Synthesis and computational study of new meta- and para-substituted ferrocenyl thioureas as potent protein kinase inhibitors and cytotoxic agents

Abstract The present study describes the synthesis, characterization, DNA binding and in vitro biological evaluation of ferrocene-enhanced thioureas. The new complexes (N1-N6) were prepared by reacting ferrocenyl anilines (A-B) with freshly prepared isothiocyanates in dry acetone. A crystallographic study of N3 revealed a supramolecular structure involving secondary non-covalent interactions (π---H and π---π). The nature and extent of the binding of these complexes with the salmon sperm DNA (SS-DNA) were examined by cyclic voltammetry and UV-Vis spectroscopy. The complexes have strong binding to DNA with binding constants ranging from 9.83 x 10 3 to 5.76 x 10 4 M -1 . The shifts in the cathodic peak potentials with the addition of DNA in the electrochemical studies of the new complexes are attributed to electrostatic interactions. This observation is an indicator of the oxidizable behavior of the complexes in the presence of DNA. The theoretically calculated energies of the frontier molecular orbitals (E HOMO and E LUMO ) and the Mulliken charge distributions for the optimized structures determined by the DFT/B3LYP method correlate well with the electrochemically determined redox potentials (correlation coefficient, 0.986). The computational measurements also led to a close agreement between the calculated and observed vibrational frequencies. The new complexes proved to be good candidates for protein kinase inhibition and cytotoxicity studies.