A stepwise mechanism for the mechanochemical synthesis of halogen-bonded cocrystal architectures

A molecular-level mechanism is proposed for two cases of mechanochemical cocrystallization via halogen bonds. The proposed stepwise mechanism is based on the observation and structural characterization of intermediates that appear in early stages of the reaction. The mechanism arises from the competition of strong and weak intermolecular halogen bonds of the N...I and S...I type and involves the initial formation of finite molecular assemblies, held together via N...I bonds that subsequently polymerize into infinite chains by cross-linking through S...I bonds. This mechanism has been observed in the synthesis of linear as well as zigzag halogen-bonded chain architectures.     

Nickel-catalyzed reductive carboxylation of styrenes using CO2

A nickel-catalyzed reductive carboxylation of styrenes using CO2 has been developed. The reaction proceeds under mild conditions using diethylzinc as the reductant. Preliminary data suggests the mechanism involves two discrete nickel-mediated catalytic cycles, the first involving a catalyzed hydrozincation of the alkene followed by a second, slower nickel-catalyzed carboxylation of the in situ formed organozinc reagent. Importantly, the catalyst system is very robust and will fixate CO2 in good yield even if exposed to only an equimolar amount introduced into the headspace above the reaction.     

He I photoelectron spectra and gas-phase electronic structures of end-functionalized [3]- and [5]-ladderanes

[3]- and [5]-ladderanes obtained by way of template-controlled syntheses conducted in the organic solid state have been characterized via He I photoelectron (PE) spectroscopy. The results provide a first correlation with X-ray crystallographic structure data and establish the reliability of quantum chemical DFT (B3LYP/6-31G*) and ab initio HF calculations in predicting geometrical and electronic structures of molecular ladder frameworks.     

Towards the total synthesis of FD-838: modular enantioselective assembly of the core

A rapid assembly of the tetracyclic core of FD-838, featuring a catalytic asymmetric Stetter reaction, is described.     

An inequality for values of Koksma’s functions of two algebraically dependent <Emphasis Type="Italic">p</Emphasis>-adic numbers

We establish a p-adic version of the inequalities linking values of Koksma’s functions of two algebraically dependent transcendental numbers and show that in a very special, but nontrivial case these inequalities become equalities.     

Atom transfer radical addition in the presence of catalytic amounts of copper(I/II) complexes with tris(2-pyridylmethyl)amine

Highly efficient atom transfer radical addition of polyhalogenated compounds to alkenes catalyzed by copper(I/II) complexes with tris(2-pyridylmethyl)amine in the presence of a radical initiator [2,2'-azobis(2-methylpropionitrile)] was reported.     

Separation and investigation of structure-mobility relationship of gonadotropin-releasing hormones by capillary zone electrophoresis in conventional and isoelectric acidic background electrolytes

Capillary zone electrophoresis (CZE) has been applied to qualitative and quantitative analysis, separation and physicochemical characterization of synthetic gonadotropin-releasing hormones (GnRHs) and their analogs and fragments. Structurally related peptides were separated in conventional and isoelectric acidic background electrolytes (BGEs), pH 2.18-2.50. Best separation was achieved in isoelectric BGE composed of 200 mM iminodiacetic acid, pH 2.32. The effective electrophoretic mobilities, m(ep), of GnRHs in five BGEs were determined and four semiempirical models correlating effective mobility with charge, q, and relative molecular mass, M(r), (m(ep) versus q/M(r)(k), where k is related to the molecular shape) were tested to describe the migration behavior of GnRHs in CZE. None of the models was found to be quite definitively applicable for the whole set of 10 GnRHs differing in size (tetrapeptide-decapeptide) and positive charge (0.91-3.00 elementary charges). Nevertheless, for the dependence of m(ep) on q/M(r)(k), the highest coefficient of correlation, R=0.995-0.999, was obtained for k close to the value 0.5 in all five acidic BGEs. This indicates that the most probable structure of GnRHs in these BGEs can be predicted as a random coil.     

In Vitro Confirmation of Siramesine as a Novel Antifungal Agent with In Silico Lead Proposals of Structurally Related Antifungals

The limited number of medicinal products available to treat of fungal infections makes control of fungal pathogens problematic, especially since the number of fungal resistance incidents increases. Given the high costs and slow development of new antifungal treatment options, repurposing of already known compounds is one of the proposed strategies. The objective of this study was to perform in vitro experimental tests of already identified lead compounds in our previous in silico drug repurposing study, which had been conducted on the known Drugbank database using a seven-step procedure which includes machine learning and molecular docking. This study identifies siramesine as a novel antifungal agent. This novel indication was confirmed through in vitro testing using several yeast species and one mold. The results showed susceptibility of Candida species to siramesine with MIC at concentration 12.5 µg/mL, whereas other candidates had no antifungal activity. Siramesine was also effective against in vitro biofilm formation and already formed biofilm was reduced following 24 h treatment with a MBEC range of 50–62.5 µg/mL. Siramesine is involved in modulation of ergosterol biosynthesis in vitro, which indicates it is a potential target for its antifungal activity. This implicates the possibility of siramesine repurposing, especially since there are already published data about nontoxicity. Following our in vitro results, we provide additional in depth in silico analysis of siramesine and compounds structurally similar to siramesine, providing an extended lead set for further preclinical and clinical investigation, which is needed to clearly define molecular targets and to elucidate its in vivo effectiveness as well.     

Rhodium(III)‐Catalyzed Allylic C(sp3)–H Activation of Alkenyl Sulfonamides: Unexpected Formation of Azabicycles

Unsaturated N‐sulfonamides undergo a Rh^III‐ catalyzed allylic C(sp³)? H activation followed by insertion with an exogenous internal alkyne. The reaction generates [3.3.0], [4.3.0], and [5.3.0] azabicyclic structures with excellent diastereoselectivity. Deuterium labeling experiments implicate a 1,3‐Rh shift as a key step in the mechanism.     

Novel criteria for fast searching for optimal method in gradient ion chromatography: an integrated approach

In this article, an integrated approach for prediction and optimization in ion chromatography (IC) was presented. The approach provides a fast and reliable insight in the elution behavior of an IC system. The predictions are based on a mathematical model that predicts ion retentions (for both isocratic and gradient modes) by using an empirical isocratic model. Other chromatographic values significant for the optimal elution conditions (resolution, peak asymmetry) are calculated quickly and easily from the predicted retention values of characteristic points of a chromatographic peak. Every day, IC users might find this approach a suitable tool for finding optimal IC elution conditions in a given system.