Understanding the hydrolysis and reactions of aminosugar Schiff base Pd(II) anticancer complexes: Dimerization and sugar displacement

• Main Authors: Alba, Laurenzo De Vera, Hatanaka, Tsubasa, Nakashima, Kazumichi, Funanashi, Yasuhiro
• Format: text
• Published: Animo Repository 2023
• Subjects: Antineoplastic agents; Amino sugars; Schiff bases; Hydrolysis; Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/11482
• Institution: De La Salle University

Background: An anticancer and anti-metastatic aminosugar Schiff base Pd(II) complex (“Pd-Oqn”) was described previously1, and multiple variants have been synthesized. We noticed rapid changes in the UV-Vis spectra in buffered aqueous solutions at physiological pH, suggesting that the hydrolysis products can explain the bioactivity of Pd-Oqn. However, understanding the hydrolysis products is complicated by 2nd order kinetics and the presence of multiple stages. In this study, we attempted to isolate and characterize the potential hydrolysis products by performing analogous reactions in organic solvents. Methods: The fully acetylated aminosugar complex Pd Oqn-Ac was treated with silver triflate and reacted with methylamine. The reaction was observed by 1H NMR. Upon recrystallization, two Pd-containing products were observed. Crystals suitable for single crystal X-ray diffraction were obtained for both products. The structures were solved using the Olex2 software package with the SHELXT structure solution program. Refinement was performed with SHELXL using the Least Squares minimization. Results: Upon treatment of the original Pd Oqn-Ac complex with silver triflate, the spectral changes in 1H NMR were consistent with the removal of the chloride ligand. Upon further reaction with methylamine, orange plate crystals were produced. X-ray diffraction analysis of this first product reveals a dimer of a bis-type complex, the monomer containing 2 aminosugar acetylated Oqn ligands (“Oqn-Ac”) coordinated to a Pd center. The dimer form is connected by a Pd-Pd bond. Further reaction causes the formation of dark violet needle crystals as the second product, which is composed of a Pd complex bound to a Schiff base of hydroxyquinoline carboxaldehyde with methylamine. This suggests that methylamine is able to replace the acetylated glucosamine which is the original amine component of the Schiff base. ORTEP view of the molecular structure of the bis-type Pd(II) complex. Hydrogens and low occupancy disordered sites are omitted for clarity. Thermal ellipsoids are drawn at a 50% probability level. (A) Structure of the whole dimer showing the Pd-Pd bond connecting the two monomers. (B) Detail of the monomer showing the coordination of the Pd center to the acetylated aminosugar Schiff base ligands. Conclusions: These findings suggest a pathway for the formation of the final hydrolysis product in aqueous solution, and the observed 2nd order kinetics of the hydrolysis reaction for the original Pd complex. We have also demonstrated that the Schiff base linkage is readily cleaved and replaced with methylamine. Acknowledgement: This work was conducted with equipment and reagents supplied by the Bioinorganic Chemistry Laboratory, Osaka University.