A Remarkable ParaCEST Activity Shown by a Co(II) Complex of Bis-Dipicolinamideacetamide With One Inner Sphere Water Molecule.

Reaction of the BDPAA (N,N-dimethyl pyridine-based tri(carboxamide)) with iron tetrafluoroborate, cobalt chloride and nickel triflate separately in methanol/acetonitrile affords the complex, [Fe(BDPAA)(H2O)](BF4)2, [Co(BDPAA)(H2O)]Cl2 and [Ni(BDPAA)(H2O)](CF3SO3)2, respectively. The solid-state structural analysis of cobalt and nickel complexes of bis-dipicolinamideacetamide (BDPAA) ligand and the solution state paraCEST studies of all three complexes are presented. Among these complexes, only Co(II)-BDPAA complex exhibits remarkable paraCEST activity due to exchangeable carboxamide NH2 protons, whereas the corresponding Fe complex shows very little CEST effect and Ni complex did not show CEST activity at all. Single crystal X-ray analysis of [Co(BDPAA)(H2O)]Cl2 indicates that the Co(II) ion exhibits a seven-coordination with N3O2 from the ligand and one inner sphere water molecule, leading to a distorted pentagonal bipyramidal (pbp) geometry. Presaturation of the picolinamide protons of the Co complex, 73 ppm distant from the bulk water signal by 25 μT pulse at 37 °C leads to an 18 % decrease in intensity of 1H NMR signals due to CEST effect. The Co-BDPAA complex shows the best CEST effect at pH around 7.4-7.6. The measured proton exchange rate constant (kex) values for the CEST peaks at 20 and 73 ppm were approximately 3.66×103 s-1 and 3.74×103 s-1, respectively.