Synthesis, crystal structure, and nuclease activity of planar mono-heterocyclic base copper(II) complexes

Abstract

A series of mononuclear copper(II) complexes having a 1:1 molar ratio of copper and the planar heterocyclic base like 1,10-phenanthroline (phen), dipyrido[3,2-d:2^',3^'-f]quinoxaline (dpq) and dipyrido[3,2-a:2^',3^'-c]phenazine (dppz) are prepared from a reaction of copper(II) nitrate.trihydrate and the base (L) in ethanol or aqueous ethanol at different temperatures. The complexes [Cu(dpq)(NO₃)₂] (2), [Cu(dpq)(NO₃)(H₂O)₂](NO₃) (3), [Cu(dpq)(NO₃)₂(H₂O)₂]·2H₂O (4·2H₂O) and [Cu(dppz)(NO₃)2(H₂O)]·H₂O (5·H₂O) have been characterized by X-ray crystallography. The crystal structures show the presence of the heterocyclic base in the basal plane. The coordination geometries of the copper(II) centers are axially elongated square-pyramidal (4+1) in 2, 3 and 5, and octahedral (4+2) in 4. The nitrate anion in the coordination sphere displays unidentate and bidentate chelating bonding modes. The axial ligand is either H₂O or NO₃ in these structures giving a Cu-L_ax distance of 2.4 Å. The one-electron paramagnetic complexes (μ≈1.8 μ_B) exhibit axial EPR spectra in DMF glass at 77 K giving g||>g⊥ with an A|| value of ~170G indicating a {d_x²-y²}¹ ground state. The complexes are redox active and display a quasireversible cyclic voltammetric response for the Cu(II)/Cu(I) couple near 0.0 V vs. SCE giving an order of the E_½ values as 5(dppz)>2-4 (dpq)>[Cu(phen)₂(H₂O)]²⁺>1 (phen). The complexes bind to calf thymus DNA giving an order 5 (dppz)>2 (dpq)>[Cu(phen)₂(H₂O)]²⁺>1 (phen). An effect of the extended planar ring in dpq and dppz is observed in the DNA binding. The complexes show nuclease activity with pUC19 supercoiled DNA in DMF/Tris-HCl buffer containing NaCl in presence of mercaptopropanoic acid as a reducing agent. The extent of cleavage follows the order: [Cu(phen)₂(H₂O)](ClO₄)₂>5>2~3~4>1. The bis-phen complex is a better cleaver of SC DNA than 1-5 having mono-heterocyclic base. Mechanistic investigations using distamycin reveal minor groove biding for the phen, dpq complexes, and a major groove binding for the dppz complex 5. The cleavage reactions are found to be inhibited in the presence of hydroxyl radical scavenger DMSO and the reactions are proposed to proceed via sugar hydrogen abstraction pathway. The ancillary ligand is found to have less effect in DNA binding but are of importance in DNA cleavage reactions.