An Improved Method for the Preparation OF 3,5-Difluorosalicylaldehyde and 3,5-Difluorosalicylic Acid #

An improved method for the synthesis of 3,5-difluorosalicylic acid (3b) and 3,5-difluorosalicylaldehyde (3a) is described. 2,4-Difluorophenol (4) undergoes a formylation reaction to afford aldehyde 3a which is oxidized to the desired acid 3b. This method avoids the use of the highly corrosive HF and fluorine gas and requires no special laboratory apparatus.

     

A Convenient Preparation of Carboxylic Acid Anhydrides Using a “Supported” Phosphorus Pentoxide Reagent

Treatment of carboxylic acids with a “supported” phosphorus pentoxide reagent provides a convenient route to the corresponding anhydrides.     

The Effects of Food on Cannabidiol Bioaccessibility

Cannabidiol (CBD) is a hydrophobic non-psychoactive compound with therapeutic characteristics. Animal and human studies have shown its poor oral bioavailability in vivo, and the impact of consuming lipid-soluble CBD with and without food on gut bioaccessibility has not been explored. The purpose of this research was to study the bioaccessibility of CBD after a three-phase upper digestion experiment with and without food, and to test lipase activity with different substrate concentrations. Our results showed that lipase enzyme activity and fatty acid absorption increased in the presence of bile salts, which may also contribute to an increase in CBD bioaccessibility. The food matrix used was a mixture of olive oil and baby food. Overall, the fed-state digestion revealed significantly higher micellarization efficiency for CBD (14.15 ± 0.6% for 10 mg and 22.67 ± 2.1% for 100 mg CBD ingested) than the fasted state digestion of CBD (0.65 ± 0.7% for 10 mg and 0.14 ± 0.1% for 100 mg CBD ingested). The increase in bioaccessibility of CBD with food could be explained by the fact that micelle formation from hydrolyzed lipids aid in bioaccessibility of hydrophobic molecules. In conclusion, the bioaccessibility of CBD depends on the food matrix and the presence of lipase and bile salts.     

Extract from the Marine Seaweed Padina pavonica Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides

The identification of compounds which protect the double-membrane of mitochondrial organelles from disruption by toxic confomers of amyloid proteins may offer a therapeutic strategy to combat human neurodegenerative diseases. Here, we exploited an extract from the marine brown seaweed Padina pavonica (PPE) as a vital source of natural bioactive compounds to protect mitochondrial membranes against insult by oligomeric aggregates of the amyloidogenic proteins amyloid-β (Aβ), α-synuclein (α-syn) and tau, which are currently considered to be major targets for drug discovery in Alzheimer’s disease (AD) and Parkinson’s disease (PD). We show that PPE manifested a significant inhibitory effect against swelling of isolated mitochondria exposed to the amyloid oligomers, and attenuated the release of cytochrome c from the mitochondria. Using cardiolipin-enriched synthetic lipid membranes, we also show that dye leakage from fluorophore-loaded vesicles and formation of channel-like pores in planar bilayer membranes are largely prevented by incubating the oligomeric aggregates with PPE. Lastly, we demonstrate that PPE curtails the ability of Aβ42 and α-syn monomers to self-assemble into larger β-aggregate structures, as well as potently disrupts their respective amyloid fibrils. In conclusion, the mito-protective and anti-aggregator biological activities of Padina pavonica extract may be of therapeutic value in neurodegenerative proteinopathies, such as AD and PD.     

Imaging of Bacterial and Fungal Cells Using Fluorescent Carbon Dots Prepared from <Emphasis Type="Italic">Carica papaya</Emphasis> Juice

In this paper, we have described a simple hydrothermal method for preparation of fluorescent carbon dots (C-dots) using Carica papaya juice as a precursor. The synthesized C-dots show emission peak at 461 nm with a quantum yield of 7.0 %. The biocompatible nature of C-dots was confirmed by a cytotoxicity assay on E. coli. The C-dots were used as fluorescent probes for imaging of bacterial (Bacillus subtilis) and fungal (Aspergillus aculeatus) cells and emitted green and red colors under different excitation wavelengths, which indicates that the C-dots can be used as a promising material for cell imaging.     

Structurally Tunable 3‐Cyanoformazanate Boron Difluoride Dyes

The straightforward synthesis of a series of 3‐cyanoformazanate boron difluoride dyes is reported. Phenyl, 4‐methoxyphenyl and 4‐cyanophenyl N‐substituted derivatives were isolated and characterized by single‐crystal X‐ray crystallography, cyclic voltammetry, and UV/Vis spectroscopy. The compounds were demonstrated to possess tunable, substituent‐dependent absorption, emission, and electrochemical properties, which were rationalized through electronic structure calculations.     

A Bioorthogonal Small‐Molecule‐Switch System for Controlling Protein Function in Live Cells

Chemically induced dimerization (CID) has proven to be a powerful tool for modulating protein interactions. However, the traditional dimerizer rapamycin has limitations in certain in vivo applications because of its slow reversibility and its affinity for endogenous proteins. Described herein is a bioorthogonal system for rapidly reversible CID. A novel dimerizer with synthetic ligand of FKBP′ (SLF′) linked to trimethoprim (TMP). The SLF′ moiety binds to the F36V mutant of FK506‐binding protein (FKBP) and the TMP moiety binds to E. coli dihydrofolate reductase (eDHFR). SLF′‐TMP‐induced heterodimerization of FKBP(F36V) and eDHFR with a dissociation constant of 0.12 μM . Addition of TMP alone was sufficient to rapidly disrupt this heterodimerization. Two examples are presented to demonstrate that this system is an invaluable tool, which can be widely used to rapidly and reversibly control protein function in vivo.