Marina E. Trusova

Unusually Stable, Versatile, and Pure Arenediazonium Tosylates: Their Preparation, Structures, and Synthetic Applicability

A new, simple, and effective method for the diazotization of a wide range of arylamines has been developed by using a polymer-supported diazotization agent in the presence of p-toluenesulfonic acid. Various pure arenediazonium tosylates with unusual stabilities can be easily prepared by this method. As a result, these salts are useful and versatile substrates for subsequent transformations, such as halogenation and Heck-type reactions. The unusual stabilities of arenediazonium tosylates are also preliminarily discussed with their X-ray structures.

Matsuda–Heck reaction with arenediazonium tosylates in water

Summary An environmentally friendly Matsuda–Heck reaction with arenediazonium tosylates has been developed for the first time. A range of alkenes was arylated in good to quantitative yields in water. The reaction is significantly accelerated when carried out under microwave heating. The arylation of haloalkylacrylates with diazonium salts has been implemented for the first time.

Organic-inorganic hybrid nanoparticles controlled delivery system for anticancer drugs

The use of organic-inorganic hybrid nanocarriers for controlled release of anticancer drugs has been gained a great interest, in particular, to improve the selectivity and efficacy of the drugs. In this study, iron oxide nanoparticles were prepared then surface modified via diazonium chemistry and coated with chitosan, and its derivative chitosan-grafted polylactic acid. The purpose was to increase the stability of the nanoparticles in physiological solution, heighten drug-loading capacity, prolong the release, reduce the initial burst effect and improve in vitro cytotoxicity of the model drug doxorubicin. The materials were characterized by DLS, ζ-potential, SEM, TGA, magnetization curves and release kinetics studies. Results confirmed the spherical shape, the presence of the coat and the advantages of using chitosan, particularly its amphiphilic derivative, as a coating agent, thereby surpassing the qualities of simple iron oxide nanoparticles. The coated nanoparticles exhibited great stability and high encapsulation efficiency for doxorubicin, at over 500μg per mg of carrier. Moreover, the intensity of the initial burst was clearly diminished after coating, hence represents an advantage of using the hybrid system over simple iron oxide nanoparticles. Cytotoxicity studies demonstrate the increase in cytotoxicity of doxorubicin when loaded in nanoparticles, indirectly proving the role played by the carrier and its surface properties in cell uptake.

Aryldiazonium tosylates as new efficient agents for covalent grafting of aromatic groups on carbon coatings of metal nanoparticles

The possibility of the spontaneous covalent modification of the surface of metal nanoparticles coated by carbon by aryldiazonium tosylates was demonstrated for the first time.

Iron-core/carbon-shell nanoparticles with intrinsic peroxidase activity: new platform for mimetic glucose detection

Artificial enzymatic mimics based on nanoparticles have become a powerful tool for the improvement of analytical performance in the detection of important bioactive compounds. For the first time the intrinsic peroxidase-like activity of Fe-core/carbon shell nanoparticles (Fe@C NPs) was studied. The catalytic process was described by a typical Michaelis–Menten curve for enzyme kinetics, and the results were comparable with those previously published. The high catalytic performance of the Fe@C NPs allows the development of a new simple procedure for glucose determination with a low detection limit of 0.21 μM. To our knowledge, this is the first study showing the ability to generate active oxygen species on the Fe@C surfaces. We suppose that our investigation will open up a new direction in medicinal applications using these promising materials.

Regioselective Zn(OAc)2-catalyzed azide–alkyne cycloaddition in water: the green click-chemistry

A new method of azide–alkyne cycloaddition (AAC) in the presence of Zn(OAc)2 as an inexpensive and environmentally friendly catalyst in neat water has been developed. The proposed methodology has been applied for the synthesis of 1,4-disubstituted-1,2,3-triazoles from terminal alkynes and 1,4,5-trisubstituted-1,2,3-triazoles from internal alkynes. It has been found that Zn-catalyzed AAC is extremely sensitive to steric hindrance in acetylenes and a method of regioselective triazole ring formation has been proposed. Particularly important is the isolation and characterization of a relatively stable Zn-containing intermediate, which has been characterized by NMR and HRMS.

The promoting effect of pyridine ligands in the Pd-catalysed Heck–Matsuda reaction

An efficient Pd-catalyzed arylation reaction of challenging acyclic olefins, in the presence of an organic ligand, has been disclosed. Commercially available cheap pyridine-based ligands are able to promote good to excellent yields for poorly efficient Heck–Matsuda arylation reactions of several allylic alcohols. A wide range of electronically different arenediazonium salts bearing either electron-releasing or withdrawing groups have been used allowing the synthesis of a range of β-aryl-methoxy-lactols. The catalytic system has been optimised, along with the reaction conditions, in order to achieve remarkable yields in less than 1 h.

Ultra-fast Suzuki and Heck reactions for the synthesis of styrenes and stilbenes using arenediazonium salts as super-electrophiles

The super-electrophilic properties of arenediazonium salts have been exploited for achieving ultra-fast palladium-catalyzed coupling reactions with turnover frequencies up to 16 200 h−1. These ultra-fast coupling reactions have been exemplified with the synthesis of prone-to-polymerization styrenes within seconds through Suzuki cross-couplings with potassium vinyltrifluoroborate. Heterocycles and functional groups such as halides were well tolerated. The ambivalent properties of potassium vinyltrifluoroborate also allowed the development of ultra-fast sequential Suzuki–Heck reactions for the preparation of symmetrical and unsymmetrical stilbenes within minutes.

Branched poly (lactic acid) microparticles for enhancing the 5-aminolevulinic acid phototoxicity

An innovative microcarrier based on a carboxy-enriched and branched polylactic acid derivative was developed to enhance the in vitro phototoxicity of the photosensitizer and prodrug 5-aminolevulinic. Microparticles, prepared by double emulsion technique and loaded with the prodrug were carefully characterized and the effect of the polymer structure on the chemical, physical and biological properties of the final product was evaluated. Results showed that microparticles have a spherical shape and ability to allocate up to 30 μg of the photosensitizer per mg of carrier despite their difference in solubility. Release studies performed in various simulated physiological conditions demonstrate the influence of the branched structure and the presence of the additional carboxylic groups on the release rate and the possibility to modulate it. In vitro assays conducted on human epithelial adenocarcinoma cells proved the not cytotoxicity of the carriers in a wide range of concentrations. The hemocompatibility and surface proteins adsorption were evaluated at different microparticles concentrations to evaluate the safety and estimate the possible microparticles residential time in the bloodstream. The advantages, of loading 5-aminolevulinic acid in the prepared carrier has been deeply described in terms of enhanced phototoxicity, compared to the free 5-aminolevulinic acid formulation after irradiation with light at 635 nm. The obtained results demonstrate the advantages of the prepared derivative compared to the linear polylactide for future application in photodynamic therapy based on the photosensitizer 5-aminolevulinic acid.

Synthesis of Five-Membered Iodine–Nitrogen Heterocycles from Benzimidazole-Based Iodonium Salts

Pseudocyclic 2-benzimidazolyl-substituted diaryliodonium salts were obtained by the reaction of the corresponding [hydroxy(tosyloxy)iodo]arenes with arenes in the presence of trifluoromethanesulfonic acid. X-ray structural analysis of these iodonium salts confirmed their pseudocyclic structure with a short (2.57-2.58 Å) noncovalent I···N interaction. Treatment of 2-benzimidazolyl-substituted diaryliodonium triflates with a base afforded novel five-membered iodine-nitrogen heterocycles.