Gülten ÖZÇAYAN, Yüksel ŞAHİN, A. Ernur SÖYLEMEZ, M. Elif ÜNSAL

Synthesis and characterization of carborane-functionalized hyperbranched polyester for boron neutron capture therapy

The purpose of this study is to synthesize new boron containing carrier compound for Boron Neutron Capture Therapy (BNCT) which is two-component radiation therapy method that especially is promising for the treatment of brain tumors and is being actively researched in many countries. For this research hyperbranched polyester (HBP), bifunctional p-carborane and carborane-functionalized HBP were synthesized. Dipentaerythritol was chosen as a core molecule of the HBP and esterified with dimethylol propionic acid. Observed characteristic ester bands and OH stretching band in the FTIR spectrum and the methyl & methylene peaks in the 1H NMR spectrum of HBP indicated that hyperbranched polyester synthesis was done successfully. A bifunctionalized p-carborane containing an acid group and a benzyl ether protected alcohol was prepared in three-step reactions. As a result of these reactions, a bifunctionalized p-carborane compound was produced with 60% yield. Then, the HBP was esterified with the bifunctional p-carborane. The characterization of the synthesized compounds was determined by FTIR and NMR spectra. The synthesis of carborane-functionalized HBP was confirmed by disappearance of HBP's OH groups and B-H stretching band observed in the FTIR spectrum of carborane-functionalized HBP and in addition, appearance of proton signals of HBP core, carborane linker and peripheral-protecting groups in the 1H-NMR spectrum. Finally, synthesized water-soluble carborane-containing HB carrying many boron atoms should be served as potential BNCT agents.

Keywords:

Bnct boron, carborane, esterification, hyperbranced polyester,

PDF

___

[1]Endo, Y (2018). Carboranes as hydrophobic pharma-cophores: applications for design of nuclear receptor ligands. In Hey-Hawkins E. & Texidior C. V. (Eds.), Boron-based compounds: Potential and emerging ap-plications in medicine (pp. 3-19). John Wiley & Sons Ltd.
[2] Parrott, M. C., Marchington, E. B., Valliant, J. F., & Adronov, A. (2005). Synthesis and properties of car-borane-functionalized aliphatic polyester dendrimers. Journal of the American Chemical Society, i27(34), 12081-12089.
[3] Barth, R. F., Coderre, J. A., Vicente, M. G. H., & Blue,T. E. (2005). Boron neutron capture therapy of cancer:current status and future prospects. Clinical Cancer Research, 11(11), 3987-4002.
[4] Hu, K., Yang, Z., Zhang, L., Xie, L., Wang, L., Xu, H., ...& Zhang, M. R. (2020). Boron agents for neutron capture therapy. Coordination Chemistry Reviews, 4C5, 213139.
[5] Hawthorne, M. F. (1993). The role of chemistry in the development of boron neutron capture therapy of can-cer. Angewandte Chemie international Edition in Eng¬lish, 32(7), 950-984.
[6] Bat, E. (2005). Synthesis and characterization of hy-perbranched and air drying fatty acid based resins [MSC Thesis, Middle East Technical University, Gradu-ate School of Natural and Applied Sciences]. Council of Higher Education Thesis Center (Thesis Number 166837).
[7] Gao, C., & Yan, D. (2004). Hyperbranched polymers: from synthesis to applications. Progress in polymer science, 29(3), 183-275.
[8] Kim, Y H. (1998). Hyperbranched polymers 10 years after. Journal of Polymer Science Part A: Polymer Chemistry, 36(11), 1685-1698.
[9] Uhrich, K. (1997). Hyperbranched polymers for drug delivery. Trends in Polymer Science, l2(5), 388-393.
[10] Cheng, K. C., & Wang, L. Y. (2002). Kinetic model of hyperbranched polymers formed in copolymerization of AB2 monomers and multifunctional core molecules with various reactivities. Macromolecules, 35(14), 5657-5664.
[11] Liu, H., Näsman, J. H., & Skrifvars, M. (2000). Radi¬cal alternating copolymerization: A strategy for hyper-branched materials. Journal of Polymer Science Part A: Polymer Chemistry, 38(17), 3074-3085.
[12] Kuchanov, S., Slot, H., & Stroeks, A. (2004). Devel-opment of a quantitative theory of polycondensation. Progress in polymer science, 29(6), 563-633.
[13] Cheng, K. C., Chuang, T. H., Tsai, T. H., Guo, W., & Su, W. F. (2008). Model of hyperbranched polymers formed by monomers A2 and Bg with end-capping molecules. European polymer journal, 44(9), 2998¬3004.
[14] Fradet, A., & Tessier, M. (2007). First Shell Substitu¬tion Effects in Hyperbranched Polymers: Kinetic- Re¬cursive Probability Analysis. Macromolecules, 40(20), 7378-7392.
[15] Jikei, M., Chon, S. H., Kakimoto, M. A., Kawauchi, S., & Imase, T (1999). Synthesis of hyperbranched aro¬matic polyamide from aromatic diamines and trimesic acid. Macromolecules, 32(6), 2061-2064.
[16] Liu, Q., Zhao, P., & Chen, Y. (2007). Divergent syn-thesis of dendrimer-like macromolecules through a combination of atom transfer radical polymerization and click reaction. Journal of Polymer Science Part A: Polymer Chemistry, 45(15), 3330-3341.
[17] Hirao, A., Matsuo, A., & Watanabe, T (2005). Precise synthesis of dendrimer-like star-branched poly (methyl methacrylate) s up to seventh generation by an itera¬tive divergent approach involving coupling and trans-formation reactions. Macromolecules, 38(21), 8701¬8711.
[18] Bai, Y, Song, N., Gao, J. P., Sun, X., Wang, X., Yu, G., & Wang, Z. Y (2005). A new approach to highly electrooptically active materials using cross-linkable, hyperbranched chromophore-containing oligomers as a macromolecular dopant. Journal of the American Chemical Society, 127(7), 2060-2061.
[19] Powell, K. T., Cheng, C., & Wooley, K. L. (2007). Com-plex amphiphilic hyperbranched fluoropolymers by atom transfer radical self-condensing vinyl (co) polym-erization. Macromolecules, 40(13), 4509-4515.
[20] Cheng, K. C., Chuang, T H., Chang, J. S., Guo, W., & Su, W. F. (2005). Effect of feed rate on structure of hyperbranched polymers formed by self-condensing vinyl polymerization in semibatch reactor. Macromol-ecules, 38(20), 8252-8257.
[21] Cheng, K. C. (2003). Kinetic model of hyperbranched polymers formed by self-condensing vinyl polymeriza-tion of AB* monomers in the presence of multifunction¬al core molecules with different reactivities. Polymer, 44(3), 877-882.
[22] Zagar, E., & Zigon, M. (2011). Aliphatic hyperbranched polyesters based on 2, 2-bis (methylol) propionic acid- Determination of structure, solution and bulk proper¬ties. Progress in Polymer Science, 36(1), 53-88.
[23] Mesias, R., & Murillo, E. A. (2015). Hyperbranched polyester polyol modified with polylactic acid. Journal of Applied Polymer Science, 132(10), 44-52.
[24] Murillo, E. A., Vallejo, P. P., Sierra, L., & López, B. L. (2009). Characterization of hyperbranched polyol poly-esters based on 2, 2-bis (methylol propionic acid) and pentaerythritol. Journal of Applied Polymer Science, 112(1), 200-207.
[25] Mishra, A. K., Jena, K. K., & Raju, K. V. S. N. (2009). Synthesis and characterization of hyperbranched poly- ester-urethane-urea/K10-clay hybrid coatings. Pro¬gress in Organic Coatings, 64(1), 47-56.
[26] Kutyreva, M. P., Usmanova, G. S., Ulakhovich, N. A., & Kutyrev, G. A. (2010). Polynuclear Cu (II) complexes with hyperbranched polyester carboxylates. Russian Journal of General chemistry, 80(4), 787-789.
[27] Murillo, E. A., Vallejo, P P, & López, B. L. (2011). Ef¬fect of tall oil fatty acids content on the properties of novel hyperbranched alkyd resins. Journal of Applied Polymer Science, 120(6), 3151-3158.
[28] Mesias, R., & Murillo, E. (2018). Hyperbranched pol-yester polyol modified with polylactic acid as a com- patibilizer for plasticized tapioca starch/polylactic acid blends. Polímeros, 28(1), 44-52.
[29] Jovicic, M., Radicevic, R., Pavlicevic, J., Bera, O., & Govedarica, D. (2020). Synthesis and characterization of ricinoleic acid based hyperbranched alkyds for coat-ing application. Progress in Organic Coatings, 148, 105832.
[30] Bat, E., Gündüz, G., Kısakürek, D., & Akhmedov, İ. M. (2006). Synthesis and characterization of hyper-branched and air drying fatty acid based resins. Pro-gress in Organic Coatings, 55(4), 330-336.
[31] Malmström, E., Johansson, M., & Hult, A. (1995). Hy-perbranched aliphatic polyesters. Macromolecules, 28(5), 1698-1703.
[32] Barth, R. F., Adams, D. M., Soloway, A. H., Alam, F, & Darby, M. V. (1994). Boronated starburst dendrimer- monoclonal antibody immunoconjugates: evaluation as a potential delivery system for neutron capture ther¬apy. Bioconjugate chemistry, 5(1), 58-66.
[33] Sauter, G., Maeda, T., Waldman, F. M., Davis, R. L., & Feuerstein, B. G. (1996). Patterns of epidermal growth factor receptor amplification in malignant gliomas. The American journal of pathology, 148(4), 1047-1053. [34] Gillies, E. R., & Frechet, J. M. (2005). Dendrimers and dendritic polymers in drug delivery. Drug discovery to-day, 10(1), 35-43.
[35] Ihre, H. R., Padilla De Jesús, O. L., Szoka, F C., & Fré- chet, J. M. (2002). Polyester dendritic systems for drug delivery applications: design, synthesis, and charac-terization. Bioconjugate chemistry, 13(3), 443-452.
[36] Yao, H., Grimes, R. N., Corsini, M., & Zanello, P (2003). Polynuclear Metallacarborane- Hydrocarbon Assemblies: Metallacarborane Dendrimers. Organo- metallics, 22(22), 4381-4383.
[37] Núñez, R., González, A., Viñas, C., Teixidor, F., Sil- lanpââ, R., & Kivekâs, R. (2005). Approaches to the preparation of carborane-containing carbosilane com-pounds. Organic letters, 7(2), 231-233.
[38] Qualmann, B., Kessels, M. M., Musiol, H. J., Sierralta, W. D., Jungblut, P W., & Moroder, L. (1996). Synthe¬sis of boron-rich lysine dendrimers as protein labels in electron microscopy. Angewandte Chemie Interna¬tional Edition in English, 35(8), 909-911.
[39] Armspach, D., Cattalini, M., Constable, E. C., House-craft, C. E., & Phillips, D. (1996). Boron-rich metalloden- drimers—mix-and-match assembly of multifunctional metallosupramolecules. Chemical Communications,(15) , 1823-1824. [40] Newkome, G. R., Keith, J. M., Baker, G. R., Escamilla, G. H., & Moorefield, C. N. (1994). Chemistry within a Unimolecular Micelle Precursor: Boron Superclusters by Site- and Depth-Specific Transformations of Den- drimers. Angewandte Chemie International Edition in English, 33(6), 666-668.
[41] Ihre, H., Padilla De Jesús, O. L., & Frechet, J. M. (2001). Fast and convenient divergent synthesis of all phatic ester dendrimers by anhydride coupling. Jour¬nal of the American Chemical Society, 123(25), 5908¬5917.
[42] Ihre, H., Hult, A., & Soderlind, E. (1996). Synthesis, characterization, and 1H NMR self-diffusion studies of dendritic aliphatic polyesters based on 2, 2-bis (hy- droxymethyl) propionic acid and 1, 1, 1-tris (hydroxy- phenyl) ethane. Journal of the American Chemical So-ciety, 118(27), 6388-6395.
[43] Ihre, H., Hult, A., Fréchet, J. M., & Gitsov, I. (1998). Double-stage convergent approach for the synthesis of functionalized dendritic aliphatic polyesters based on 2, 2-bis (hydroxymethyl) propionic acid. Macromol-ecules, 31(13), 4061-4068.
[44] Padilla De Jesús, O. L., Ihre, H. R., Gagne, L., Fréchet, J. M., & Szoka, F. C. (2002). Polyester dendritic sys¬tems for drug delivery applications: in vitro and in vivo evaluation. Bioconjugate chemistry, 13(3), 453-461.
[45] Galie, K. M., Mollard, A., & Zharov, I. (2006). Polyes¬ter-based carborane-containing dendrons. Inorganic chemistry, 45(19), 7815-7820.
[46] Mollard, A., & Zharov, I. (2006). Tricarboranyl pen- taerythritol-based building block. Inorganic chemistry, 45(25), 10172-10179.
[47] Dubey, R., Kushal, S., Mollard, A., Vojtovich, L., Oh, P, Levin, M. D., ... & Olenyuk, B. Z. (2015). Tumor target-ing, trifunctional dendritic wedge. Bioconjugate chem-istry, 26(1), 78-89.
[48] Benhabbour, S. R., Parrott, M. C., Gratton, S. E., & Adronov, A. (2007). Synthesis and properties of car- borane-containing dendronized polymers. Macromol-ecules, 40(16), 5678-5688.

ISSN: 2149-9020
Yayın Aralığı: Yılda 4 Sayı
Başlangıç: 2016
Yayıncı: TENMAK Bor Araştırma Enstitüsü

Arşiv