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

In order to therapeutically destroy neoplasms, chemotherapy or radiotherapy is usually applied, and in isotope medicine short-lived radionuclides are injected into the tumor (⁵⁹Fe, ⁹⁰Y, ⁹⁵Zr, ⁹⁹mTc, ¹⁰⁶Ru, ^114*In, ¹⁴⁷Eu, ¹⁴⁸Eu, ¹⁵⁵Eu, ¹⁷⁰Tm, ¹⁷⁷mLu, ¹⁸⁸Re, ²¹⁰Po, ²²²Rn, ²³⁰U, ²³⁷Pu, ²⁴⁰Cm, ²⁴¹Cm, ²⁵³Es). Binary (or neutron capture) therapy is a technology designed to selectively treat malignant tumors and using drugs tropic to tumors containing non-radioactive nuclides (¹⁰B, ¹¹³Cd, ¹⁵⁷Gd at al.). Triadic therapy is the sequential introduction into the body of a combination of two or more separately inactive and harmless components, tropic to tumor tissues and capable of selectively accumulating in them or entering into chemical interaction with each other and destroying tumor neoplasms under certain sensitizing external influences. The aim of this work is to quantum-chemically simulate the electronic structure and to analyze the thermodynamic stability of new doxorubicino-fullerenol agents for the treatment of tumor neoplasms. The need for preliminary studies on the modeling of such objects is due to the extremely 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/10.1201/9780429201493

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., Kotuska Y. RF/Microwave interaction with biological tissues. 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 А. G., Kuten S. А., 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. Dikusar E. A., Pushkarchuk A. L., Bezyazychnaya T. V., Akishina E. A., Soldatov А. G., Kuten S. А., Stepin S. G., Nizovtsev A. P., Kilin S. Ya., Potkin V. I. Quantum-chemical modeling of cortisone-fullerenol agents of cancer therapy. Vestsi Natsyyanal’nai akademii navuk Belarusi. Seryya khimichnykh navuk = Proceedings of the National Academy of Sciences of Belarus. Chemical Series, 2021, vol. 57, no. 4, pp. 400–407 (in Russian). https://doi.org/10.29235/1561-8331-2021-57-4-400-407

6. Dikusar E. A., Pushkarchuk A. L., Bezyazychnaya T. V., Akishina E. A., Soldatov A. G., Kuten S. А., Stepin S. G., Nizovtsev A. P., Kilin S. Ya., Babichev L. F., Potkin V. I. Prospects for creating radon-containing agents in radionuclide therapy. Vestnik farmatsii [Pharmacy Bulletin], 2021, no. 3 (93), pp. 64–72. (in Russian).

7. 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, no. 2, pp. 83−92 (in Russian). https://doi.org/10.17650/1818-8346-2013-8-2-83-92

8. Dikusar E. A., Pushkarchuk A. L., Bezyazychnaya T. V., Kosandrovich Е. G., Soldatov А. G., Kuten S. А., Stepin S. G., Nizovtsev A. P., Kilin S. Ya. Tetracozahydroxybacminsterfullerenol – reagent of the future. Khimicheskie reaktivy, reagenty i protsessy malotonnazhnoi khimii: tez. dokl. XXXI Mezhdunarod. nauch.-tekhn. konf.: Reaktiv – 2018, 2–4 okt. 2018 g., Minsk, Belarus’ [Chemical reagents, reagents and processes of low-tonnage chemistry: Proceedings of the XXXI International Scientific and Technical Conference “Reagent-2018”, October 2–4. 2018, Minsk, Belarus = Minsk, Belaruskaya nauka Publ., 2018, pp. 22 (in Russian).

9. Shmidt M. W., Baldridge K. K., Boatz J. A., Elbert S. T., Gordon M. S., Jensen J. H., Koseki S., Matsunaga N., Nguyen K. A., Su S. J., Midus T. L., Dupnis M., Montgomery J. A. General Atomic and Molecular Electronic-Structure System. Journal of Computational Chemistry, 1993, vol. 14, no. 7, pp. 1347–1363.

10. Huzinaga S., Andzelm J., Radzio-Andzelm E., Sakai Y., Tatewaki H., Klobukowski M. Gaussian Basis Sets for Molecular Calculations. Amsterdam: Elsevier, 1984. https://doi.org/10.1016/c2009-0-07152-9

11. Acramone F. Doxorubicin: Anticancer Antibiotics. Medicinal chemistry, a series of monographs. Academic Press, Elsiver, 1981, vol. 17. 369 p. https://doi.org/10.1016/c2012-0-01427-5

12. Averin P. S., Lopes de Gerenyu A. V., Balabushevich N. G. Polyelectrolyte microand nanoparticles with doxorubicin. Moscow University Chemistry Bulletin, 2016, vol. 71, no. 2, pp. 140–145. https://doi.org/10.3103/s0027131416020012

13. Pan C., Liu Y., Zhou M., Wang W., Shi M., Xing M., Liao W. Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment. International Journal of Nanomedicine, 2018, vol. 13, pp. 1119–1137. https://doi.org/10.3389/fphar.2020.598155

14. Xu B., Yuan L., Hu Y., Xu Z., Qin J.-J., Cheng X.-D. Synthesis, Characterization, Cellular Uptake, and in vitrio Anticancer Activity of Fullerenol-Doxorubicin Conjugates. Frontieres in Pharmacology, 2021, vol. 11, no. article 598155 (10 p.). https://doi.org/10.3389/fphar.2020.598155

15. Gilbertsen S. R., Butt M., Memon Z., Vouche K., Hickey M., Baker R., Abecassis T., Atassi M. M., Riaz R., Cella A., Burns D., Ganger J. L., Benson D., Mulcahy A. B., Kulik M. F., Lewandowski L. Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clinical Gastroenterology and Hepatology, 2013, vol. 11, no. 10, pp. 1358–1365. https://doi.org/10.1016/j.cgh.2013.04.028

16. 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

17. 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

18. Thayer J. S. Relativistic Effects and the Chemistry of the Heavier Main Group Elements. Barysz M., Ishikawa Ya. (eds.). Relativistic Methods of Chemists (Challenges and Advances in Computational Chemistry and Physics). N.-Y.: Springer, 2010, ch. 2, pp. 63–97. https://doi.org/10.1007/978-1-4020-9975-5_2

19. Laeter J. R., Bohlke J. K., De Bievre P., Hidaka H., Peiser H.S., Rosman K. J. R., Taylor 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

20. Dikusar E. A., Zelenkovskii V. M., Pushkarchuk A. L., Rudakov D. A., Kilin S. Ya., Soldatov A. G., Kholoptsev A. V., Batrakov G. F. Estimation the possibility of using endohedral radon-222-containing derivatives of C60 and C80 buckminsterfullerenes as nanorobots – fighters of tumor neoplasms. Meditsinskie novosti = Medical News, 2013, no. (3), pp. 11–12 (in Russian).

21. Dikusar E. A., Zelenkovskii V. M., Pushkarchuk A. L., Kilin S. Ya., Soldatov A. G., Kuten S. A., Khmialeuski A. N., Babicheu L. F. Quantum chemical designing of endohedral containing Po210 derivatives of buckminsterfullerene C60 – C80 for development of radionuclide nanosized agents for cancer therapy. Nonlinear Dynamics and Applications: Proceedings of the 21-th Annual Seminar (NPCS’2014). Minsk, 2014, vol. 20, pp. 50–55.

22. Banaru A. M., Banaru D. A. Crystal structural regularities of the structure of crystalline hydrates with infinite H2O... OH2 motifs. Krasnoyarsk, SIC., 2021. 196 p. (in Russian). https://doi.org/10.12731/978-5-907208-48-3

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

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

25. 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

26. Tosteson D. C. (ed.). Transport Across Single Biological Membranes. Giebisch G., C. Tosteson D., Ussing H. H. (eds.). Membrane Transport in Biology. Berlin; Heidelberg; N.-Y.: Springer-Verlag, 1979, vol. 2. 444 p. https://doi.org/10.1007/978-3-642-46375-4

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

28. 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

29. 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

30. Mostapenko V. M., Turnov N. Ya. The Casimir effect and its applications. Moscow: Energoatomizdat Publ., 1990. 216 p. (in Russian).

31. Putz M. V., Putz A. M. DFT chemical reactivity driven by biological activity: applications for the toxicological fate of chlorinated PAHs. Putz M. V., Mingos M. P. (eds.). Applications of Density Functional Theory to Biological and Bioinorganic Chemistry. Springer Link, Berlin, 2013, pp. 181–231. https://doi.org/10.1007/978-3-642-32750-6_6

32. Oganessian Yu. Ts., Utyonkov V. K., Lobanov Yu. V., Abdullin F. Sh., Polyakov A. N., Shirokovsky I. V., Tsyganov Yu. S., Gulbekian G.G., Lobanov Yu. V., Abdullin F. Sh., Shirokovsky I. V., Bogomolov S.L., Gikal B. N., Mezentsev A. N., Iliev S., Subbotin V. G., Sukhov A. M., Voinov A. A., Buklanov G. V., Subotic K., Zagrebaev V. I., Itkis M. G., Patin J. B., Moody K. J., Wild J. F., Stoyer M. A., Stoyer N. J., Shaughnessy D. A., Kenneally J. M., Lougheed R. W. Heavy Element Research at Dubna. Nuclear Physics A, 2004, vol. 734, no. 1–4, pp. 109–123. https://doi.org/10.1016/j.nuclphysa.2004.01.020

33. Sundqvist B. Fullerens under high pressure. Kadish K. M., Ruoff R. S. (eds.). Fullerens: chemistry, physics, and technology. N.-Y., Wiley-Interscience, 2000. 984 p.