Synthesis, characterization, and crystal structure of RNA targeted l- and d-phenylalanine-(1,10-phen)–copper(ii) conjugate complexes: comparative in vitro RNA binding profile of enantiomers and their biological evaluation by morphological studies and antibacterial activity

Abstract

New ternary chiral Cu(II) complexes 1a and b derived from L- and D-phenylalanine and 1,10-phenanthroline were synthesized and characterized thoroughly by single crystal X-ray diffraction and other spectroscopic techniques viz. UV-vis, IR, EPR, ESI-MS and elemental analysis. The complexes crystallized in the monoclinic P21 space group, possessing the lattice parameters a = 5.74690(10) Å, b = 20.6365(2) Å, c = 9.28010(10) Å, α = γ = 90°, and β = 98.2040(10) in complex 1a and a = 5.728(5) Å, b = 20.587(5) Å, c = 9.252(5) Å, α = γ = 90°, and β = 98.308(5) in complex 1b per unit cell, respectively. Comparative in vitro RNA binding studies of the L- and D-enantiomeric complexes, 1a and b, were carried out by a variety of optical spectroscopy techniques viz. UV-vis, fluorescence, and circular dichroism. Because copper is a redox metal ion, cyclic voltammetry was employed to evaluate the enantioselective RNA binding of the complexes. The results demonstrated that the L-enantiomer of Cu(II) complex, 1a, binds more strongly to the t-RNA motif than the D-enantiomer, thereby underlining the differential disposition of the enantiomers and the site preference of RNA for the L-enantiomer over the D-enantiomer. Furthermore, the comparative K_b, K and K_sv values of the L- and D-complexes demonstrated significant increases for the L-enantiomer of the copper complex, 1a, in comparison to its D-enantiomeric form, 1b. SEM analysis divulged surface morphological alteration of complexes 1a and b, evidenced by the formation of hollow tubes and a concrete-like structure with the RNA condensate, which was less pronounced in SEM micrographs of the complex 1b condensate. Complexes 1a and b were evaluated by the agar well diffusion method and demonstrated significant antibacterial activity.