Molecular modeling for Cu(II)-aminopolycarboxylate complexes: structures, conformational energies, and ligand binding...

A ligand field molecular mechanics (LFMM) force field (FF) has been developed for d(9) 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.