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 (k_ex) values for the CEST peaks at 20 and 73 ppm were approximately 3.66×10³ s^-1 and 3.74×10³ s^-1, respectively.