Structure-Reactivity Studies in Copper(II)-Catalyzed Phosphodiester Hydrolysis

We have investigated the ability of a series of three related copper complexes Cu([9-11]aneN(3))X(2) to hydrolyze the activated phosphodiesters bis(4-nitrophenyl) phosphate (BNPP) and ethyl 4-nitrophenyl phosphate (ENPP). The compound Cu([10]aneN(3))Br(2) crystallizes in the monoclinic space group C2/c, a = 20.693(4) Å, b = 11.429(2) Å, c = 20.138(4) Å, beta = 104.78(3) degrees, V = 4605(2) Å(3), and Z = 16. The compound Cu([11]aneN(3))Br(2) crystallizes in the orthorhombic space group Pnma, a = 13.7621(10) Å, b = 8.7492(13) Å, c = 10.0073(10) Å, V = 1205.0(2) Å(3), and Z = 4. The structure of Cu([9]aneN(3))Cl(2) was previously reported (Inorg. Chem. 1980, 19, 1379). The crystal structures of the three complexes show a progression in geometry from square pyramidal to distorted trigonal bipyramidal as the size of the macrocycle increases. Larger macrocycles also result in the copper ion being pulled closer to the plane defined by the three ligand nitrogens, which in turn results in an increase in the sum of the three N-Cu-N angles from 249 degrees to 257 degrees to 278 degrees along with a concomitant decrease in the X-Cu-X angle. Significantly, the rate constant for the hydrolysis of BNPP by Cu([9-11]aneN(3))X(2) increases by nearly an order of magnitude as the ligand size increases from a nine-membered to an 11-membered ring. Correlations have been made between the catalytic ability of Cu([9-11]aneN(3))X(2) and the structural and electronic properties of the complexes. All three catalysts exist in a monomer-dimer equilibrium in solution, with the monomer being the catalytically active species. As the ligand size increases, the dimer formation constant (K(f)) decreases due to steric constraint, thereby increasing the concentration of active species and hence the rate of hydrolysis. The contributions of Lewis acidity and steric constraint on both substrate binding (K(2)) and P-O bond cleavage (k(3) or k(cat)) are less important than the dimerization equilibrium constant in determining the rate of the reaction.