Interaction of the anion [2-B₁₀H₉O(CH₂)₄O]− with secondary amines

Objectives. One of the most promising methods of treating malignant tumors is 10B-neutron capture therapy. While compounds based on cluster boron anions [B_nH_n]2− (n = 10, 12) are often used as boron-containing agents due to the very high specific concentration of boron atoms per particle, the use of such compounds is associated with the need to develop new methods for the functionalization of boron clusters associated with the production of boron-containing derivatives containing biologically active functional groups. One of the most convenient methods of modification of [B_nH_n]2− (n = 10, 12) anions is the interaction of their derivatives containing cyclic oxonium-type substituents with negatively charged or neutral nucleophilic reagents. The disclosure of substituents of this type leads to the formation of closo-borates with functional groups separated from the cluster by an alkoxyl spacer chain. The purpose of this study is to develop methods for the synthesis of derivatives of the closo-decaborate anion [B₁₀H₁₀]2− with pendant nitrogen-containing groups.
Methods. The general control of the reactions of the disclosure of cyclic substituents was carried out on the basis of ¹¹B nuclear magnetic resonance (NMR) spectroscopy data. The structure of the obtained derivatives, including the nature of the attached functional groups, was determined using ¹H, ¹³C attached proton test (APT) NMR and infrared (IR) spectroscopy data. The molecular weight of the synthesized compounds was confirmed by electrospray ionization mass-spectrometry (ESI–MS).
Results. The interaction of the anion [2-B₁0H₉O(CH₂)₄O]− with secondary amines (dimethylamine, dipropylamine, diallylamine, dibutylamine, diisobutylamine, morpholine, di-sec-butylamine) in an ethanol environment is investigated. As a result of the reactions, a cyclic substituent is shown to expand with the addition of a nucleophilic reagent. Seven new derivatives of the closodecaborate anion with pendant nitrogen-containing groups have been synthesized.
Conclusions. A developed method for obtaining closo-decaborates with ammonium groups separated from the boron cluster by an alkoxyl spacer group is presented. It is shown that the use of amines of various structures does not fundamentally affect the course of the reactions, allowing the composition and structure of the target derivatives to be effectively regulated. The resulting compounds can be involved in further modification reactions due to a reactive pendant group, as well as being suitable for use as effective polydentate ligands. Closo-decaborates with pendant nitrogen-containing groups and their derivatives are of considerable interest in the synthesis of compounds for use in 10B-neutron capture therapy of malignant tumors.

1. Zhao X., Yang Z., Chen H., Wang Z., Zhou X., Zhang H. Progress in three-dimensional aromatic-like closo-dodecaborate. Coord. Chem. Rev. 2021;444:214042. https://doi.org/10.1016/j.ccr.2021.214042

2. Sivaev I. B., Prikaznov A.V., Naoufal D. Fifty years of the closo-decaborate anion chemistry. Collect. Czechoslov. Chem. Commun. 2010;75(11):1149–1199. https://doi.org/10.1135/cccc2010054

3. Sivaev I.B., Bregadze V.I., Sjöberg S. Chemistry of closo-dodecaborate anion [B12H12]2-: a review. Collect. Czechoslov. Chem. Commun. 2002;67(6):679–727. https://doi.org/10.1135/cccc20020679

4. Pakhomov S., Kaszynski P., Young V.G. 10-Vertex closo-boranes as potential π linkers for electronic materials. Inorg. Chem. 2000;39(10):2243–2245. https://doi.org/10.1021/ic991350t

5. Paskevicius M., Hansen B.R., Jørgensen M., Richter B., Jensen T.R. Multifunctionality of silver closoboranes. Nat. Commun. 2017;8(1):15136. https://doi.org/10.1038/ncomms15136

6. Ringstrand B. Boron clusters as structural elements of novel liquid crystalline materials. Liquid Crystals Today. 2013;22(2):22–35. https://doi.org/10.1080/1358314X.2013.829932

7. Zharkov D.O., Yudkina A.V., Riesebeck T., Loshchenova P.S., Mostovich E.A., Dianov G.L. Boroncontaining nucleosides as tools for boron-neutron capture therapy. Am. J. Cancer Res. 2021;11(10):4668–4682.

8. Goszczyński T.M., Fink K., Boratyński J. Icosahedral boron clusters as modifying entities for biomolecules. Expert Opin. Biol. Ther. 2018;18(sup1):205–213. https://doi.org/10.1080/14712598.2018.1473369

9. Ali F., Hosmane N.S., Zhu Y. Boron chemistry for medical applications. Molecules. 2020;25(4):828. https://doi.org/10.3390/molecules25040828

10. Bregadze V.I., Sivaev I.B., Glazun S.A. Polyhedral boron compounds as potential diagnostic and therapeutic antitumor agents. Anti-Cancer Agents Med. Chem. (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2006;6(2):75–109. http://doi.org/10.2174/187152006776119180

11. Barth R.F., Mi P., Yang W. Boron delivery agents for neutron capture therapy of cancer. Cancer Commun. 2018;38(1):1–15. https://doi.org/10.1186/s40880-018-0299-7

12. Jørgensen M., Hansen B.R., Lee Y.S., Cho Y.W., Jensen T.R. Crystal Structures and Energy Storage Properties of Ammine Sodium Decahydro-closo-decaboranes (Na2B10H10·nNH3, n = 1, 2). J. Phys. Chem. C. 2019;123(33):20160–20166. https://doi.org/10.1021/acs.jpcc.9b06084

13. Suzuki M. Boron neutron capture therapy (BNCT): a unique role in radiotherapy with a view to entering the accelerator-based BNCT era. Int. J. Clin. Oncol. 2020;25(1):43–50. https://doi.org/10.1007/s10147-019-01480-4

14. Moss R.L. Critical review, with an optimistic outlook, on Boron Neutron Capture Therapy (BNCT). Appl. Radiat. Isot. 2014;88:2–11. https://doi.org/10.1016/j.apradiso.2013.11.109

15. Matveev E.Y., Kubasov A.S., Razgonyaeva G.A., Polyakova I.N., Zhizhin K.Y., Kuznetsov N.T. Reactions of the [B10H10]2− anion with nucleophiles in the presence of halides of group IIIA and IVB elements. Russ. J. Inorg. Chem. 2015;60(7):776–785. https://doi.org/10.1134/S0036023615070104

16. Zhizhin K.Y., Zhdanov A.P., Kuznetsov N.T. Derivatives of closo-decaborate anion [B10H10]2− with exo-polyhedral substituents. Russ. J. Inorg. Chem. 2010;55(14):2089–2127. https://doi.org/10.1134/S0036023610140019

17. Stogniy M.Y., Erokhina S.A., Sivaev I.B., Bregadze V.I. Nitrilium derivatives of polyhedral boron compounds (boranes, carboranes, metallocarboranes): Synthesis and reactivity. Phosphorus, Sulfur, Silicon Relat. Elem. 2019;194(10):983–988. https://doi.org/10.1080/10426507.2019.1631312

18. Klyukin I.N., Zhdanov A.P., Matveev E.Y., Razgonyaeva G.A., Grigoriev M.S., Zhizhin K.Y., Kuznetsov N.T. Synthesis and reactivity of closo-decaborate anion derivatives with multiple carbon–oxygen bonds. Inorg. Chem. Commun. 2014;50:28–30. https://doi.org/10.1016/j.inoche.2014.10.008

19. Klyukin I.N., Kubasov A.S., Limarev I. P., et al. The new approach to formation of exo boron–oxygen bonds from the decahydro-closo-decaborate(2-) anion. Polyhedron. 2015;101:215–222. https://doi.org/10.1016/j.poly.2015.09.025

20. Nelyubin A.V., Klyukin I.N., Novikov A.S., et al. Nucleophilic addition of amino acid esters to nitrilium derivatives of closo-decaborate anion. Mendeleev Commun. 2021;31(2):201–203. https://doi.org/10.1016/J.MENCOM.2021.03.018

21. Nelyubin A.V., Selivanov N.A., Bykov A.Y., et al. Primary Amine Nucleophilic Addition to Nitrilium Closo-Dodecaborate [B12H11NCCH3]−: A Simple and Effective Route to the New BNCT Drug Design. Int. J. Mol. Sci. 2021;22(24):13391. https://doi.org/10.3390/ijms222413391

22. Kubasov A.S., Turishev E.S., Polyakova I.N., Matveev E.Y., Zhizhin K.Y., Kuznetsov N.T. The method for synthesis of 2-sulfanyl closo-decaborate anion and its S-alkyl and S-acyl derivatives. J. Organomet. Chem. 2017;828:106–115. https://doi.org/10.1016/j.jorganchem.2016.11.035

23. Kubasov A.S., Matveev E.Y., Turyshev E.S., Polyakova I.N., Nichugovskiy A.I., Zhizhin K.Y., Kuznetsov N.T. Synthesis and stability studies of derivatives of the 2-sulfanyl-closo-decaborate anion [2-B10H9SH]2−. Inorganica Chim. Acta. 2018;477:277–283. https://doi.org/10.1016/j.ica.2018.03.013

24. Semioshkin A. A., Sivaev I. B., Bregadze V. I. Cyclic oxonium derivatives of polyhedral boron hydrides and their synthetic applications. Dalton Trans. 2008;(8):977–992. https://doi.org/10.1039/B715363E

25. Orlova A.V., Kondakov N.N., Kimel B.G., Kononov L.O., Kononova E.G., Sivaev I.B., Bregadze V.I. Synthesis of novel derivatives of closo‐dodecaborate anion with azido group at the terminal position of the spacer. Appl. Organomet. Chem. 2007;21(2):98–100. https://doi.org/10.1002/aoc.1151

26. Matveev E.Yu., Akimov S.S., Kubasov A.S., Nichugovskiy A.I., Nartov A.S., Retivov V.M., Zhizhin K.Yu., Kuznetsov N.T. Reaction of the [B10H9O2C4H8]– anion with C-nucleophiles. Rus. J. Inorg. Chem. 2017;62(6):808–813 https://doi.org/10.1134/S0036023617060146

27. Matveev E.Y., Limarev I.P., Nichugovskii A.I., Bykov A.Y., Zhizhin K.Y., Kuznetsov N.T. Derivatives of closo-decaborate anion with polyamines. Rus. J. Inorg. Chem. 2019;64(8):977–983. https://doi.org/10.1134/S0036023619080084

28. Bregadze V.I., Sivaev I.B., Dubey R.D., Semioshkin A., Shmal’ko A.V., Kosenko I.D., Hosmane N.S. Boron‐Containing Lipids and Liposomes: New Conjugates of Cholesterol with Polyhedral Boron Hydrides. Chem. Eur. J. 2020;26(61),13832–13841. https://doi.org/10.1002/chem.201905083

29. Grin M.A., Semioshkin A.A., Titeev R.A., et al. Synthesis of a cycloimide bacteriochlorin p conjugate with the closo-dodecaborate anion. Mendeleev Commun. 2007;17(1):14–15. https://doi.org/10.1016/j.mencom.2007.01.005

30. Matveev E.Y., Akimov S.S., Kubasov A.S., Retivov V.M., Zhizhin K.Y., Kuznetsov N.T. The method for obtaining a derivative closo-decaborate anion with pendante DTPA-group. Fine Chem. Technol.2019;14(1):59–65. https://doi.org/10.32362/2410-6593-2019-14-1-59-65

31. Zhizhin K.Yu., Mustyatsa V.N., Malinina E.A., et al. Interaction of closo-decaborate anion B10H10 2– with cyclic ethers. Russ. J. Inorg. Chem. 2004;49(2):180–189.

32. Becker H., Domshke G., Fanghanel E. Organikum. Organisch-chemisches Grundpraktikum. Berlin: VEB Deutscher Verlag der Wissenschaften; 1990. 751 p.