Macrocyclic copper(II) complexes containing diazacyclam-based ligand: spectral, structural and docking studies

The macrocyclic copper complex, [Cu(ACE)(NO₃)₂] (ACE = 1,3,6,10,12,15-hexaazatricyclo[13.3.1.1^6,10]eicosane), was synthesized by template condensation from a mixture of N¹-(2-aminoethyl)-1,3-diaminopropane, formaldehyde and copper(II) nitrate. Replacement of the nitrate with thiocyanato and azido ligands gives [Cu(ACE)NSC]NSC (2) and the 1D-coordination polymer, [Cu(ACE)(μ-N₃)]_n[N₃]_n (3), respectively. Complex 1, [Cu(ACE)(NO₃)]NO₃, is an intermediate product in which one of the nitrate ions is separated from its parent molecule. The formation of 1 allowed us to conclude that the mechanism of ion exchange in the parent molecule is similar to S_N1. These complexes have been characterized by FT-IR spectroscopy and X-ray crystallography. In the crystal structures of 1 and 2, the copper(II) ion has a distorted square pyramidal geometry in which the N₄-donor ACE ligand lies on the equatorial plane and other ligand occupies the axial position. The copper(II) ion in 3 has an octahedral geometry, coordinating to one ACE ligand in the equatorial plane and two N-donor bridging azido groups in the axial positions. In all structures, owing to the Jahn-Teller effect, the coordinated bond length of the axial position is longer than the equatorial ones. The ability of the ACE ligand and its complexes 1 and 2, along with their analogues, to interact with 10 selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II and B-DNA) was investigated by docking calculations and compared with that of doxorubicin.