Chiral Carborane Acids Decorated with Binol-Based Phosphonates: Synthesis, Characterization, and Application.

The syntheses of hexabrominated closo-carborates decorated with different chiral Binol-derived phosphonates and their conjugate acids are described. X-ray diffraction analysis reveals a polymeric structure for the sodium salt with the anionic units connected by [B-Br-Na-O═P]+ linkages. For the acid, coordination of the proton to the phosphonate's P═O oxygen atom is assumed. The pKa value was estimated by combining experiments and computations. Application of these Brønsted acids as chiral catalysts in an imino-ene and a Mukaiyama-Mannich reaction was moderately successful.

Improved pH measurement of mobile phases in reversed-phase liquid chromatography.

Mobile phase pH is a critically important parameter in reversed-phase liquid chromatographic (RPLC) separations involving analytes that display acidic or basic properties in the pH range used for the mobile phase. The main problem in measuring mobile phase pH lies in the fact that RPLC mobile phases are typically aqueous-organic mixtures. In addition to experimental difficulties, the pH values refer to different aqueous-organic compositions that cannot be correctly compared. Given this situation, the unified pH (wabspH, also termed as ) based on the absolute chemical potential of the solvated proton has been proposed as a rigorous way of characterising mobile phase acidity that is fully inter-comparable between mobile phases of any composition. Here we report the wabspH values of 78 reversed-phase liquid chromatography-mass spectrometry mobile phases that were carefully measured by potential differences in a symmetric cell with two glass electrode half-cells and almost ideal ionic liquid triethylamylammonium bis((trifluoromethyl)sulfonyl)imide [N2225][NTf2] salt bridge with multiple overlapping measurements. The system of altogether 300 ΔwabspH values was anchored to the pH value of standard pH 7.00 aqueous buffer solution. The consistency standard deviation of the whole set of measurements was 0.09 pH units. In addition to the differential potentiometric reference method, simpler measurement methods that use double junction reference or double junction combined electrodes were tested and were found suitable for routine laboratories if high accuracy is not required.

Rigorous pH measurement in non-aqueous solution: measurement method and reference values in ethanol.

The recently introduced unified pH ([Formula: see text]) concept enables rigorous pH measurements in non-aqueous and mixed media while at the same time maintaining comparability to the conventional aqueous pH scale. However, its practical application is hindered by a shortage of reference [Formula: see text] values. In order to improve this situation, the European Metrology Research Project (EMPIR) UnipHied ("Realisation of a UnipHied pH scale") launched an interlaboratory comparison among highly experienced electrochemistry expert laboratories to assign the first such reference [Formula: see text] values by adopting an extensive statistical treatment of the reported measurement data: to phosphate buffer in water-ethanol mixture (50 wt% of ethanol) and ammonium formate buffer in pure ethanol. Two different measurement setups - one capable of being easily adopted in industrial applications - have been used to demonstrate the robustness of [Formula: see text] measurement. This is an important step towards wider adoption of the [Formula: see text] concept in practice, like liquid chromatography, biofuels analysis and electrocatalysis.

The Unified Redox Scale for All Solvents: Consistency and Gibbs Transfer Energies of Electrolytes from their Constituent Single Ions.

We have devised the unified redox scale Eabs H2O , which is valid for all solvents. The necessary single ion Gibbs transfer energy between two different solvents, which only can be determined with extra-thermodynamic assumptions so far, must clearly satisfy two essential conditions: First, the sum of the independent cation and anion values must give the Gibbs transfer energy of the salt they form. The latter is an observable and measurable without extra-thermodynamic assumptions. Second, the values must be consistent for different solvent combinations. With this work, potentiometric measurements on silver ions and on chloride ions show that both conditions are fulfilled using a salt bridge filled with the ionic liquid [N2225 ][NTf2 ]: if compared to the values resulting from known pKL values, the silver and chloride single ion magnitudes combine within a uncertainty of 1.5 kJ mol-1 to the directly measurable transfer magnitudes of the salt AgCl from water to the solvents acetonitrile, propylene carbonate, dimethylformamide, ethanol, and methanol. The resulting values are used to further develop the consistent unified redox potential scale Eabs H2O that now allows to assess and compare redox potentials in and over six different solvents. We elaborate on its implications.

Multifunctional Organocatalysts - Singly-Linked and Macrocyclic Bisphosphoric Acids for Asymmetric Phase-Transfer and Brønsted-Acid Catalysis.

The linking of phosphoric acids via covalent or mechanical bonds has proven to be a successful strategy for the design of novel organocatalysts. Here, we present the first systematic investigation of singly-linked and macrocyclic bisphosphoric acids, including their synthesis and their application in phase-transfer and Brønsted acid catalysis. We found that the novel bisphosphoric acids show dramatically increased enantioselectivities in comparison to their monophosphoric acid analogues. However, the nature, length and number of linkers has a profound influence on the enantioselectivities. In the asymmetric dearomative fluorination via phase-transfer catalysis, bisphosphoric acids with a single, rigid bisalkyne-linker give the best results with moderate to good enantiomeric excesses. In contrast, bisphosphoric acids with flexible linkers give excellent enantioselectivities in the transfer-hydrogenation of quinolines via cooperative Brønsted acid catalysis. In the latter case, sufficiently long linkers are needed for high stereoselectivities, as found experimentally and supported by DFT calculations.

Ionization and lipophilicity in nonpolar media mimicking the cell membrane interior.

Ionization and lipophilicity may vary with the environment. Therefore, in this study we provide some insight in the performances of different experimental techniques (potentiometry, UV-vis, shake-flask and chromatography) to determine ionization and lipophilicity in more nonpolar systems than those commonly used in drug discovery. To this purpose a pool of 11 compounds of pharmaceutical interest was firstly submitted to a few experimental techniques to measure pKa in water, water/acetonitrile mixtures and pure acetonitrile. Then we measured logP/logD with shake-flask and potentiometry in octanol/water and toluene/water and also determined a chromatographic lipophilicity index (log k'80 PLRP-S) in a nonpolar system. Results show that ionization decreases for both acids and bases in a coherent, significant but not dramatical extent when water is present in the system, but the picture is completely different in pure acetonitrile. Lipophilicity may vary or not with the environment according to the chemical structure of the investigated compounds as also revealed by electrostatic potential maps. Since the internal core of cell membranes is largely nonpolar, our results support the need of extending the pool of physicochemical descriptors to be determined in the various stages of drug discovery programs and indicate some experimental strategies for their determination.

Theoretical Study on Fluorinated Derivatives of Sulfolane, Cyclopentanone, and Gamma-Butyrolactone.

In this paper, fluorinated compounds based on sulfolane, cyclopentanone, and gamma-butyrolactone are studied computationally, focusing on their applicability in electrochemical devices and acid-base-related studies. Candidates for solvents with (1) high polarity, (2) good electrochemical stability, and (3) low basicity were searched for. Some of the compounds are studied here for the first time. Electrochemical stabilities, dielectric constants, boiling points, basicities, and lipophilicities were estimated using DFT and COSMO-RS methods with empirical corrections. The effect of fluorination on these properties as well as the bond parameters was studied. The possible synthesis routes of the proposed compounds are outlined. Some molecules display a combination of estimated properties favorable for a solvent, although none of the studied compounds are expected to surpass acetonitrile and propylene carbonate by the width of the electrochemical stability window.

Quantifying Acidity in Heterogeneous Systems: Biphasic pKa Values.

Acidities of lipophilic compounds, such as various ligands or catalysts, in systems consisting of an aqueous phase at equilibrium with a water-immiscible phase (lipid bilayers, phase transfer catalysis, sensor membranes, to name just few) are typically approximated by the aqueous pKa values. Our research shows that such approximations can lead to seriously biased estimations of the acidities as the bulk of solvated H+ ions reside in the aqueous phase, while the lipophilic species─both neutral acid and anion─predominantly reside in the organic phase. Therefore, the use of aqueous pKa in such situations is not justified. In this work, we provide a more accurate description of the acidities of acids in such systems by applying the biphasic pKa concept. Biphasic pKa values (pKaow values) of 35 acids of various structures and chemical properties were determined in a 1-octanol:water system. We provide detailed descriptions of the UV-vis and NMR measurement methods. The directly obtained (apparent) pKaow values depend on concentration. Concentration-independent values were obtained by extrapolating the apparent values to zero concentration using a Debye-Hückel model.

Design of Novel Uncharged Organic Superbases: Merging Basicity and Functionality.

ConspectusOne of the constant challenges of synthetic chemistry is the molecular design and synthesis of nonionic, metal-free superbases as chemically stable neutral organic compounds of moderate molecular weight, intrinsically high thermodynamic basicity, adaptable kinetic basicity, and weak or tunable nucleophilicity at their nitrogen, phosphorus, or carbon basicity centers. Such superbases can catalyze numerous reactions, ranging from C-C bond formation to cycloadditions and polymerization, to name just a few. Additional benefits of organic superbases, as opposed to their inorganic counterparts, are their solubility in organic reaction media, mild reaction conditions, and higher selectivity. Approaching such superbasic compounds remains a continuous challenge. However, recent advances in synthetic methodology and theoretical understanding have resulted in new design principles and synthetic strategies toward superbases. Our computational contributions have demonstrated that the gas-phase basicity region of 350 kcal mol-1 and even beyond is easily reachable by organosuperbases. However, despite record-high basicities, the physical limitations of many of these compounds become quickly evident. The typically large molecular weight of these molecules and their sensitivity to ordinary reaction conditions prevent them from being practical, even though their preparation is often not too difficult. Thus, obviously structural limitations with respect to molecular weight and structural complexity must be imposed on the design of new synthetically useful organic superbases, but strategies for increasing their basicity remain important.The contemporary design of novel organic superbases is illustrated by phosphazenyl phosphanes displaying gas-phase basicities (GB) above 300 kcal mol-1 but having molecular weights well below 1000 g·mol-1. This approach is based on a reconsideration of phosphorus(III) compounds, which goes along with increasing their stability in solution. Another example is the preparation of carbodiphosphoranes incorporating pyrrolidine, tetramethylguanidine, or hexamethylphosphazene as a substituent. With gas-phase proton affinities of up to 300 kcal mol-1, they are among the top nonionic carbon bases on the basicity scale. Remarkably, the high basicity of these compounds is achieved at molecular weights of around 600 g·mol-1. Another approach to achieving high basicity through the cooperative effect of multiple intramolecular hydrogen bonding, which increases the stabilization of conjugate acids, has recently been confirmed.This Account focuses on our efforts to produce superbasic molecules that embody many desirable traits, but other groups' approaches will also be discussed. We reveal the crucial structural features of superbases and place them on known basicity scales. We discuss the emerging potential and current limits of their application and give a general outlook into the future.

A Chemically Fuelled Molecular Automaton Displaying Programmed Migration of Zn2+ Between Alternative Binding Sites.

A molecular system comprising a cationic zinc complex and an amino acid-derived ambident ligand having phosphate and carboxylate binding sites undergoes a series of rearrangements in which the metal cation migrates autonomously from one site to another. The location of the metal is identified by the circular dichroism spectrum of a ligated bis(2-quinolylmethyl)-(2-pyridylmethyl)amine (BQPA) chromophore, which takes a characteristic shape at each binding site. Migration is fuelled by the decomposition of trichloroacetic acid to CO2 and CHCl3 , which progressively neutralises the acidity of the system as a function of time, revealing in sequence binding sites of increasing basicity. The migration rate responds to control by variation of the temperature, water content and triethylamine concentration, while an excess of fuel controls the duration of an induction period before the migration event.

Electrochemistry and Reactivity of Chelation-stabilized Hypervalent Bromine(III) Compounds.

Hypervalent bromine(III) reagents possess a higher electrophilicity and a stronger oxidizing power compared to their iodine(III) counterparts. Despite the superior reactivity, bromine(III) reagents have a reputation of hard-to-control and difficult-to-synthesize compounds. This is partly due to their low stability, and partly because their synthesis typically relies on the use of the toxic and highly reactive BrF3 as a precursor. Recently, we proposed chelation-stabilized hypervalent bromine(III) compounds as a possible solution to both problems. First, they can be conveniently prepared by electro-oxidation of the corresponding bromoarenes. Second, the chelation endows bromine(III) species with increased stability while retaining sufficient reactivity, comparable to that of iodine(III) counterparts. Finally, their intrinsic reactivity can be unlocked in the presence of acids. Herein, an in-depth mechanistic study of both the electrochemical generation and the reactivity of the bromine(III) compounds is disclosed, with implications for known applications and future developments in the field.

Measurements and Utilization of Consistent Gibbs Energies of Transfer of Single Ions: Towards a Unified Redox Potential Scale for All Solvents.

Utilizing the "ideal" ionic liquid salt bridge to measure Gibbs energies of transfer of silver ions between the solvents water, acetonitrile, propylene carbonate and dimethylformamide results in a consistent data set with a precision of 0.6 kJ mol-1 over 87 measurements in 10 half-cells. This forms the basis for a coherent experimental thermodynamic framework of ion solvation chemistry. In addition, we define the solvent independent pe abs H 2 O - and the E abs H 2 O values that account for the electronating potential of any redox system similar to the pH abs H 2 O value of a medium that accounts for its protonating potential. This E abs H 2 O scale is thermodynamically well-defined enabling a straightforward comparison of the redox potentials (reducities) of all media with respect to the aqueous redox potential scale, hence unifying all conventional solvents' redox potential scales. Thus, using the Gibbs energy of transfer of the silver ion published herein, one can convert and unify all hitherto published redox potentials measured, for example, against ferrocene, to the E abs H 2 O scale.

Novel Lipophilic Fluorophores with Highly Acidity-Dependent Two-Photon Response.

Lipophilic fluorophores are widely implemented in nonlinear microscopy; however, few existing membrane-specific probes combine the high brightness of two-photon excited fluorescence (2PEF) with pH sensitivity. Herein we describe four novel two-photon excited fluorophores, based on a coumarin 151 core structure, where lipophilicity is induced by a covalently attached phosphazene moiety. Changing the environmental acidity using trifluoromethanesulfonic (triflic) acid leads to profound changes in the linear fluorescence and 2PEF characteristics, due to chromophores' switching between neutral- and protonated forms. We characterize this dependence by measuring the two-photon absorption (2PA) spectra over the region λ2PA =550-1000 nm, observing 2PA cross sections of σ2PA =10-20 GM, with an associated 2PEF brightness of 10-13 GM, in neutral solutions of both acetonitrile and n-octanol. Although quantum chemical modelling and NMR measurements show that, at high chromophore concentrations, protonation may be accompanied by a dimerization process, these dimers likely do not form at the lower concentrations used in optical spectroscopy.

One Hundred Carboxylate Receptors.

This work presents a compilation of binding constant (logKass) values in DMSO-d6/H2O (0.5% m/m) for a variety of receptors with 12 carboxylate anions (formate, acetate, lactate, pivalate, sorbate, hexanoate, benzoate, glyphosate, glucuronate, ibuprofen, naproxen, and ketoprofen). A total of 489 logKass values are listed for 100 anion receptor molecules. Most logKass values originate from previously published articles, along with some values for previously unpublished receptor molecules, spanning a workflow of 8 years. The purpose of this study is to serve as a comprehensive information source for selecting suitable receptor candidates to be used in practical carboxylate sensing applications, such as constructing ion-selective electrodes (ISE-s). To support such decision making, all receptors are presented together with lipophilicity (logPo/w) data.

Macrocyclic versus open-chain carbazole receptors for carboxylate binding.

The anion recognition properties of six synthetic acyclic and macrocyclic carbazole-based receptors have been studied by 1H-NMR as well as with COSMO-RS calculations towards acetate, benzoate, lactate, sorbate and formate. The receptors differed by the number and geometry of hydrogen-bond donor (HBD) sites, the nature and length of the linker(s) between the HBD sites and the cyclic or non-cyclic nature. The binding ability of the receptors is strongly influenced by the structure and steric variables of the receptors and anions. It was found that when urea was replaced with the flexible diglycolyl as the connecting linker between carbazole subunits, the carboxylate binding affinity of the receptor decreased significantly. The effects of the receptors' structure on anion binding have been investigated and several intriguing cases have been identified and analysed. The current findings shed light on carboxylate anion binding and contribute to the systematic synthesis of receptors with beneficial functional selectivity for carboxylate anions.

On-off-on Control of Molecular Inversion Symmetry via Multi-stage Protonation: Elucidating Vibronic Laporte Rule.

The Laporte rule dictates that one- and two-photon absorption spectra of inversion-symmetric molecules should display alternatively forbidden electronic transitions; however, for organic fluorophores, drawing clear distinction between the symmetric- and non-inversion symmetric two-photon spectra is often obscured due to prevalent vibronic interactions. We take advantage of consecutive single- and double-protonation to break and then reconstitute inversion symmetry in a nominally symmetric diketopyrrolopyrrole, causing large changes in two-photon absorption. By performing detailed one- and two-photon titration experiments, with supporting quantum-chemical model calculations, we explain how certain low-frequency vibrational modes may lead to apparent deviations from the strict Laporte rule. As a result, the system may be indeed considered as an on-off-on inversion symmetry switch, opening new avenues for two-photon sensing applications.

Bis(4-benzhydryl-benzoxazol-2-yl)methane - from a Bulky NacNac Alternative to a Trianion in Alkali Metal Complexes.

A novel sterically demanding bis(4-benzhydryl-benzoxazol-2-yl)methane ligand 6 (4-BzhH2 BoxCH2 ) was gained in a straightforward six-step synthesis. Starting from this ligand monomeric [M(4-BzhH2 BoxCH)] (M=Na (7), K (81 )) and dimeric [{M(4-BzhH2 BoxCH)}2 ] (M=K (82 ), Rb (9), Cs (10)) alkali metal complexes were synthesised by deprotonation. Abstraction of the potassium ion of 8 by reaction with 18-crown-6 resulted in the solvent separated ion pair [{(THF)2 K@(18-crown-6)}{bis(4-benzhydryl-benzoxazol-2-yl)methanide}] (11), including the energetically favoured monoanionic (E,E)-(4-BzhH2 BoxCH) ligand. Further reaction of 4-BzhH2 BoxCH2 with three equivalents KH and two equivalents 18-crown-6 yielded polymeric [{(THF)2 K@(18-crown-6)}{K@(18-crown-6)K(4-Bzh BoxCH)}]n (n→∞) (12) containing a trianionic ligand. The neutral ligand and herein reported alkali complexes were characterised by single X-ray analyses identifying the latter as a promising precursor for low-valent main group complexes.

Acid-Base and Anion Binding Properties of Tetrafluorinated 1,3-Benzodiazole, 1,2,3-Benzotriazole and 2,1,3-Benzoselenadiazole.

The influence of fluorination on the acid-base properties and the capacity of structurally related 6-5 bicyclic compounds - 1,3-benzodiazole 1, 1,2,3-benzotriazole 2 and 2,1,3-benzoselenadiazole 3 to σ-hole interactions, i. e. hydrogen (1 and 2) and chalcogen (3) bondings, is studied experimentally and computationally. The tetrafluorination increases the Brønsted acidity of the diazole and triazole scaffolds and the Lewis acidity of selenadiazole scaffold decreases the basicity. Increased Brønsted acidity facilitates anion binding via the formation of hydrogen bonds; particularly, tetrafluorinated derivative of 1 (compound 4) binds Cl- . Increased Lewis acidity of tetrafluorinated derivative of 3 (compound 10), however, is not enough for binding with Cl- and F- via chalcogen bonds in contrast to previously studied Te analog of 10. It is suggested that the maximum positive values of molecular electrostatic potential at the σ-holes, VS,max , can be a reasonable metric for design and synthesis of new anion receptors with selenadiazole-diazole/triazole hybrids as a special target. Related chlorinated compounds are also discussed.

Quantitative electrospray ionization efficiency scale: 10 years after.

RATIONALE: The first comprehensive quantitative scale of the efficiency of electrospray ionization (ESI) in the positive mode by monoprotonation, containing 62 compounds, was published in 2010. Several trends were found between the compound structure and ionization efficiency (IE) but, possibly because of the limited diversity of the compounds, some questions remained. This work undertakes to align the new data with the originally published IE scale and carry out statistical analysis of the resulting more extensive and diverse data set to derive more grounded relationships and offer a possibility of predicting logIE values. METHODS: Recently, several new IE studies with numerous compounds have been conducted. In several of them, more detailed investigations of the influence of compound structure, solvent properties, or instrument settings have been conducted. IE data from these studies and results from this work were combined, and the multilinear regression method was applied to relate IE to various compound parameters. RESULTS: The most comprehensive IE scale available, containing 334 compounds of highly diverse chemical nature and spanning 6 orders of magnitude of IE, has been compiled. Several useful trends were revealed. CONCLUSIONS: The ESI ionization efficiency of a compound by protonation is mainly affected by three factors: basicity (expressed by pKaH in water), molecular size (expressed by molar volume or surface area), and hydrophobicity of the ion (expressed by charge delocalization in the ion or its partition coefficient between a water-acetonitrile mixture and hexane). The presented models can be used for tentative prediction of logIE of new compounds (under the used conditions) from parameters that can be computed using commercially available software. The root mean square error of prediction is in the range of 0.7-0.8 log units.

Quantitative mineralogical analysis of clay-containing materials using ATR-FT-IR spectroscopy with PLS method.

A universal method for quantitative analysis of clay components, in terms of mineral composition, using ATR-FT-IR spectroscopy (in the mid-IR and far-IR regions) combined with partial least squares (PLS) regression technique (ATR-FT-IR-PLS) is reported. For the PLS method development, altogether 222 samples covering natural clay sources and various archaeological/cultural heritage artefacts were used as calibration and validation standards. This is the largest calibration set used for creating an ATR-FT-IR-PLS method for clay minerals. The quantitative compositions of these standards containing combinations of altogether 29 minerals for the PLS method were determined using XRD analysis. The developed ATR-FT-IR with PLS method is quick and easy to use, and enables analysis of very small sample amounts (down to a few mg). This is very important when working with samples from archaeological and cultural heritage objects. The developed ATR-FT-IR-PLS method enables quantifying the contents of 7 main classes of minerals in different clays with a root mean square error of prediction (RMSEP) ranging from 0.9 to 5.1 g/100g. This means that in some cases, depending also on the content of the mineral in the sample, the accuracy is at a semiquantitative level. This quantitative method was successfully applied to 11 cultural heritage case-study samples.