Copper(i) and nickel(ii) complexes with 1 : 1 vs. 1 : 2 coordination of ferrocenyl hydrazone ligands: Do the geometry and composition of complexes affect DNA binding/cleavage, protein binding, antioxidant and cytotoxic activities?

Abstract

A new series of geometrically different complexes containing ferrocenyl hydrazone ligands were synthesised by reacting suitable precursor complex [MCl 2 (PPh 3 ) 2 ] with the ligands HL 1 or HL 2 (where M = Cu(II) or Ni(II); HL(5) and [Ni(L 2 ) 2 ] (6) were characterised by various spectral studies. Among them, complexes 3 and 5 characterised by single crystal X-ray diffraction showed a distorted tetrahedral structure for the former with 1 : 1 metal-ligand stoichiometry, but a distorted square planar geometry with 1 : 2 metal-ligand stoichiometry in the case of the latter. Systematic biological investigations like DNA binding, DNA cleavage, protein binding, free radical scavenging and cytotoxicity activities were carried out using all the synthesised compounds and the results obtained were explained on the basis of structure-activity relationships. The binding constant (K b ) values of the synthesised compounds are found to be in the order of magnitude 10 3 -10 5 M −1 and also they exhibit significant cleavage of supercoiled (SC) pUC19 DNA in the presence of H 2 O 2 as co-oxidant. The conformational changes of bovine serum albumin (BSA) upon binding with the above complexes were also studied. In addition, concentration dependent free radical scavenging potential of all the synthesised compounds (1-6) was also carried out under in vitro conditions. Assays on the cytotoxicity of the above complexes against HeLa and A431 tumor cells and NIH 3T3 normal cells were also carried out. † Electronic supplementary information (ESI) available: Crystal packing diagram of the unit cell of complexes 3 and 5 (Fig. S1 and S2), Electronic absorption spectra of binding of ligands 1 and 2 with DNA (Fig. S3), Electronic absorption spectra of binding of complexes 3, 4 and 5 with DNA (Fig. S4 and S5), Circular dichroism spectra of DNA and ligands 1 and 2 (Fig. S6), Circular dichroism spectra of DNA and complexes 3, 4 (Fig. S7), Emission spectra of binding of complexes 3, 4 and 5 with BSA (Fig. S8 and S9), Synchronous spectra (Δλ = 15 and 60 nm) of binding of complexes 3, 4 and 5 with BSA (Fig. S10, S11 and S12). CCDC reference numbers 796259 and 822888 for complexes 3 and 5.

Variation in the biomolecular interactions of nickel(ii) hydrazone complexes upon tuning the hydrazide fragment

“…All the complexes did not cause any damage to the healthy cells (NIH 3T3) indicating that they are non-toxic to normal cells as expected for a better drug. On comparison with that of the other reported nickel hydrazone complexes 63 our complexes showed better activity and the same was included in Table 6. However, the hydrazone ligands 1-3 and the nickel precursor complex did not show any activity under the same experimental conditions.…”

Effect of Structure and Composition of Copper and Cobalt Complexes with Schiff Base Ligands on their DNA/Protein Interaction and Cytotoxicity

“…In order to differentiate these above types of quenching, representative UV/Vis absorption spectroscopy of BSA in the absence and presence of complex 1 is shown in Figure 10 (for complexes 2 , 3 and 4 , see Figure S7, Supporting Information). The weak absorption peak at 279 nm showed an increase in intensity in the absence of metal complex, which revealed that the fluorescence quenching mainly due to static quenching procedure by forming a complex‐BSA ground state 30,31…”

“…Synchronous fluorescence spectra provide information on the molecular microenvironment, particularly in the vicinity of the fluorophore functional groups. For BSA, the synchronous fluorescence Δ λ value of 15 nm is the characteristic of the tyrosine residues, and the Δ λ value of 60 nm is the characteristic of the tryptophan residues 30,31. In order to research the structural changes of BSA in presence of complexes, synchronous fluorescence spectra with addition of complexes were recorded at both Δ λ = 15 nm and 60 nm.…”

Copper(II) Complexes Based on Aminohydroxamic Acids: Synthesis, Structures, In Vitro Cytotoxicities and DNA/BSA Interactions

“…Because the change in hypochromism and strong bathochromic shift usually are related to the intercalative binding, which can be explicated as the function of the aromatic chromophore and DNA base pairs [15]. In order to quantitatively measure the binding strength of complexes with DNA, the binding constants K b can be obtained by using the following formula [16]:…”