リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Development of Boron Carriers Equipped with Mono- and Dimeric Macrocyclic Polyamines and Their Zinc(II) Complexes for Boron Neutron Capture Therapy」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Development of Boron Carriers Equipped with Mono- and Dimeric Macrocyclic Polyamines and Their Zinc(II) Complexes for Boron Neutron Capture Therapy

上田 大貴 Hiroki Ueda 東京理科大学 DOI:info:doi/10.20604/00003683

2022.06.17

概要

Boron neutron capture therapy (BNCT) is a binary therapeutic method for the treatment of certain type of cancers such as malignant glioma, malignant melanoma and recurrent head and neck cancer and is based on a combination of boron (1°B) delivery agents and thermal neutron radiation. The nuclear reaction between 1°B atoms and thermal neutrons ('n) yield heavy particles, tHe?* (a) and List ions, which induce the destruction of biomolecules within short path length of 5-9 um, resulting in that cytotoxic effect is limited to cells that contain 10B. To date, only two boron-containing drugs, sodium mercaptoborate (BSH) and I-4-boronophenylalanine (BPA) have been used for clinical cancer treatment, and both have some drawbacks in terms of the tumor type that can be treated. Therefore, the discovery of more efficient and less toxic boron delivery agents would be highly desirable. This background has prompted us to develop the novel boron delivery agents functionalized with macrocyclic polyamine scaffolds such as [9]aneN3, [12]aneN4, and [15]aneNs and their Zn? complexes. In this manuscript, we report on the design, synthesis and biological evaluation of boron-containing mono- and dimeric macrocyclic polyamines and their Zn?* complexes for boron neutron capture therapy.

In Chapter 2, we report on the design and synthesis of boron carriers equipped with 9-, 12-, and 15-membered macrocyclic polyamines and the corresponding Zn?* complexes. It is known that polyamines are essential molecules for various cellular functions including protein synthesis and DNA replication, and that an increase in the concentration of them associated with a cell growth activation of cancer cells. In addition, it has been known that macrocyclic polyamines form stable complexes with intracellular metal ions and that Zn?+-[12]aneN4 complexes selectively recognize with thymidine (dT) part in DNA. Therefore, we expected that macrocyclic polyamines having boron units would be efficiently uptaken into cancer cells and that the thermal neutron irradiation would induce effective DNA damage when 1°B atoms are accumulated near DNA molecules. In this study, we synthesized monomeric [9]aneNs, [12]aneN4, and [15]aneNs compounds containing cyclic boron ester units in natural abundant ratio (B/B = 19.9/ 80.1) and examined their biological activities such as cytotoxicity and intracellular uptake. Thereafter, some promising compounds were selected and their corresponding 1°B-enriched forms were prepared for BNCT experiments. It was found that these monomeric B carriers were efficiently taken up to cancer cells (A549 and HeLa S3 cells) possibly via polyamine transport system. In addition, the results of in vitro BNCT studies indicate that [12]aneN4- and [15]aneNs-type 10B-enriched macrocycles effectively inhibit the proliferation of cancer cells upon thermal neutron irradiation, possibly via the interaction with DNA.

In Chapter 3, we report on the design and synthesis of DNA-targeting boron agents that are bound with homo- and hetero-dimers of macrocyclic polyamines and their corresponding Zn?+ complexes. It was expected that the dizinc(II) complexes of these ligands would interact with two adjacent thymidine (thymidy1(3'-5')thymidine, d(TpT)) units, resulting in more efficient contact with DNA and its more efficient breakdown upon irradiation with thermal neutrons. In this work, the boron-containing macrocyclic polyamine dimers and the corresponding Zn?+ complexes were synthesized. We examined their interaction with calf-thymus DNA (cDNA) and evaluated their cytotoxicity and intracellular uptake activity using both cancer and normal cell lines. It was found that homo- and heterodimer of macrocyclic polyamines and their Zn?* complexes interact with double-stranded DNA and that they are much less cytotoxic than the monomers. The results of in vitro BNCT experiments using 10B-enriched forms of selected compounds indicate that the cytotoxic effect of dimeric 10B carriers is almost same as that of 10B-BPA and weaker than that of the monomeric [12]aneN4- and [15]aneNs-type macrocycles reported in Chapter 2, possibly due to their lower boron uptake and unexpected interactions with intracellular biomolecules. These data suggest that the 10B carriers based on monomeric [12]aneN4 and [15]aneNs described in Chapter 2 are preferable for BNCT than ditopic macrocyclic polyamine-type 1°B carriers.

In conclusion, we have successfully developed the novel candidates for DNA-targeting BNCT agent equipped with mono- and dimeric macrocyclic polyamines and their Zn?+ complexes. We believe that these findings afford important and useful information regarding the fundamental chemistry of boron containing drugs and the design and synthesis of safer and more effecient BNCT agents.

参考文献

(1) Sung, H.; Ferlay, J.; Siegel, R. L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249.

(2) Hosmane, N. S.; Maguire, J. A.; Zhu, Y.; Takagaki, M. Boron and Gadolinium Neutron Capture Therapy for Cancer Treatment. World Scientific Publishing: Singapore, 2012.

(3) (a) Taylor, H. J.; Goldhaber, M. Detection of Nuclear Disintegration in a Photographic Emulsion. Nature 1935, 135, 341. (b) Barth, R. F.; Soloway, A. H.; Fairchild, R. G. Boron Neutron Capture Therapy of Cancer. Cancer Res. 1990, 50, 1061–1070. (c) Hu, K.; Yang, Z.; Zhang, L.; Xie, L.; Wang, L.; Xu, H.; Josephson, L.; Liang, S. H.; Zhang, M.-R. Boron Agents for Neutron Capture Therapy. Coord. Chem. Rev. 2020, 405, 213139.

(4) (a) Rinard, P. M. Neutron Interactions with Matter. In Reilly, D.; Ensslin, N.; Smith, H.; Kreiner, S., editors, Passive Nondestructive Assay of Nuclear Materials. Nuclear Regulatory Commission, 1991. (b) Salt, C.; Lennox, A. J.; Takagaki, M.; Maguire, J. A.; Hosmane, N. S. Boron and Gadolinium Neutron Capture Therapy. Russ. Chem. Bull., Int. Ed. 2004, 53, 1871–1888.

(5) 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, 43–50.

(6) Kanno, H.; Nagata, H.; Ishiguro, A.; Tsuzuranuki, S.; Nakano, S.; Nonaka, T.; Kiyohara, K.; Kimura, T.; Sugawara, A.; Okazaki, Y.; Takae, S.; Nakabayashi, T.; Arai, H.; Suzuki, H. Designation Products: Boron Neutron Capture Therapy for Head and Neck Carcinoma. The Oncologist 2021, 26, e1250–1255.

(7) (a) Suzuki, M.; Sakurai, Y.; Hagiwara, S.; Masunaga, S.; Kinashi, Y.; Nagata, K.; Maruhashi, A.; Kudo, M.; Ono, K. First Attempt of Boron Neutron Capture Therapy (BNCT) for Hepatocellular Carcinoma. Jpn. J. Clin. Oncol. 2007, 37, 376–381. (b) Suzuki, M.; Suzuki, O.; Sakurai, Y.; Tanaka, H.; Kondo, N.; Kinashi, Y.; Masunaga, S.; Maruhashi, A.; Ono, K. Reirradiation for Locally Recurrent Lung Cancer in the Chest Wall with Boron Neutron Capture Therapy (BNCT). Int. Canc. Conf. J. 2012, 1, 235–238. (c) Suzuki, M. New Application for Boron Neutron Capture Therapy. Radioisotopes 2015, 64, 59–66. (d) Malouff, T. D.; Seneviratne, D. S.; Ebner, D. K.; Stross, W. C.; Waddle, M. R.; Trifiletti, D. M.; Krishnan, S. Boron Neutron Capture Therapy: A Review of Clinical Applications. Front. Oncol. 2021, 11, 601820.

(8) (a) Hawthorne, M. F. The Role of Chemistry in the Development of Boron Neutron Capture Therapy of Cancer. Angew. Chem. Int. Ed. Engl. 1993, 32, 950–984. (b) Morin, C. The Chemistry of Boron Analogues of Biomolecules. Tetrahedron 1994, 50, 12521–12569. (c) Soloway, A. H.; Tjarks, W.; Barnum, B. A.; Rong, F.-G.; Barth, R. F.; Codogni, I. M.; Wilson, J. G. The Chemistry of Neutron Capture Therapy. Chem. Rev. 1998, 98, 1515–1562. (d) Barth, R. F.; Coderre, J. A.; Vicente, M. G. H.; Blue, T. E. Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects. Clin. Cancer Res. 2005, 11, 3987–4002. (e) Luderer, M. J.; de la Puente, P.; Azab, A. K. Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy. Pharm. Res. 2015, 32, 2824–2836. (f) Barth, R. F.; Mi, P.; Yang, W. Boron Delivery Agents for Boron Neutron Capture Therapy of Cancer. Canc. Commun. 2018, 38, 35. (g) Cerecetto, H.; Couto, M. Medicinal Chemistry of Boron-Bearing Compounds for BNCT-Glioma Treatment: Current Challenges and Perspectives. In Glioma – Contemporary Diagnostic and Therapeutic Approaches, Omerhodžić, I.; Arnautović, K. Eds., IntechOpen, U.K. 2018.

(9) Kruger, P. G. Some Biological Effects of Nuclear Disintegration Products on Neoplastic Tissue. Proc. Natl. Acad. Sci. 1940, 26, 181–192.

(10) (a) Godwin, J. T.; Farr, L. E.; Sweet, W. H.; Robertson, J. S. Pathological Study of Eight Patients with Glioblastoma Multiforme Treated by Neutron Capture Therapy Using Boron 10. Cancer 1955, 8, 601–615. (b) Sweet, W. H.; Soloway, A. H.; Brownell, G. L. Boron-Slow Neutron Capture Therapy of Gliomas. Acta Radiol. Ther. Phys. 1963, 1, 114–121. (c) Slatkin, D. N. A History of Boron Neutron Capture Therapy of Brain Tumors. Brain 1991, 114, 1609–1629.

(11) Knoth, W. H.; Sauer, J. C.; England, D. C.; Hertler, W. R.; Muetterties, E. L. Chemistry of Boranes. ⅩⅠⅩ. Derivative Chemistry of B10H10 –2 and B12H12 –2 . J. Am. Chem. Soc. 1964, 89, 3973–3983.

(12) Soloway, A. H.; Hatanaka, H.; Davis, M. A. Penetration of Brain and Brain Tumor. Ⅶ. Tumor-Binding Sulfhydryl Boron Compounds. J. Med. Chem. 1967, 10, 714– 717.

(13) (a) Hatanaka, H. A Revised Boron-Neutron Capture Therapy for Malignant Brain Tumors. J. Neurol. 1975, 209, 81–94. (b) Hatanaka, H.; Nakagawa, Y. Clinical Results of Long-Surviving Brain Tumor Patients Who Underwent Boron Neutron Capture Therapy. Int. J. Radiat. Oncol. Biol. Phys. 1994, 28, 1061–1066.

(14) Snyder, H. R.; Reedy, A. J.; Lennarz, W. J. Synthesis of Aromatic Boronic Acids. Aldehydo Boronic Acids and a Boronic Acid Analog of Tyrosine. J. Am. Chem. Soc. 1958, 80, 835–838.

(15) (a) Ichihashi, M.; Nakanishi, T.; Mishima, Y. Specific Killing Effect of 10B-Paraboronophenylalanine in Thermal Neutron Capture Therapy of Malignant Melanoma: In Vitro Radiobiological Evaluation. J. Invest. Dermatol. 1982, 78, 215–218. (b) Mishima, Y.; Ichihashi, M.; Tsuji, M.; Hatta, S.; Ueda, M.; Honda, C.; Suzuki, T. Treatment of Malignant Melanoma by Selective Thermal Neutron Capture Therapy Using Melanoma-Seeking Compound. J. Invest. Dermatol. 1989, 92, 312S–325S.

(16) Mishima, Y.; Honda, C.; Ichihashi, M.; Obara, H.; Hiratsuka, J.; Fukuda, H.; Karashima, H.; Kobayashi, T.; Kanda, K.; Yoshino, K. Treatment of Malignant Melanoma by Single Thermal Neutron Capture Therapy with Melanoma-Seeking 10BCompound. The Lancet 1989, 334, 388–389.

(17) (a) Coderre, J. A.; Button, T. M.; Micca, P. L.; Fisher, C. D.; Nawrocky, M. M.; Liu, H. B. Neutron Capture Therapy of The 9L Rat Gliosarcoma Using The pBoronophenylalanine-fructose Complex. Int. J. Radiat. Oncol. Biol. Phys. 1994, 30, 643–652. (b) Shull, B. K.; Spielvogel, D. E.; Head, G.; Gopalaswamy, R.; Sankar, S.; Devito, K. Studies on the Structure of the Complex of the Boron Neutron Capture Therapy Drug, L-p-Boronophenylalanine, with Fructose and Related Carbohydrates: Chemical and 13C NMR Evidence for the β-D-Fructofuranose 2,3,6-(pPhenylalanylorthoboronate) Structure. J. Pharm. Sci. 2000, 89, 215–222.

(18) (a) Kato, I.; Ono, K.; Sakurai, Y.; Ohmae, M.; Maruhashi, A.; Imahori, Y.; Kirihata, M.; Nakazawa, M.; Yura, Y. Effectiveness of BNCT for Recurrent Head and Neck Malignancies. Appl. Radiat. Isot. 2004, 61, 1069–1073. (b) Kankaanranta, L.; Seppälä, T.; Koivunoro, H.; Saarilahti, K.; Atula, T.; Collan, J.; Salli, E.; Kortesniemi, M.; Uusi-Simola, J.; Välimäki, P.; Mäkitie, A.; Seppänen, M.; Minn, H.; Revitzer, H.; Kouri, M.; Kotiluoto, P.; Seren, T.; Auterinen, I.; Savolainen, S.; Joensuu, H. Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head and Neck Cancer: Final Analysis of a Phase Ⅰ/Ⅱ Trial. Int. J. Radiat. Oncol. Biol. Phys. 2012, 82, e67–e75. (c) Barth, R. F.; Vicente, M. G. H.; Harling, O. K.; Kinger Ⅲ, W. S.; Riley, K. J.; Binns, P. J.; Wagner, F. M.; Suzuki, M.; Aihara, T.; Kato, I.; Kawabata, S. Current Status of Boron Neutron Capture Therapy of High Grade Gliomas and Recurrent Head and Neck Cancer. Radiat. Oncol. 2012, 7, 146. (d) Suzuki, M.; Kato, I.; Aihara, T.; Hiratsuka, J.; Yoshimura, K.; Niimi, M.; Kimura, Y.; Ariyoshi, Y.; Haginomori, S.; Sakurai, Y.; Kinashi, Y.; Masunaga, S.; Fukushima, M.; Ono, K.; Maruhashi, A. Boron Neutron Capture Therapy Outcomes for Advanced or Recurrent Head and Neck Cancer. J. Radiat. Res. 2014, 55, 146–153.

(19) Ishiwata, K.; Ido, T.; Mejia, A. A.; Ichihashi, M.; Mishima, Y. Synthesis and Radiation Dosimetry of 4-Boron-2-[ 18F]fluoro-D,L-phenylalanine: a Target Compound for PET and Boron Neutron Capture Therapy. Appl. Radiat. Isot. 1991, 42, 325–328.

(20) (a) Kabalka, G. W.; Smith, G. T.; Dyke, J. P.: Reid, W. S.; Desmond Longford, C. P.; Roberts, T. G.; Reddy, N. K.; Buonocore, E.; Hübner, K. F. Evaluation of Fluorine18-BPA-Fructose for Boron Neutron Capture Treatment Planning. J. Nucl. Med. 1997, 38, 1762–1767. (b) Aihara, T.; Hiratsuka, J.; Morita, N.; Uno, M.; Sakurai, Y.; Maruhashi, A.; Ono, K.; Harada, T. First Clinical Case of Boron Neutron Capture Therapy for Head and Neck Cancer Malignancies using 18F-BPA PET. Head Neck 2006, 28, 850–855. (c) Barth, R. F.; Zhang, Z.; Liu, T. A Realistic Appraisal of Boron Neutron Capture Therapy as a Cancer Treatment Nodality. Canc. Commun. 2018, 38, 36.

(21) Wongthai, P.; Hagiwara, K.; Miyoshi, Y.; Wiriyasermkul, P.; Wei, L.; Ohgaki, R.; Kato, I.; Hamase, K.; Nagamori, S.; Kanai, Y. Boronophenylalanine, a Boron Delivery agent for Boron Neutron Capture Therapy, is Transported by ATBo,+, LAT1 and LAT2. Cancer Sci. 2015, 106, 279–286.

(22) Watanabe. T.; Hattori, Y.; Ohta, Y.; Ishimura, M.; Nakagawa, Y.; Sanada, Y.; Tanaka, H.; Fukutani, S.; Masunaga, S.; Hiraoka, M.; Ono, K.; Suzuki, M.; Kirihata, M. Comparison of the Pharmacokinetics Between L-BPA and L-FBPA Using the Same Administration Dose and Protocol: a Validation Study for the Theranostic Approach Using [18F]-L-BPA Positron Emission Tomography in Boron Neutron Capture Therapy. BMC Canc. 2016, 16, 859.

(23) Yokoyama, K.; Miyatake, S.; Kajimoto. Y.; Kawabata, S.; Doi, A.; Yoshida, T.; Asano, T.; Kirihata, M.; Ono, K.; Kuroiwa, T. Pharmacokinetic Study of BSH and BPA in Simultaneous Use for BNCT. J. Neuro. Oncol. 2006, 78, 227–232.

(24) (a) Woodburn, K.; Phadke, A. S.; Morgan, A. R. An in Vitro Study of Boronated Porphyrins for Potential Use in Boron Neutron Capture Therapy. Bioorg. Med. Chem. Lett. 1993, 3, 2017−2022. (b) Toi, H.; Nagai, Y.; Aoyama,Y.; Kawabe, H.; Aizawa, K.; Ogoshi, H. Preparation of Porphyrins Having Phenylboronic Acid Groups. Chem. Lett. 1993, 22, 1043–1046. (c) Miura, M.; Micca, P. L.; Fisher, C. D.; Heinrichs, J. C.; Donaldson, J. A.; Finkel, G. C.; Slatkin, D. N. Synthesis of a Nickel Tetracarboranylphenylporphyrin for Boron Neutron Capture Therapy: Biodistribution and Toxicity in Tumor-bearing Mice. Int. J. Cancer 1996, 68, 114−119. (d) Chayer, S.; Jaquinod, L.; Smith, K. M.; Vicente, M. G. H. Synthesis of Carboranylpyrroles. Tetrahedron Lett. 2001, 42, 7759−7761. (e) Sibrian-Vazquez, M.; Hao, E.; Jensen, T. J.; Vicente, G. H. Enhanced Cellular Uptake with a Cobaltacarborane-Porphyrin-HIV1 Tat 48–60 Conjugate. Bioconjugate Chem. 2006, 17, 928–934. (f) Koo, M.-S.; Ozawa, T.; Santos, R. A.; Lamborn, K. R.; Bollen, A. W.; Deen, D. F.; Kahl, S. B. Synthesis and Comparative Toxicology of a Series of Polyhedral Borane AnionSubstituted Tetraphenyl Porphyrins. J. Med. Chem. 2007, 50, 820–827. (g) El-Zaria, M. E.; Ban, H. S.; Nakamura, H. Boron-Containing Protoporphyrin IX Derivatives and Their Modification for Boron Neutron Capture Therapy: Synthesis, Characterization, and Comparative In Vitro Toxicity Evaluation. Chem. Eur. J. 2010, 16, 1543–1552. (h) Bhupathiraju, N. V. S. D. K.; Vicente, M. G. H. Synthesis and Cellular Studies of Polyamine Conjugates of a Mercaptomethyl-carboranylporphyrin. Bioorg. Med. Chem. 2013, 21, 485–495.

(25) Kahl, S. B.; Koo, M.-S. Synthesis of Tetrakis-carborane-carboxylate Esters of 2,4- Bis-(α,β-dihydroxyethyl)-deuteroporphyrin Ⅸ. J. Chem. Soc., Chem. Commun. 1990, 1769–1771.

(26) (a) Hill, J. S.; Kahl, S. B.; Kaye, A. H.; Stylli, S. S.; Koo, M.-S.; Gonzales, M. F.; Vardaxis, N. J.; Johnson, C. I. Selective Tumor Uptake of a Boronated Porphyrin in an Animal Model of Cerebral Glioma. Proc. Natl. Acad. Sci. 1992, 89, 1785–1789. (b) Dagrosa, M. A.; Viaggi, M.; Rebagliati, R. J.; Batistoni, D.; Kahl, S. B.; Juvenal, G. J.; Pisarev, M. A. Biodistribution of Boron Compounds in as Animal Model of Human Undifferentiated Thyroid Cancer for Boron Neutron Capture Therapy. Mol. Pharm. 2005, 2, 151–156.

(27) Dagrosa, M. A.; Crivello, M.; Perona, M.; Thorp, S.; Cruz, G. A. S.; Pozzi, E.; Casal, M.; Thomasz, L.; Cabrini, R.; Kahl, S.; Juvenal, G. J.; Pisarev, M. A. First Evaluation of the Biologic Effectiveness Factors of Boron Neutron Capture Therapy (BNCT) in a Human Colon Carcinoma Cell Line. Int. J. Radiat. Oncol. Biol. Phys. 2011, 79, 262– 268.

(28) Rosenthal, M. A.; Kavar, B.; Hill, J. S.; Morgan, D. J.; Nation, R. L.; Stylli, S. S.; Basser, R. L.; Uren, S.; Geldard, H.; Green, M. D.; Kahl, S. B.; Kaye, A. H. Phase Ⅰ and Pharmacokinetic Study of Photodynamic Therapy for High-Grade Gliomas Using a Novel Boronated Porphyrin. J. Clin. Oncol. 2001, 19, 519–524.

(29) Arnér, E. J.; Eriksson, S. Mammalian Deoxyribonucleoside Kinase. Pharmac. Ther. 1995, 67, 155–186.

(30) (a) Jagarlamudi, K. K.; Shaw, M. Thymidine Kinase 1 as Tumor Biomarker: Technical Advances Offer New Potential to An Old Biomarker. Biomark. Med. 2018, 12, 1035–1048. (b) Bitter, E. E.; Townsend, M. H.; Erickson, R.; Allen, C.; O´Neill, K. L. Thymidine Kinase 1 Through The Ages: A Comprehensive Review. Cell Biosci. 2020, 10, 138.

(31) (a) Liao, T. K.; Podrebarac, E. G.; Cheng, C. C. Boron-Substituted Pyrimidines. J. Am. Chem. Soc. 1964, 86, 1869−1870. (b) Schinazi, R. F.; Prusoff, W. H. Synthesis and Properties of Boron and Silicon Substituted Uracil or 2’-Deoxyuridine. Tetrahedron Lett. 1978, 50, 4981−4984. (c) Schinazi, R. F.; Prusoff, W. H. Synthesis of 5-(Dihydroxyboryl)-2´-deoxyuridine and Related Boron-Containing Pyrimidines. J. Org. Chem. 1985, 50, 841–847. (d) Reynolds, R. C.; Trask, T. W.; Sedwick, W. D. 2,4-Dichloro-5-(1-o-carboranylmethyl)-6-methylpyrimidine: A Potential Synthon for 5-(1-o-carboranylmethyl)pyrimidines. J. Org. Chem. 1991, 56, 2391−2395. (e) Tjarks, W.; Anisuzzaman, A. K. M.; Liu, L.; Soloway, A. H.; Barth, R. F.; Perkins, D. J.; Adams, D. M. Synthesis and in Vitro Evaluation of Boronated Uridine and Glucose Derivatives for Boron Neutron Capture Therapy. J. Med. Chem. 1992, 35, 1628–1633. (f) Wyzlic, I. M.; Tjarks, W.; Soloway, A. H.; Anisuzzaman, A. K. M.; Rong, F.-G.; Barth, R. F. Strategies for the Design and Synthesis of Boronated Nucleic Acid and Protein Components as Potential Delivery Agents for Neutron Capture Therapy. Int. J. Radiat. Oncol. Biol. Phys. 1994, 28, 1203–1213. (g) Goudgaon, N. M.; El-Kattan, G. F.; Schinazi, R. F. Boron Containing Pyrimidines, Nucleosides, and Oligonucleotides for Neutron Capture Therapy. Nucleosides Nucleotides 1994, 13, 849–880. (h) Kattan, G. F.; Lesnikowski, Z. J.; Yao, S.; Tanious, F.; Wilson, W. D.; Schinazi, R. F. Carboranyl Oligonucleotides. 2. Synthesis and Physicochemical Properties of Dodecathymidylate Containing 5-(o-Carboran-1-yl)-2´-deoxyuridine. J. Am. Chem. Soc. 1994, 116, 7494−7501. (i) Tjarks, W. The Use of Boron Clusters in The Rational Design of Boronated Nucleosides for Boron Neutron Capture Therapy. J. Organomet. Chem. 2000, 614–615, 37–47. (j) Al-Madhoun, A. S.; Tjarks, W.; Eriksson, S. The Role of Thymidine Kinases in the Activation of Pyrimidine Nucleoside Analogues. Mini-Rev. Med. Chem. 2004, 4, 341–350. (k) Nizioł, J.; Zieliński, Z.; Leś, A.; Dąbrowska, M.; Rode, W.; Ruman, T. Synthesis, Reactivity and Biological Activity of N(4)-Boronated Derivatives of 2’-Deoxycytidine. Bioorg. Med. Chem. 2014, 22, 3906–3912. (l) Nizioł, J.; Uram, Ł.; Szuster, M.; Sekuła, J.; Ruman, T. Biological Activity of N(4)-boronated Derivatives of 2’-Deoxycytidine, Potential Agents for Boron Neutron Capture Therapy. Bioorg. Med. Chem. 2015, 23, 6297– 6304. (m) Novopashina, D. S.; Vorobyeva, M. A.; Venyaminova, A. Recent Advances in the Synthesis of High Boron-Loaded Nucleic Acids for BNCT. Front. Chem. 2021, 9, 619052.

(32) Al-Madhoun, A. S.; Johnsamuel, J.; Yan, J.; Ji, W.; Wang, J.; Zhuo, J.-C.; Lunato, A. J.; Woollard, J. E.; Hawk, A. E.; Cosquer, G. Y.; Blue, T. E.; Eriksson, S.; Tjarks, W. Synthesis of a Small Library of 3-(Carboranylalkyl)thymidines and Their Biological Evaluation as Substrates for Human Thymidine Kinase 1 and 2. J. Med. Chem. 2002, 45, 4018–4028.

(33) (a) Al-Madhoun, A. S.; Johnsamuel, J.; Barth, R. F.; Tjarks, W.; Eriksson, S. Evaluation of Human Thymidine Kinase 1 Substrates as New Candidates for Boron Neutron Capture Therapy. Cancer Res. 2004, 64, 6280–6286. (b) Barth, R. F.; Yang, W.; Al-Madhoun, A. S.; Johnsamuel, J.; Byun, Y.; Chandra, S.; Smith, D. R.; Tjarks, W.; Eriksson, S. Boron Containing Nucleosides as Potential Delivery Agents for Neutron Capture Therapy of Brain Tumors. Cancer Res. 2004, 64, 6287–6295. (c) Byun, Y.; Thirumamagal, B. T. S.; Yang, W.; Eriksson, S.; Barth, R. F.; Tjarks, W. Preparation and Biological Evaluation of 10B-Enriched 3-[5-{2-(2,3-dihydroxyprop1-yl)-o-carboran-1-yl}pentan-1-yl]thymidine (N5-2OH), a New Boron Delivery Agent for Boron Neutron Capture Therapy of Brain Tumors. J. Med. Chem. 2006, 49, 5513–5523. (d) Tjarks, W.; Tiwari, R.; Byun, Y.; Narayanasamy, S.; Barth, R. F. Carboranyl Thymidine Analogues for Neutron Capture Therapy. Chem. Commun. 2007, 4978–4991. (e) Barth, R. F.; Yang, W.; Wu, G.; Swindall, M.; Byun, Y.; Narayanasamy, S.; Tjarks, W.; Tordoff, K.; Moeschberger, M. L.; Eriksson, S.; Binns, P. J.; Riley, K. J. Thymidine Kinase 1 as a Molecular Target for Boron Neutron Capture Therapy of Brain Tumors. Proc. Natl. Acad. Sci. 2008, 105, 17493–17497.

(34) (a) Gerner, E. W.; Meyskens, F. L. Polyamines and Cancer: Old Molecules, New Understanding. Nat. Rev. Cancer, 2004, 4, 781–792. (b) Miller-Fleming, L.; OlinSandoval, V.; Campbell, K.; Ralser, M. Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell. J. Mol. Biol. 2015, 427, 3389–3406.

(35) (a) Palmer, A. J.; Wallace, H. M. The Polyamine Transport System as a Target for Anticancer Drug Development. Amino Acids, 2010, 38, 415–422. (b) Nowotarski, S. L.; Woster, P. M.; Casero, R. A. Polyamines and Cancer: Implications for Chemoprevention and Chemotherapy. Expert Rev. Mol. Med. 2013, 15, e3. (c) Murray-Stewart, T. R.; Woster, P. M.; Casero, R. A. Targeting Polyamine Metabolism for Cancer Therapy and Prevention. Biochem. J. 2016, 473, 2937–2953.

(36) (a) Edwards, M. L.; Snyder, R. D.; Stemerick, D. M. Synthesis and DNA-Binding Properties of Polyamine Analogues. J. Med. Chem. 1991, 34, 2414–2420. (b) Bergeron, R. J.; McManis, J. S.; Liu, C. Z.; Feng, Y.; Weimar, W. R.; Luchetta, G. R.; Wu, Q.; Ortiz-Ocasio, J.; Vinson, J. R. T.; Kramer, D.; Porter, C. Antiproliferative Properties of Polyamine Analogues: A Structure–Activity Study. J. Med. Chem. 1994, 37, 3464–3476. (c) Casero, R. A.; Woster, P. M. Terminally Alkylated Polyamine Analogues as Chemotherapeutic Agents. J. Med. Chem. 2001, 44, 1–26. (d) Casero, R. A.; Marton, L. J. Targeting Polyamine Metabolism and Function in Cancer and Other Hyperproliferative Diseases. Nat. Rev. Drug Discovery 2007, 6, 373–390. (e) Casero, R. A.; Woster, P. M. Recent Advances in the Development of Polyamine Analogues as Antitumor Agents. J. Med. Chem. 2009, 52, 4551–4573.

(37) (a) Cai, J.; Soloway, A. H. Synthesis of Carboranyl Polyamines for DNA Targeting. Tetrahedron Lett. 1996, 37, 9283–9286. (b) Cai, J.; Soloway, A. H.; Barth, R. F.; Adams, D. M.; Hariharan, J. R.; Wyzlic, I. M.; Radcliffe, K. Boron-Containing Polyamines as DNA Targeting Agents for Neutron Capture Therapy of Brain Tumors: Synthesis and Biological Evaluation. J. Med. Chem. 1997, 40, 3887–3896. (c) Ghaneolhosseini, H.; Tjarks, W.; Sjӧberg, S. Synthesis of Novel Boronated Acridinesand Spermidines as Possible Agents for BNCT. Tetrahedron 1998, 54, 3877–3884. (d) Martin, B.; Possémé, F.; Le Barbier, C.; Carreaux, F.; Carboni, B.; Seiler, N.; Moulinoux, J.-P.; Delcros, J-G. N-Benzylpolyamines as Vectors of Boron and Fluorine for Cancer Therapy and Imaging: Synthesis and Biological Evaluation. J. Med. Chem. 2001, 44, 3653–3664. (e) Pan, X. Q.; Wang, H.; Shukla, S.; Sekido, M.; Adams, D. M.; Tjarks, W.; Barth, R. F.; Lee, R. J. Boron-Containing Folate ReceptorTargeted Liposomes as Potential Delivery Agents for Neutron Capture Therapy. Bioconjugate Chem. 2002, 13, 435–442. (f) El-Zaria, M. E.; Dörfler, U.; Gabel, D. Synthesis of (Aminoalkylamine)-N-aminoalkyl)azanonaborane(11)-Derivatives for Boron Neutron Capture Therapy. J. Med. Chem. 2002, 45, 5817–5819. (g) Lee, J.-D.; Lee, Y.-J.; Jeong, H.-J.; Lee, J. S.; Lee, C.-H.; Ko, J.; Kang, S. O. Practical Synthesis of Aminoethyl-o-carboranes. Organometallics 2003, 22, 445–449. (h) El-Zaria, M. E. Synthesis and Biological Evaluation of Novel Azanonaboranes as Potential Agents for Boron Neutron Capture Therapy. Appl. Organomet. Chem. 2005, 19, 683–689. (i) El-Zaria, M. E.; Genady, A. R.; Gabel, D. Azanonaboranes Containing Imidazole Derivatives for Boron Neutron Capture Therapy: Synthesis, Cheracterization, and In Vitro Toxicity Evaluation. Chem. Eur. J. 2006, 12, 8084–8089.

(38) Zhuo, J.-C.; Cai, J.; Soloway, A. H.; Barth, R. F.; Adams, D. M.; Ji, W.; Tjarks, W. Synthesis and Biological Evaluation of Boron-Containing Polyamines as Potential Agents for Neutron Capture Therapy of Brain Tumors. J. Med. Chem. 1999, 42, 1282– 1292.

(39) Hattori, Y.; Kusaka, S.; Mukumoto, M.; Ishimura, M.; Ohta, Y.; Takenaka, H.; Uehara, K.; Asano, T.; Suzuki, M.; Masunaga, S.; Ono, K.; Tanimori, S.; Kirihata, M. Synthesis and in Vitro Evaluation of Thiododecaborated α, α-Cycloalkylamino Acids for the Treatment of Malignant Brain Tumors by Boron Neutron Capture Therapy. Amino Acids 2014, 46, 2715–2720.

(40) Futamura, G.; Kawabata, S.; Nonoguchi, N.; Hiramatsu, R.; Toho, T.; Tanaka, H.; Masunaga, S.; Hattori, Y.; Kirihata, M.; Ono, K.; Kuroiwa, T. Evaluation of a Novel Sodium Borocaptate-Containing Unnatural Amino Acid as a Boron Delivery Agent for Neutron Capture Therapy of the F98 Rat Glioma. Radiat. Oncol. 2017, 12, 26.

(41) (a) Srivastava, R. R.; Singhaus, R. R.; Kabalka, G. W. 4-Dyhidroxyborylphenyl Analogues of 1-Aminocyclobutanecarboxylic Acids: Potential Boron Neutron Capture Therapy Agents. J. Org. Chem. 1999, 64, 8495–8500. (b) Kabalka, G. W.; Das, B. C.; Das, S. Synthesis of Novel Boron Containing Unnatural Cyclic Amino Acids as Potential Therapeutic Agents. Tetrahedron Lett. 2001, 42, 7145–7146. (c) Das, B. C.; Das, S.; Li, G.; Bao, W.; Kabalka, G. W. Synthesis of a Water Soluble Carborane Containing Amino Acid as a Potential Therapeutic Agent. Synlett 2001, 9, 1419–1420. (d) Kabalka, G. W.; Yao, M.-L. Synthesis of a Potential Boron Neutron Capture Therapy Agent: 1-Aminocyclobutane-1-carboxylic Acid Bearing a Butylboronic Acid Side Chain. Synthesis 2003, 18, 2890–2893. (e) Kabalka, G. W.; Yao, M.-L. Synthesis of a Novel Boronated 1-Aminocyclobutanecarboxylic Acid as a Potential Boron Neutron Capture Therapy Agent. Appl. Organometal. Chem. 2003, 17, 398–402. (f) Kabalka, G. W.; Yao, M.-L.; Navarane, A. Synthesis of a Boronated Amino Acid as a Potential Neutron Therapy Agent: 1-Amino-3- [(dihydroxyboryl)ethyl]-cyclobutanecarboxylic Acid. Tetrahedron Lett. 2005, 46, 4915–4917. (g) Kabalka, G. W.; Yao, M.-L.; Wu, Z. Hydroboration of AlkeneContaining Hydantoins. Org. Process Res. Dev. 2006, 10, 1059–1061. (h) Kabalka, G. W.; Yao, M. -L.; Marepally, S. R.; Chandra, S. Biological Evaluation of Boronated Unnatural Amino Acids as New Boron Carriers. Appl. Radiat. Isot. 2009, 67, S374– S379. (i) Chandra, S.; Barth, R. F.; Haider, S. A.; Yang, W.; Huo, T.; Shaikh, A. L.; Kabalka, G. W. Biodistribution and Subcellular Localization of an Unnatural BoronContaining Amino Acid (Cis-ABCPC) by Imaging Secondary Ion Mass Spectrometry for Neutron Capture Therapy of Melanomas and Gliomas. PloS One 2013, 8, No. e75377.

(42) (a) Warburg, O. On the Origin of Cancer Cells. Science 1956, 123, 309-314. (b) Heiden, M. G. V.; Cantley, L. C.; Thompson, C. B. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science 2009, 324, 1029–1033.

(43) (a) Maurer, J. L.; Serino, A. J.; Hawthorne, M. F. Hydrophilically Augmented Glycosyl Carborane Derivatives for Incorporation in Antibody Conjugation Reagents. Organometallics. 1988, 7, 2519−2524. (b) Tietze, L. F.; Bothe, U. Ortho-Carboranyl Glycosides of Glucose, Mannose, Maltose and Lactose for Cancer Treatment by Boron Neutron-Capture Therapy. Chem. Eur. J. 1998, 7, 1179−1183. (c) Giovenzana, G. B.; Lay, L.; Monti, D.; Palmisano, G.; Panza, L. Synthesis of Carboranyl Derivatives of Alkynyl Glycosides as Potential BNCT Agents. Tetrahedron 1999, 55, 14123–14136. (d) Tietze, L. F.; Bothe, U.; Schuberth, I. Preparation of a New Carboranyl Lactoside for the Treatment of Cancer by Boron Neutron Capture Therapy: Synthesis and Toxicity of Fluoro Carboranyl Glycosides for in Vivo 19FNMR Spectroscopy. Chem. Eur. J. 2000, 6, 836−842. (e) Tietze, L. F.; Bothe, U.; Griesbach, U.; Nakaichi, M.; Hasegawa, T.; Nakamura, H.; Yamamoto, Y. Carboranyl Bisglycosides for the Treatment of Cancer by Boron Neutron Capture Therapy. ChemBioChem 2001, 2, 326−334. (f) Tietze, L. F.; Bothe, U.; Griesbach, U.; Nakaichi, M.; Hasegawa, T.; Nakamura, H.; Yamamoto, Y. ortho-Carboranyl Glycosides for the Treatment of Cancer by Boron Neutron Capture Therapy. Bioorg. Med. Chem. 2001, 9, 1747–1752. (g) Tietze, L. F.; Griesbach, U.; Schuberth, I.; Bothe, U.; Marra, A.; Dondoni, A. Novel Carboranyl C-Glycosides for the Treatment of Cancer by Boron Neutron Capture Therapy. Chem. Eur. J. 2003, 9, 1296–1302. (h) Ronchi, S.; Prosperi, D.; Compostella, F.; Panza, L. Synthesis of Novel Carborane-hybrids Based on a Trizine Scaffold for Boron Neutron Capture Therapy. Synlett 2004, 6,1007−1010. (i) Orlova, A. V.; Kononov, L. O.; Kimel, B. G.; Sivaev, I. B.; Bregadze, V. I. Conjugates of Polyhedral Boron Compounds with Carbohydrates. 4. Hydrolytic Stability of Carborane-Lactose Conjugates Depends on the Structure of a Spacer between Carborane Cage and Sugar Moiety. Appl. Organomet. Chem. 2006, 20, 416–420. (j) Satapathy, R.; Dash, B. P.; Bode, B. P.; Byczynski, E. A.; Hosmane, S. N.; Bux, S.; Hosmane, N. S. New Classes of Carborane-appended 5-Thio-D-glucopyranose Derivatives. Dalton Trans. 2012, 41, 8982–8988.

(44) (a) Thimon, C.; Panza, L.; Morin, C. Synthesis of a Glycosylated ortho-Carboranyl Amino Acid. Synlett 2003, 34, 1399−1402. (b) Ronchi, S.; Prosperi, D.; Thimon, C.; Morin, C.; Panza, L. Synthesis of Mono- and Bisglucuronoylated Carboranes. Tetrahedron Asymmetry 2005, 16, 39−44. (c) Imperio, D.; Del Grosso, E. D.; Fallarini, S.; Lombardi, G.; Panza, L. Synthesis of Suger-Boronic Acid Derivatives: A Class of Potential Agents for Boron Neutron Capture Therapy. Org. Lett. 2017, 19, 1678–1681. (d) Imperio, D.; Muz, B.; Azab, A. K.; Fallarini, S.; Lombardi, G.; Panza, L. A Short and Convenient Synthesis of closo-Dodecaborate Sugar Conjugates. Eur. J. Org. Chem. 2019, 7228–7232. (e) Imperio, D.; Del Grosso, E.; Fallarini, S.; Lombardi, G.; Panza, L. Anomeric Sugar Boronic Acid Analogues as Potential Agents for Boron Neutron Capture Therapy. Beilstein J. Org. Chem. 2019, 15, 1355–1359.

(45) (a) Lechtenberg, B.; Gabel, D. Synthesis of (B12H11S)2- Containing Glucuronoside as Potential Prodrug for BNCT. J. Organomet. Chem. 2005, 690, 2780–2782. (b) Genady, A. R.; El-Zaria, M. E. Novel Glycosylated Carboranylquinazolines for Boron Neutron Capture Therapy of Tumors: Synthesis, Characterization, and in Vitro Toxicity Studies. Appl. Organomet. Chem. 2008, 22, 227–232. (c) Tsurubuchi, T.; Shirakawa, M.; Kurosawa, W.; Matsumoto, K.; Ubagai, R.; Umishio, H.; Suga, Y.; Yamazaki, J.; Arakawa, A.; Maruyama, Y.; Seki, T.; Shibui, Y.; Yoshida, F.; Zaboronok, A.; Suzuki, M.; Sakurai, Y.; Tanaka, H.; Nakai, K.; Ishikawa, E.; Matsumura, A. Evaluation of a Novel Boron-Containing α-D-Mannopyranoside for BNCT. Cells 2020, 9, 1277.

(46) Tanaka, T.; Sawamoto, Y.; Aoki, S. Concise and Versatile Synthesis of Sulfoquinovosyl Acyl Glycerol Derivatives for Biological Applications. Chem. Pharm. Bull. 2017, 65, 566–572.

(47) Itoh, T.; Tamura, K.; Ueda, H.; Tanaka, T.; Sato, K.; Kuroda, R.; Aoki, S. Design and Synthesis of Boron Containing Monosaccharides by the Hydroboration of D-Glucal for Use in Boron Neutron Capture Therapy (BNCT). Bioorg. Med. Chem. 2018, 26, 5922–5933.

(48) (a) Ahrens, V. M.; Frank, R.; Boehnke, S.; Schütz, C. L.; Hampel, G.; Iffland, D. S.; Bings, N. H.; Hey-Hawkins, E.; Beck-Sickinger, A. G. Receptor-Mediated Uptake of Boron-Rich Neuropeptide Y Analogues for Boron Neutron Capture Therapy. ChemMedChem 2015, 10, 164–172. (b) Isono, A.; Tsuji, M.; Sanada, Y.; Matsushita, A.; Masunaga, S.; Hirayama, T.; Nagasawa, H. Design, Synthesis, and Evaluation of Lipopeptide Conjugates of Mercaptoundecahydrododecaborate for Boron Neutron Capture Therapy. ChemMedChem 2019, 14, 823–832. (c) Nakase, I.; Katayama, M.; Hattori, Y.; Ishimura, M.; Inaura, S.; Fujiwara, D.; Takatani-Nakase, T.; Fujii, I.; Futaki, S.; Kirihata, M. Intracellular Target Delivery of Cell-penetrating Peptideconjugated Dodecaborate for Boron Neutron Capture Therapy (BNCT). Chem. Commun. 2019, 55, 13955–13958. (d) Kawai, K.; Nishimura, K.; Okada, S.; Sato, S.; Suzuki, M.; Takata, T.; Nakamura, H. Cyclic RGD-Functionalized closoDodecaborate Albumine Conjugates as Integrin Targeting Boron Carriers for Neutron Capture Therapy. Mol. Pharmaceutics 2020, 17, 3740–3747.

(49) (a) Miyajima, Y.; Nakamura, H.; Kuwata, Y.; Lee, J.-D.; Masunaga, S.; Ono, K.; Maruyama, K. Transferrin-Loaded nido-Carborane Liposomes: Tumor-Targeting Boron Delivery System for Neutron Capture Therapy. Bioconjugate Chem. 2006, 17, 1314–1320. (b) Nakamura, H. Liposomal Boron Delivery for Neutron Capture Therapy. Academic Press, 2009, 465, 179–208. (c) Ueno, M.; Ban, H. S.; Nakai, K.; Inomata, R.; Kaneda, Y.; Matsumura, A.; Nakamura, H. Dodecaborate Lipid Liposomes as New Vehicles for Boron Delivery System of Neutron Capture Therapy. Bioorg. Med. Chem. 2010, 18, 3059–3065. (d) Koganei, H.; Tachikawa, S.; El-Zaria, M. E.; Nakamura, H. Synthesis of Oligo-closo-dodecaborates by Hüisgen Click Reaction as Encapsulated Agents for the Preparation of High-boron-content Liposomes for Neutron Capture Therapy. New J. Chem. 2015, 39, 6388–6394. (e) Luderer, M. J.; Muz, B.; Alhallak, K.; Sun, J.; Wasden, K.; Guenther, N.; Puente, P.; Federico, C.; Azab, A. K. Thermal Sensitive Liposomes Improve Delivery of Boronated Agents for Boron Neutron Capture Therapy. Pharm. Res. 2019, 36, 144.

(50) (a) Ali, F.; Hosmane, N. S.; Zhu, Y. Boron Chemistry for Medical Applications. Molecules 2020, 25, 828. (b) Pitto-Barry, A. Polymers and Boron Neutron Capture Therapy (BNCT): A Potent Combination. Polym. Chem. 2021, 12, 2035–2044.

(51) (a) Paxton, R. J.; Beatty, B. G.; Varadarajan, A.; Hawthorne, M. F. Carboranyl Peptide-Antibody Conjugates for Neutron Capture Therapy: Preparation, Characterization, and in Vivo Evaluation. Bioconjugate Chem. 1992, 3, 241–247. (b) Barth, R. F.; Adams, D. M.; Soloway, A. H.; Alam, F.; Darby, M. V. Boronated Starburst Dendrimer-Monoclonal Antibody Immunoconjugates: Evaluation as a Potential Delivery System for Neutron Capture Therapy. Bioconjugate Chem. 1994, 5, 58–66. (c) Wu, G.; Barth, R. F.; Yang, W.; Chatterjee, M.; Tjarks, W.; Ciesielski, M. J.; Fenstermaker, R. A. Site-Specific Conjugation of Boron-Containing Dendrimers to Anti-EGF Receptor Monoclonal Antibody Cetuximab (IMC-C225) and Its Evaluation as a Potential Delivery Agent for Neutron Capture Therapy. Bioconjugate Chem. 2004, 15, 185–194.

(52) (a) Wyzlic, I. M.; Soloway, A. H. A General, Convenient Way to CarboraneContaining Amino Acids for Boron Neutron Capture Therapy. Tetrahedron Lett. 1992, 33, 7489−7490. (b) Nemoto, H.; Iwamoto, S.; Nakamura, H.; Yamamoto, Y. A New Water-soluble p-Boronophenylalanine Derivatives for Neutron Capture Therapy. Chem. Lett. 1993, 22, 465−468. (c) Prashar, J. K.; Moore, D. E. Synthesis of Carboranyl Phenylalanine for Potential Use in Neutron Capture Therapy of Melanoma. J. Chem. Soc., Perkin. Trans. 1 1993, 1051−1053. (d) Karnbrock, W.; Musiol, H.-J.; Moroder, L. Enantioselective Synthesis of S-o-Carboranylalanine via Methylated Bislactim Ethers of 2,5-Diketopiperazines. Tetrahedron 1995, 51, 1187– 1196. (e) Denniel, V.; Bauchat, P.; Danion, D.; Danion-Bougot, R. Hydroboration of Vinylglycine and Allylglycine as a Route to Boron-derivatives of α-Amino Acids. Tetrahedron Lett. 1996, 37, 5111–5114. (f) Radel, P. A.; Kahl, S. B. Enantioselective Synthesis of L- and D-Carboranylalanine. J. Org. Chem. 1996, 61, 4582–4588. (g) Hattori, Y.; Kusaka, S.; Mukumoto, M.; Uehara, K.; Asano, T.; Suzuki, M.; Masunaga, S.; Ono, K.; Tanimori, S.; Kirihata, M. Biological Evaluation of DodecaborateContaining L-Amino Acids for Boron Neutron Capture Therapy. J. Med. Chem. 2012, 55, 6980–6984. (h) Li, R.; Zhang, J.; Guo, J.; Xu, Y.; Duan, K.; Zheng, J.; Wan, H.; Yuan, Z.; Chen, H. Application of Nitroimidazole–Carborane-Modified Phenylalanine Derivatives as Dual-Target Boron Carriers in Boron Neutron Capture Therapy. Mol. Pharmaceutics. 2020, 17, 202–211. (i) Laskova, J.; Kosenko, I.; Ananyev, I.; Stogniy, M.; Sivaev, I.; Bregadze, V. ʺFree of Baseʺ Sulfa-Michael Addition for Novel o-Carboranyl-DL-Cysteine Synthesis. Crystals. 2020, 10, 1133.

(53) (a) Danhier, F.; Feron, O.; Préat, V. To Exploit The Tumor Microenvironment: Passive and Active Tumor Targeting of Nanocarriers for Anti-Cancer Drug Delivery. J. Contr. Rel. 2010, 148, 135–146. (b) Kikuchi, S.; Kanoh, D.; Sato, S.; Sakurai, Y.; Suzuki, M.; Nakamura, H. Maleimide-Functionalized closo-Dodecaborate Albumin Conjugates (MID-AC): Unique Ligation at Cysteine and Lysine Residues Enables Efficient Boron Delivery to Tumor for Neutron Capture Therapy. J. Control. Release 2016, 237, 160–167. (c) Sato, S.; Ishii, S.; Nakamura, H. Development of Albumincloso-Dodecaborate Conjugates as Boron Carriers for Neutron-Capture Therapy Ru(bpy)3-Photocatalyzed Modification of Thyrosin. Eur. J. Inorg. Chem. 2017, 4406–4410. (d) Nakamura, H.; Kikuchi, S.; Kawai, K.; Ishii, S.; Sato, S. closoDodecaborate-Conjugated Human Serum Albumins: Preparation and in vivo Selective Boron Delivery to Tumor. Pure Appl. Chem. 2018, 90, 745–753. (e) Ishii, S.; Sato, S.; Asami, H.; Hasegawa, T.; Kohno, J.; Nakamura, H. Design of S–S Bond Containing Maleimide-Conjugated closo-Dodecaborate (SSMID): Identification of Unique Modification Sites on Albumin and Investigation of Intracellular Uptake. Org. Biomol. Chem. 2019, 17, 5496–5499. (f) Matsumura, Y. Cancer Stromal Targeting Therapy to Overcome The Pitfall of EPR Effect. Adv. Drug Deliv. Rev. 2020, 154– 155, 142–150.

(54) Kitamura, M.; Suzuki, T.; Abe, R.; Ueno, T.; Aoki, S. 11B NMR Sensing of d-Block Metal Ions in Vitro and in Cells Based on the Carbon-Boron Bond Cleavage of Phenylboronic Acid-Pendant Cyclen (Cyclen = 1,4,7,10-Tertaazacyclododecane). Inorg. Chem. 2011, 50, 11568–11580.

(55) (a) Tanaka, T.; Nishiura, Y.; Araki, R.; Saido, T.; Abe, R.; Aoki, S. 11B NMR Probes of Copper(Ⅱ): Finding and Implications of the Cu2+ -Promoted Decomposition of ortho-Carborane Derivatives. Eur. J. Inorg. Chem. 2016, 1819–1834. (b) Tanaka, T.; Araki, R.; Saido, T.; Abe, R.; Aoki, S. 11B NMR/MRI Sensing of Copper(Ⅱ) Ions In Vitro by the Decomposition of a Hybrid Compound of a nido-o-Carborane and a Metal Chelator. Eur. J. Inorg. Chem. 2016, 3330–3337.

(56) (a) Mislick, K. A.; Baldeschwieler, J. D. Evidence for the Role of Proteoglycans in Cation-Mediated Gene Transfer. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 12349– 12354. (b) Belting, M.; Persson, S.; Fransson, L.-Å. Proteoglycan Involvement in Polyamine Uptake. Biochem. J. 1999, 338, 317–323. (c) Belting, M.; Mani, K.; Jönsson, M.; Cheng, F.; Sandgren, S.; Jonsson, S.; Ding, K.; Delcros, J.-G.; Fransson, L.-Å. Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells. J. Biol. Chem. 2003, 278, 47181–47189. (d) Welch, J. E.; Bengtson, P.; Svensson, K.; Wittrup, A.; Jenniskens, G. J.; Ten Dam, G. B.; Van Kuppevelt, T. H.; Belting, M. Single Chain Fragment Anti-heparan Sulfate Antibody Targets the Polyamine Transport System and Attenuates Polyamine-Dependent Cell Proliferation. Int. J. Oncol. 2008, 32, 749–756. (e) Uemura, T.; Stringer, D. E.; Blohm-Mangone, K. A.; Gerner, E. W. Polyamine Transport is Mediated by Both Endocytic and Solute Carrier Transport Mechanisms in the Gastrointestinal Tract. Am. J. Physiol.: Gastrointest. Liver Physiol. 2010, 299, G517–G522. (f) Christianson, H. C.; Belting, M. Heparin Sulfate Proteoglycan as a Cell-surface Endocytosis Receptor. Matrix Biol. 2014, 35, 51–55. (g) Abdulhussein, A. A.; Wallace, H. M. Polyamines and Membrane Transporters. Amino Acids 2014, 46, 655–660. (h) Nikitovic, D.; Berdiaki, A.; Spyridaki, I.; Krasanakis, T.; Tsatsakis, A.; Tzanakakis, G. N. Proteoglycans– Biomarkers and Targets in Cancer Therapy. Front. Endocrinol. 2018, 9, 69.

(57) It is reported that macrocyclic polyamine-modified lipids and chitosan are utilized for gene transfection. See: (a) Li, C.; Tian, H.; Rong, N.; Liu, K.; Liu, F.; Zhu, Y.; Qiao, R.; Jiang, Y. Chitosan Grafted with Macrocyclic Polyamines on C-2 and C-6 Positions as Nonviral Gene Vectors: Preparation, Characterization, and In Vitro Transfection Studies. Biomacromolecules 2011, 12, 298–305. (b) Li, L.; Zhao, F.; Zhao, B.; Zhang, J.; Li, C.; Qiao, R. Chitosan Grafted with Phosphorylcholine and Macrocyclic Polyamine as an Effective Gene Delivery Vector: Preparation, Characterization, and In Vitro Transfection. Macromol. Biosci. 2015, 15, 912–926. (c) Chang, D.-C.; Zhang, Y.-M.; Zhang, J.; Liu, Y.-H.; Yu, X.-Q. Cationic Lipids with a Cyclen Headgroup: Synthesis and Structure–Activity Relationship Studies as Non-viral Gene Vectors. RSC Adv. 2017, 7, 18681–18689.

(58) (a) Yang, R.; Zompa, L. J. Metal Complexes of Cyclic Triamines. 1. Complexes of 1,4,7-Triazacyclononane ([9]aneN3) with Nickel(Ⅱ), Copper(Ⅱ), and Zinc(Ⅱ). Inorg. Chem. 1976, 15, 1499–1502. (b) Kimura, E. Macrocyclic Polyamines as Biological Cation and Anion Complexones – An Application to Calculi Dissolution. Biomimetic and Bioorganic Chemistry: Topics in Current Chemistry: Springer, 1985; Vol. 128, 113–141.

(59) (a) Kodama, M.; Kimura, E. Thermodynamic and Kinetic Effects of 12-Membered Macrocycles Polarographic Studies of 1,4,7,10-Tetra-azacyclododecanecopper(Ⅱ). J. Chem. Soc., Dalton Trans. 1976, 116–120. (b) Ohshima, R.; Kitamura, M.; Morita, A.; Shiro, M.; Yamada, Y.; Ikekita, M.; Kimura, E.; Aoki, S. Design and Synthesis of a Fluorescent Probe for Zn2+, 5,7-Bis(N,N-dimethylaminosulfonyl)-8- hydroxyquinoline-Pendant 1,4,7,10-Tetraazacyclododecane and Zn2+ -Dependent Hydrolytic and Zn2+ -Independent Photochemical Reactivation of Its Benzenesulfonyl-Caged Derivative. Inorg. Chem. 2010, 49, 888–899.

(60) Kodama, M.; Kimura, E. Effects of Cyclization and Ring Size on Complex Formation Between Penta-amine Ligands and Copper(Ⅱ). J. Chem. Soc., Dalton Trans. 1978, 104–110.

(61) (a) Kodama, M.; Kimura, E. Equilibria of Complex Formation Between Several Bivalent Metal Ions and Macrocyclic Tri- and Penta-amines. J. Chem. Soc., Dalton Trans. 1978, 1081–1085. (b) Kimura, E.; Yatsunami, T. Synthesis of Some Cyclic Derivatives of Spermidine and Spermine. Chem. Pharm. Bull. 1980, 28, 994–997. (c) Diez-Castellnou, M.; Salassa, G.; Mancin, F.; Scrimin, P. The Zn(Ⅱ)-1,4,7- Trimethyl-1,4,7-Triazacyclononane Complex: A Monometallic Catalyst Active in Two Protonation States. Front. Chem. 2019, 7, 469. (d) Savastano, M.; Fiaschi, M.; Ferraro, G.; Gratteri, P.; Mariani, P.; Bianchi, A.; Bazzicalupi, C. Sensing Zn2+ in Aqueous Solution with a Fluorescent Scorpiand Macrocyclic Ligand Decorated with an Anthracene Bearing Tail. Molecules. 2020, 25, 1355.

(62) (a) Kimura, E. Model Studies for Molecular Recognition of Carbonic Anhydrase and Carboxypeptidase. Acc. Chem. Res. 2001, 34, 171–179. (b) Aoki, S.; Kagata, D.; Shiro, M.; Takeda, K.; Kimura, E. Metal Chelation-Controlled Twisted Intramolecular Charge Transfer and Its Application to Fluorescent Sensing of Metal Ions and Anions. J. Am. Chem. Soc. 2004, 126, 13377–13390. (c) Aoki, S.; Zulkefeli, M.; Kitamura, M.; Hisamatsu, Y. Supramolecular Host and Catalysts Formed by the Synergistic Molecular Assembly of Multinuclear Zinc(Ⅱ) Complexes in Aqueous Solution. In Synergy in Supramolecular Chemistry; Nabeshima, T., Ed.; CRC: Boca Raton, FL, USA, 2015; pp 33–56. (d) Kimura, E.; Koike, T.; Aoki, S. Evolution of ZnⅡ –Macrocyclic Polyamines to Biological Probes and Supramolecular Assembly. In Macrocyclic and Supramolecular Chemistry: How Izatt-Christensen Award Winners Shaped the Field; Izatt, R. M., Ed.; John Wiley & Sons: Hoboken, NJ, USA, 2016; pp 417–445.

(63) (a) Kimura, E. Evolution of Macrocyclic Polyamines from Molecular Science to Supramolecular Science. Bull. Jpn. Soc. Coord. Chem. 2012, 59, 26–47. (b) Itoh, S.; Sonoike, S.; Kitamura, M.; Aoki, S. Design and Synthesis of Chiral Zn2+ Complexes Mimicking Natural Aldolases for Catalytic C–C Bond Forming Reactions in Aqueous Solution. Int. J. Mol. Sci. 2014, 15, 2087–2118.

(64) (a) Inouye, Y.; Kanamori, T.; Yoshida, T.; Bu, X.; Shionoya, M.; Koike, T.; Kimura, E. Inhibition of Human Immunodeficiency Virus Proliferation by Macrocyclic Polyamines and Their Metal Complexes. Biol. Pharm. Bull., 1994, 17, 243–250. (b) Inouye, Y.; Kanamori, T.; Yoshida, T.; Koike, T.; Shionoya, M.; Fujioka, H.; Kimura, E. Differential Contribution of Metal Complexation and Dimerization to the Chemotherapeutic Potential of Bicyclen-ZnⅡ 2 Complex against Human Immunodeficiency Virus. Biol. Pharm. Bull., 1996, 19, 456–458.

(65) (a) Shionoya, M.; Kimura, E.; Shiro, M. A New Ternary Zinc(Ⅱ) Complex with [12]aneN4 (= 1,4,7,10-Tetraazacyclododecane) and AZT (= 3’-Azido-3’- deoxythymine). Highly Selective Recognition of Thymidine and Its Related Nucleosides by a Zinc(Ⅱ) Macrocyclic Tetraamine Complex with Novel Complementary Associations. J. Am. Chem. Soc. 1993, 115, 6730–6737. (b) Kikuta, E.; Murata, M.; Katsube, N.; Koike, T.; Kimura, E. Novel Recognition of Thymine Base in Double-Stranded DNA by Zinc(Ⅱ)–Macrocyclic Tetraamine Complexes Appended with Aromatic Groups. J. Am. Chem. Soc. 1999, 121, 5426–5436. (c) Kimura, E.; Kikuta, E. Why Zinc in Zinc Enzymes? From Biological Roles to DNA Based-Selective Recognition. J. Biol. Inorg. Chem. 2000, 5, 139–155. (d) Kimura, E.; Kikuta, E. Macrocyclic Zinc(Ⅱ) Complexes for Selective Recognition of Nucleobases in Single- and Double-Stranded Polynucleotides. Prog. React. Kinet. Mech. 2000, 25, 1–64. (e) Aoki, S.; Kimura, E. Zinc‒Nucleic Acid Interaction. Chem. Rev. 2004, 104, 769–788. (f) del Mundo, I. M.; Siters, K. E.; Fountain, M. A.; Morrow, J. R. Structural Basis for Bifunctional Zinc(Ⅱ) Macrocyclic Complex Recognition of Thymine Bulges in DNA. Inorg. Chem. 2012, 51, 5444–5457.

(66) (a) Richman, J. E.; Atkins, T. J. Nitrogen Analogs of Crown Ethers. J. Am. Chem. Soc. 1974, 96, 2268–2270. (b) Atkins, T. J.; Richman, J. E.; Oettle, W. F. Macrocyclic Polyamines: 1,4,7,10,13,16-Hexaazacyclooctadecane. Org. Synth. 2003, 6, 652. (c) Cao, R.; Müller, P.; Lippard, S. J. Tripodal Tris-tacn and Tris-dpa Platforms for Assembling Phosphate-Templated Trimetallic Centers. J. Am. Chem. Soc. 2010, 132, 17366–17369. (d) Brown, A; Bunchuay, T.; Crane, C. G.; White, N. G.; Thompson, A. L.; Beer, P. D. A Bis-Triazacyclononane Tris-Pyridyl N9- Azacryptand “Beer Can” Receptor for Completion of Alkali Metal and Lead(Ⅱ) Cations. Chem. Eur. J. 2018, 24, 10434–10442.

(67) Pieters, G.; Cazzolaro, A.; Bonomi, R.; Prins, L. J. Self-assembly and Selective Exchange of Oligoanions on the Surface of Monolayer Protected Au Nanoparticles in Water. Chem. Commun. 2012, 48, 1916–1918.

(68) (a) Qu, D.-H.; Wang, Q.-C.; Ren, J.; Tian, H. A Light-Driven Rotaxane Molecular Shuttle with Dual Fluorescence Addresses. Org. Lett. 2004, 6, 2085–2088. (b) Liu, Y.; Zhang, S.; Miao, Q.; Zheng, L.; Zong, L.; Cheng, Y. Fluorescent Chemosensory Conjugated Polymers Based on Optically Active Polybinaphthyls and 2,2’-Bipyridyl Units. Macromolecules 2007, 40, 4839–4847.

(69) (a) Corey, E. J.; Danheiser, R. L.; Chandrasekaran, S. New Reagents for the Intermolecular Pinacolic Coupling of Ketones and Aldehydes. J. Org. Chem. 1976, 41, 260–265. (b) Chen, C.-Y.; Chen, C.-T. Reaction-Based and Single Fluorescent Emitter Decorated Ratiometric Nanoprobe to Detect Hydrogen Peroxide. Chem. Eur. J. 2013, 19, 16050–16057.

(70) Cappuccio, F. E.; Suri, J. T.; Cordes, D. B.; Wessling, R. A.; Singaram, B. Evaluation of Pyranine Derivatives in Boronic Acid Based Saccharide Sensing: Significance of Charge Interaction Between Dye and Quencher in Solution and Hydrogel. J. Fluoresc. 2004, 14, 521–533.

(71) (a) Takeuchi, M.; Mizuno, T.; Shinmori, H.; Nakashima, M.; Shinkai, S. Fluorescence and CD Spectroscopic Sugar Sensing by a Cyanine-appended Diboronic Acid Probe. Tetrahedron 1996, 52, 1195–1204. (b) Pathak, R.; Nhlapo, J. M.; Govender, S.; Michael, J. P.; van Otterlo, W. A. L.; de Koning, C. B. A Concise Synthesis of Novel Naphtho[α]carbazoles and Benzo[c]carbazoles. Tetrahedron 2006, 62, 2820–2830.

(72) Kimura, E.; Aoki, S.; Koike, T.; Shiro, M. A Tris(ZnⅡ –1,4,7,10- tetraazacyclododecane) Complex as a New Receptor for Phosphate Dianions in Aqueous Solution. J. Am. Chem. Soc. 1997, 119, 3068–3076.

(73) (a) Itoh, S.; Kitamura, M.; Yamada, Y.; Aoki, S. Chiral Catalysts Dually Functionalized with Amino Acid an Zn2+ Complex Components for Enantioselective Direct Aldol Reactions Inspired by Natural Aldolases: Design, Synthesis, Complexation Properties, Catalytic Activities, and Mechanistic Study. Chem. Eur. J. 2009, 15, 10570–10584. (b) Itoh, S.; Sonoike, S.; Kitamura, M.; Aoki, S. Design and Synthesis of Chiral Zn2+ Complexes Mimicking Natural Aldolases for Catalytic C– C Bond Forming Reactions in Aqueous Solution. Int. J. Mol. Sci. 2014, 15, 2087– 2118.

(74) Rodal, S. K.; Skretting, G.; Garred, Ø.; Vilhardt, F.; van Deurs, B.; Sandvig, K. Extraction of Cholesterol with Methyl-β-Cyclodextrin Perturbs Formation of Clathrin-Coated Endocytic Vesicles. Mol. Biol. Cell. 1999, 10, 961–974.

(75) (a) Macia, E.; Ehrlich, M.; Massol, R.; Boucrot, E.; Brunner, C.; Kirchhausen, T. Dynasore, a Cell-Permeable Inhibitor of Dynamin. Dev. Cell 2006, 10, 839–850. (b) Dutta, D.; Donaldson, J. G. Search for Inhibitors of Endocytosis. Cell. Logist. 2012, 2, 203–208.

(76) (a) Lagana, A.; Vadnais, J.; Le, P. U.; Nguyen, T. N.; Laprade, R.; Nabi, I. R.; Noël, J. Regulation of the Formation of Tumor Cell Pseudopodia by the Na+ /H+ Exchanger NHE1. J. Cell Sci. 2000, 113, 3649–3662. (b) Koivusalo, M.; Welch, C.; Hayashi, H.; Scott, C. C.; Kim, M.; Alexander, T.; Touret, N.; Hahn, K. M.; Grinstein, S. Amiloride Inhibits Micropinocytosis by Lowering Submembranous pH and Preventing Rac1 and Cdc42 Signaling. J. Cell Biol. 2010, 188, 547–563.

(77) (a) Schneider, C. A.; Rasband, W. S.; Eliceiri, K. W. NIH Image to ImageJ: 25 Years of Image Analysis. Nat. Methods. 2012, 9, 671–675. (b) Guzmán, C.; Bagga, M.; Kaur, A.; Westermarck, J.; Abankwa, D. ColonyArea: An ImageJ Plugin to Automatically Quantify Colony Formation in Clonogenic Assays. PloS One 2014, 9, No. e92444.

(78) (a) Hartman, T.; Carlsson, J. Radiation Dose Heterogeneity in Receptor and Antigen Mediated Boron Neutron Capture Therapy. Radiother. Oncol. 1994, 31, 61–75. (b) Ono, K.; Tanaka, H.; Tamari, Y.; Watanabe, T.; Suzuki, M.; Masunaga, S. Proposal for Determining Absolute Biological Effectiveness of Boron Neutron Capture Therapy―the Effect of 10B(n,α)7Li Dose can be Predicted from the Nucleocytoplasmic Ratio or the Cell Size. J. Radiat. Res. 2019, 60, 29–36.

(79) (a) Kimura, E.; Ikeda, T.; Aoki, S.; Shionoya, M. Macrocylic Zinc(Ⅱ) Complexes for Selective Recognition of Nucleobases in Single- and Double-Stranded Polynucleotides. J. Biol. Inorg. Chem. 1998, 3, 259–267. (b) Zulkefeli, M.; Sogon, T.; Takeda, K.; Kimura, E.; Aoki, S. Design and Synthesis of a Stable Supramolecular Trigonal Prism Formed by the Self-Assembly of a Linear Tetrakis(Zn2+—cyclen) Complex and Trianionic Trithiocyanuric Acid in Aqueous Solution and Its Complexation with DNA (Cyclen = 1,4,7,10- Tetraazacyclododecane). Inorg. Chem. 2009, 48, 9567–9578. (c) Kimura, E.; Kitamura, H.; Ohtani, K.; Koike, T. Elaboration of Selective and Efficient Recognition of Thymidine Beas in Dinucleotides (TpT, ApT, CpT, and GpT), SingleStranded d(GTGACGCC), and Double-Stranded d(CGCTAGCG)2 by Zn2+— Acridinylcyclen (Acridinylcyclen = (9-Acridinyl)methyl-1,4,7,10- tetraazacyclododecane) J. Am. Chem. Soc. 2000, 122, 4668–4677.

(80) Aoki, S.; Kikuchi, C.; Kitagawa, Y.; Hasegawa, Y.; Sonoike, S.; Saga, Y.; Hatanaka, M. Evaluation of Zn2+ Coordination Structures in Chiral Zn2+ Complexes Based on Shape Measurement Factors: Relationships between Activity and the Coordination Structure. Eur. J. Inorg. Chem. 2019, 4740–4751.

(81) The complexation properties of metal-free [15]aneN5 and larger macrocyclic polyamines with organic anions were reported in Refs. 58b, 63 and 82. On the other hand, the complexation of their Zn2+ complexes with dT and other imide-type guest molecules is yet to be studied. To the best of our knowledge, this is the first observation of the electrostatic interaction of Zn2+ –[15]aneN5 complexes with the double-stranded DNA and the details will be reported elsewhere (we consider that it is not easy to directly and quantitatively compare the affinity of ctDNA with these B-carriers, which exhibit different interaction modes with DNA).

(82) (a) Lehn, J. M. Supramolecular Chemistry: Concepts and Perspectives; VCH: Weinheim, New York, 1995. (b) Kimura, E. Macrocyclic Polyamines as Biological Cation and Anion Complexones: An Application to Calculi Dissolution, Biomimetic and Bioorganic Chemistry; Topics in Current Chemistry; Springer-Verlag Berlin: Heidelberg, 1985; Vol. 128, pp 113–141. (c) Kimura, E. Macrocyclic Polyamines with Intelligent Functions, Tetrahedron, 1992, 48, 6175–6217.

(83) Hawthorne, M. F.; Lee, M. W. A Critical Assessment of Boron Target Compounds for Boron Neutron Capture Therapy. J. Neuro. Oncol. 2003, 62, 33–45.

(84) (a) Aoki, S.; Sugimura, C.; Kimura, E. Efficient Inhibition of Photo[2 + 2]cycloaddition of Thymidilyl(3´‒5´)thymidine and Promotion of Photosplitting of the cis-syn-Cyclobutane Thymine Dimer by Dimeric Zinc(Ⅱ)‒Cyclen Complexes Containing m- and p-Xylyl Spacers. J. Am. Chem. Soc. 1998, 120, 10094–10102. (b) Kimura, E.; Kikuchi, M.; Kitamura, H.; Koike, T. Selective and Efficient Recognition of Thymidylylthymidine (TpT) by Bis(ZnⅡ ‒Cyclen) and Thymidylylthymidylylthymidine (TpTpT) by Tris(ZnⅡ ‒Cyclen) at Neutral pH in Aqueous Solution. Chem. Eur. J. 1999, 5, 3113–3123. (c) Aoki, S.; Kimura, E. Highly Selective Recognition of Thymidine Mono- and Diphosphate Nucleotides in Aqueous Solution by Ditopic Receptors Zinc(Ⅱ)‒Bis(cyclen) Complexes (Cyclen = 1,4,7,10-Tetraazacyclododecane). J. Am. Chem. Soc. 2000, 122, 4542–4548. (d) Kikuta, E.; Aoki, S.; Kimura, E. A New Type of Potent Inhibitors of HIV-1 TAR RNA‒Tat Peptide Binding by Zinc(Ⅱ)‒Macrocyclic Tetraamine Complexes. J. Am. Chem. Soc. 2001, 123, 7911–7912.

(85) (a) Harrisson, P.; Morris, J.; Marder, T. B.; Steel, P. G. Microwave-Accelerated Iridium-Catalyzed Borylation of Aromatic C–H Bonds. Org. Lett. 2009, 11, 3586– 3589. (b) Wang, Z.; Sun, J.; Jia, X. Self-Immolative Nanoparticles Triggered by Hydrogen Peroxide and pH. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1962– 1969.

(86) Cao, S.; Wang, Y.; Peng, X. The Leaving Group Strongly Affects H2O2-Induced DNA Cross-Linking by Arylboronates. J. Org. Chem. 2014, 79, 501–508.

(87) Notni, J.; Görls, H.; Anders, E. Zinc Thiolate Complexes [ZnLn(SR)]+ with Azamacrocyclic Ligands: Synthesis and Structural Properties. Eur. J. Inorg. Chem. 2006, 48, 1444–1455.

(88) Wiedemann, T.; Voit, G.; Tchernook, A.; Roesle, P.; Göttker-Schnetmann, I.; Mecking, S. Monofunctional Hyperbranched Ethylene Oligomers. J. Am. Chem. Soc. 2014, 136, 2078–2085.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る