Addressing the Opioids Lipophilicity Challenge via a Straightforward and Simultaneous H NMR-Based log/ Determination, Both Separately and in Mixtures.

A systematic study of trends in the lipophilicity of prominent representatives of the opioid family, including natural, semisynthetic, synthetic, and endogenous neuropeptide opioids, is described. This was enabled by a straightforward H NMR-based log/ determination method developed for compounds holding at least one aromatic hydrogen atom. Moreover, the new method enables a direct simultaneous log determination of opioid mixtures, overcoming the high sensitivity of this family to the measurement conditions, which is critical when a determination of the exact Δlog values of matched pairs is required.

Species-specific lipophilicities of fluorinated diketones in complex equilibria systems and their potential as multifaceted reversible covalent warheads.

Combined molecular, physicochemical and chemical properties of electrophilic warheads can be applied to create covalent drugs with diverse facets. Here we study these properties in fluorinated diketones (FDKs) and their multicomponent equilibrium systems in the presence of protic nucleophiles, revealing the potential of the CF(CO) group to act as a multifaceted warhead for reversible covalent drugs. The equilibria compositions of various FDKs in water/octanol contain up to nine species.

Placing CF in the Center: Major Physicochemical Changes Upon a Minor Structural Alteration in Gem-Difunctional Compounds.

Fluorine atoms play an important role in all branches of chemistry and accordingly, it is very important to study their unique and varied effects systematically, in particular, the structure-physicochemical properties relationship. The present study describes exceptional physicochemical effects resulting from a H/F exchange at the methylene bridge of gem-difunctional compounds. The Δlog P values, that is, the change in lipophilicity, observed for the CH /CF replacement in various α,α-phenoxy- and thiophenoxy-esters/amides, diketones, benzodioxoles and more, fall in the range of 0.

Studying Lipophilicity Trends of Phosphorus Compounds by P-NMR Spectroscopy: A Powerful Tool for the Design of P-Containing Drugs.

Systematically studying the lipophilicity of phosphorus compounds is of great importance for many chemical and biological fields and particularly for medicinal chemistry. Here, we report on the study of trends in the lipophilicity of a wide set of phosphorus compounds relevant to drug design including phosphates, thiophosphates, phosphonates, thiophosphonates, bis-phosphonates, and phosphine chalcogenides. This was enabled by the development of a straightforward log determination method for phosphorus compounds based on P-NMR spectroscopy.

Structure dependent stability and antioxidant capacity of strawberry polyphenols in the presence of canola protein.

Polyphenol stability in processed food affects sensorial and health-promoting properties. Thus, understanding the effects of various food components on polyphenols degradation, as a function of their chemical structure, can contribute to optimal product engineering. The current study focuses on the impact of polyphenol structure on polyphenol-protein interactions in correlation with their stability and total antioxidant capacity (TAC) during shelf-life.

Modulation of the H-Bond Basicity of Functional Groups by α-Fluorine-Containing Functions and its Implications for Lipophilicity and Bioisosterism.

Modulation of the H-bond basicity (p) of various functional groups (FGs) by attaching fluorine functions and its impact on lipophilicity and bioisosterism considerations are described. In general, H/F replacement at the α-position to H-bond acceptors leads to a decrease of the p value, resulting, in many cases, in a dramatic increase in the compounds' lipophilicity (log ). In the case of α-CFH, we found that these properties may also be affected by intramolecular H-bonds between CFH and the FG.

Solar and Visible Light Assisted Peptide Coupling.

Amino acid and peptide couplings are widely used in fields related to pharma and materials. Still, current peptide synthesis continues to rely on the use of expensive, water sensitive, and waste-generating coupling reagents, which are often prepared in multi-step sequences and used in excess. Herein is described a peptide coupling reaction design that relies mechanistically on sun-light activation of a 4-dimethylamino-pyridine-alkyl halide charge-transfer complex to generate a novel coupling reagent in situ.

Impact-induced gelation in aqueous methylcellulose solutions.

Aqueous methylcellulose is an "abnormal" inverse-freezing fluid, which gelates when heated. We ventured to stimulate this phase-transition by mechanical impact, whose resulting shockwaves and local heat could be uptaken by the endothermic gelation. High-speed photography was used to observe this transition in microsecond timescales.

Proposed Proton-Transfer Mechanism for the Initial Decomposition Steps of BTATz.

The first steps in the gas-phase decomposition mechanism of N3,N6-bis (1 H-tetrazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine, BTATz, anions and the kinetic isotope effects in these processes were studied using combined multistage mass spectrometry (MS/MS) and computational techniques. Two major fragmentation processes, the exergonic loss of nitrogen molecules and the endergonic loss of hydrazoic acid, were identified. The observation of a primary isotope effect supported by calculations suggests that the loss of a nitrogen molecule from the tetrazole ring involves proton migration, either to or within the terazole ring, as a rate-determining step.

Sunlight assisted direct amide formation via a charge-transfer complex.

We report on the use of charge-transfer complexes between amines and carbon tetrachloride, as a novel way to activate the amine for photochemical reactions. This principle is demonstrated in a mild, transition metal free, visible light assisted, dealkylative amide formation from feedstock carboxylic acids and amines. The low absorption coefficient of the complex allows deep light penetration and thus scale up to a gram scale.

Multifarenes: new modular cavitands.

Multifarenes, a new class of macrocycles, which are constructed of alternating building blocks, are conveniently accessible by three complementary syntheses that provide modularity and scalability. In addition to metal-ion coordination, these cavitands show increased flexibility with increasing ring size, offering opportunities for induced fit to guest molecules.

Chemisorbed monolayers of corannulene penta-thioethers on gold.

Penta(tert-butylthio)corannulene and penta(4-dimethylaminophenylthio)corannulene form highly stable monolayers on gold surfaces, as indicated by X-ray photoelectron spectroscopy (XPS). Formation of these homogeneous monolayers involves multivalent coordination of the five sulfur atoms to gold with the peripheral alkyl or aryl substituents pointing away from the surface. No dissociation of C-S bonds upon binding could be observed at room temperature.

Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12.

Genetic disorders of excessive salt loss from sweat glands have been observed in pseudohypoaldosteronism type I (PHA) and cystic fibrosis that result from mutations in genes encoding epithelial Na+ channel (ENaC) subunits and the transmembrane conductance regulator (CFTR), respectively. We identified a novel autosomal recessive form of isolated salt wasting in sweat, which leads to severe infantile hyponatremic dehydration. Three affected individuals from a small Bedouin clan presented with failure to thrive, hyponatremic dehydration and hyperkalemia with isolated sweat salt wasting.

Switchable cucurbituril-bipyridine beacons.

4-Aminobipyridine derivatives form strong inclusion complexes with cucurbit[6]uril, exhibiting remarkably large enhancements in fluorescence intensity and quantum yields. The remarkable complexation-induced pK(a) shift (DeltapK(a)=3.3) highlights the strong charge-dipole interaction upon binding.