Recognition of AMP, ADP and ATP through Cooperative Binding by Cu(II) and Zn(II) Complexes Containing Urea and/or Phenylboronic Acid Moieties

We report a series of Cu(II) and Zn(II) complexes with different ligands containing a dipicolyl unit functionalized with urea groups that may contain or not a phenylboronic acid function. These complexes were designed for the recognition of phosphorylated anions through coordination to the metal ion reinforced by hydrogen bonds involving the anion and NH groups of urea. The complexes were isolated and several adducts with pyrophosphate were characterized using X-ray diffraction measurements. Coordination of one of the urea nitrogen atoms to the metal ion promoted the hydrolysis of the ligands containing 1,3-diphenylurea units, while ligands bearing 1-ethyl-3-phenylurea groups did not hydrolyze significantly at room temperature. Spectrophotometric titrations, combined with (1)H and (31)P NMR studies, were used in investigating the binding of phosphate, pyrophosphate (PPi), and nucleoside 5′-polyphosphates (AMP, ADP, ATP, CMP, and UMP). The association constants determined in aqueous solution (pH 7.0, 0.1 M MOPS) point to a stronger association with PPi, ADP, and ATP as compared with the anions containing a single phosphate unit. The [CuL(4)](2+) complex shows important selectivity for pyrophosphate (PPi) over ADP and ATP.