Synthesis, Characterization and DNA-Binding Affinity of a New Zinc(II) Bis(5-methoxy-indol-3-yl)propane-1,3-dione Complex

• Main Authors: Luca Scapinello, Guglielmo Vesco, Luca Nardo, Angelo Maspero, Federico Vavassori, Simona Galli, Andrea Penoni
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Pharmaceuticals
• Subjects: zinc(II) complexes; indoles; β-diketone; DNA ligand; metallodrug; DNA-targeted chemotherapy
• Online Access: https://www.mdpi.com/1424-8247/14/8/760

The novel zinc(II) µ-oxo-bridged-dimeric complex [Zn₂(µ-O)₂(BMIP)₂] (BMIP = 1,3-bis(5-methoxy-1-methyl-1<i>H</i>-indol-3-yl)propane-1,3-dione), <b>1</b>, was synthetized and fully characterized. The spectral data indicate a zincoxane molecular structure, with the BMIP ligand coordinating in its neutral form via its oxygen atoms. Structural changes in <b>1</b> in dimethylsulfoxide (DMSO) were evidenced by means of spectroscopic techniques including infrared absorption and nuclear magnetic resonance, showing DMSO entrance in the coordination sphere of the metal ion. The resulting complex [Zn₂(µ-O)₂(BMIP)₂(DMSO)], <b>2</b>, readily reacts in the presence of <i>N</i>-methyl-imidazole (NMI), a liquid-phase nucleoside mimic, to form [Zn₂(µ-O)₂(BMIP)₂(NMI)], <b>3</b>, through DMSO displacement. The three complexes show high thermal stability, demonstrating that <b>1</b> has high affinity for hard nucleophiles. Finally, with the aim of probing the suitability of this system as model scaffold for new potential anticancer metallodrugs, the interactions of <b>1</b> with calf thymus DNA were investigated in vitro in pseudo-physiological environment through UV-Vis absorption and fluorescence emission spectroscopy, as well as time-resolved fluorescence studies. The latter analyses revealed that [Zn₂(µ-O)₂(BMIP)₂(DMSO)] binds to DNA with high affinity upon DMSO displacement, opening new perspectives for the development of optimized drug substances.