Quantum-chemical modeling of cortisone-fullerenol agents of cancer therapy

In order to therapeutically destroy oncological neoplasms, chemotherapy or radiotherapy is usually applied, and in isotope medicine – short-lived radio nuclides are injected into the tumor (⁵⁹Fe, ⁹⁰Y, ⁹⁵Zr, ^99mTc, ¹⁰⁶Ru, ^114*In, ¹⁴⁷Eu, ¹⁴⁸Eu, ¹⁵⁵Eu, ¹⁷⁰Tm, ¹⁸⁸Re, ²¹⁰Po, ²²²Rn, ²³⁰U, ²³⁷Pu, ²⁴⁰Cm, ²⁴¹Cm, ²⁵³Es). Binary (or neutron capture) therapy is a technology developed for the selective effect on malignant tumors using drugs that are tropic to tumors and contain non-radioactive nuclides (¹⁰B, ¹¹³Cd, ¹⁵⁷Gd at al.). Triadic therapy involves the sequential introduction into the body of a combination of two or more separately inactive and harmless components, which are tropic to tumor tissues and capable of selectively accumulating in them or chemically interacting with each other and destroying tumor neoplasms under the action of certain sensitizing external influences. The aim of this work is quantum-chemical simulation of the electronic structure and analysis of the thermodynamic stability of new cortisone-fullerenol agents for the treatment of tumor neoplasms. The need for preliminary studies of modeling such objects is due to the very high labor intensity, cost and complexity of their practical production.

1. Mayles P., Nahum A., Rosenwald J. C. Handbook of Radiation Therapy Physics: Theory and Practice. Taylon & Francis, 2007. 1450 p. https://doi.org/10.1201/9781420012026

2. Hosmane N. S., Maquire J. A., Zhu Y. Boron and Gadolinium Neutron Capture Therapy for Cancer Treatment. World Scientific Publishing Co. Pte. Ltd., 2012. 300 p. https://doi.org/10.1142/8056

3. Vorst A. V., Rosen A., Kotsuka Y. RF/Microwave Interaction with Biological Tissues. IEEE Press, Wiley Interscience, A John Wiley &Sons., Inc., Publ., 2006. 346 p. https://doi.org/10.1002/0471752053

4. Dikusar E. A., Pushkarchuk A. L., Bezyazychnaya T. V., Potkin V. I., Soldatov A. G., Kutsen S. A., Stepin S. G., Nizovtsev A. P., Kilin S. Ya. Quantum-chemical modeling of methotrexate fullerenol radionuclide agents for cancer therapy. Vestsi Natsyyanal’nai akademii navuk Belarusi. Seryya khimichnykh navuk = Proceedings of the National Academy of Sciences of Belarus. Chemical series, 2019, vol. 55, no. 2, pp. 163–170 (in Russian). https://doi.org/10.29235/1561-8331-2019-55-2-163-170

5. Orlova M. A., Trofimova T. P., Orlov A. P., Shatalov O. A., Napolov Yu. K., Svistunov A. A., Chekhonin V. P. Antitumor activity of fullerene derivatives and their possible use for target drug delivery. Onkogematologiya = Oncohematology, 2013, vol. 8, no. 2, pp. 83–92 (in Russian). https://doi.org/10.17650/1818-8346-2013-8-2-83-92

6. Neese F., Wennmohs F., Becker U., Riplinger Ch. The ORCA quantum chemistry program package. The Journal of Chemical Physics, 2020, vol. 152, no. 22, pp. 224108(1)–224108(18). https://doi.org/10.1063/5.0004608

7. Ghosh S. K., Chattaraj P. K. Concepts and Methods in Modern Theoretical Chemistry. Atoms, Molecules and Clusters. CRC Press, 2013. 856 p. https://doi.org/10.1201/9780429069598

8. Tomasi J., Mennucci B., Cammi R. Quantum Mechanical Continuum Solvation Models. Chemical Reviews, 2005, vol. 105, no. 8, pp. 2999–3094. https://doi.org/10.1021/cr9904009

9. Grimme S., Antony J., Ehrlich S., Krieg H. A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. Journal of Chemical Physics, 2010, vol. 132, no. 15, pp. 154104(1)–154104(19). https://doi.org/10.1063/1.3382344

10. Alonso D., Hernández-Castillo D., Almagro L., González-Alemán R., Molero D., Herranz M. Á., Medina-Páez E., Coro J., Martínez-Álvarez R., Suárez M., Martín N. Diastereoselective Synthesis of Steroid–[60]Fullerene Hybrids and Theoretical Underpinning. Journal of Organic Chemistry, 2020, vol.85, no. 4, pp.2426–2437. https://doi.org/10.1021/acs.joc.9b03121

11. Fizer L., Fizer M. Steroids. Moscow, Mir Publ., 1964, pp. 619–748 (in Russian).

12. Adelstein S. J., Manning F. J. Isotopes for Medicine and the Life Sciences. Washington, DC, The National Academies Press., 1995. 144 p. https://doi.org/10.17226/4818

13. Bergmann H., Sinzinger H. Radioactive Isotopes in Clinical Medicine and Research. Basel, Rirkhäuser Verlag, 1995. 300 p. https://doi.org/10.1007/978-3-0348-7340-6

14. Thayer J. S. Relativistic Effects and the Chemistry of the Heavier Main Group Elements. Barysz M., Ishikawa Ya. (ed.). Relativistic Methods of Chemists (Challenges and Advances in Computational Chemistry and Physics). N.-Y., Springer, 2010, vol. 10, pp. 63–97. https://doi.org/10.1007/978-1-4020-9975-5_2

15. Laeter J. R. Böhlke J. K., Bièvre P., Hidaka H., Peiser H. S., Rosman K. J. R., Taylor P. D. P. Atomic weights of the elements. Review 2000 (IUPAC Technical Report). Pure and Applied Chemistry, 2003, vol. 75, no. 6, pp. 683–800. https://doi.org/10.1351/pac200375060683

16. Seydel J. K. Wiese M. Drug-Membrane Interactions: Analysis, Drug Distribution, Modeling. Weinheim, Wiley-VCH Verlag GmbH&Co. KGaA, 2002. 362 p. https://doi.org/10.1002/3527600639

17. Oren I., Sarel J., Kessel A., Ben-Tal N. Free Diffusion of Steroid Hormones Across Biomembranes: A Simplex Search with Implicit Solvent Model Calculations. Biophysical Journal, 2004, vol. 87, no. 2, pp. 768–779. https://doi.org/10.1529/biophysj.103.035527

18. Dikusar E. A., Potkin V. I., Pushkarchuk A. L., Bezyazychnaya T. V., Soldatov A. G., Kutsen S. A., Kilin S. Ya., Nizovtsev A. P. Quantum-chemical modeling of estrone-containing bisfullerenol radionuclide agents for the treatment of oncological diseases. Nanostruktury v kondensirovannykh sredakh: sbornik nauchnykh statei [Nanostructures in condensed matter. Collection of scientific articles]. Minsk: A. V. Luikov Heat and Mass Transfer Institute of NAS of Belarus, 2016, pp. 67–70 (in Russian).

19. Goloviznin V. M., Kondratenko P. S., Matveev L. V., Korotkin I. A., Dranikov I. L. Anomalous Radionuclide Diffusion in Highly Heterogeneous Geological Formations. Moscow, Nauka Publ., 2010. 342 p. (in Russian).

20. Yeagle P. L. (ed.). The Structure of Biological Membrans. 3rd ed. CRC Press Book: Tailor and Frances Gr., 2011. 398 p. https://doi.org/10.1201/b11018

21. Tosteson D. C. (ed.). Transport Across Single Biological Membranes. Vol. 2. Berlin, Heidelberg, N.-Y., Springer-Verlag,1979. 444 p. https://doi.org/10.1007/978-3-642-46375-4

22. Ting G., Chang C.-H., Wang H.-E., Lee T.-W. Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy. Journal of Biomedicine and Biotechnology, 2010, vol. 2010, Article ID 953537. https://doi.org/10.1155/2010/953537

23. Coenen H. H., Moerlein S. M., Stöckin G. No-Carrier-Added Radiohalogenation Methods with Heavy Halogens. Radiochem. Acta, 1983, vol. 34, no. 1–2, pp. 47−68. https://doi.org/10.1524/ract.1983.34.12.47

24. Sandler S. I. Chemical, biochemical, and engineering thermodynamics. John Wiley & Sons, 2017. 1040 p.

25. Demerel Y. Nonequilibrium thermodynamics: Transport and rate processes in physical, chemical and biological systems. 3rd ed. Amsterdam, Oxford: Elsevier Science, 2014. 792 p. https://doi.org/10.1016/C2012-0-00459-0

26. Mullin J. W. Crystallization. 4 th ed. Oxford, Butterworth Heinemann, 2001. 356 p. https://doi.org/10.1016/B978-0-7506-4833-2.X5000-1