Molecular Modeling for Cu(II)-Aminopolycarboxylate Complexes: Structures, Conformational Energies, and
Ligand Binding Affinities.

A ligand field molecular mechanics (LFMM) force field (FF) has been developed for d⁹ copper(II) complexes of aminopolycarboxylate ligands. Training data were derived from density functional theory (DFT) geometry optimizations of 14 complexes comprising potentially hexadentate N₂O₄, tetrasubstituted ethylenediamine (ed), and propylenediamine cores with various combinations of acetate and propionate side arms. The FF was
validated against 13 experimental structures from X-ray crystallography including hexadentate N₂O₄ donors where the nitrogens donors are forced to be cis and bis-tridentate ONO ligands which generate complexes with trans nitrogen donors. Stochastic conformational searches for [Cu{ed(acetate)_n(propionate)_4-n}]^2- , n = 0–4, were carried out and the lowest conformers for each system reoptimized with DFT. In each case, both DFT and LFMM predict the same lowest-energy conformer and the structures and energies of the higher-energy conformers
are also in satisfactory agreement. The relative interaction energies for n = 0, 2, and 4 computed by molecular mechanics correlate with the experimental log β binding affinities. Adding in the predicted log β values for n = 1 and 3 suggest for this set of complexes a monotonic decrease in log β as the number of propionate arms increases.