On the origin of the relative stability of ZnIINTA and ZnIINTPA metal complexes. An insight from the IQA, IQF, and π-FARMS methods

Relative stability of Zn-II complexes with nitrilotriacetic acid (ZnNTA) and nitrilotri-3-propionic acid (ZnNTPA) was investigated. Classical analysis of individual interactions using local indices failed to explain the preferential formation of ZnNTA. This work shows that the preferential formation of ZnNTA is not due to the size of coordination five-membered rings or the absence of the steric CH--HC contacts, as commonly considered. By combining interacting quantum atoms/fragments, IQA/IQF-defined properties implemented in the pi-FARMS (preorganized-interacting fragment attributed relative molecular stability) method, (i) several measures of Zn-II affinity to NTPA were shown to be consistently greater than to NTA and (ii) larger stability of ZnNTA was attributed to coordinated water molecules. Being smaller, NTA occupies less space around the metal center. This results in less destabilised ZnAOH(2) coordination bonds and preorganization energy of H2O fragments being smaller in ZnNTA. Only by summing preorganization energies (of ligand and water fragments) and binding energy between fragments (using pi-FARMS method) we recovered the experimental trend. Importantly, the fundamental origin of all major energy components controlling relative stability of metal complexes was pin-pointed using the pi-FARMS method.