Complexation behaviour of piceatannol ligand with Ti(IV) and Zr(IV) metal ions: a combined DFT and deep learning investigation

A theoretical investigation of the metal chelation ability of piceatannol ligand (PIC) with Ti(IV) and Zr(IV) metal ions is undertaken in this work utilizing DFT/B3LYP-GD3/6–31 + G(d,p) level theory in gas and DMSO. PIC is a naturally occurring polyphenolic stilbene having anticancer properties. Interaction of the deprotonated form of PIC with metal ions forms [TiL 2 ] and [ZrL 2 ] complexes. The stability of the complexes is evaluated using geometrical parameters, binding energy, and thermodynamic properties like ∆ H and ∆ G . The observed results indicate the higher stability of [TiL 2 ] complexes. Topology, NCI, and IRI analyses were used to explore the metal–ligand interactions in formed complexes. This establishes the metal–oxygen bonds in both complexes as an ionic bonding domain on the boundary of the intermediate bonding regime, which comprises dative bonding with a weak covalent character. The interaction of PIC with metal ions is less favourable in implicit DMSO. This is due to the presence of a solvent, which may compete with the ligand for interaction with the ion, reducing complex stability. The ligand and complexes are examined against protein kinase B using deep learning–based GNINA 1.0 software, and the results show a higher negative binding affinity of the [TiL 2 ] complex in comparison with others. These complexes outperform PIC as an anti-cancer drug candidate by inhibiting Akt kinase.