Metabolomics is a rapidly developing branch of science that concentrates on identifying biologically active molecules with potential biomarker properties. To define the best biomarkers for diseases, metabolomics uses both models (in vitro, animals) and human, as well as, various techniques such as mass spectroscopy, gas chromatography, liquid chromatography, infrared and UV–VIS spectroscopy and nuclear magnetic resonance. The last one takes advantage of the magnetic properties of certain nuclei, such as 1H, 13C, 31P, 19F, especially their ability to absorb and emit energy, what is crucial for analyzing samples. Among many spectroscopic NMR techniques not only one-dimensional (1D) techniques are known, but for many years two-dimensional (2D, for example, COSY, DOSY, JRES, HETCORE, HMQS), three-dimensional (3D, DART-MS, HRMAS, HSQC, HMBC) and solid-state NMR have been used. In this paper, authors taking apart fundamental division of nuclear magnetic resonance techniques intend to shown their wide application in metabolomic studies, especially in identifying biomarkers.

Leflunomide is a disease-modifying antirheumatic drug with antiinflammatory and immunosuppressive activity used for the treatment of psoriatic and rheumatoid arthritis. It undergoes rapid metabolization to teriflunomide, a metabolite that is responsible for the biological activity of leflunomide. Continuing our investigations on the interactions of biologically important azahetarenes with the environment, we focused on leflunomide and its active metabolite, teriflunomide, considering the interactions teriflunomide–amino acid within the target protein (dihydroorotate dehydrogenase) using density functional theory, as well as ONIOM techniques. The results of theoretical studies have shown that the interactions of teriflunomide with tyrosine and arginine involve principally the amide fragment of teriflunomide. The presence of the internal hydrogen bond between (Z)-teriflunomide carbonyl oxygen and enolic hydroxyl decreases the interaction strength between teriflunomide and tyrosine or arginine. Even the E isomer of teriflunomide would usually provide a stronger interaction teriflunomide—amino acid than the Z isomer with the internal hydrogen bond.Graphical AbstractThe interactions of leflunomide and teriflunomide within receptor cavityᅟElectronic supplementary materialThe online version of this article (doi:10.1007/s00894-015-2643-z) contains supplementary material, which is available to authorized users.

Phenolic acids constitute a family of natural compounds that can be found in a wide variety of plants and food. Among them only ferulic, p-coumaric, chlorogenic, and caffeic acids were recently investigated. There are no data about antioxidant activity of single molecules of fertaric, coutaric, caftaric, dactylifric, and neochlorogenic acids and prenyl caffeate. In a continuation of our attempts to clarify their antioxidant activity, we present herein in silico studies concerning four mechanisms of interaction of phenolic antioxidants with free radicals: hydrogen atom transfer (HAT), (sequential proton loss electron transfer (SPLET), single electron transfer followed by proton transfer, and transition metals chelation, determining several parameters such as bond dissociation enthalpy; proton affinity; adiabatic ionization potential; highest occupied molecular orbital, lowest unoccupied molecular orbital, singly occupied molecular orbital; spin density; stabilization energy (DE ISO ); deprotonation enthalpy/energy (DH acidity and DG acidity ); and second-order perturbation energy E(2). We have proved that for all studied compounds the HAT mechanism was preferred in vacuum as well as in benzene and amyl acetate solvent media, whereas SPLET approach was significantly exposed especially in water. The most active antioxidants (according to the HAT approach) were compounds prenyl caffeate, methyl caffeate, and caffeic acid phenethyl ester, whereas the activity of trans and cis isomers of chicoric derivatives was related to the SPLET protocol. We also observed that trans isomers of caffeic, ferulic, and p-coumaric derivatives were not enough effective in all environments, when compared with other studied molecules. Moreover, we have noticed that the ortho position of the phenylic ring influenced profitably on antioxidant activity in all analyzed compounds.

The paper verifies our recently described NMR approach for the determination of interaction sites between a heterocyclic ligand and magnesium ions. The method is based on the comparison of chemical shifts of condensed pyrazole derivative before and after the complexation with magnesium salt and is supported by DFT (B3LYP/6-31G(d,p) level of theory, CPCM solvation model, GIAO method) and classical molecular dynamics theoretical calculations.

Vascular endothelial growth factor receptor 2 (VEGFR2) is a key receptor in the angiogenesis process. The VEGFR2 expression is upregulated in many cancers so this receptor is an important target for anticancer agents. In the present paper, we analyse interactions of several dimeric indazoles, previously investigated for anticancer activity, with the amino acids present in the VEGFR2 binding pocket. Using the docking method and MD simulations as well as theoretical computations (SAPT0, PIEDA, semi-empirical PM7), we confirmed that these azoles can efficiently bind into the kinase pocket and their poses can be stabilised by the formation of hydrogen bonds, π–π stacking, π–cation, and hybrid interactions with some amino acids of the kinase cavity like Ala866, Lys868, Glu885, Thr916, Glu917, and Phe918.