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

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.

Keywords

• hyaluronic acid
• borates
• solid state synthesis
• Fourier transform infrared spectroscopy
• nuclear magnetic resonance
• boron neutron capture therapy