Molecular modeling for Cu(II)‐aminopolycarboxylate complexes: Structures, conformational energies, and ligand binding affinities

Abstract

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.

Theoretical study of copper binding to GHK peptide

“…Ligand field molecular mechanics (LFMM) was introduced by Deeth and co-workers, including explicit d-electron energy terms for transition metals to the standard MM expression 38,39 . This has previously been used to study small 40,41 and large metal-biomolecular systems such as metalloproteins 42,43 , including a range of transition metals such as Cu and Pt [44][45][46][47][48][49] . Recently, our group showed that LFMM is suitable for predicting geometries and exploring the conformational space of transition-metals such as Cu(II) and Pt(II) when bound to amyloid-β peptide, although we found this method fails to reproduce DFT energy 44 .…”

Molecular modeling of zinc paddlewheel molecular complexes and the pores of a flexible metal organic framework

“…In our work deriving accurate FFs targeted at specific transition-metal/ligand combinations, we have used both experimental and/or quantum chemical data [ 27 – 35 ]. Here, we focus on a particular class of flexible MOFs which incorporate the four-bladed zinc paddlewheel (ZPW) motif and construct a new, specialized valence FF, ZPW-FF, based on molecular ZPW complexes which then automatically captures the types of structural change displayed by [Zn 2 (bdc) 2 (dabco)] n as a function of adsorbate.…”