Molecular Structure and Dynamics of Aminopolycarboxylates and their Lanthanide Ion Complexes.

Abstract

Molecular mechanics calculations and molecular dynamics simulations have been used to examine the molecular structures and dynamics of the four aminopolycarboxylate ligands, DOTA (1,4,7,10-tetraazacyclododecane-N,N'',N",N''''''-tetraacetic acid), DTPA (1,4,7-triazaheptane-1,1,4,7,7-pentaacetic acid), OTTA (1-oxa-4,7,10-triazacyclododecane-N,N'',N''''-triacetic acid), DO3A (1,4,7,10-tetraazacyclododecane-N,N'',N''''-triacetic acid), and their Gd(III) ion complexes. The results indicate that the in vacuo stability of the complexes is determined mainly by the number of liganding atoms and their charges, and by the increase in conformational energy of the ligand by complexation. The calculated reaction energies for complexation of DOTA, DTPA and DO3A with a Gd(III) ion are in reasonable agreement with the relative order of magnitude of experimental log K values. Molecular dynamics simulations of the complexation reactions of DOTA and DTPA with a hydrated Gd(III) ion suggest cation coordination to one of the carboxylate groups as the first step in the formation of the complex.