, we found that the substituent positions greatly affect both the catalytic efficiency and selectivity in CO2 reduction. More importantly, the HCOOH selectivity shows a dramatic increase from 14 to 83% upon switching the solvent media from pure organic to an aqueous/organic mixture, where the H2 selectivity shows a reverse phenomenon. The enhanced HCOOH selectivity and the drastic decrease in the H2 yield are well rationalized by the fact that the catalytic CO2 hydrogenation is not only driven photochemically via the attack of RhIII(H)Cp*(LH2-·) on CO2 but also partly bypassed by a dark H2 addition reaction yielding [RhIII(H)Cp*(L)]- from [RhIIICp*(L)Cl]+, which was also separately investigated under dark conditions. A combination of experimental and theoretical approaches was made to clarify the pKa values of catalyst intermediates together with the abundant species responsible for the major catalytic processes. Our DFT studies unveil that the exceptionally large structural strain given by the steric contacts between the 6,6'-dihydroxyl groups and the Cp* moiety plays a significant role in bringing about an outstanding catalytic performance of the 6,6'-substituted derivative. The intrinsic reaction coordinate calculations were carried out to clarify the mechanism of hydride transfer steps leading to generating formate together with the heterolytic H2 cleavage steps leading to afford the key hydridorhodium intermediates. This study represents the first report on the water-induced high selectivity in CO2-to-HCOOH conversion, shedding new light on the strategy to control the efficiency and selectivity in the catalysis of CO2 reduction.

Unlocking the Potential of Push-Pull Pyridinic Photobases: Aggregation-Induced Excited-State Proton Transfer.

The pH effect on the photophysics of three push-pull compounds bearing dimethoxytriphenylamine (TPA-OMe) as electron donor and pyridine as electron acceptor, with different ortho-functionalization (-H, -Br, -TPA-OMe), is assessed through steady-state and time-resolved spectroscopic techniques in DMSO/water mixed solutions and in water dispersions over a wide pH range. The enhanced intramolecular charge transfer upon protonation of the pyridineleads to the acidochromic (from colorless to yellow) and acido(fluoro)chromic (from cyan to pink) behaviours of the investigated compounds. In dilute DMSO/buffer mixtures these molecules exhibited low pKa values (≤ 3.5) and short singlet lifetimes. Nevertheless, it is by exploiting the aggregation phenomenon in aqueous environment that the practical use of these compounds largely expands: i) the basicity increases (pKa ≈ 4.5) approaching the optimum values for pH-sensing in cancer cell recognition; ii) the fluorescence efficiencies are boosted due to Aggregation-Induced Emission (AIE), making these compounds appealing as fluorescent probes; iii) longer singlet lifetimes enable Excited-State Proton Transfer, paving the way for the application of these molecules as photobases (pKa* = 9.1). The synergy of charge and proton transfers combined to the AIE behaviour in these pyridines allows tunable multi-responsive optical properties providing valuable information for the design of new light-emitting photobases.

Force Field Limitations of All-Atom Continuous Constant pH Molecular Dynamics.

All-atom constant pH molecular dynamics simulations offer a powerful tool for understanding pH-mediated and proton-coupled biological processes. As the protonation equilibria of protein side chains are shifted by electrostatic interactions and desolvation energies, pKa values calculated from the constant pH simulations may be sensitive to the underlying protein force field and water model. Here we investigated the force field dependence of the all-atom particle mesh Ewald (PME) continuous constant pH (PME-CpHMD) simulations of a mini-protein BBL. The replica-exchange titration simulations based on the Amber ff19sb and ff14sb force fields with the respective water models showed significantly overestimated pKa downshifts for a buried histidine (His166) and for two glutamic acids (Glu141 and Glu161) that are involved in salt-bridge interactions. These errors (due to undersolvation of neutral histidines and overstabilization of salt bridges) are consistent with the previously reported pKa's based on the CHARMM c22/CMAP force field, albeit in larger magnitudes. The pKa calculations also demonstrated that ff19sb with OPC water is significantly more accurate than ff14sb with TIP3P water, and the salt-bridge related pKa downshifts can be partially alleviated by the atom-pair specific Lennard-Jones corrections (NBFIX). Together, these data suggest that the accuracies of the protonation equilibria of proteins from constant pH simulations can significantly benefit from improvements of force fields.

Localized Transformation of 2D Perovskite by Protonated Metformin for Efficient Carbon‐Based Perovskite Photovoltaic and Photo‐Charging Applications

AbstractDimensional engineering is promising for achieving a high power conversion efficiency (PCE) and long‐term stability of perovskite solar cells (PSCs). However, insulated organic spacers in 2D perovskites often severely hinder carrier transport between the internal layers of devices. Herein, the “protonation‐induced localized transformation of 2D perovskites” is proposed to overcome the low carrier transport and conductivity of 2D/3D perovskite heterojunctions. Metformin, with its multiple amine groups and a substantial difference between its pKa value and perovskites, is protonated in an acidic environment or directly converted into the hydrochloride salt for the surface passivation of methylammonium lead iodide. This leads to the transformation of disorderedly oriented layered 2D perovskite into vertically oriented ones at grain boundaries. Consequently, the PCE of a carbon‐based PSC treated by protonated metformin increased considerably, reaching an optimal level of 14.13%. Additionally, applying this passivation strategy to a planar device (ITO/4PADCP/perovskite/PCBM/BCP/Ag) increased PCE from 20.82% to 22.09%, confirming the applicability of the strategy. To demonstrate the practical stability, an integrated PSC–supercapacitor device is assembled, which shows good cycling stability. This article introduces a novel method to improve carrier transport in 2D/3D perovskite heterojunctions, promoting the extensive utilization of dimensional engineering.

PH-Dependent Assembly and Stability of Toll-Like Receptor 3/dsRNA Signaling Complex: Insights from Constant pH Molecular Dynamics and Metadynamics Simulations.

The pH-dependent assembly of Toll-like receptors (TLRs), which triggers a threshold-like response, is a key principle in immune signaling. While crystallography has revealed the intricate structure of these assembly complexes, the mechanisms underlying their pH dependency remain unclear. Herein, constant pH simulations and metadynamics are employed to investigate the pH-dependent assembly and stability of the TLR3/dsRNA signaling complex. The findings demonstrate that system pH regulates complex assembly and stability by modulating the protonation and charge states of histidines. Histidines in TLR3 act as pH-dependent, positively charged binding sites that capture negatively charged dsRNA. Additionally, these histidines form a [H682⁺]-[E626⁻] dipole, facilitating the assembly of two TLR3 molecules into an antisymmetric dimer through dipole-dipole interactions. Surprisingly, TLR3 can shift the pKa values of key histidines from their model pKa of 6.5, increasing protonation likelihood and enhancing ligand binding. Notably, the aromatic residue Phe84, located within the dsRNA binding site [His39⁺-His60⁺-Phe84-His108⁺], alters the pKa of His60 through cation-π interactions with its protonated state. This study offers new insights into the molecular mechanisms underlying pH-dependent immune signaling via higher-order assemblies and suggests potential applications for histidine in self-assembling biomaterials.

Enhanced and Efficient Predictions of Dynamic Ionization through Constant-pH Adiabatic Free Energy Dynamics.

Dynamic or structurally induced ionization is a critical aspect of many physical, chemical, and biological processes. Molecular dynamics (MD) based simulation approaches, specifically constant pH MD methods, have been developed to simulate ionization states of molecules or proteins under experimentally or physiologically relevant conditions. While such approaches are now widely utilized to predict ionization sites of macromolecules or to study physical or biological phenomena, they are often computationally expensive and require long simulation times to converge. In this article, using the principles of adiabatic free energy dynamics, we introduce an efficient technique for performing constant pH MD simulations within the framework of the adiabatic free energy dynamics (AFED) approach. We call the new approach pH-AFED. We show that pH-AFED provides highly accurate predictions of protein residue pKa values, with a MUE of 0.5 pKa units when coupled with driven adiabatic free energy dynamics (d-AFED), while reducing the required simulation times by more than an order of magnitude. In addition, pH-AFED can be easily integrated into most constant pH MD codes or implementations and flexibly adapted to work in conjunction with enhanced sampling algorithms that target collective variables. We demonstrate that our approaches, with both pH-AFED standalone as well as pH-AFED combined with collective variable based enhanced sampling, provide promising predictive accuracy, with a MUE of 0.6 and 0.5 pKa units respectively, on a diverse range of proteins and enzymes, ranging up to 186 residues and 21 titratable sites. Lastly, we demonstrate how this approach can be utilized to understand the in vivo performance engineered antibodies for immunotherapy.

Tunable Activated Esters Enable Lysine-Selective Protein Labeling and Profiling.

Lysine residues on protein surfaces are abundant and often found in enzyme active sites, making them critical targets for studying undruggable proteins. However, the varied microenvironment surrounding lysine residues results in a wide range of pKa values, complicating site-specific covalent binding. In this study, we address the challenges posed by the diverse reactivity of amino side chains by modulating the amide reaction activity of heteroaromatic activated esters. By fine-tuning the type, position, and number of heteroatoms, we successfully rationalized the regulation of their amide reaction activity, leading to the design of probes for selective lysine labeling within the proteome for profiling purposes. Systematic optimization of these esters' reactivity and selectivity has yielded a series of effective probes suitable for both in vitro and cellular applications. These findings significantly enhance our understanding of protein functions and mechanisms, facilitated by the precise identification and analysis of protein labeling and profiling.

Basicity of MnIII-Hydroxo Complexes Controls the Thermodynamics of Proton-Coupled Electron Transfer Reactions.

Several manganese-dependent enzymes utilize MnIII-hydroxo units in concerted proton-electron transfer (CPET) reactions. We recently demonstrated that hydrogen bonding to the hydroxo ligand in the synthetic [MnIII(OH)(PaPy2N)]+ complex increased rates of CPET reactions compared to the [MnIII(OH)(PaPy2Q)]+ complex that lacks a hydrogen bond. In this work, we determine the effect of hydrogen bonding on the basicity of the hydroxo ligand and evaluate the corresponding effect on CPET reactions. Both [MnIII(OH)(PaPy2Q)]+ and [MnIII(OH)(PaPy2N)]+ react with strong acids to yield MnIII-aqua complexes [MnIII(OH2)(PaPy2Q)]2+ and [MnIII(OH2)(PaPy2N)]2+, for which we determined pKa values of 7.6 and 13.1, respectively. Reactions of the MnIII-aqua complexes with one-electron reductants yielded estimates of reduction potentials, which were combined with pKa values to give O-H bond dissociation free energies (BDFEs) of 77 and 85 kcal mol-1 for the MnII-aqua complexes [MnII(OH2)(PaPy2Q)]+ and [MnII(OH2)(PaPy2N)]+. Using these BDFEs, we performed an analysis of the thermodynamic driving force for phenol oxidation by these complexes and observed the unexpected result that slower rates are associated with more asynchronous CPET. In addition, reactions of acidic phenols with the MnIII-hydroxo complexes show rates that deviate from the thermodynamic trends, consistent with a change in mechanism from CPET to proton transfer.

Marketable and Banned Pesticides in Agriculture: Categorization, Simulation, and Crystallography Review

Pesticides are playing a dominant role in modern cultivation practices to increase agricultural production but are also criticized for environmental depletion and soil and underground water degradation in field applications. An imperative need for greener pesticides has emerged in alignment with new innovations in agrarian and agricultural practices. This study provides a comprehensive review of marketable and banned pesticides that have been applied in past times or are still in use in agriculture. The collected literature production disclosed 35 distinct pesticides that were identified either isolated or in mixtures and residues. These pesticides are primarily applied in agricultural fields, but some of them were also criticized for human implications. Then, these 35 pesticides were grouped into four categories: insecticides (18), herbicides (9), fungicides (6), and acaricides (2). Furthermore, their molecular types, chemical structures, pKa or log Kow values were presented. Based on their chemical structure, the pesticides were also organized into two domains: “marketable simulated” and “banned simulated”, representing 43% and 57% of total pesticides, respectively. The simulations were generated by linking the elemental composition of each pesticide in the corresponding category; therefore, three “marketable simulated” (the acaricides were not marketable representative) and four “banned simulated” were demonstrated. In addition, the calculation of “adjustment factors” (−0.33 up to +0.50) and the “as calculated/marketable (or banned) simulated pesticides” ratios (0.946 up to 1.013) enabled the identification of four clusters of homogeneous characteristics: cluster 1: “Insecticides, Fungicides, marketable”, cluster 2: “Herbicides, marketable”, cluster 3: “Insecticides, Fungicides, banned”, and cluster 4: “Acaricides, Herbicides, banned”. Subsequently, the composition of the elements of C and H enabled the crystallography characterization of only the “marketable” pesticides, not those that are “banned”, with compounds that have been already registered in the “Crystallography Open Database”. Conclusively, implications, challenges, and future research recommendations have been proposed.

Cyclometalated Iridium(III) Complex with Substituted Benzimidazole: pH Directed Organelle-Specific Localization Within Lysosome.

We report the synthesis and pH dependent emission spectral behaviour of four emissive iridium(III) complexes (Ir1-Ir4) with two isomeric pairs of bis-trifluoromethyl appended benzimidazole ligands. The imidazolyl hydrogen(N-H) has been replaced by phenyl groups (N-Ph) in two ligands to understand the impact of hydrogen bonding on the photophysical properties of the complexes and it indeed plays interesting role in the charge-transfer dynamics. The pH dependent electronic spectral change is observed for two of the complexes. The enhancement of emission intensity is observed at different wavelength for pH<7 and pH>7 for Ir1 and Ir3. The emission sensing of biogenic amines with pka values ranging from 5.80-9.74 is reported along with cellular imaging. The complex Ir1 specifically localizes within lysosome (pH=4.5-5) and thus image this organelle with great precision. The detail electronic spectra and electrochemical behaviour were reported here along with TDDFT results.

Effect of organic acid additives on sulfite oxidation in a calcium-based slurry

The forced oxidation of sulfite ions was conducted to obtain high-quality gypsum in the flue gas desulfurization system. The effects of formic, lactic, acrylic, acetic, propionic, and hexanoic acids added to calcium-based slurry on sulfite oxidation were investigated in this study. Sulfite oxidation was inhibited when the pKa value of organic acids was small or the carbon chain was long. In the identical slurry pH 6, the SO4 2- fractions of slurries with formic and lactic acids, which have the smallest pKa values, were lower than half that of the additive-free slurry. The addition of hexanoic acid with the longest carbon chain showed a similar SO4 2- fraction to that of additive-free slurry. These results indicate that the inhibitory effect on sulfite oxidation is more expressed by the acidity of organic acids. The SO4 2- fraction in the slurry affects the growth and quality of gypsum crystals. The slurry with acetic acid presented the highest SO4 2- fraction and resulted in the formation of high-quality gypsum crystals. The findings of this study can contribute to the selection of organic acid additives with high desulfurization efficiency and the production of high-quality gypsum.

Determination of pKa of triazolo[5,1-c][1,2,4]triazines in non-aqueous media by potentiometric titration

In this work, for the first time, an approach was suggested for determining the pKa of triazolo[5,1-c][1,2,4]triazine compounds in N,N-dimethylformamide using potentiometric titration. It was noted that change in system potential in the titration curves of triazolo[5,1-с][1,2,4]triazine are observed for compounds containing either H+ located at the nitrogen atom in position 1 or an –NH2 group. The calculated pKa values of the studied molecules correspond to the pKa values of moderately strong acids and are in the range of 2–8. The relationship was established between the acidity of the heterocyclic fragment and the presence of electron donor substituents. The obtained pKa values of the compounds correlate with the calculated possible deprotonation centers of the molecule. It was found that determining the acidity constants of substances is useful for clarifying the mechanisms of their transformations. The possibility of establishing a relationship between the structure of the compound, pKa, and probable biological activity was shown.

What Is the Protonation State of Proteins in Crystals? Insights from Constant pH Molecular Dynamics Simulations.

X-ray crystallography is an important technique to determine the positions of atoms in a protein crystal. However, because the native environment in which proteins function, is not a crystal, but a solution, it is not a priori clear if the crystal structure represents the functional form of the protein. Because the protein structure and function often depend critically on the pH, the question arises whether proton affinities are affected by crystallization. X-ray diffraction usually does not reveal protons, which makes it difficult to experimentally measure pKa shifts in crystals. Here, we investigate whether this challenge can be addressed by performing in silico titration with constant pH molecular dynamics (MD) simulations. We compare the computed pKa values of proteins between solution and crystal environment and analyze these differences in the context of molecular interactions. For the proteins considered in this work, pKa shifts were mostly found for residues at the crystal interfaces, where the environment is more apolar in the crystal than in water. Although convergence was an obstacle, our simulations suggest that in principle it is possible to apply constant pH MD to protein crystals routinely and assess the effect of crystallization on protein function more systematically than with standard MD simulations. We also highlight technical challenges that need to be addressed to make MD simulations of crystals more reliable.

Circumventing Kinetic Barriers to Metal Hydride Formation with Metal-Ligand Cooperativity.

We report the two-electron, one-proton mechanism of cobalt hydride formation for the conversion of [CoIIICp(PPh2NBn2)(CH3CN)]2+ to [HCoIIICp(PPh2NBn2)]+. This complex catalytically converts CO2 to formate under CO2 reduction conditions, with hydride formation as a key elementary step. Through a combination of electrochemical measurements, digital simulations, theoretical calculations, and additional mechanistic and thermochemical studies, we outline the explicit role of the PPh2NBn2 ligand in the proton-coupled electron transfer (PCET) reactivity that leads to hydride formation. We reveal three unique PCET mechanisms, and we show that the amine on the PPh2NBn2 ligand serves as a kinetically accessible protonation site en route to the thermodynamically favored cobalt hydride. Cyclic voltammograms recorded with proton sources that span a wide range of pKa values show four distinct regimes where the mechanism changes as a function of acid strength, acid concentration, and timescale between electrochemical steps. Peak shift analysis was used to determine proton transfer rate constants where applicable. This work highlights the astute choices that must be made when designing catalytic systems, including the basicity and kinetic accessibility of protonation sites, acid strength, acid concentration, and timescale between electron transfer steps, to maximize catalyst stability and efficiency.

Tricyanomethane or Dicyanoketenimine-Silylation makes the Difference.

Pseudohalides such as tricyanomethanide, [C(CN)3]-, are well known in chemistry, biochemistry and industrial chemistry. The protonated species HC(CN)3, a classic hydrogen pseudohalide Brønsted acid, is a very strong acid with a pKa value of -5. However, HC(CN)3 is difficult to handle as it tends to decompose rapidly or, more precisely, to oligo- and polymerize. Therefore, silylated pseudohalide compounds with the [Me3Si]+ as the "big organometallic proton" have become interesting, exhibiting similar chemical properties but better kinetic protection. Here, the stepwise silylation of the pseudohalide anion [C(CN)3]- is reported, forming the heavier homologue of HC(CN)3, namely [Me3Si][C(CN)3], and in presence of two additional [Me3Si]+ cations even the dicationic species [(Me3Si-NC)3C]2+ as stable [B(C6F5)4]- salt. Surprisingly, in contrast to the protonated species HC(CN)3, in which the proton is bound to the central carbon atom of [C(CN)3]-, silylation of the [C(CN)3]- anion occurs at one of the three terminal nitrogen atoms, thus forming the long-sought dicyanoketenimine [Me3Si-NC-C(CN)2]. All further silylation steps take place exclusively on the terminal N atoms of the three CN groups and not on the central carbon atom, until the intriguing, highly symmetrical dication, [(Me3Si-NC)3C]2+, is finally generated. The experimental data are supported by quantum chemical calculations in terms of thermodynamics and chemical bonding.

A Novel Method for Combination of Ionic Conductivity and pH-metry Methods for the Determination of the Aqueous Solubility of a New Diisopropylammonium Hydrogenmaleate Crystalline Molecule

Dissociation constant, solubility, and thermodynamic data are very important physicochemical parameters for biological substances and their knowledge is of fundamental importance for the validation of drugs. In addition to their low cost and accessibility, Conductometric and pH-metric methods seem to be particularly suitable for the determination of these parameters given the often weak acidic or basic nature of drugs. These parameters were determined for a new synthesized diisopropylammonium hydrogenmaleate (iPr2NH2-MA) crystalline molecule. Conductometric and pH-metric methods were used for this characterization. The pH-metric method lead to pKa1 = 3.6, pKa2 = 6.7 and pKa3 = 7.5, while the conductometric method made it possible to determine two pKa values which are pKa1 = 3.5 and pKa3 = 7.8. The values of the thermodynamic parameters calculated for the enthalpy change (∆rH0) and the entropy change (∆S) of the iPr2NH2-MA acidic dissociation reaction are of the order of ∆H = 25. 36 ± 0.06 kJ.mol-1 and ∆S = 6.08 ± 0.18 kJ.mol-1.K-1. In addition, the Gibbs free energy change (ΔG) of the molecule decreased as a function of temperature. The solubility varied between 1 and 84 mg mL-1 for pH values comprised between 3.5 and 8.5 and reached its maximum Smax = 84 mg mL-1 at pH 5.6. The dissociation process was found to be is non-spontaneous, endothermic and entropically favorable. These results demonstrated on the one hand the reliability and effectiveness of the Conductometric and pH-metric methods for the characterization of molecules with acidic and/or basic sites, and on the other hand the excellent physical and chemical properties of diisopropylammonium hydrogenmaleate (iPr2NH2-MA) crystalline molecule.