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

• Published in: Polymers 2018-02, Vol.10 (2), p.181
• Main Authors: Zelenetskii, Alexander N, Uspenskii, Sergey, Zaboronok, Alexander, Cherkaev, Georgij, Shchegolihin, Alexander, Mathis, Bryan J, Selyanin, Mikhail, Yamamoto, Tetsuya, Matsumura, Akira
• Format: Article
• Language: English
• Subjects: Borates; Boron compounds; Chemical bonds; Chemical compounds; Deformation; Fourier transforms; H alpha line; Hyaluronic acid; NMR; Nuclear capture; Nuclear magnetic resonance; Oxygen atoms; Pharmacology; Phase transitions; Solid state; Synthesis; Therapy
• ISSN: 2073-4360; 2073-4360
• DOI: 10.3390/polym10020181

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 C 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.