Authorization required.

A complex of molecular fluid spectroscopy (Fluid spectrum) equipped with special cells for measuring vibrational infrared (IR) spectra, as well as nuclear magnetic resonance (NMR) spectra in a wide range of state parameters, including supercritical ones.

A unique pressure and temperature support and control system has been created for the IR spectroscopy complex, which allows it to operate in the range P=1 bar – 1000 bar and maintain a set pressure with an accuracy of 0.1 bar and in the range from room temperature to T~400 °C with an accuracy of 1 °C. The versatility of the system allows it to be used with various types of experimental cells (for IR and NMR spectroscopy), reactors that allow for various processes based on the use of supercritical fluid technologies, in particular, the rapid expansion of supercritical solutions (RESS).

  1. NMR spectroscopy of liquids (1D, 2D, 3D);
  2. NMR spectroscopy of fluids
  3. IR spectroscopy of fluids
Ilya Khodov 🥼 🤝
Head of Laboratory
M Kiselev
Principal researcher
Roman Oparin
Senior Researcher
Konstantin Belov 🤝
Junior researcher
Valentina Sobornova
Research intern
Maksim Kuzymikov
Research intern

Research directions

Investigation of the spatial structure and features of the interaction of small molecules of medicinal compounds

+
In recent years, interdisciplinary studies of biologically active substances in a fluid solvent have been carried out at the molecular fluid spectroscopy complex. In particular, for molecules of a number of medicinal compounds in supercritical carbon dioxide.

Publications and patents

Sobornova V.V., Belov K.V., Krestyaninov M.A., Khodov I.A.
2024-07-28 citations by CoLab: 4 PDF Abstract
The study presents a thorough and detailed analysis of bicalutamide’s structural and conformational properties. Quantum chemical calculations were employed to explore the conformational properties of the molecule, identifying significant energy differences between conformers. Analysis revealed that hydrogen bonds stabilise the conformers, with notable variations in torsion angles. Conformers were classified into ‘closed’ and ‘open’ types based on the relative orientation of the cyclic fragments. NOE spectroscopy in different solvents (CDCl3 and DMSO-d6) was used to study the conformational preferences of the molecule. NOESY experiments provided the predominance of ‘closed’ conformers in non-polar solvents and a significant presence of ‘open’ conformers in polar solvents. The proportions of open conformers were 22.7 ± 3.7% in CDCl3 and 59.8 ± 6.2% in DMSO-d6, while closed conformers accounted for 77.3 ± 3.7% and 40.2 ± 6.2%, respectively. This comprehensive study underscores the solvent environment’s impact on its structural behaviour. The findings significantly contribute to a deeper understanding of conformational dynamics, stimulating further exploration in drug development.
Dereven’kov I.A., Osokin V.S., Khodov I.A., Makarov S.V.
2024-07-01 citations by CoLab: 0 Abstract
This study explores the modification of nitrosylcobinamide, explicitly focusing on meso-bromination, and its impact on the dissociation rate of nitric oxide (NO). meso-Brominated aquahydroxocobinamide was efficiently synthesized from meso-brominated cyanocobalamin via hydrolysis, followed by decyanation step. Its reaction with Angeli's salt produces meso-brominated nitrosylcobinamide (NOCbi-Br). NOCbi-Br exhibits stability in the presence of dioxygen comparable to that of the unmodified NOCbi in neutral aqueous solutions. However, in the presence of L-histidine the oxidation of NOCbi-Br by oxygen is significantly slower than unmodified NOCbi, indicating potential differences in ligand affinities. Furthermore, the rate constant for NO release from NOCbi-Br was lower than that of unmodified NOCbi, suggesting that meso-bromination strengthens the Co(II)–NO bond. These findings underscore the utility of meso-modification in tailoring the properties of corrinoids as nitric oxide donors, with potential implications for therapeutic applications.
Wei Y., Zhong C., Sun Y., Ma S., Ni M., Wu X., Yan Y., Yang L., Khodov I.A., Ge J., Li Y., Lin D., Wang Y., Bao Q., Zhang H., et. al.
2024-06-27 citations by CoLab: 6 PDF Abstract
AbstractGridization is an emerging molecular integration technology that enables the creation of multifunctional organic semiconductors through precise linkages. While Friedel-Crafts gridization of fluorenols is potent, direct linkage among fluorene molecules poses a challenge. Herein, we report an achiral Pd-PPh3-cataylized diastereoselective (>99:1 d.r.) gridization based on the C-H-activation of fluorene to give dimeric and trimeric windmill-type nanogrids (DWGs and TWGs). These non-conjugated stereo-nanogrids showcase intramolecular multiple H…H interactions with a low field shift to 8.51 ppm and circularly polarized luminescence with high luminescent dissymmetry factors (|gPL | = 0.012). Significantly, the nondoped organic light-emitting diodes (OLEDs) utilizing cis-trans-TWG1 emitter present an ultraviolet electroluminescent peak at ~386 nm (CIE: 0.17, 0.04) with a maximum external quantum efficiency of 4.17%, marking the highest record among nondoped ultraviolet OLEDs based on hydrocarbon compounds and the pioneering ultraviolet OLEDs based on macrocycles. These nanohydrocarbon offer potential nanoscafflolds for ultraviolet light-emitting optoelectronic applications.
Mamardashvili G.M., Kaigorodova E.Y., Khodov I.A., Mamardashvili N.Z.
2024-04-01 citations by CoLab: 3 Abstract
The study explores the interactions between 5,10,15,20-tetra(N-methylpyridyl)porphyrin (H2P) and sodium dodecyl sulfate (SDS) at concentrations below the critical micelle concentration (CMC) in aqueous solutions employing spectrophotometric and fluorescence methods. The composition and structure of the complexes involved in the association of H2P with premicellar SDS aggregates of varying compositions denoted as [H2P-5·SDS], [H2P-10·SDS] and [H2P-20·SDS] were characterized using mass spectrometry, DOSY, and 1D NOESY techniques. Possible reasons for the decrease in the intensity of absorption and emission of porphyrin in micellar aggregates of SDS compared to porphyrin in an aqueous environment are analyzed. The research has revealed that SDS can act as both a catalyst and an inhibitor, depending on its concentration in the reaction of complexation of H2P with metal cations (Co2+). The spectrophotometric approach examined interaction processes between 5,10,15,20-tetra(N-methylpyridyl)porphyrinate Co(III) and premicellar SDS aggregates, which proceed similarly to the processes with the porphyrin ligand. The study demonstrated the impact of premicellar aggregates on the binding capacity of Co(III) porphyrinate with electron-donating molecules using imidazole as an illustrative example.
Belov K.V., Dyshin A.A., Khodov I.A.
2024-03-01 citations by CoLab: 3 Abstract
Arbidol is a pharmaceutical compound of significant importance due to its versatile applications in antiviral and Immunomodulatory therapies. The present study reports on the identification of multiple arbidol conformers in a supercritical carbon dioxide solution. The conformers were characterized based on various dihedral angles and the analysis of NOESY spectra. The study reveals distinct conformer groups, namely the "opened" and "closed" conformations, based on the angle τ2 that governs the alignment of the phenyl ring around the indole moiety of the compound. The analysis of the chemical shifts in the 1H NMR spectra of ARB in different solvents (supercritical carbon dioxide, deuterochloroform, and hexadeutero-dimethyl sulfoxide) reveals variations in the proton signals, indicating changes in the conformation of arbidol molecules and the impact of ring currents from the phenyl fragment. The nuclear Overhauser effect spectroscopy analysis of arbidol in supercritical carbon dioxide confirms the presence of distinct conformer groups and their internuclear distances. The distances H22-H25/29 and H22-H10 are found to be indicative of the "closed" conformer group, with values consistent with previous studies. The proportions of "opened" and "closed" conformer groups in supercritical carbon dioxide are calculated using the experimental distances and compared with theoretical calculations. The preference of the conformer group in supercritical carbon dioxide is found to be the "closed" group, similar to previous studies on arbidol forms. Overall, this study provides insights into the conformational behavior of arbidol in supercritical carbon dioxide and highlights the potential of supercritical carbon dioxide as a promising medium for developing new arbidol forms.
Mamardashvili G.M., Lazovskiy D.A., Khodov I.A., Efimov A.E., Mamardashvili N.Z.
Polymers Q1 Q1 Open Access
2024-02-23 citations by CoLab: 1 PDF Abstract
In the original publication [...]
Dereven’kov I.A., Osokin V.S., Kulev V.A., Khodov I.A., Koifman O.I., Makarov S.V.
2024-02-08 citations by CoLab: 0
Belov K.V., Krestyaninov M.A., Dyshin A.A., Khodov I.A.
2024-02-01 citations by CoLab: 5 Abstract
This research extends the understanding of lidocaine conformer distributions under various isobaric conditions (10, 20, and 30 MPa) and temperatures (35, 50, and 70 °C). Employing quantum chemical calculations and NOESY spectroscopy, the study explores the influence of lidocaine conformers on micronized particle sizes. Results reveal that Trans-conformers, stabilized by intramolecular hydrogen bonds, dominate under specific conditions, impacting the formation of lidocaine dimers. The NOESY analysis demonstrates consistent conformer proportions, highlighting the stability of ethyl fragment positions. These findings contribute significantly to comprehending lidocaine's behavior during the rapid expansion from supercritical to aqueous solution (RESAS) process, offering crucial insights for pharmaceutical formulation design.
Belov K.V., Dyshin A.A., Krestyaninov M.A., Sobornova V.V., Khodov I.A., Kiselev M.G.
2023-12-01 citations by CoLab: 1 Abstract
The possibilities of nuclear Overhauser effect spectroscopy (NOESY) for conformational analysis of fenamate (e.g., flufenamic acid) molecules were shown. It was established that the proportions of conformer groups changed by up to 32% on passing from a system with pure DMSO to a solvent based on SC-CO2 with a 2 mol % DMSO addition. The results showed that the conformational equilibrium of small drug-like molecules can be controlled using supercritical fluids for slightly soluble compounds. This is promising for the micronization of fenamates by the RESS, SAS, and DELOS methods.
Belov K., Brel V., Sobornova V., Fedorova I., Khodov I.
2023-11-24 citations by CoLab: 5 PDF Abstract
1,5-Diaryl-3-Oxo-1,4-Pentadiene derivatives are intriguing organic compounds with a unique structure featuring a pentadiene core, aryl groups, and a ketone group. This study investigates the influence of fluorine atoms on the conformational features of these derivatives in deuterated chloroform (CDCl3) solution. Through nuclear magnetic resonance (NMR) spectroscopy and quantum chemical calculations, we discerned variations in interatomic distances and established predominant conformer proportions. The findings suggest that the non-fluorinated entity exhibits a uniform distribution across various conformer groups. The introduction of a fluorine atom induces substantial alterations, resulting in the predominance of a specific conformer group. This structural insight may hold the key to their diverse anticancer activities, previously reported in the literature.
Zavalishin M.N., Pimenov O.A., Belov K.V., Khodov I.A., Gamov G.A.
2023-11-01 citations by CoLab: 3 Abstract
Interaction of metals with serum albumins is of special interest as it may mediate the toxic or beneficial action of metal ions and their metal complexes that are often considered (pro)drugs. Among metals, gold(III) draws special attention because of the antibacterial activity of its complexes reported recently. The paper focuses on the interactions between bovine and human serum albumins and gold(III) species in aqueous solutions. Tetrachloroaurate(III) hydrolysis, protein self-association and interactions involving chloride ions are accounted for to determine the most probable stoichiometric composition of gold(III) associated with proteins and the binding constants. The data obtained are used to calculate the equilibrium composition of the solution containing [AuCl4]-, biologically active hydrazone derived from pyridoxal 5’-phosphate and serum albumin at different pH values.
Khodov I.A., Belov K.V., Sobornova V.V., Dyshin A.A., Kiselev M.G.
2023-10-01 citations by CoLab: 9 Abstract
This research determined the proportions of lidocaine conformer groups in a supercritical carbon dioxide environment at constant pressures (10, 20 and 30 MPa) and temperatures of 35°C, 50°C and 70°C for the first time. Results show that the proportions of Cis-conformers and Trans-conformers depend on temperature, with the proportion of Cis-conformers increasing with increasing temperature and the ratio of Trans-conformers increasing with decreasing temperature. Thus, on the 10 MPa isobar, as the temperature increases from 35°C to 70°C, the Trans-/Cis-conformers ratio changes from 99.4%/0.6% to 88.9%/11.1%. On the 20 MPa isobar at the same temperatures the conformer distribution changes from 53.3%/46.7% to 95.6%/4.4%, and on the 30 MPa isobar the corresponding values are 4.8%/95.2% and 46.5%/53.5%. It is intriguing how the proportions of conformer groups vary with temperature, and this knowledge could be beneficial for micronizing different compounds using supercritical fluid technologies.
Sobornova V.V., Maltceva O.V., Khodov I.A., Mamardashvili N.Z.
2023-10-01 citations by CoLab: 1 Abstract
The methodology of 1H NMR study of the kinetics of the Ni(II) and Zn(II) cations complex formation with 2-aza-5,10,15,20-tetraphenyl-21-carbaporphyrin ([2-N, 21-CH]TPP I) was developed. The processes rate constants are determined using the pseudo-first and pseudo-second order models. It was shown that this methodology allows for identification and evaluation with high accuracy of the effects of donor-acceptor and solvation interactions that occur in the processes of the d-metal cations complex formation with the inverted tetrapyrrole macrocyclic ligands.
Khodov I.A., Belov K.V., Krestyaninov M.A., Sobornova V.V., Dyshin A.A., Kiselev M.G.
2023-08-01 citations by CoLab: 10 Abstract
This work investigated the effect of DMSO-d6 on the conformation of lidocaine and fenamates. Using lidocaine as a model compound, the study investigated the influence of DMSO-d6 on the conformational preferences of fenamates, which have similar fragment structures to the molecule. The NOESY spectra of mefenamic, flufenamic and tolfenamic acid were compared in a mixture of scCO2+DMSO-d6 at the same state parameters as lidocaine (45°C and 9 MPa). The two-position exchange model was used to calculate the proportions of fenamate conformer groups in scCO2+DMSO-d6. The addition of DMSO-d6 did not significantly alter the conformation of mefenamic acid, and the ratio of conformers was determined to be 75.3 / 24.7, which is very close to the previously measured in pure scCO2. The results showed that the addition of DMSO-d6 did not significantly alter the conformation of lidocaine and mefenamic acid. This suggests that adding 2 %, DMSO-d6 can be used to evaluate the structure of poorly soluble drug compounds using the NOESY method in supercritical carbon dioxide. The findings of this study are encouraging.
Dereven’kov I.A., Osokin V.S., Khodov I.A., Sobornova V.V., Ershov N.A., Makarov S.V.
2023-07-22 citations by CoLab: 3 Abstract
Cyanocobalamin (CNCbl), a medicinal form of vitamin B12, is resistant to glutathione (GSH), and undergoes intracellular processing via reductive decyanation producing the Co(II)-form of Cbl (Cbl(II)) mediated by the CblC-protein. Alteration of the CblC-protein structure might inhibit CNCbl processing. Here, we showed that introducing a bromine atom to the C10-position of the CNCbl corrin ring facilitates its reaction with GSH leading to the formation of Cbl(II) and cyanide dissociation. In a neutral medium, the reaction between C10-Br-CNCbl and GSH proceeds via the complexation of the reactants further leading to dimethylbenzimidazole (DMBI) substitution and electron transfer from GSH to the Co(III)-ion. The reaction is accelerated upon the GSH thiol group deprotonation. The key factors explaining the higher reactivity of C10-Br-CNCbl compared with unmodified CNCbl towards GSH are increasing the electrode potential of CNCbl two-electron reduction upon meso-bromination and the substantial labilization of DMBI, which was shown by comparing their reactions with cyanide and the pKa values of DMBI protonation (pKa base-off). Aquacobalamin (H2OCbl) brominated at the C10-position of the corrin reacts with GSH to give Cbl(II) via GSH complexation and subsequent reaction of this complex with a second GSH molecule, whereas unmodified H2OCbl generates glutathionyl-Cbl, which is resistant to further reduction by GSH.

Lab address

Иваново, ул. Академическая, д. 1
Authorization required.