We report the synthesis of the ligand H(2)MeNO2A (1,4-bis(carboxymethyl)-7-methyl-1,4,7-triazacyclononane) and a detailed experimental and computational study of the hyperfine coupling constants (HFCCs) on the inner-sphere water molecules of [Mn(MeNO2A)] and related Mn2+ complexes relevant as potential contrast agents in magnetic resonance imaging (MRI). Nuclear magnetic relaxation dispersion (NMRD) profiles, O-17 NMR chemical shifts, and transverse relaxation rates of aqueous solutions of [Mn(MeNO2A)] were recorded to determine the parameters governing the relaxivity in this complex and the O-17 and H-1 HFCCs. DFT calculations (TPSSh model) performed in aqueous solution (PCM model) on the[Mn(MeNO2A)(H2O)]center dot xH(2)O and [Mn(EDTA)(H2O)](2)center dot xH(2)O (x = 0-4) systems were used to determine theoretically the O-17 and H-1 HFCCs responsible for the O-17 NMR chemical shifts and the scalar contributions to O-17 and H-1 NMR relaxation rates. The use of a mixed cluster/continuum approach with the explicit inclusion of a few second-sphere water molecules is critical for an accurate calculation of HFCCs of coordinated water molecules. The impact of complex dynamics on the calculated HFCCs was evaluated with the use of molecular dynamics simulations within the atom-centered density matrix propagation (ADMP) approach. The O-17 and H-1 HFCCs calculated for these complexes and related systems show an excellent agreement with the experimental data. Both the H-1 and O-17 HFCCs (A(iso) values) are dominated by the spin delocalization mechanism. The A(iso) values are significantly affected by the distance between the oxygen atom of the coordinated water molecule and the Mn2+ ion, as well as by the orientation of the water molecule plane with respect to the Mn-O vector.