Synthesis, Biophysical Interaction of DNA/BSA, Equilibrium and Stopped-Flow Kinetic Studies, and Biological Evaluation of bis(2-Picolyl)amine-Based Nickel(II) Complex

Abstract

Reaction of bis(2-picolyl)amine (<b>BPA</b>) with Ni(II) salt yielded [(BPA)NiCl₂(H₂O)] (<b>NiBPA</b>). The Ni(II) in <b>NiBPA</b> bound to a <b>BPA</b> ligand, two chloride, and one aqua ligands. Because most medications inhibit biological processes by binding to a specific protein, the stopped-flow technique was used to investigate DNA/protein binding in-vitro, and a mechanism was proposed. <b>NiBPA</b> binds to DNA/protein more strongly than <b>BPA</b> via a static quenching mechanism. Using the stopped-flow technique, a mechanism was proposed. BSA interacts with <b>BPA</b> via a fast reversible step followed by a slow irreversible step, whereas <b>NiBPA</b> interacts via two reversible steps. DNA, on the other hand, binds to BPA and <b>NiBPA</b> via the same mechanism through two reversible steps. Although BSA interacts with <b>NiBPA</b> much faster, <b>NiBPA</b> has a much higher affinity for DNA (2077 M) than BSA (30.3 M). Compared to <b>NiBPA</b>, BPA was found to form a more stable BSA complex. When <b>BPA</b> and <b>NiBPA</b> bind to DNA, the Ni(II) center was found to influence the rate but not the mechanism, whereas, for BSA, the Ni(II) center was found to change both the mechanism and the rate. Additionally, <b>NiBPA</b> exhibited significant cytotoxicity and antibacterial activity, which is consistent with the binding constants but not the kinetic stability. This shows that in our situation, biological activity is significantly more influenced by binding constants than by kinetic stability. Due to its selectivity and cytotoxic activity, complex <b>NiBPA</b> is anticipated to be used in medicine.