Structure-reactivity studies in copper(II)-catalyzed phosphodiester hydrolysis

We have investigated the ability of a series of three related copper comple xes Cu([9-11]aneN(3))X-2 to hydrolyze the activated phosphodiesters bis(4-n itrophenyl) phosphate (BNPP) and ethyl LC-nitrophenyl phosphate (ENPP). The compound Cu([10]aneN(3))Br-2 crystallizes in the monoclinic space group C2 /c, a = 20.693(4) Angstrom, b = 11.429(2) Angstrom, c = 20.138(4) Angstrom, beta = 104.78(3)degrees, V = 4605(2) Angstrom(3), and Z = 16. The compound Cu([11]aneN(3))Br-2 crystallizes in the orthorhombic space group Pnma, a = 13.7621(10) Angstrom, b = 8.7492(13) Angstrom, c = 10.0073(10) Angstrom, V = 1205.0(2) Angstrom(3), and Z = 4. The structure of Cu([9]aneN(3))Cl-2 wa s previously reported (Inorg. Chem. 1980, 19, 1379). The crystal structures of the three complexes show a progression in geometry from square pyramida l to distorted trigonal bipyramidal as the size of the macrocycle increases . Larger macrocycles also result in the copper ion being pulled closer to t he plane defined by the three, ligand nitrogens, which in turn results in a n increase in the sum of the three N-Cu-N angles from 249 degrees to 257 de grees 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]an eN(3))X-2 increases by nearly an order of magnitude as the ligand size incr eases from a. nine-membered to an 11-membered ring. Correlations have been made between the catalytic ability of Cu([9-11]aneN3)X2 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 catalytic ally active species. As the ligand size increases, the dimer formation cons tant (K-f) decreases due to steric constraint, thereby increasing the conce ntration of active species and hence the rate of hydrolysis. The contributi ons of Lewis acidity and steric constraint on bath substrate binding (K-2.) and P-O bond cleavage (k(3) or k(cat)) are less important than the dimeriz ation equilibrium constant in determining the rate of the reaction.