Vladimir Vasil'EVich Klochkov

This work studies the complexation process of the transition metal ion Mn2+ and statins (atorvastatin, fluvastatin) using high-resolution NMR spectroscopy and molecular dynamics (MD). Analysis of 1H-NMR spectra showed that the addition of Mn2+ ion to a solution of statins in a suitable solvent lead to changes in the line shape and chemical shifts of the CH2-14, CH-15, and CH2-16 signals (for atorvastatin) and CH2-2, CH-3, CH2-4, CH-5 signals (for fluvastatin). NMR DOSY spectra revealed changes in the self-diffusion coefficients (D) of statins in the presence of the Mn2+ ion compared to statins in a pure suitable solvent. Based on the results of the experiment, an assumption was made regarding the possible localization of the binding of the Mn2+ ion with the statin molecules. This assumption is consistent with the results of molecular dynamics simulations of the corresponding systems.

In this study, two low-concentration solutions of 1,4,5,8-Naphthalene tetracarboxylic dianhydride (NTCDA) in two imidazolium-based ionic liquids (IL), EMIM-DCA and EMIM-Ac, at room temperature were mixed; after around ten days of storage, the formation of two variants of electron-withdrawing molecules of Naphthalene tetracarboxylic diimide NTCDI-R derivatives were detected. Their radical anions (RA) were registered by EPR via irradiating the resulting mixture of both solutions with visible or UV light. Chemical shift recording and precise concentration control of NTCDA in ionic liquid solutions were accomplished using 500 MHz and 700 MHz ¹H NMR. The formation of the NTCDA^•− upon light illumination was also confirmed by NMR, which showed paramagnetic broadening of the ¹H line due to the electron chemical exchange between NTCDA and NTCDA^•− after light-on and light-off modes. The time-dependent line broadening is in quantitative agreement with the corresponding EPR data for the light-on-/light-off-dependent concentration of NTCDA^•−. The putative structure of R in NTCDI-R was calculated by DFT. The possibility of using NTCDI-R^•− as a spin probe for studying molecular diffusion in high viscous ionic liquid is assessed.

Understanding how drugs interact with metal ions is essential for predicting their stability, how well they are absorbed in the body, and possible side effects. Pravastatin is a commonly used statin to prevent cardiovascular heart disease and has several functional groups that can bind metal ions, but its interactions with transition metals and lanthanides are not well studied. This work examines the complexation process of pravastatin with transition metal ions zinc (Zn ²⁺ ), nickel (Ni ²⁺ ) and lanthanide gadolinium (Gd ³⁺ ) using high‐resolution NMR spectroscopy. It was found that the presence of ions (Ni ²⁺ , Gd ³⁺ ) in an aqueous solution of pravastatin causes broadening of ¹ H NMR signals, leading to a change in signal intensity in the HMQC spectra and disappearance of the correlation between the ¹ H and ¹³ C signals in the HMBC spectra. No significant changes were observed in the NMR spectra of similar experiments of pravastatin with zinc salt. The DOSY NMR spectrum of pravastatin in the presence of ions (Gd ³⁺ , Ni ²⁺ , and Zn ²⁺ ) revealed a change in self‐diffusion coefficients compared to the parent structure. An assumption about the possible centers of localization of Gd ³⁺ and Ni ²⁺ ions near the pravastatin molecule has been made.

The work is devoted to investigation of the process of complexation of lovastatin with transition metal ions (cobalt and gadolinium) by 1H, 1H-13C heteronuclear multiple bond correlation (HMBC) nuclear magnetic resonance (NMR) and molecular dynamics (MD) methods. According to the obtained results, Co2+ ions interact with lovastatin at a more external position possibly favoring oxygen-rich regions in the periphery of the molecule. Gd3+ ions tend to localize in a more internal region of the lovastatin ring that contains groups 14-17 compared to Co2+.

Unsaturated γ-lactams (3-pyrrolin-2-ones) are an important class of five-membered nitrogen-containing heterocycles that play a significant role as structural motifs in numerous natural products and synthesized compounds with a wide range of biological activities. These motifs are also successfully used as intermediates in organic transformations and allow access to more diverse compounds and previously inaccessible structures. In this work, method for the synthesis of two types of novel heterocyclic compounds containing an unsaturated γ-lactam ring and two sulfur atoms was developed. Reactive and easily available substrates of 5-methoxy-2(5H)-furanone series were involved into the reactions with ammonia and benzylamine and converted into the corresponding dithioderivatives of 5-hydroxy-3-pyrrolin-2-one, difficult to access by other methods. The molecular and crystal structures of four novel sulfur-containing compounds were characterized by single-crystal X-ray diffraction. These heterocyclic systems are promising candidates for further functionalization and biological screening.

The spectral characteristics of cyclosporin C (CsC) with the addition of Dy³⁺ ions in acetonitrile (CD₃CN) and CsC with Dy³⁺ incorporated into dodecylphosphocholine (DPC) micelle in deuterated water were investigated by high-resolution NMR spectroscopy. The study was focused on the interaction between Dy³⁺ ions and CsC molecules in different environments. Using a combination of one-dimensional and two-dimensional NMR techniques, we obtained information on the spatial features of the peptide molecule and the interaction between CsC and the metal ion. The non-uniform effect of the metal ion on different NMR signals of CsC was observed. The paramagnetic attenuation parameter was calculated for the amide, alpha, and beta protons of CsC upon the addition of Dy³⁺. The metal ion was found to interact with the polar part of the DPC micelle, and the ion also has a significant effect on the NMR signals of amino acid residues from Sar₃ to d-Ala₈. This pattern is reproduced in both environments studied here and also agrees with earlier investigations of the CsA–Dy³⁺ complex.