2020 Volume 3 Issue 2

INEOS OPEN, 2020, 3 (2), 70–74  Journal of Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences Download PDF Electronic supplementary information DOI: 10.32931/io2008a

Synthesis of Novel Conjugates of closo-Dodecaborate Derivatives with Cholesterol

Abstract

New closo-dodecaborate-containing cholesterols are synthesized by the ring-opening reactions of the cyclic oxonium derivatives of [B₁₂H₁₂]^2– with modified cholesterol. The compounds obtained are of potential interest for the delivery of liposomal drugs in boron neutron capture therapy of cancer.

Key words: polyhedral boron hydrides, closo-dodecaborate, cholesterol, liposomes, boron neutron capture therapy (BNCT).

 

Introduction

 Boron neutron capture therapy (BNCT) is a promising binary method for the treatment of cancer, which is based on the selective accumulation of the non-radioactive isotope ¹⁰B in tumor cells and their subsequent treatment with low-energy thermal neutrons [1–4]. The most important requirements to novel boron compounds for BNCT are the minimum tumor concentrations in the range of 20–35 μg ¹⁰B per gram of tumor tissue and the selective delivery to tumor cells [5]. At present, there are two boron compounds that have been extensively studied in clinical BNCT trials: l-p-dihydroxy-borylphenylalanine (BPA) [6] and disodium mercaptoundecahydro-closo-dodecaborate (BSH) (Fig. 1) [7–11]. In some cases, the treatment efficiency can be improved by a combination of BPA and BSH. However, both of the boron carriers are not ideal for the targeted delivery of the therapeutic amount of ¹⁰B toward the tumor. The results of clinical studies with these compounds are not very attractive because of their low selectivities and long retention times in tumors [12, 13].

Figure 1. l-p-Dihydroxy-borylphenylalanine (BPA) and disodium mercaptoundecahydro-closo-dodecaborate (BSH).

Among a broad range of boron compounds, of particular interest as promising agents for BNCT are the functional derivatives of closo-dodecaborate dianion [B₁₂H₁₂]^2– [1, 14]. It was shown that the oxonium derivatives of the closo-dodecaborate dianion are useful synthons for the preparation of various derivatives with biologically active molecules for medical application [15–18] through ring-opening reactions with different nucleophiles [19–25].

The use of liposomes is a high-tech method for the targeted delivery of drugs to cancer cells [26, 27]. Due to the high permeability of blood vessel walls inside a tumor, liposomes are capable of passive targeting and penetrating into the tumor [28, 29]. In addition, the introduction of vector molecules into the composition of the liposome membrane surface can improve the targeting properties for tumors [30, 31]. The liposomal transport can also be used to deliver different types of boron polyhedral hydrides to the tumor, which on their own are not able to penetrate through cell membranes [32, 33]. The reported examples of liposomes based on polyhedral hydrides, such as the derivatives of boranes and carboranes [34–37], were produced both by the encapsulation of boron compounds in an aqueous core of liposomes and by the incorporation of boron-containing lipids in a liposome bilayer [38–40].

One of the observed differences between tumor and normal cells is the rate of metabolism of low-density lipoproteins. This difference stems from the increased need of tumor cells for cholesterol for the formation of new cell membranes. Therefore, the synthesis of boron-containing derivatives of cholesterol can become an efficient approach for the boron delivery to cancer cells using liposomes. Herein, we report on the synthesis of novel conjugates of the closo-dodecaborate dianion ([B₁₂H₁₂]^2–) with cholesterol by the nucleophilic opening of the cyclic oxonium derivatives of [B₁₂H₁₂]^2–.

Results and discussion

Recently, we have synthesized a series of cholesterols conjugated with cobalt bis(1,2-dicarbollide)(-1) [41] and closo-dodecaborate [42] via a click-reaction. Poly(ethylene glycol) units are widely used as covalent modifiers of biological macromolecules and particulates as well as linkers for bioconjugates with various biologically relevant molecules. The oxonium derivatives of closo-dodecaborate react with alcohols to give the corresponding substituted derivatives of closo-dodecaborate [18, 43]. The syntheses of the closo-dodecaborate-containing cholesterols by the ring-opening reactions of the cyclic oxonium derivatives with cholesterol alcoholate were described only in a conference abstract [44], which did not include any experimental procedure. Our attempts to obtain the related conjugates with a flexible poly(ethylene glycol) spacer by the ring-opening reaction of [B₁₂H₁₂]^2– with cholesterol using NaH were not successful.

In this work, we used closo-dodecaborate derivatives with different oxonium cycles 1–4 and the cholesterol derivative modified with the hydroxy group, namely, 3β-(2-hydroxyethoxy)cholest-5-ene 5, which was synthesized according to the published procedure by the nucleophilic substitution of cholesterol tosylate with ethylene glycol [45]. The cholesterol–closo-dodecaborate conjugates were obtained in a simple one-step procedure based on the nucleophilic ring-opening reactions of the oxonium derivatives of boron clusters 1–4 with modified cholesterol 5. It was found that compounds 1–4 react with modified cholesterol 5 in the presence of two-fold molar excess of NaH used as a strong base for the generation of an alcoholate ion, resulting in new cholesterol derivatives of the closo-dodecaborate dianion. In all cases, the reaction course was monitored by thin-layer chromatography using CH₂Cl₂–CH₃OH (10:1) mixture as an eluent. Dianionic derivatives 6–9 were isolated as Cs salts and purified by precipitation from a methanol solution in good yields (Scheme 1). This afforded the cholesterol derivatives of [B₁₂H₁₂]^2– featuring different spacers between the boron cage and the biological macromolecule. The ring-opening of 1,4-dioxane-substituted [B₁₂H₁₂]^2– under the action of the modified cholesterol afforded compounds 7 and 9 bearing hydrophilic –(CH₂CH₂O)₂– spacers, whereas the tetrahydrofuran and tetrahydropyran analogs gave rise to compounds 6 and 8 bearing lipophilic –(CH₂)_4–5– spacers between the boron cage and the bioactive part of the molecule. These spacers can be considered as long units featuring high flexibility degrees and biocompatibility, which can be introduced using a simple synthetic procedure.

Scheme 1. Synthesis of closo-dodecaborate derivatives of cholesterol 6–9.

The structures of all novel conjugates 6–9 were unambiguously confirmed by the NMR and IR spectroscopic as well as HRMS (ESI) data (see Experimental). The ¹¹B NMR spectra of compounds 6–9 display four signals in 1:5:5:1 ratio, which is characteristic of monosubstituted boron clusters with the B–O bond. The signal of B(1)–O substituted boron atom at δ ~ 6.0–6.5 ppm appeared to be shifted by ~3 ppm compared to that of starting compounds 1–4 (δ ~ 9.2–9.6 ppm), which is typical for a transition from the BO⁺R₂ system to the B(1)–OR [18] system and unequivocally proves the opening of the oxonium ring. The ¹H NMR spectra of compounds 6–9 display the characteristic signals of Cst(6)H alkene protons of the cholesterol unit at δ = 5.31, 5.32, 5.32, and 5.31 ppm, respectively. The positions and number of the signals of the cholesterol moiety in the ¹Н and ¹³C{¹H} NMR spectra of the resulting compounds are in good agreement with the previously reported data [46]. The IR spectra of compounds 6–9 show characteristic absorption bands of the BH groups (see Experimental). Compounds 6–9 will be used to obtain boronated liposomes in order to study the delivery of new boron clusters to cancer cells for a BNCT experiment.

Experimental

General remarks

Oxonium derivatives of closo-dodecaborate 1–4 [33] and 3β-(2-hydroxyethoxy)cholest-5-ene 5 [45] were synthesized according to the published procedures. Sodium hydride (60% dispersion in mineral oil) and cesium fluoride were purchased from Sigma-Aldrich and used without further purification. Tetrahydrofuran was distilled via a standard technique. Cholesterol, methanol, and CH₂Cl₂ were commercial reagents of analytical grade. The reaction course was monitored by thin-layer chromatography (Merck F245 silica gel on aluminum plates) and visualized using 0.5% PdCl₂ in 1% HCl in aq. MeOH (1:10). The NMR spectra at 400.1 MHz (¹H), 128.4 MHz (¹¹B), and 100.0 MHz (¹³C) were measured in (CD₃)₂SO on a Bruker Avance 400 spectrometer. The residual signals of the NMR solvent relative to Me₄Si were used as the internal references for the ¹H and ¹³C NMR spectra. The ¹¹B NMR spectra were referenced using BF₃·Et₂O as an external standard. The IR spectra were recorded on a SHIMADZU IR Prestige-21 spectrometer. The high-resolution mass spectra (HRMS) were measured on a Brukermict OTOF II instrument using electrospray ionization (ESI). The measurements were carried out in a negative ion mode (interface capillary voltage 3200 V); mass range from m/z 50 to m/z 3000; external or internal calibration was performed with ESI Tuning Mix, Agilent. A syringe injection was used for solutions in MeCN/H₂О (1:1) (flow rate 3 µL/min). Nitrogen was applied as a dry gas; the interface temperature was set at 180 ^oC. The electron ionization mass spectra were obtained with a Kratos MS 890 instrument operating in the mass range of 50–800.

Syntheses

General procedure for the synthesis of closo-dodecaborate conjugates with cholesterol (6–9). Sodium hydride (60% dispersion in mineral oil, 2.0 eq.) was added to a solution of 3β-(2-hydroxyethoxy)cholest-5-ene 5 (1.2 eq.) in THF (30 mL) under an argon atmosphere. The resulting mixture was stirred for 1 h. Then, the corresponding oxonium derivative (1.0 eq.) was added. The reaction mixture was refluxed for 8 h. After cooling to room temperature, methanol (3–4 drops) was added to remove the excess of sodium hydride. The solvent was evaporated in vacuo. The resulting residue was dissolved in MeOH (5 mL). Then, a solution of CsF (1.5 eq.) in MeOH (5 mL) was added. The resulting precipitate was collected by filtration and dried in vacuo to give the target products as white solids.

[3β-Chol-(O(CH₂)₂)₂(CH₂)₃O-(B₁₂H₁₁)]Cs₂ (6). The compound was prepared according to the general procedure from tetrahydropyran derivative of closo-dodecaborate 1 (0.32 g), 3β-(2-hydroxyethoxy)cholest-5-ene 5 (0.35 g), and sodium hydride (60% dispersion in mineral oil, 0.07 g). Yield: 0.40 g (64%). ¹H NMR ((CD₃)₂SO, δ, ppm, J/Hz): 5.31 (s, 1H, Cst(6)H), 3.50 (m, 2H, CH₂O), 3.42 (m, 2H, CH₂O), 3.22 (m, 2H, CH₂O), 3.17 (m, 2H, CH₂O), 3.10 (m, 1H, Cst(3)H), 2.31 (m, 1H), 2.10 (m, 2H), 1.94 (m, 4H), 1.79 (m, 6H), 1.43 (m, 12H), 1.32 (m, 12H), 1.14 (m, 14H), 0.94 (s, 3H, Cst(19)H₃), 0.89 (d, 3H, J = 6.6, Cst(21)H₃), 0.85 (s, 3H, Cst(26)H₃), 0.83 (s, 3H, Cst(27)H₃), 0.64 (s, 3H, Cst(18)H₃). ¹³C NMR ((CD₃)₂SO, δ, ppm): 141.0 (Cst(5)), 121.5 (Cst(6)), 78.9 (Cst(3)), 71.0 (O-CH₂), 70.2 (O-CH₂), 68.5 (O-CH₂), 67.1 (O-CH₂), 56.6 (Cst(14)), 56.0 (Cst(17)), 50.1 (Cst(9)), 42.3 (Cst(4)), 39.4 (Cst(12)), 39.2 (Cst(13)), 37.2 (Cst(24)), 36.8 (Cst(1)), 36.1 (Cst(10)), 35.7 (Cst(22)), 32.2 (CH₂), 31.9 (Cst(20)), 31.8 (Cst(8)), 29.9 (Cst(2)), 28.5 (CH₂), 28.3 (Cst(7)), 27.9 (Cst(16)), 24.3 (Cst(25)), 23.7 (Cst(15)), 23.1 (Cst(23)), 22.9 (Cst(26), Cst(27)), 21.1 (Cst(11)), 19.5 (Cst(19)), 19.0 (Cst(21)), 12.2 (Cst(18)). ¹¹B NMR ((CD₃)₂SO, δ, ppm, J/Hz): 6.4 (s, 1B, B-O), –16.8 (d, 5B, J = 132), –18.3 (d, 5B, J = 142), –23.0 (d, 1B, J = 110). HRMS (ESI) m/z: found 328.3266 [C₃₄H₇₀B₁₂O₃]^2–; calcd 328.3273. IR (solid, ν, cm^–1): 2478 (BH).

[3β-Chol-(O(CH₂)₂)₃O-(B₁₂H₁₁)]Cs₂ (7). The compound was prepared according to the general procedure from 1,4-dioxane derivative of closo-dodecaborate 2 (0.20 g), 3β-(2-hydroxyethoxy)cholest-5-ene 5 (0.22 g), and sodium hydride (60% dispersion in mineral oil, 0.04 g). Yield: 0.35 g (90%). ¹H NMR ((CD₃)₂SO, δ, ppm, J/Hz): 5.32 (s, 1H, Cst(6)H), 3.62 (m, 2H, CH₂O), 3.37 (m, 10H, CH₂O), 3.13 (m, 1H, Cst(3)H), 2.35 (m, 1H), 2.10 (m, 2H), 1.87 (m, 7H), 1.49 (m, 7H), 1.34 (m, 9H), 1.10 (m, 14H), 0.94 (s, 3H, Cst(19)H₃), 0.89 (d, 3H, J = 6.3, Cst(21)H₃), 0.85 (s, 3 H, Cst(26)H₃), 0.83 (s, 3 H, Cst(27)H₃), 0.64 (s, 3 H, Cst(18)H₃). ¹³C NMR ((CD₃)₂SO, δ, ppm): 141.0 (Cst(5)), 121.6 (Cst(6)), 79.0 (Cst(3)), 72.6 (O-CH₂), 70.4 (O-CH₂), 70.2 (O-CH₂), 69.6 (O-CH₂), 67.5 (O-CH₂), 66.9 (O-CH₂), 56.7 (Cst(14)), 56.0 (Cst(17)), 50.1 (Cst(9)), 42.3 (Cst(4)), 39.4 (Cst(12)), 39.0 (Cst(13)), 37.2 (Cst(24)), 36.8 (Cst(1)), 36.1 (Cst(10)), 35.7 (Cst(22)), 31.9 (Cst(20)), 31.9 (Cst(8)), 31.2 (Cst(2)), 28.4 (Cst(7)), 27.9 (Cst(16)), 24.3 (Cst(25)), 23.7 (Cst(15)), 23.1 (Cst(23)), 22.9 (Cst(26), Cst(27)), 21.1 (Cst(11)), 19.6 (Cst(19)), 19.0 (Cst(21)), 12.2 (Cst(18)). ¹¹B NMR ((CD₃)₂SO, δ, ppm, J/Hz): 6.0 (s, 1B, B-O), –16.8 (d, 5B, J = 137), –18.1 (d, 5B, J = 146), –22.7 (d, 1B, J = 117).  HRMS (ESI) m/z: found 321.3200 [C₃₃H₆₈B₁₂O₃]^2–; calcd 321.3194. IR (solid, ν, cm^–1): 2476 (BH).

[3β-Chol-(O(CH₂)₂)₂(CH₂)₂O-(B₁₂H₁₁)]Cs₂ (8). The compound was prepared according to the general procedure from tetrahydrofuran derivative of closo-dodecaborate 3 (0.32 g), 3β-(2-hydroxyethoxy)cholest-5-ene 5 (0.36 g), and sodium hydride (60% dispersion in mineral oil, 0.07 g). Yield: 0.35 g (55%). ¹H NMR ((CD₃)₂SO, δ, ppm, J/Hz): 5.32 (s, 1H, Cst(6)H), 3.51 (m, 2H, CH₂O), 3.43 (m, 4H, CH₂O), 3.22 (m, 2H, CH₂O), 3.11 (m, 1H, Cst(3)H), 2.32 (m, 1H), 2.08 (m, 1H), 1.95 (m, 2H), 1.82 (m, 4H), 1.50 (m, 6H), 1.35 (m, 16H), 1.11 (m, 10H), 0.95 (s, 3H, Cst(19)H₃), 0.90 (d, 3H, Cst(21)H₃, J=6.4,), 0.85 (s, 3H, Cst(26)H₃), 0.84 (s, 3H, Cst(27)H₃), 0.65 (s, 3H, Cst(18)H₃).¹³C NMR ((CD₃)₂SO, δ, ppm): 141.0 (Cst(5)), 121.5 (Cst(6)), 78.9 (Cst(3)), 71.2 (O-CH₂), 70.2 (O-CH₂), 68.2 (O-CH₂), 67.1 (O-CH₂), 56.6 (Cst(14)), 56.0 (Cst(17)), 50.1 (Cst(9)), 42.3 (Cst(4)), 39.4 (Cst(12)), 39.2 (Cst(13)), 37.2 (Cst(24)), 36.8 (Cst(1)), 36.1 (Cst(10)), 35.7 (Cst(22)), 31.9 (Cst(20)), 31.8 (Cst(8)), 28.8 (CH₂), 28.5 (Cst(2)), 28.3 (Cst(7)), 27.9 (Cst(16)), 24.3 (Cst(25)), 23.7 (Cst(15)), 23.1 (Cst(23)), 22.9 (Cst(26),Cst(27)), 21.1 (Cst(11)), 19.5 (Cst(19)), 19.0 (Cst(21)), 12.2 (Cst(18)). ¹¹B NMR ((CD₃)₂SO, δ, ppm, J/Hz): 6.5 (s, 1B, B-O), –16.8 (d, 5B, J = 126), –18.3 (d, 5B, J = 134), –23.0 (d, 1B, J = 132). HRMS (ESI) m/z: found 972.7805 [C₃₃H₆₈B₁₂O₄]^2–; calcd 972.7814. IR (solid, ν, cm^–1): 2480 (BH).

[3β-Chol-(O(CH₂)₂)₃O-(B₁₂H₁₀I)]Cs₂ (9). The compound was prepared according to the general procedure from 1-iodine-7-(1,4-dioxane) derivative of closo-dodecaborate 4 (0.30 g), 3β-(2-hydroxyethoxy)cholest-5-ene 5 (0.52 g), and sodium hydride (60% dispersion in mineral oil, 0.10 g). Yield: 0.26 g (49%). ¹H NMR ((CD₃)₂SO, δ, ppm): 5.31 (br. s, 1H, Cst(6)H), 3.49 (m, 10H, CH₂O), 3.14 (m, 3H, CH₂O, Cst(3)H), 2.10 (m, 2H), 1.87 (m, 8H), 1.41 (m, 17H), 1.36 (m, 9H), 1.10 (m, 14H), 0.95 (br. s, 3H, Cst(19)H₃), 0.84 (br. s, 9H, Cst(21)H₃, Cst(26)H₃, Cst(27)H₃), 0.65 (s, 3H, Cst(18)H₃). ¹³C NMR ((CD₃)₂SO, δ, ppm): 141.0 (Cst(5)), 121.5 (Cst(6)), 79.0 (Cst(3)), 72.5 (O-CH₂), 70.4 (O-CH₂), 70.2 (O-CH₂), 69.7 (O-CH₂), 67.6 (O-CH₂), 66.9 (O-CH₂), 56.7 (Cst(14)), 56.0 (Cst(17)), 50.1 (Cst(9)), 42.3 (Cst(4)), 39.4 (Cst(12)), 39.1 (Cst(13)), 37.2 (Cst(24)), 36.8 (Cst(1)), 36.1 (Cst(10)), 35.7 (Cst(22)), 31.9 (Cst(20)), 31.9 (Cst(8)), 28.4 (Cst(2)), 28.3 (Cst(7)), 27.9 (Cst(16)), 24.3 (Cst(25)), 23.7 (Cst(15)), 23.2 (Cst(23)), 22.9 (Cst(26), Cst(27)), 21.1 (Cst(11)), 19.6 (Cst(19)), 19.0 (Cst(21)), 12.2 (Cst(18)). ¹¹B NMR ((CD₃)₂SO, δ, ppm, J/Hz): 6.1 (s, 1B), –15.5 (d, 1B, J = 142), –16.6 (d, 4B, J = 151), –18.1 (d, 4B, J = 149), –21.4 (m, 2B). HRMS (ESI) m/z: found 392.2658 [C₃₃H₆₇B₁₂IO₄]^2–; calcd 392.2652. IR (solid, ν, cm^–1): 2486 (BH).

Conclusions

A series of closo-dodecaborate-containing cholesterols were synthesized by the nucleophilic cleavage of the cyclic oxonium derivatives of these boron clusters under the action of the hydroxy-modified cholesterol. The resulting boronated cholesterols can be used for liposomal drug delivery in boron neutron capture therapy of cancer. The structures of all the novel compounds were unequivocally confirmed using IR and NMR spectroscopy as well as high-resolution mass spectrometry.

Acknowledgements

This work was supported by the Russian Foundation for Basic Research, project no. 20-33-70011. The NMR studies and spectral characterization were performed using the equipment of the Center for Molecular Composition Studies of INEOS RAS operating with the financial support of the Ministry of Science and Higher Education of the Russian Federation.

Electronic supplementary information

Electronic supplementary information (ESI) available online: ¹H, ¹¹B, ¹¹B{¹H}, and ¹³C NMR, IR and ESI-HRMS spectra of compounds 6–9. For ESI, see DOI: 10.32931/io2008a

References

1. M. F. Hawthorne, Angew. Chem., Int. Ed., 1993, 32, 950–984. DOI: 10.1002/anie.199309501
2. A. H. Soloway, W. Tjarks, B. A. Barnum, F.-G. Rong, R. F. Barth, I. M. Codogni, J. G. Wilson, Chem. Rev., 1998, 98, 1515–1562. DOI: 10.1021/cr941195u
3. I. B. Sivaev, V. I. Bregadze, Eur. J. Inorg. Chem., 2009, 1433–1450. DOI: 10.1002/ejic.200900003
4. R. F. Barth, Z. Zhang, T. Liu, Сancer Commun., 2018, 38, 36. DOI: 10.1186/s40880-018-0280-5
5. V. I. Bregadze, I. B. Sivaev, in: Boron Science: New Technologies and Applications, N. S. Hosmane (Ed.), CRC Press, Boca Raton, 2012, pp. 181–207.
6. Y. Mishima, M. Ichihashi, S. Hatta, C. Honda, K. Yamamura, T. Nakagawa, Pigm. Cell Res., 1989, 2, 226–234. DOI: 10.1111/j.1600-0749.1989.tb00196.x
7. A. H. Soloway, H. Hatanaka, M. A. Davis, J. Med. Chem., 1967, 10, 714–717. DOI: 10.1021/jm00316a042
8. Y. Nakagawa, H. Hatanaka, J. Neuro-Oncol., 1997, 33, 105–115. DOI: 10.1023/A:1005781517624
9. V. I. Bregadze, I. B. Sivaev, S. A. Glazun, Anti-Cancer Agents Med. Chem., 2006, 6, 75–109. DOI: 10.2174/187152006776119180
10. R. F. Barth, P. Mi, W. Yang, Сancer Commun., 2018, 38, 35. DOI: 10.1186/s40880-018-0299-7
11. H. Ichikawa, E. Taniguchi, T. Fujimoto, Y. Fukumori, Appl. Radiat. Isot., 2009, 67, S111–S114. DOI: 10.1016/j.apradiso.2009.03.026
12. M. Sibrian-Vazquez, M. G. H. Vicente, in: Boron Science: New Technologies and Applications, N. S. Hosmane (Ed.), CRC Press, Boca Raton, 2012, pp. 209–241.
13. R. F. Barth, H. Joensuu, Radiother. Oncol., 2007, 82, 119–122. DOI: 10.1016/j.radonc.2007.01.010
14. I. B. Sivaev, V. I. Bregadze, N. T. Kuznetsov, Russ. Chem. Bull., 2002, 51, 1362–1374. DOI: 10.1023/A:1020942418765
15. M. A. Grin, A. A. Semioshkin, R. A. Titeev, R. A. Nizhnik, J. N. Grebenyuk, A. F. Mironov, V. I. Bregadze, Mendeleev Commun., 2007, 17, 14–15. DOI: 10.1016/j.mencom.2007.01.005
16. A. Semioshkin, O. Tsaryova, O. Zhidkova, V. Bregadze, D. Wöhrle, J. Porphyrins Phthalocyanines, 2006, 10, 1293–1300. DOI: 10.1142/S1088424606000661
17. E. Justus, D. T. Izteleuova, A. V. Kazantsev, M. M. Axatov, E. Lork, D. Gabel, Collect. Czech. Chem. Commun., 2007, 72, 1740–1754. DOI: 10.1135/cccc20071740
18. A. Semioshkin, A. Ilinova, I. Lobanova, V. Bregadze, E. Paradowska, M. Studzińska, A. Jabłońska, Z. J. Lesnikowski, Tetrahedron, 2013, 69, 8034–8041. DOI: 10.1016/j.tet.2013.06.100
19. I. B. Sivaev, N. Yu. Kulikova, E. N. Nizhnik, M. V. Vichuzhanin, Z. A. Starikova, A. A. Semioshkin, V. I. Bregadze, J. Organomet. Chem., 2008, 693, 519–525. DOI: 10.1016/j.jorganchem.2007.11.027
20. A. A. Semioshkin, Yu. N. Las'kova, O. B. Zhidkova, V. I. Bregadze, Russ. Chem. Bull., 2008, 57, 1996–1998. DOI: 10.1007/s11172-008-0268-4
21. S. Xuan, M. G. H. Vicente, in: Boron-Based Compounds: Potential and Emerging Applications in Medicine, E. Hey-Hawkins, C. Viñas Teixidor (Eds.), Wiley, 2018, ch. 3.2, pp. 298–342. DOI: 10.1002/9781119275602.ch3.2
22. I. B. Sivaev, A. A. Semioshkin, B. Brellochs, S. Sjöberg, V. I. Bregadze, Polyhedron, 2000, 19, 627–632. DOI: 10.1016/S0277-5387(00)00293-X
23. A. A. Semioshkin, I. B. Sivaev, V. I. Bregadze, Dalton Trans., 2008, 977–992. DOI: 10.1039/B715363E
24. I. B. Sivaev, A. A. Semioshkin, V. I. Bregadze, Appl. Radiat. Isot., 2009, 67, S91–S93. DOI: 10.1016/j.apradiso.2009.03.022
25. I. B. Sivaev, V. I. Bregadze, in: Boron Science: New Technologies and Applications, N. S. Hosmane (Ed.), CRC Press, Boca Raton, 2012, pp. 623–637.
26. S. B. Kahl, D. Pate, B. H. Laster, E. A. Popenoe, R. G. Fairchild, in: Progress in Neutron Capture Therapy for Cancer, B. J. Allen, D. E. Moore, B. V. Harrington (Eds.), Springer, Boston, 1992, pp. 365–368. DOI: 10.1007/978-1-4615-3384-9_80
27. D. A. Feakes, J. K. Spinler, F. R. Harris, Tetrahedron, 1999, 55, 11177–11186. DOI: 10.1016/S0040-4020(99)00640-7
28. B. S. Pattni, V. V. Chupin, V. P. Torchilin, Chem. Rev., 2015, 115, 10938–10966. DOI: 10.1021/acs.chemrev.5b00046
29. T. O. B. Olusanya, R. R. H. Ahmad, D. M. Ibegbu, J. R. Smith, A. A. Elkordy, Molecules, 2018, 23, 907. DOI: 10.3390/molecules23040907
30. C. O. Noble, D. B. Kirpotin, M. E. Hayes, C. Mamot, K. Hong, J. W. Park, C. C. Benz, J. D. Marks, D. C. Drummond, Expert Opin. Ther. Targets, 2004, 8, 335–353. DOI: 10.1517/14728222.8.4.335
31. G. T. Noble, J. F. Stefanick, J. D. Ashley, T. Kiziltepe, B. Bilgicer, Trends Biotechnol., 2014, 32, 32–45. DOI: 10.1016/j.tibtech.2013.09.007
32. D. A. Feakes, K. Shelly, C. B. Knobler, M. F. Hawthorne, Proc. Natl. Acad. Sci. U. S. A., 1994, 91, 3029–3033. DOI: 10.1073/pnas.91.8.3029
33. M. F. Hawthorne, D. A. Feakes, K. Shelly, in: Cancer Neutron Capture Therapy, Y. Mishima (Ed.), Springer, Boston, 1996, pp. 27–36. DOI: 10.1007/978-1-4757-9567-7_2
34. M. F. Hawthorne, Trends Mol. Med., 1998, 4, 174–181. DOI: 10.1016/S1357-4310(98)01226-X
35. G. S. Terstappen, R. Roncarati, J. Dunlop, R. Peri, Future Med. Chem., 2010, 5, 715–730. DOI: 10.4155/fmc.10.180
36. D. Alberti, A. Toppino, S. Geninatti Crich, C. Meraldi, C. Prandi, N. Protti, S. Bortolussi, S. Altieri, S. Aime, A. Deagostino, Org. Biomol. Chem., 2014, 12, 2457–2467. DOI: 10.1039/c3ob42414f
37. H. Koganei, M. Ueno, S. Tachikawa, L. Tasaki, H. S. Ban, M. Suzuki, K. Shiraishi, K. Kawano, M. Yokoyama, Y. Maitani, K. Ono, H. Nakamura, Bioconjugate Chem., 2013, 24, 124–132. DOI: 10.1021/bc300527n
38. E. M. Heber, M. F. Hawthorne, P. J. Kueffer, M. A. Garabalino, S. I. Thorp, E. C. C. Pozzi, A. M. Hughes, C. A. Maitz, S. S. Jalisatgi, D. W. Nigg, P. Curotto, V. A. Trivillin, A. E. Schwint, Proc. Natl. Acad. Sci. U. S. A., 2014, 111, 16077–16081. DOI: 10.1073/pnas.1410865111
39. C. A. Maitz, A. A. Khan, P. J. Kueffer, J. D. Brockman, J. Dixson, S. S. Jalisatgi, D. W. Nigg, T. A. Everett, M. F. Hawthorne, Transl. Oncol., 2017, 10, 686–692. DOI: 10.1016/j.tranon.2017.05.003
40. M. Białek-Pietras, A. B. Olejniczak, S. Tachikawa, H. Nakamura, Z. J. Leśnikowski, Bioorg. Med. Chem., 2013, 21, 1136–1142. DOI: 10.1016/j.bmc.2012.12.039
41. A. A. Druzina, A. V. Shmalko, E. P. Andreichuk, O. B. Zhidkova, I. D. Kosenko, A. Semioshkin, I. B. Sivaev, S. Mandal, Z. Shen, V. I. Bregadze, Mendeleev Commun., 2019, 29, 628–630. DOI: 10.1016/j.mencom.2019.11.007
42. A. A. Druzina, I. D. Kosenko, O. B. Zhidkova, Russ. Chem. Bull., 2020, 69, 1080–1084. DOI: 10.1007/s11172-020-2870-z
43. T. Peymann, K. Kück, D. Gabel, Inorg. Chem., 1997, 36, 5138–5139. DOI: 10.1021/ic970647t
44. T. Schaffran, E. Justus, D. Awad, P. Fan, D. Gabel, 4th Eur. Meeting on Boron Chemistry, Bremen, 2007.
45. M. Berg, S. Nozinovic, M. Engeser, A. Lützen, Eur. J. Org. Chem., 2015, 5966–5978. DOI: 10.1002/ejoc.201500657
46. N. R. Schmuff, B. M. Trost, J. Org. Chem., 1983, 48, 1404–1412. DOI: 10.1021/jo00157a002