Role and Perspective of Molecular Simulation-Based Investigation of RNA–Ligand Interaction: From Small Molecules and Peptides to Photoswitchable RNA Binding

Aberrant RNA–protein complexes are formed in a variety of diseases. Identifying the ligands that interfere with their formation is a valuable therapeutic strategy. Molecular simulation, validated against experimental data, has recently emerged as a powerful tool to predict both the pose and energetics of such ligands. Thus, the use of molecular simulation may provide insight into aberrant molecular interactions in diseases and, from a drug design perspective, may allow for the employment of less wet lab resources than traditional in vitro compound screening approaches. With regard to basic research questions, molecular simulation can support the understanding of the exact molecular interaction and binding mode. Here, we focus on examples targeting RNA–protein complexes in neurodegenerative diseases and viral infections. These examples illustrate that the strategy is rather general and could be applied to different pharmacologically relevant approaches. We close this study by outlining one of these approaches, namely the light-controllable association of small molecules with RNA, as an emerging approach in RNA-targeting therapy.     

Interaction of Crown Ether‐Annelated Styryl Dyes with Double‐Stranded DNA

DNA‐binding properties of 15‐crown‐5‐derived mono‐ and bis‐styryl dyes were investigated in the presence of calf thymus DNA. To access the factors that influence the DNA association in the series of these ligands, the structure of the molecules was varied by either changing size of the heterocyclic moiety or altering the position of the styryl substituents. The major binding mode for the monostyryl dyes is intercalation. Notably, binding of the dyes to the nucleic acids leads to a fluorescence enhancement by a factor of up to 54. Therefore, these cationic styryl derivatives may be applied as fluorescent “light‐up” probes for DNA detection.     

Encapsulation-Controlled Photoisomerization of a Styryl Derivative: Stereoselective Formation of the Anti Z-Isomer in the Cucurbit[7]uril Cavity

The photochemical isomerization of a styrylpyridinium dye ( SP ) bearing an unsymmetrically attached benzo-15-crown-5 ether has been studied in aqueous solution in the absence and presence of cucurbit[7]uril (CB[7]). The detailed analysis of the UV/Vis and NMR spectra showes that the isomeric composition of the photostationary mixtures of SP can be modulated by the host-guest complexation with CB[7]. It was found that steric hindrance caused by encapsulation of SP in the host cavity induces the exclusive formation of the anti conformer of Z- SP in contrast with the mixture of both anti and syn conformers obtained during photoisomerization of the dye without CB[7]. Remarkably, the displacement of anti Z- SP from CB[7] does not lead to the transformation of the anti Z-isomer into the syn Z-isomer pointing out the conformational memory of the system. The results provide an interesting example of the supramolecular stereorecognition by the achiral CB[7] host.     

Investigation of parameters of inductively coupled plasma and its use in steel nitriding

Parameters of inductively coupled plasma (ICP) discharges in a mixture of gases N₂, H₂, and Ar at a total pressure of 1.5 × 10^–3 mbar and a partial pressure ratio N₂: H₂: Ar = 2: 12: 1 are discussed. The plasma properties are analyzed using Langmuir probes and optical emission spectroscopy. The ICP discharge is used for the nitriding of specimens made of Russian grade 30ChGSA structural steel. The nitriding experiments are performed at different bias voltages V_b in the range of–200 V to +100 V with respect to the walls of the discharge chamber. The surface hardness of the treated specimens depends substantially on the bias voltage, being much higher than the initial value in all cases. The obtained results demonstrate the possibility of increasing the surface hardness up to 1000 HV (4–5 times the initial values) at the bias voltage equal to the floating potential.     

Fused Bis(hemi-indigo): Broad-Range Wavelength-Independent Photoswitches

Wavelength-independent conversion of organic photoswitches in the photostationary state is a rare phenomenon that opens up a way for many practical applications. In this work, three fused bis(hemi-indigo) derivatives with different substitution patterns were synthesized and their photoswitching was investigated by optical spectroscopy, real-time NMR spectroscopy and TD-DFT calculations. We disclosed that the Z-E photoisomerization of the meta-bis(hemi-indigo) derivative was remarkably independent of the irradiation wavelength from UV up to yellow light. The wavelength-independent forward photoswitching together with the inhibited backward photoisomerization, high thermal stability of the photoinduced isomers as well as significant overlap between the photoswitch absorption and the solar spectrum allows to suggest bis(hemi-indigo) derivatives as promising candidates for molecular solar thermal energy storage (MOST) systems.     

Macroheterocycles. 7. Synthesis and extraction capacity of some dibenzo-18-crown-6-derivatives

Derivatives that contain vinyl, formyl, acetyl, carboxy, carbethoxy, -carboxyvinyl, or -carbethoxyvinyl groups in the benzene rings were synthesized from dibenzo-18-crown-6. The ability of the synthesized crown ethers to extract picrates of alkali metals from the aqueous phase to the chloroform phase was investigated.See [1] for Communication 6.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 599–603, May, 1981.     

Catalytic epoxidation of α,β-and β,γ-unsaturated bicyclic ketones with hydrogen peroxide

The possibility of preparing epoxides from α,β-and β,γ-unsaturated bicyclic ketones formed as by-products in liquid-phase oxidation of cyclohexane with atmospheric oxygen (a stage in production of caprolactam, adipic acid, and other products) was examined. The reaction products were analyzed by gel chromatography and mass spectrometry.     

Catalytic oxidation of olefins and alcohols with hydrogen peroxide in a two-phase system giving mono- and dicarboxylic acids

The present study considered the influence of various factors on the catalytic activity of systems based on a combination of tetrakis(oxodiperoxotungsto)phosphate(3−) with quaternary ammonium cations, for example, with methyltri-n-octylammonium [Me(n-C₈H₁₇)₃N]⁺. The catalysts were tested in oxidation of cycloolefins (cyclohexene and cyclooctene), alcohols (octan-1-ol and phenylmethanol), and unsaturated fatty acids (cis-9-octadecenoic and 12-hydroxy-9Z-octadecenoic acids) with a 30% hydrogen peroxide solution. These reactions proceed under mild conditions (atmospheric pressure, 80–90 °C) to give carboxylic acids. The catalytic systems were characterized by vibrational (IR and Raman) spectroscopy. The state of the systems formed from various precursors, viz., polyoxometallates and phase-transfer catalysts, was studied. It was demonstrated for the first time that the structure formation of peroxo complexes depends on the nature of the halide anion of the quaternary ammonium salt used. The melting points of individual catalytic complexes were determined. The optimal conditions for oxidation were found. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1794–1801, August, 2005.