1H NMR Elucidation of Observed Stable Sugar-NaCl-water Complexes in Aqueous Solution

The solvation of sugars in aqueous media matters in the understanding of biological systems and carbohydrate transformations. Generally, 2 – 4 water units were proposed to interact with each hydroxyl group in monosaccharides via different types of hydrogen bondings at room temperature in previous studies. Presence of NaCl was known to perturb hydrogen bondings of sugar hydrates. However, direct evidence to elucidate mechanism at atom level is very rare even though “NaCl Effect” was well known in biomass chemical transformations. Here we report 1H NMR elucidation evidences of mono/disaccharides hydrates in different concentration of NaCl aqueous solutions. We here conclude two new findings: 1) under ideal usage of NaCl, different mono/disaccharides hydrates are likely to be converted into a stable sugar-NaCl-water form; 2) pKa value of different hydroxyls in mono/disaccharides has intangible influence on hydrate form change induced by NaCl. An ideal NaCl usage based on maximum of 1H NMR shift was proposed.

Molecular chaperone ability to inhibit amyloid-derived neurotoxicity, but not amorphous protein aggregation, depends on a conserved pH-sensitive Asp residue

Proteins can self-assemble into amyloid fibrils or amorphous aggregates and thereby cause disease. Molecular chaperones can prevent both these types of protein aggregation, but the respective mechanisms are not fully understood. The BRICHOS domain constitutes a disease-associated small heat shock protein-like chaperone family, with activities against both amyloid toxicity and amorphous protein aggregation. Here, we show that the activity of two BRICHOS domain families against Alzheimer’s disease associated amyloid-β neurotoxicity to mouse hippocampi in vitro depends on a conserved aspartate residue, while the ability to suppress amorphous protein aggregation is unchanged by Asp to Asn mutations. The conserved Asp in its ionized state promotes structural flexibility of the BRICHOS domain and has a pKa value between pH 6.0–7.0, suggesting that chaperone effects against amyloid toxicity can be affected by physiological pH variations. Finally, the Asp is evolutionarily highly conserved in >3000 analysed BRICHOS domains but is replaced by Asn in some BRICHOS families and animal species, indicating independent evolution of molecular chaperone activities against amyloid fibril formation and non-fibrillar amorphous protein aggregation.

pKa Determination of Carvedilol by Spectrophotometry

Proper knowledge of the pKa value of a compound is of uttermost importance for understanding the behavior of a drug inside the body. The pKa value of Nonselective alpha-1 and beta-blocker Carvedilol shows controversies in literature, whereas values between 7.7 and 8.7 have been previously reported. In this research paper, the pKa value of Carvedilol was re-evaluated using UV-vis spectroscopy. The analytical wavelength used was 241nm. The obtained sigmoid pattern was non-linear fitted using the Boltzmann sigmoidal algorithm. The determined pKa was 7.77 ± 0.09. This value is in accordance with some of the literature publications. Since extensive statistics and multiple replicate experiments were performed, it is assumed that 7.8 is the true pKa value of Carvedilol.

Recent Advance on Benzofuranones: Synthesis and Transformation via C-H Functionalization

Benzofuranone is a sort of important skeleton in many fields, such as natural products, pharmaceuticals, building blocks, antioxidants and dyes. Their efficient synthesis and transformations have attracted great attentions in organic synthesis. They can be synthesized by Friedel−Crafts reaction, intramolecular dehydration ring-closing reaction and transition-metal-catalyzed reaction, etc. And their direct utilization to prepare other functional molecules enhances their further application. Due to their low pKa value and easy enolization ability, the transformation of benzofuranones via C(3)-H bond functionalization is a hot issue in the last ten years. Herein, we highlight the advances on the synthesis of benzofuranones and its transformation via C-H functionalization. Some of other transformations related to benzofuranones are also referred in this review.

Protonation and electrostatic interactions based fluorescence probes for selective detection of picric acid (2,4,6-trinitrophenol)-An explosive material

The picric acid due to its low pKa value possesses distinct physico-chemical features among all other nitro aromatic derivatives to design fluorescent probes for its’ sensitive and selective detection.The...

Determination of pKa and Degradation Products of the Mutated BRAF Inhibitor Vemurafenib and UPLC Assay in Human Urine

In this study, the pKa value of vemurafenib was determined by the dependence of the retention factor on the pH of the mobile phase. The change of pKa in the different acetonitrile fraction ranging between 57.5 and 62.5% (v/v) was studied by using an LC-UV method. Additionally, a simple, reliable, and rapid UPLC method has been developed for the determination of vemurafenib in human urine. Efavirenz was used as an internal standart. For vemurafenib and efavirenz, selectivity factors were found as 1.204. The asymmetry and capacity factors were obtained as 1.100 and 7.532 for vemurafenib. Vemurafenib was exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were detected by LC/MS/MS method.