The dynamics of water exchange in gadolinium DOTA complexes studied by transition path sampling and potential of mean force methods

The mechanism of water exchange at the Gd centre of the two isomers of [Gd( III) DOTA]-(gadolinate(1-), [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetato(4-)-N1, N4, N7, N10, O1, O4, O7, O10]) has been explored using transition path sampling and potential of mean force methods to sample those regions of phase space inaccessible to standard molecular dynamics simulation. We find that there are definite differences in the details of the solvent rearrangement accompanying the exchange of the capping water molecule for the two isomers. We conclude that these solvent effects, rather than any differences in the binding energy of the capping water, are central in determining the exchange rate. We find that the potential of mean force studies yield absolute and relative rates of water exchange for the two isomers that are in good agreement with experiment.