Polymorphism

Полиморфизм − способность вещества существовать в различных кристаллических структурах, называемых полиморфными модификациями (их принято обозначать греческими буквами α, β, γ и т. д.) образовывать различные устойчивые кристаллические решётки, соответствующие минимумам на поверхности энергии Гиббса. Полиморфизм как способность вещества существовать в нескольких кристаллических формах с различными физико-химическими свойствами, но имеющих одинаковый химический состав, является чрезвычайно важным фактором, определяющим лечебный эффект лекарственных средств.

Development of novel pharmaceutical forms of drug compounds and materials for biomedical use

Head of the department: 
Perlovich German Leonidovich
Scope of research: 

Transition to personalized medicine, high-tech health care and health protection technologies, including those based on rational administration of drug compounds, is impossible without developing materials for medical use and new generation drugs. The research community and pharmaceutical industry have recently paid a lot of attention to developing bioavailable preparations. A literature analysis shows that about 40% of commercial substances and 80% of compounds being developed now by pharmaceutical companies are poorly soluble in aqueous media. This fact considerably lowers the therapeutic effectiveness of drug compounds and causes side effects. The solubility and permeability parameters can be improved by applying conceptually new approaches based on fine-tuning of physicochemical properties of multicomponent molecular crystals (cocrystals). The economic effect of such pharmaceutical systems is comparable with launching a new drug on the market. Besides, the innovative technologies we are working at can increase the lifetime of generic compounds on the market as the compounds acquire better functional properties and a new brand name. The research department's studies concern the properties of individual active pharmaceutical ingredients (drug compounds / lead compounds) in biological media and crystals. We are also designing pharmaceutical systems for targeted delivery of drug molecules to their sites of action.

Key words: 
Biopolymers
Drug compounds
Membrane permeability
Pluronics
Polymorphism
Distribution
Solubility
Delivery systems
Cocrystals
Sublimation
Cyclodextrins
Cooperation: 

- South-West University "Neofit Rilski" (Blagoevgrad, Bulgaria);

- Indian Institute of Chemical Technology (IICT) (Hyderabad, India);

- Sat-sun Yen University (Guangzhou, China);

- Tianjin University of Technology (China);

- Beijing Institute of Technology (China);

- Shanghai Institute of Materia Medica, Chinese Academy of Sciences (Shanghai, China);

- University of Cape Town, Department of Chemistry, Center of Supramolecular Chemistry (Cape Town, Republic of South Africa);

- Institute of Pharmaceutics, University of Tromsø, (Norway);

- Institute of Chemical Sciences, University of Bologna (Italy);

- Biomedical Research Center (Borstel, Germany);

- Federal Institute for Materials Research and Testing (Berlin, Germany);

- Institute of Pharmaceutics, University of Helsinki (Finland);

- Pharmaceutical and Analytical R&D, AstraZeneca R&D (Molndal, Sweden);

- Institute of Pharmaceutics, University of Glasgow (Scotland);

- Institute of Physics and Chemistry, University of Southern Denmark (Odense, Denmark);

- Institute of Physiologically Active Substances, RAS (Chernogolovka);

- Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, RAS (Chernogolovka);

- Institute of General and Inorganic Chemistry, RAS (Moscow).

Publications: 

1. Perlovich G.L. Thermodynamic characteristics of cocrystal formation and melting points for rational design of pharmaceutical two-component systems // CrystEngComm. – 2015. – V. 17. – P. 7019 – 7028. DOI: 10.1039/c5ce00992h

2. Perlovich G.L. Prediction of solubility of two-component molecular crystals // CrystEngComm. - 2022. – V. 24. – Art. 2217 DOI: 10.1039/d2ce00105e

3. Surov A.O., Voronin A.P., Drozd K.V., Gruzdev M.S., Perlovich G.L., Prashanth J., Balasubramanian S. Polymorphic forms of antiandrogenic drug nilutamide: structural and thermodynamic aspects // Phys. Chem. Chem. Phys. -  2021. – V. 23(16). – P. 9695-9708. DOI: 10.1039/d1cp00793a.

4. Surov A.O., Churakov A.V., Perlovich G.L. Three Polymorphic Forms of Ciprofloxacin Maleate: Formation Pathways, Crystal Structures, Calculations and Thermodynamic Stability Aspects // Cryst. Growth Des. – 2016. – V. 16(11). – P. 6556-6567. DOI: 10.1021/acs.cgd.6b01277

5. Volkova T.V., Simonova O.R., Perlovich G.L. Another move towards bicalutamide dissolution and permeability improvement with acetylated beta-cyclodextrin solid dispersion // Pharmaceutics. – 2022. - V. 14(7). – Art. 1472. DOI: 10.3390/pharmaceutics14071472

6. Volkova T.V., Simonova O.R., Perlovich G.L. Permeability of diverse drugs through a lipid barrier: impact of pH and cyclodextrin // Journal of Molecular Liquids. – 2022. – V. 357(9). – Art. 115931. DOI: 10.1016/j.molliq.2022.11913

7. Blokhina S.V., Sharapova A.V., Ol’khovich M.V., Volkova T.V., Perlovich G.L., Solubility, lipophilicity and membrane permeability of some fluoroquinolone antimicrobials // Eur. J. Pharm. Sci. – 2016. – V. 105. – P. 29-37. DOI: 10.1016/j.ejps.2016.07.01

8. Blokhina S.V., Ol'khovich M.V., Sharapova A.V., Levshin I.B., Perlovich G.L. Thermodynamic insights to solubility and lipophilicity of new bioactive hybrids triazole with thiazolopyrimidines // J. Mol. Liq. – 2021. – Art. 114662. DOI: 10.1016/j.molliq.2020.114662.

9. Drozd, K.V., Manin A.N., Voronin A.P., Boycov D.E., Churakov A.V., Perlovich G.L. A combined experimental and theoretical study of miconazole salts and cocrystals: crystal structures, DFT computations, formation thermodynamics and solubility improvement // Phys. Chem. Chem. Phys. -  2021. - V. 23(21). – P.12456-12470. DOI: 10.1039/D1CP00956G

10. Drozd K.V., Manin A.N., Churakov A.V., Perlovich G.L. Novel Drug-Drug Cocrystal of Carbamazepine with para-Aminosalicylic Acid: Screening, Crystal Structure and Comparative Study of Carbamazepine Cocrystals Formation Thermodynamics // CrystEngComm. -  2017. - V. 19. – P. 4273-4286. DOI: 10.1039/C7CE00831G

Development of approaches and methods of physical chemistry for studying multicomponent supramolecular, molecular and ion-molecular systems as materials of the future

Head of the department: 
Kiselev Mikhail Grigorievich
Scope of research: 

- Gaining new knowledge about the physicochemical processes of formation of solution structure when predicting the behavior of liquid phase and fluid systems in response to external influences.

- Developing the theory of solutions and simulation approaches to describing liquid phase systems based on using computational chemistry methods and experimental studies of a variety of properties of multicomponent systems within a wide range of parameters of states including supercritical conditions.

- Establishing the regularities in the effect of the structure of compounds on their thermodynamic properties in multicomponent solutions to better study the mechanism of intermolecular interactions.

- Identifying the role of solvophobic effects on the physicochemical parameters of liquid phase systems within a wide range of pressure and temperature values. - Structural analysis of liquid phase and fluid systems based on modern methods of structural chemistry.

- Studying the effect of the composition of composite proton-conducting membranes based on polymers dopes with ionic liquids on their electrochemical and physicochemical properties.

- Based on dipyrromethene dyes obtaining new luminescent sensors, nanostructured biocompatible systems of delivery of biomarkers, photosensitizers, mono-/multilayer components of OLED devices with photoinduced electron transfer.

- Studying the interactions of biopolymers with macroheterocyclic compounds for medical purposes. - Finding regularities in interactions of macroheterocyclic and heteroaromatic compounds with biopolymers, establishing the effect of the nature of ligands on the strength of their binding with the polymer, ligand localization in the polymer in order to develop transport systems, sensors based on macroheterocyclic compounds and photothermosensitive polymer complexes based on polymers and heteroaromatic compounds.

- Synthesis of iron-containing dendrimer complexes based on spin equilibrium systems.

Key words: 
Supramolecular systems
Photoactive compounds
Polymorphism
Solvation
Supercritical fluids
Delivery systems
Machine learning
Cooperation: 

- Leipzig University (Germany);

- University of Coimbra (Portugal);

- University of Lille (Lille, France);

- Tianjin University (China);

- New York University Shanghai (China);

- Kazan Federal University (Kazan);

- Kazan State Medical University (Kazan);

- Zavoisky Physical Technical Institute (Kazan);

- Saint Petersburg State University (Saint Petersburg);

- A.N.Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences (Moscow);

- N. D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences (Moscow);

- Lobachevsky State University of Nizhny Novgorod (Nizhny Novgorod);

- Privolzhsky Research Medical University (Nizhny Novgorod);

- M.N. Mikheev Institute of Metal Physics of the Ural Branch of the Russian Academy of Sciences (Ekaterinburg);

- Ivanovo State University of Chemistry and Technology (Ivanovo);

- Nanomaterials Research Institute of Ivanovo State University (Ivanovo);

- Ivanovo State University (Ivanovo).

Publications: 

1. Barannikov V.P., Smirnov V.I., Kurbatova M.S. The thermochemical behavior of glycyl-L-histidine and β-alanyl-L-histidine peptides in (SDS + phosphate-buffered saline) micellar solution at pH = 7.4 // Journal of Molecular Liquids. – 2021. – V.331. – P. 115766. https://doi.org/10.1016/j.molliq.2021.115766

2. Khodov I.A. et al. Exploring the Conformational Equilibrium of Mefenamic Acid Released from Silica Aerogels via NMR Analysis // International Journal of Molecular Sciences. – 2023. – V.24. – P. 6882. https://doi.org/10.3390/ijms24086882

3. Oparin R.D. et al. Polymorphism and conformations of mefenamic acid in supercritical carbon dioxide // The Journal of Supercritical Fluids, – 2019. – V.152. – P. 104547. https://doi.org/10.1016/j.supflu.2019.104547

4. Bumagina N. A. et al. Basic structural modifications for improving the practical properties of BODIPY // Coordination Chemistry Reviews. – 2022. V. 469. P. 214684. https://doi.org/10.1016/j.ccr.2022.214684

5. Lebedeva N.S. et al. Theoretical and experimental study of interaction of macroheterocyclic compounds with ORF3a of SARS-CoV-2 // Scientific reports. – 2021. – V.11. – No 1. – P. 19481. https://doi.org/10.1038/s41598-021-99072-8

6. Gruzdev M. S., Chervonova U. V., Vorobeva V. E., Kolker A. M. Highly branched mesomorphic iron(III) complexes with a long alkyl fragments on periphery // Journal of Molecular Liquids. – 2020. – V. 320. – P. 114505. https://doi.org/10.1016/j.molliq.2020.114505

7. Shmukler L.E., Fedorova I.V., Fadeeva Yu. A., Safonova L.P. The physicochemical properties and structure of alkylammonium protic ionic liquids of RnH4-nNX (n = 1 – 3) family. A mini–review // Journal of Molecular Liquids. – 2021. – V. 321. – P. 114350. https://doi.org/10.1016/j.molliq.2020.114350

8. Ramenskaya L.M, Grishina E.P, Kudryakova N.O. Comparative study of atmospheric ionic liquids based on bis(trifluoromethylsulfonyl)imide anion and alkyl substituted cations of ammonium, pyrrolidinium and imidazolium // Journal of Molecular Liquids, – 2020. – V. 312. – P. 113368. V. 312, 113368. http://dx.doi.org/10.1016/j.molliq.2020.113368

9. Andrey V. Kustov et al. Monocationic Chlorin as a Promising Photosensitizer for Antitumor and Antimicrobial Photodynamic Therapy // Pharmaceutics – 2023. – V. 15. – P. 61. https://www.mdpi.com/1999-4923/15/1/61

10. Ksenofontov A.A et al. Accurate prediction of 11B NMR chemical shift of BODIPYs via machine learning // Physical Chemistry Chemical Physics. – 2023. – V.25. – P. 9472. https://pubs.rsc.org/en/content/articlehtml/2023/cp/d3cp00253e