Synthesis and binding properties of hybrid cyclophane-azamacrocyclic receptors

Three new azamacrocyclic-cyclophane hybrid receptors L-1, L-2, and L-3 have been synthesized that incorporate either 1,4,7,10-tetraazacyclododecane (cyclen) or 1,4,7-triazacyclononane (tacn) unit(s) tethered via a short amidic spacer to an electron donor and a H-bonding crown ether polycycle. The crown ether is designed to act as a host toward biologically relevant guests, whereas the macrocycle can coordinate a zinc(II) or a copper(II) ion. The pK(a) of this bound water in the zinc(II) complex of L-1 and L-2 is similar to7.5. Isothermal calorimetry experiments carried out on [ZnL1(OH2)](CF3SO3)(2) and [Zn2L2(OH2)(2)](CF3SO3)(4) in buffered water (pH 7.4) at 25 degreesC show that the host strongly binds a series of phosphate derivatives. In comparison, the complex [CuL3(OH2)(2)](CF3SO3)(2) is a poor receptor toward phosphate substrates.