Center for Magnetic Resonance

A.A. Vereschagin, V.V. Sizov, P.S. Vlasov, E.V. Alekseeva, A.S. Konev, O.V. Levin

“Water-stable [Ni(salen)]-type electrode material based on phenylazosubstituted salicylic aldehyde imine ligand”

New Journal of Chemistry, 2017, 41, 13918-13928
DOI: 10.1039/c7nj03526h

A novel electrode material was prepared by electrochemical oxidation of [4,4′-phenylazo-2,2′-(ethylenediimino-κ2N-methyl)diphenolate-κ2O]nickel, a [Ni(II)(salen)]-type complex, in chlorinated solvent. The chemical structure of the material was explored by FTIR, NMR and XPS techniques to determine the main components of the material and the nature of the linkage between them. The morphology of the material films was explored by SEM analysis. The electrochemical properties of the new material were studied by a set of voltammetric methods and an unusual stability of the material in aqueous medium was observed.

M.M. Efremova, R.R. Kostikov, A.V. Stepakov, T.L. Panikorovsky, V.S. Shcherbakova, A.V. Ivanov, A.P. Molchanov

“Unusual Lewis-acid catalyzed formal (3+3)-cycloaddition of azomethine imines and nitrones to N-vinylpyrroles”

Tetrahedron, 2017, 73, 671-680
DOI: 10.1016/j.tet.2016.12.034

The addition of Lewis acids change the reaction mechanism of the cycloaddition of N-vinylpyrroles with azomethine imine and C,N-diarylnitrones. The formal (3+3)-cycloaddition is observed instead of (3+2)-dipolar cycloaddition, which take place in the absence of catalysts. This unusual (3+3)-cycloaddition leads to heterocyclic compounds with pyrazolo[1,2-a]pyrrolo[1,2-d][1,2,4]triazine- and pyrrolo[2,1-d][1,2,5]oxadiazine cores, which are difficultly achievable by other methods.

G. P. Kantin, M. Yu. Krasavin

“Microwave-promoted reaction of N-alk-1-enyl chloroacetamides with sodium azide unexpectedly yields 1H-imidazol-5(4H)-ones”

Mendeleev Commun., 2017, 27, 95-96
DOI: 10.1016/j.mencom.2017.01.031

A novel method to prepare biologically relevant 1H-imidazol-5(4H)-ones from aliphatic amines, isobutyraldehyde, chloroacetyl chloride and sodium azide under microwave irradiation has been developed.

M. Chizhova, D. Dar’in, M. Krasavin

“Complications in the Castagnoli-Cushman reaction: An unusual course of reaction between cyclic anhydrides and sterically hindered indolenines”

Tetrahedron Letters, 2017, 58(35), 3470-3473
DOI: 10.1016/j.tetlet.2017.07.077

Attempted reaction of indolenines (which represent rather sterically hindered cyclic imines) with a series of dicarboxylic acid anhydrides yielded no expected product, the Castagnoli-Cushman lactam. Instead, products presumably formed via N-acyliminium species trapping by a carboxylate anion. Among them, hydrolytically labile 2:2 adducts of an indolenine and a cyclic anhydride, containing a 16-membered cyclic core, are particularly intriguing. This result contradicts the recently reported successful Castagnoli-Cushman reaction of indolenines with homophthalic anhydride suggesting a mechanistic switch in the course of the reaction.

S. O. Rabdano, S. A. Izmailov, D. A. Luzik, A. Groves, I. S. Podkorytov, N. R. Skrynnikov

“Onsеt of Disоrdеr and Protein Aggregation Due to Oxidation-Induced Intermolecular Disulfide ”

Scientific Reports, 2017, 7, 11161
DOI: 10.1038/s41598-017-10574-w

We have investigated the behavior of second RNA-recognition motif (RRM2) of neuropathological protein TDP43 under the effect of oxidative stress as modeled in vitro. Toward this end we have used the specially adapted version of H/D exchange experiment, NMR relaxation and diffusion measurements, dynamic light scattering, controlled proteolysis, gel electrophoresis, site-directed mutagenesis and microsecond MD simulations. Under oxidizing conditions RRM2 forms disulfide-bonded dimers that experience unfolding and then assemble into aggregate particles (APs). These particles are strongly disordered, highly inhomogeneous and susceptible to proteolysis; some of them withstand the dithiothreitol treatment. They can recruit/release monomeric RRM2 through thiol-disulfide exchange reactions. By using a combination of dynamic light scattering and NMR diffusion data we were able to approximate the size distribution function for the APs. The key to the observed aggregation behavior is the diminished ability of disulfide-bonded RRM2 dimers to refold and their increased propensity to misfold, which makes them vulnerable to large thermal fluctuations. The emerging picture provides detailed insight on how oxidative stress can contribute to neurodegenerative disease, with unfolding, aggregation, and proteolytic cleavage as different facets of the process.

S. Kalinin, S. Kopylov, T. Tuccinardi, A. Sapegin, D. Dar’in, A. Angeli, C.T. Supuran, M. Krasavin

“Lucky Switcheroo: Dramatic Potency and sеlеctivity Improvement of Imidazoline Inhibitors of Human Carbonic Anhydrase VII”

ACS Med. Chem. Lett, 2017, 8 (10), 1105–1109.
DOI: 10.1021/acsmedchemlett.7b00300

A substantial improvement of potency and selectivity of imidazoline-based inhibitors of hCA VII (a promising target for the treatment of seizures and neuropathic pain) was achieved by simply switching the position of the benzenesulfonamide moiety from N1 (as in the earlier reported series) to C2. Selectivity indices vs the off-target isoforms (hCA I, I, I and IV) greater than 100 were reached, which is exceedingly rare for hCA VII inhibitors. The drastic profile improvement of the new series has been rationalized by an additional hydrogen bonding with the nonconserved Q69 residue in the active site of hCA VII (absent in the other three isoforms studied), which also results in a favorable accommodation of the inhibitor’s lipophilic periphery in the nearby hydrophobic pocket. The robustness of the docking simulations was tested and confirmed by molecular dynamics simulations