Development of a synthetic route towards N4,N9-disubstituted 4,9-diaminoacridines: On the way to multi-stage antimalarials

A multi-step synthetic route towards N⁴,N⁹-disubstituted 4,9-diaminoacridines that, to the best of our knowledge, has no precedence in the literature, has been developed. The target structures are likely to reveal interesting biological activities in the near future, not only due to their mepacrine-like core, but also because they embed simultaneously the pharmacophores of chloroquine and primaquine, antimalarial drugs that act at different stages of malaria infection.     

Styrene‐N‐phenylacrylamide co‐polymer modified silica monolith particles with an optimized mixing ratio of monomers as a new stationary phase for the separation of peptides in high performance liquid chromatography

A stationary phase was prepared by chemical derivatization of the support particles with a layer of copolymer composed of styrene and N‐phenyl acrylamide. Silica monolith particles of ca. 2.6 µm (volume‐based average) have been prepared as the support particles by sol‐gel reaction followed by differential sedimentation. The particles were reacted with 3‐chloropropyl trimethoxysilane followed by sodium diethyldithiocarbamate to introduce an initiator moiety. Then, the copolymer layer was immobilized via reversible addition‐fragmentation transfer polymerization. The resultant phase was packed in glass‐lined stainless‐steel micro‐columns (1 x 150 mm) and evaluated for the separation of a mixture composed of five peptides (Trp‐Gly, Thr‐Tyr‐Ser, angiotensin I, isotocin and bradykinin). The effect of monomer mixing ratio (styrene versus N‐phenyl acrylamide) on the chromatographic separation efficiency of the stationary phase was examined. A number of theoretical plates (N) as high as 33 600 plates/column (224 000 plates/m, 4.46 µm plate height) was achieved using the column packed with the optimized stationary phase. The column‐to‐column reproducibility based on three columns packed with three different batches of stationary phase was found satisfactory in separation efficiency, retention factor, and asymmetry factor.     

An optimized mixed‐mode stationary phase based on silica monolith particles for the separation of peptides and proteins in high‐performance liquid chromatography

A phase with both hydrophobic and hydrophilic functionalities has been synthesized by modification of ground silica monolith particles with C18 and 1‐[3‐(trimethoxysilyl)propyl] urea ligands. A series of phases was prepared by changing the ratio of the two ligands to determine the optimal ratio in view of separation efficiency. The resultant optimized stationary phase was packed in narrow‐bore glass‐lined stainless‐steel columns (1 × 300 mm and 2.1 × 100 mm) and used for the separation of synthetic peptides and proteins. The average numbers of theoretical plates (N) of 52 100/column (174 000/m, 5.75 µm plate height) and 35 500/column (118 000/m, 8.47 µm plate height) were achieved with the 300 mm column at a flow rate of 25 µL/min (0.86 mm/s) in 60:40 v/v acetonitrile/30 mM aqueous ammonium formate for the mixture of peptides (Thr‐Tyr‐Ser, Val‐Ala‐Pro‐Gly, angiotensin I, isotocin, and bradykinin) and for the mixture of proteins (myoglobin, human serum albumin, and insulin), respectively. Fast analysis of the peptides and proteins was also carried out at a flow rate of 0.9 mL/min (6.88 mm/s) with the 100 mm column and all the analytes were eluted within 2 min with good separation efficiency.     

Comparative Study of Alkali-Cation-Based (Li+, Na+, K+) Electrolytes in Acetonitrile and Alkylcarbonates

The development of a suitable functional electrolyte is urgently required for fast-charging and high-voltage alkali-ion (Li, Na, K) batteries as well as next-generation hybrids supercapacitors. Many recent works focused on an optimal selection of electrolytes for alkali-ion based systems and their electrochemical performance but the understanding of the fundamental aspect that explains their different behaviour is rare. Herein, we report a comparative study of transport properties for LiPF₆, NaPF₆, KPF₆ in acetonitrile (AN) and a binary mixture of ethylene carbonate (EC), dimethyl carbonate (DMC): (EC/DMC : 1/1, weigh) through conductivities, densities and viscosities measurements in wide temperature domain. By application of the Stokes-Einstein, Nernst-Einstein, and Jones Dole equations, the effective ionic solvated radius of cation (r_eff), the ionic dissociation coefficient (α_D) and structuring Jones Dole's parameters (A, B) for salt are calculated and discussed according to solvent or cation nature as a function of temperature. From the results, we demonstrate that better mobility of potassium can be explained by the nature of the ion-ion and ion-solvent interactions due to its polarizability. In the same time, the predominance of triple ions in the case of K⁺, is a disadvantage at high concentration.     

Bioconjugation with Maleimides: A Useful Tool for Chemical Biology

Maleimide chemistry stands out in the bioconjugation toolbox by virtue of its synthetic accessibility, excellent reactivity, and practicability. The second-generation of clinically approved antibody–drug conjugates (ADC) and much of the current ADC pipeline in clinical trials contain the maleimide linkage. However, thiosuccinimide linkages are now known to be less robust than once thought, and ergo, are correlated with suboptimal pharmacodynamics, pharmacokinetics, and safety profiles in some ADC constructs. Rational design of novel generations of maleimides and maleimide-type reagents have been reported to address the shortcomings of classical maleimides, allowing for the formation of robust bioconjugate linkages. This review highlights the main strategies for rational reagent design that have allowed irreversible bioconjugations in cysteines, reversible labelling strategies and disulfide re-bridging.     

The speciation of vanadium in human serum

A knowledge of the speciation of vanadium in human serum is essential for an understanding of the biotransformation of antidiabetic vanadium complexes in human blood and of how vanadium is transported to the target cells. Such information may be acquired by two completely different approaches: separation techniques and modeling calculations. This review focuses on the latter.The two major metal ion binders in human serum are apotransferrin (apoTf) and human serum albumin (HSA), the interactions of which with V^IVO and V^V are discussed in detail. A partially new model for HSA–V^IVO interactions is introduced, in which the two binding sites (one for two and one for one metal ion) compete not only with each other, but also with hydrolysis of the metal ion.Focus is also placed on the possibility and importance of ternary complex formation between V^IVO, serum proteins and drug candidate ligands (maltol (mal), 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone (dhp), acetylacetone (acac) and picolinic acid, (pic)): the structures and formation constants of different ternary complexes reported by the different research groups are critically reviewed.The serum speciations for V^IVO and V^V are calculated through use of the most recent stability constants; at biologically relevant concentrations (～1 μM, but definitely <10 μM) the apoTf complexes predominate for both metal ions. This has the consequences that the primary role of the drug candidate ligands of the original complexes is a carrier function until the vanadium is taken up into the serum, and the vanadium ion itself is the active metabolite responsible for the antidiabetic effect.     

Corrigendum to “Absolute configurations of griseorhodins A and C” [Tetrahedron Lett. 58 (50) (2017) 4721–4723]

The known antibiotic and cytotoxic compounds griseorhodin A (1) and griseorhodin C (2) were produced in solid culture by Streptomyces puniceus AB10, which was isolated from the leaf-cutter ant Acromyrmex rugosus rugosus. Their absolute configurations were unambiguously established as 6S,6aS,7S,8S and 6R,6aS,7S,8R, respectively, using vibrational circular dichroism (VCD) and density functional theory (DFT) calculations.     

Copper corrosion in buffered and non-buffered synthetic seawater: a comparative study

The electrochemical behaviour of copper in neutral buffered and non-buffered synthetic seawater and in pure chloride solutions has been studied by cyclic voltammetry, weight loss measurements, open circuit potential and scanning electron microscopy (SEM). Values of the repassivation potentials of Cu in non-buffered and buffered synthetic seawater, at 50 mV s^–1, were 0.12 and 0.46 V vs. SCE, respectively. The sharpness, heights and location of the different peaks as well as their charges were shown to be influenced by the composition of the solution, buffering conditions, deoxygenation, polarization potential and time. High chloride concentrations lead to higher oxidation charges. The anodic and the cathodic charges were shown to increase as the chloride concentration increases. The open circuit potential transients of copper in non-deoxygenated, non-buffered synthetic seawater indicate pitting from the beginning of the exposure, while in buffered solutions the pitting appeared only after a quite long exposure period, i.e. after 40 days. Corrosion rates of Cu samples after 3 months of immersion were higher in solutions of pure chloride (0.5 M) than in synthetic seawater. After six months the differences were even more noticeable. SEM images have showed a somewhat higher density of pits on copper samples immersed in the chloride solution (0.5 M), in comparison with those in synthetic seawater.