Enantiomeric recognition of chiral L– and D–penicillamine Zinc(ii) complexes: DNA binding behavior and cleavage studies

Abstract

Two designed L–/D–penicillamine based enantiomeric Zn(II) complexes 1a and 1b of 1,10–phenanthroline were synthesized and structurally characterized. The interactions of the complexes with CT DNA have been explored by absorption, fluorescence and CD measurements, revealing that both the complexes interact with DNA via electrostatic binding. All the corroborative results indicated the enantiopreferential selective binding of L–form of the complex over the D–form. A gel electrophoretic pictogram of the complexes 1a and 1b demonstrates their ability to cleave pBR322 DNA through hydrolytic process; validated by T4 religation assays; furthermore, the L–form of the complex exhibited more pronounced cleavage than the D–form. However, both complexes preferred the minor groove of the DNA double helix. Interaction studies with mononucleotides revealed that both the enantiomers possess high affinity towards the A–T base pairs of DNA, consistent with the previous reports on stereospecific selectivity of Zn(II) complexes. These studies were further supported by molecular docking studies and the resulting binding energy of docked metal complexes 1a and 1b were found to be −306.4 and −289.1 KJ mol⁻¹, respectively. The more negative relative binding energy of L–form of complex suggests greater propensity for DNA than the D–enantiomer.