Polycomplexes of Hyaluronic Acid and Borates in a Solid State and Solution: Synthesis, Characterization and Perspectives of Application in Boron Neutron Capture Therapy

固态和溶液中的透明质酸和硼酸盐多聚复合物:合成、表征及在硼中子俘获疗法中的应用前景

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作者:Alexander N Zelenetskii, Sergey Uspenskii, Alexander Zaboronok, Georgij Cherkaev, Alexander Shchegolihin, Bryan J Mathis, Mikhail Selyanin, Tetsuya Yamamoto, Akira Matsumura

Abstract

In this report, we propose a new polyborate fragment synthesis strategy along the whole chain of the polysaccharide hyaluronic acid (HA) to produce boron neutron capture therapy (BNCT) compounds. Under high pressure and deformatory solid-state conditions, polymolecular system formation takes place due to association of phase-specific transition components into a more or less distinct microscopic organization. Fourier transform infrared (FTIR) spectroscopy shows that HA and polyborates form a network of cyclic polychelate complexes. HA acts as a multidentate ligand using carboxylic and hydroxyl proton donor groups to link oxygen atoms in B⁻O⁻B bonds and borate-anions B⁻O(-): O⁻H···O, O⁻H···(-)O. With free electron pairs in heteroatoms ⁻O(:)···B, ⁻N(:)···B, HA can act simultaneously as an electron donor. Nuclear magnetic resonance (NMR) with 13C and ¹H reveals a preserved complex interaction after both solubilizing and attenuating the HA-polyborate system. Stability of the product in water, low cost, ease of synthesis and scalability of manufacturing indicate that HA-polyborate complexes might have advantages over current chemotherapeutic approaches in creating therapeutic agents for BNCT.

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