The synthesis and characterization of three ligands and their respective heterobinuclear FeZn complexes were carried out, with the goal of mimicking the active site of purple acid phosphatases (PAPs). The ligand 2-hydroxy-3-(((2-hydroxy-5-methyl-3-(((2-(pyridin-2-yl)ethyl)(pyridin-2-ylmethyl)amino)methyl)benzyl)(pyridin-2ylmethyl)amino)methyl)-5-methylbenzaldehyde (HL) was synthesized and its complex (FeZnL) was used as a basis for comparison with similar complexes previously published in the literature. Subsequent modifications were conducted in the aldehyde group, where 1,2-ethanediamine and 1,4-diaminobutane were used as side chain derivatives. The compounds FeZnL (1), FeZnL-et (2) and FeZnL-but (3) were characterized by spectroscopic methods (infrared and UV-Vis) and ESI-MS spectrometry. Theoretical calculations were performed to provide insights into the complex structures with FeZn structures. The hydrolytic activity was analyzed both with the model substrate 2,4-BDNPP and with DNA catalyzed by complexes 1, 2 and 3.

Two new complexes of Ru(II) with mixed ligands were prepared: [Ru(bpy)2smp](PF6) (1) and [Ru(phen)2smp](PF6) (2), in which smp = sulfamethoxypyridazine; bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline. The complexes have been characterized by elemental and conductivity analyses; infrared, NMR, and electrospray ionization mass spectroscopies; and X-ray diffraction of single crystal. Structural analyses reveal a distorted octahedral geometry around Ru(II) that is bound to two bpy (in 1) or two phen (in 2) via their two heterocyclic nitrogens and to two nitrogen atoms from sulfamethoxypyridazine—one of the methoxypyridazine ring and the sulfonamidic nitrogen, which is deprotonated. Both complexes inhibit the growth of chronic myelogenous leukemia cells. The interaction of the complexes with bovine serum albumin and DNA is described. DNA footprinting using an oligonucleotide as substrate showed the complexes’ preference for thymine base rich sites. It is worth notifying that the complexes interact with the Src homology SH3 domain of the Abl tyrosine kinase protein. Abl protein is involved in signal transduction and implicated in the development of chronic myelogenous leukemia. Nuclear magnetic resonance (NMR) studies of the interaction of complex 2 with the Abl-SH3 domain showed that the most affected residues were T79, G97, W99, and Y115.

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A novel metal complex was synthesized containing a purine derived ligand in order to increase its binding to DNA. We observed a huge increase in nuclease activity and, quite interestingly, an improvement on DNA sequence selectivity. A potential site of specific cleavage in the presence of a reductant in the reaction medium is suggested. We were able to synthesize a novel metal nuclease with improved activity on DNA, and with sequence specificity when exposed to a coreactant, this opens up new possibilities to create site specific and redox status modulated artificial nucleases.