Extendable stapling of unprotected peptides by crosslinking two amines with o-phthalaldehyde

Peptide modification methods that do not rely on the cysteine residue are underdeveloped, and their development could greatly expand the current toolbox for peptide chemistry. During the course of preliminary investigations into the classical ortho-phthalaldehyde (OPA)-amine-thiol condensation reaction, we found that in the absence of thiol, OPA readily condenses with two primary alkyl amines to form a class of underexplored isoindolin-1-imine compounds under mild aqueous conditions. From the intramolecular version of this OPA-2amines reaction, an efficient and selective methodology using mild reaction conditions has been developed for stapling unprotected peptides via crosslinking of two amino groups in both an end-to-side and side-to-side fashion. The stapling method is superfast and broadly applicable for various peptide substrates with the reacting amino groups separated by a wide range of different amino acid units. The macrocyclization reactions of selected substrates are completed within 10 seconds at 5 mM concentration and within 2 minutes at 50 μM concentration. Importantly, the resulting cyclized peptides with an isoindolinimine linkage can be extended in a one-pot sequential addition manner with several different electron-deficient π electrophiles, thereby generating more complex structures.

Stationary Phases for Green Liquid Chromatography

Industrial research, including pharmaceutical research, is increasingly using liquid chromatography techniques. This involves the production of large quantities of hazardous and toxic organic waste. Therefore, it is essential at this point to focus interest on solutions proposed by so-called “green chemistry”. One such solution is the search for new methods or the use of new materials that will reduce waste. One of the most promising ideas is to perform chromatographic separation using pure water, without organic solvents, as a mobile phase. Such an approach requires novel stationary phases or specific chromatographic conditions, such as an elevated separation temperature. The following review paper aims to gather information on stationary phases used for separation under purely aqueous conditions at various temperatures.

Lewis Acid-Assisted Reduction of Nitrite to Nitric and Nitrous Oxide via the Elusive Nitrite Radical Dianion

Reduction of nitrite anions [NO2]- takes place in a myriad of environments such as in the soil as part of the biogeochemical nitrogen cycle as well as in acidified nuclear waste. Nitrite reduction typically takes place within the coordination sphere of a redox active transition metal. Lewis acid coordination, however, can dramatically modify the reduction potential of this polyoxoanion to allow for reduction under non-aqueous conditions (-0.74 V vs. NHE). This strategy enables the isolation of a borane-capped nitrite dianion [NO2]2- along with its spectroscopic study consistent with reduction to the N(II) oxidation state. Protonation of the nitrite dianion results in facile loss of nitric oxide (NO) while reaction of the nitrite dianion with nitric oxide results in disproportionation to nitrous oxide (N2O) and nitrite, connecting three redox levels in the global nitrogen cycle.

Visible-light-mediated Regioselective Synthesis of Novel Thiazolo[3,2-b][1,2,4]triazoles: Advantageous Synthetic Application of Aqueous Conditions

From a green chemistry perspective, sustainable irradiations as the power source and water as solvent have certainly grabbed the attention of chemists in recent times as these efforts reduce hazardous...

Hypophosphite Addition to Alkenes Under Solvent-Free and Non-Acidic Aqueous Conditions

Hypophosphite adds to alkenes in high yields under solvent-free conditions at elevated temperature, including ,-unsaturated carboxylates. The reaction proceeds by a radical mediated pathway. Hypophosphite addition is also effective under...

An Extensive Review on Chitosan as Versatile Material for Pharmaceutical and Biomedical Application

Chitosan is a polysaccharide and is derived from chitin. Chitosan every now and then referred to as a soluble chitin. chitosan is strongly basic polysaccharide. chitosan shows physiochemical and biological properties. This review presents the common source for chitosan manufacturing that is crabs and shrimp. According to researchers it is just a fat inhibitor. some of the application of chitosan in pharmaceutics/drug delivery and in biomedical field are also highlighted. Chitosan act as a diluent, as mucoadhesive excipient, as permeation enhancer, in vaccines delivery, as parenteral delivery, chitosan as food additive, cosmetics industry. chitosan also has a number of medicinal benefits. Chitosan is employed in a variety of applications because it is soluble in acidic aqueous conditions (food, cosmetics, biomedical and pharmaceutical applications). We give a quick overview of the chemical modifications of chitosan, a field in which a number of syntheses have been proposed but not yet realised on a large scale. This review focuses on current articles on these materials' high-value-added applications in medicine and cosmetics.

Formation of supramolecular nanostructures via in situ self-assembly and post-assembly modification of a biocatalytically constructed dipeptide hydrazide

The in situ self-assembly of a biocatalytically constructed dipeptide hydrazide gives rise to supramolecular hydrogels, consisting of networks of supramolecular nanoarchitectures, under mild aqueous conditions. Moreover, the post-assembly modification via hydrazone bond formation enables the decoration of the prefabricated supramolecular architectures.

Simple Ion–Gas Mixtures as a Source of Key Molecules Relevant to Prebiotic Chemistry

Very simple chemistry can result in the rapid and high-yield production of key prebiotic inorganic molecules. The two reactions investigated here involve such simple systems, (a) carbon disulfide (CS2) and acetate (CH3COO¯) and (b) sulfur dioxide (SO2) and formate (HCOO¯). They have been carried out under non-aqueous conditions, either in an organic solvent or with a powdered salt exposed to the requisite gas. Under such dry conditions the first reaction generated the thioacetate anion [CH3COS]¯ while the second produced the radical [SO2·]¯anion. Anhydrous conditions are not rare and may have arisen on the early earth at sites where an interface between different phases (liquid/gas or solid/gas) could be generated. This is one way to rationalize the formation of molecules and ions (such as we have produced) necessary in the prebiotic world. Interpretation of our results provides insight into scenarios consistent with the more prominent theories of abiogenesis.

Kinetic Study on the Reactivity of Azanone (HNO) toward Cyclic C-Nucleophiles

Azanone (HNO) is an elusive electrophilic reactive nitrogen species of growing pharmacological and biological significance. Here, we present a comparative kinetic study of HNO reactivity toward selected cyclic C-nucleophiles under aqueous conditions at pH 7.4. We applied the competition kinetics method, which is based on the use of a fluorescein-derived boronate probe FlBA and two parallel HNO reactions: with the studied scavenger or with O2 (k = 1.8 × 104 M−1s−1). We determined the second-order rate constants of HNO reactions with 13 structurally diverse C-nucleophiles (k = 33–20,000 M−1s−1). The results show that the reactivity of HNO toward C-nucleophiles depends strongly on the structure of the scavenger. The data are supported with quantum mechanical calculations. A comprehensive discussion of the HNO reaction with C-nucleophiles is provided.