Experimental basicities of some of the strongest superbases ever measured (phosphonium ylides) are reported, and by employing these compounds, the experimental self-consistent basicity scale of superbases in THF, reaching a pKα (estimate of pKa) of 35 and spanning more than 30 pKa units, has been compiled. Basicities of 47 compounds (around half of which are newly synthesized) are included. The solution basicity of the well-known t-Bu-N═P4(dma)9 phosphazene superbase is now rigorously linked to the scale. The compiled scale is a useful tool for further basicity studies in THF as well as in other solvents, in particular, in acetonitrile. A good correlation between basicities in THF and acetonitrile spanning 25 orders of magnitude gives access to experimentally supported very high (pKa > 40) basicities in acetonitrile, which cannot be directly measured. Analysis of structure-basicity trends is presented.

An NMR-based relative binding affinity measurement method has been developed in which differences in the binding affinities of different hosts toward a particular guest (ΔlogK(ass) values) are measured in the same solution. As an advancement, the method allows the simultaneous determination of several ΔlogK(ass) values in a single run. As a proof of principle, the method was used to measure binding affinity differences of a number of indolocarbazole- and urea-based synthetic receptors toward acetate ion in DMSO-d6/H2O (99.5%:0.5% m/m). As a result, a binding affinity scale containing 33 receptors and spanning 2.32 log units with excellent self-consistency (consistency standard deviation = 0.01 log unit) was created. Together with the very good agreement of the results with those obtained by UV-vis spectrophotometry, this demonstrates the high accuracy of the method and the fact that the NMR and UV-vis techniques can be used interchangeably (in spite of the very different concentrations used in these techniques). Additionally, it was found for symmetrical receptor molecules from the same compound family that there is a correlation between the acetate binding affinity of a receptor and the (15)N chemical shift of the nitrogen atoms of its binding centers.

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.

Comprehensive analysis of high‐resolution mass spectra of aged natural dammar resin obtained with Fourier transform ion cyclotron resonance mass spectrometer (FT‐ICR‐MS) using matrix‐assisted laser desorption/ionization (MALDI) and atmospheric pressure chemical ionization (APCI) is presented. Dammar resin is one of the most important components of painting varnishes. Dammar resin is a terpenoid resin (dominated by triterpenoids) with intrinsically very complex composition. This complexity further increases with aging. Ten different solvents and two‐component solvent mixtures were tested for sample preparation. The most suitable solvent mixtures for the MALDI‐FT‐ICR‐MS analysis were dichloromethane‐acetone and dichloromethane‐ethanol. The obtained MALDI‐FTMS mass spectrum contains nine clusters of peaks in the m/z range of 420–2200, and the obtained APCI‐FTMS mass spectrum contains three clusters of peaks in the m/z range of 380–910. The peaks in the clusters correspond to the oxygenated derivatives of terpenoids differing by the number of C15H24 units. The clusters, in turn, are composed of subclusters differing by the number of oxygen atoms in the molecules. Thorough analysis and identification of the components (or groups of components) by their accurate m/z ratios was carried out, and molecular formulas (elemental compositions) of all major peaks in the MALDI‐FTMS and APCI‐FTMS spectra were identified (and groups of possible isomeric compounds were proposed). In the MALDI‐FTMS and APCI‐FTMS mass spectrum, besides the oxidized C30, triterpenoids also peaks corresponding to C29 and C31 derivatives of triterpenoids (demethylated and methylated, correspondingly) were detected. MALDI and APCI are complementary ionization sources for the analysis of natural dammar resin. In the MALDI source, preferably polar (extensively oxidized) components of the resin are ionized (mostly as Na+ adducts), whereas in the APCI source, preferably nonpolar (hydrocarbon and slightly oxidized) compounds are ionized (by protonation). Either of the two ionization methods, when used alone, gives an incomplete picture of the dammar resin composition. Copyright © 2012 John Wiley & Sons, Ltd.

Cancer cells express high levels of CK2, and its inhibition leads to apoptosis. CK2 has therefore emerged as a new drug target for cancer therapy. A biligand inhibitor ARC-772 was constructed by conjugating 4-(2-amino-1,3-thiazol-5-yl)benzoic acid and a carboxylate-rich peptoid. ARC-772 was found to bind CK2 with a K value of 0.3 nm and showed remarkable CK2 inhibitory selectivity in a panel of 140 protein kinases (Gini coefficient: 0.75 at c=100 nm). ARC-775, the acetoxymethyl ester prodrug of ARC-772, was efficiently taken up by cells. Once internalized, the inhibitor is activated by cellular esterase activity. In HeLa cancer cells ARC-775 was found to activate caspase-3 (an apoptosis marker) at sub-micromolar concentrations (EC =0.3 μm), a 20-fold lower extracellular concentration than CX-4945, the only CK2 inhibitor under clinical trials. At micromolar concentrations, ARC-775 was also found to inhibit ADP-induced aggregation of human platelets. The overall results of this study demonstrate that oligo-anionic biligand inhibitors have good potential for drug development.