Lanthanide chelates are effective agents for improving contrast in MR images. Optimizing the relaxation of inner sphere water molecules is a common focus of research in this field. However, the efforts to design an optimal contrast agent have commonly over-looked the relationship of water position and water exchange kinetics. This work explores structural conformation, the impact of very fast water exchange kinetics on hydration, and differing tumbling rates for regioisomers of a number of lanthanide chelates. We have grown crystals of LnDOTMA and obtained structural data by X-ray diffraction that provide a picture of the chelate during water exchange and demonstrate that chelate conformation is associated with water position. We observe increased population of the major isomer with increased water exchange rates in variable temperature 1H NMR studies of HoDOTMA. This suggests that water position and water exchange rates are linked. We therefore recommend that accurate water exchange data be included in the application of the SBM equations when interpreting experimental data. As further support of this recommendation, we measured water exchange kinetics with 17O NMR for the rigid GdNB-DOTMA chelates. These results were used in the fitting of 1H NMRD profiles to establish tumbling parameters. Similar results were also observed in the less rigid GdNB-DOTA, establishing the first identification of regioisomers in these chelates and their biphenyl derivatives. Binding studies of GdBP-DOTA indicate that the side isomer is a more effective agent, but it is the minor species in solution. Our work herein shows that predicting efficacy of contrast agents with SBM equations requires a more complete consideration of chelate hydration (q/r6).