Bioactivity of new ferrocene incorporated N,N′-disubstituted ureas: Synthesis, structural elucidation and DFT study

Abstract We report here the synthesis, structural characterization and biological assessment of three new ferrocene incorporated ureas ( 1 – 3 ). The synthesis of these complexes was accomplished by the deprotection of ferrocene-based thioureas to the corresponding oxo analogues using NaOH (aq) and mercuric chloride. The new ferrocenyl ureas were characterized by FT-IR, multinuclear ( 1 H and 13 C) NMR, AAS and elemental analysis. Furthermore, the single-crystal X-ray structure of compound 2 was also determined. The DNA binding potency of these ureas was evaluated by UV–Vis spectroscopy and cyclic voltammetry (CV). The three complexes interact electrostatically with DNA and have impressive binding constants ranging from 3.42 × 10 4 to 8.15 × 10 4  M −1 . The diffusion coefficients of the drug–DNA adducts are lower than is that for the free drug indicating the formation of a high molecular weight complex that diffuses slowly towards the electrode. The small binding site size of 0.509 ( 1 ), 0.528 ( 2 ) and 0.473 ( 3 ) base pairs is also indicative of an electrostatic mode of interaction. The DFT calculated HOMO and LUMO energies correlate well with the experimentally determined redox potential values. The synthesized ureas ( 1 – 3 ) were screened for their antibacterial, antifungal and protein kinase inhibition potency. These compounds play a significant role in arresting microbial growth and are potent protein kinase inhibitors.