Experimental and ONIOM computational evaluation of DNA- and BSA-binding and cytotoxic activity of a mononuclear Pd(II) complex with piroxicam

Abstract Binding studies of a new mononuclear Pd(II) complex, trans -[Pd(Pir) 2 ] (Pir − is piroxicam), with fish sperm deoxyribonucleic acid (FS-DNA) and bovine serum albumin (BSA) were investigated. The results reveal that the complex interacts with FS-DNA by two binding modes, viz ., electrostatic and minor groove binding. The interaction of the Pd(II) complex with BSA changes the polarity of the microenvironment around the tyrosine and tryptophan residues of BSA. An in vitro cytotoxicity study of the effect of the complex on K562 cell lines indicates that the complex exhibits the best cell growth-inhibitory effect among the reported oxicam complexes with an IC 50 value of 11.7 μM. Also, the Pd(II) complex shows a remarkable increase in the cytotoxic activity in comparison to Pir − and Pd(OAc) 2 . Molecular docking was also used for modeling the binding of the Pd(II) complex to DNA and BSA. In addition, hybrid QCH/MM ONIOM ( the Our own N - layered Integrated molecular Orbital and molecular Mechanics) method, based on the quantum mechanics/molecular mechanics (QM/MM) methodology, was carried out to investigate the interaction of the Pd(II) complex with DNA and BSA. Based on the QM/MM calculations, the variation in the structural parameters due to insertion of the Pd(II) complex into the minor grooves of DNA were determined. In addition, the QM/MM calculations were used to interpret the interaction of the Pd(II) complex with DNA using the calculated UV spectrum of the complex in different environments.