The conformational behavior of four [Ln(DOTA)(H(2)O)](-) systems (Ln = La, Gd, Ho, and Lu) has been characterized by means of ab initio calculations performed in vacuo and in aqueous solution, the latter by using the polarizable continuum model (PCM). Calculated molecular geometries and conformational energies of the [Ln(DOTA)(H(2)O)](-) systems, and interconversion mechanisms, barriers, and (13)C NMR spectra of the [Lu(DOTA)](-) complex are compared with experimental values. For each system, geometry optimizations, performed in vacuo and in solution at the HF/3-21G level and using a 46+4f(n) core electron effective core potential (ECP) for lanthanides, provide two minima corresponding to a square antiprismatic (A) and an inverted antiprismatic (IA) coordination geometry. All the systems are nonacoordinated, with the exception of the IA isomer of the Lu complex that, from in solution calculations, is octacoordinated, in agreement with experimental data. On comparing the in vacuo relative free energies calculated at different theory levels it can be seen that the nonacoordinated species dominates at the beginning of the lanthanide series while the octacoordinated one does so at the end. Furthermore, on passing along the series the IA isomer becomes less and less favored with respect to A and for the Lu complex a stabilization of the IAisomer is observed in solution (but not in vacuo), in agreement with the experimental data. Investigation of the A<-->IA isomerization process in the [Lu(DOTA)](-) system provides two different interconversion mechanisms: a single-step process, involving the simultaneous rotation of the acetate arms, and a multistep path, involving the inversion of the cyclen cycle configuration. While in vacuo the energy barrier for the acetate arm rotation is higher than that involved in the ring inversion (23.1 and 13.1 kcal mol(-)(1) at the B3LYP/6-311G level, respectively), in solution the two mechanisms present comparable barriers (14.7 and 13.5 kcal mol(-)(1)), in fairly good agreement with the experimental values. The NMR shielding constants for the two isomers of the [Lu(DOTA)](-) complex have been calculated by means of the ab initio GIAO and CSGT methods, and using a 46-core-electron ECP for Lu. The calculated (13)C NMR chemical shifts are in close agreement with the experimental values (rms 3.3 ppm, at the HF/6-311G level) and confirm the structural assignment of the two isomers based on experimental NMR spectra in solution. The results demonstrate that our computational approach is able to predict several physicochemical properties of lanthanide complexes, allowing a better characterization of this class of compounds for their application as contrast agents in medical magnetic resonance imaging (MRI).