Enantiomeric in vitro DNA binding, pBR322 DNA cleavage and molecular docking studies of chiral l- and d-ternary copper(II) complexes of histidine and picolinic acid
•Synthesis of enantiomeric l/d-histidine–Cu(II)/Ni(II) complexes of picolinic acid.•In vitro DNA binding of Cu(II) complexes revealed electrostatic mode of binding.•1(a and b) displayed efficient pBR322 DNA oxidative cleavage activity.•The molecular docking studies confirmed binding of complexes in minor groove of DNA.•In complexes 1–2(a and b)l-form possess greater antimicrobial activity.
Novel chiral ternary Cu(II) and Ni(II) complexes of l/d-histidine and picolinic acid, 1 and 2(a and b) were synthesized and characterized by elemental analysis, molar conductance and spectroscopic data (IR, NMR, EPR, UV–vis). In vitro DNA binding profile of both Cu(II) and Ni(II) complexes have been investigated by UV–vis titrations, while fluorescence spectroscopy, circular dichroism and viscosity measurements were carried out for Cu(II) complexes 1(a and b). Both the enantiomers of 1 and 2(a and b) bind to CT DNA via electrostatic interactions and the intrinsic binding constant, Kb values for complexes 1 and 2(a and b) were found to be 5.6 × 104, 9.8 × 103, 8.2 × 103 and 6.7 × 103 M−1, respectively suggesting greater binding propensity of l-form of Cu(II) complex 1a. The DNA cleavage activity of complexes 1(a and b), investigated by agarose gel electrophoresis suggested an oxidative pathway for DNA cleavage. Further, the molecular docking studies of complexes 1(a and b) were carried out with B-DNA revealing that the complexes bind to the adenine–thymine residues in the minor groove of the DNA. The resulting binding energies of docked metal complexes 1(a and b) were found to be −265.1 and −218.9 KJ mol−1, respectively. Furthermore, enantiomeric complexes 1 and 2(a and b) were screened for in vitro antimicrobial activity.
Graphical abstractInteraction of complex 1a with DNA.Figure optionsDownload full-size imageDownload as PowerPoint slide
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 130, 5 January 2014, Pages 170–178