Zinc(II) tweezers containing artificial peptides mimicking the active site of phosphotriesterase: the catalyzed hydrolysis of the toxic organophosphate parathion.

Two new ligand-containing histidine based on N,N',N″-tris(N-benzyl-L-histidinyl)tri(2-aminoethyl)amine, L(1), namely N,N',N″-tris[(1S)-2-methoxy-2-oxy-1-(1-benzylimidazol-4-ylmethyl)]nitrilotriacetamide L(2) and N,N',N″-tris{N-benzyl-N-[N-benzyl-N-(N-benzyl-L-histidinyl)-L-histidinyl]-L-histidinyl}tri(2-aminoethyl)amine L(3) were prepared. Zinc(II) binding studies by these ligand systems were analyzed by means of potentiometric and (1)H NMR titrations in aqueous methanol (33 % v/v). Subsequently their zinc(II) complexes L(1)Zn(H(2)O)(2) x HClO(4) (1), L(2)Zn(OH(2))(2) x H(2)O (2), and (L(3)Zn(3)(H(2)O)(3)(6)·3HClO(4)x 5H(2)O (3), respectively were synthesized and characterized. The reactivity of the trinuclear complex (3) toward the hydrolysis of the toxic organophosphate parathion was investigated and compared with that of the mononuclear reference complex (1). From the pH dependence of the apparent rate constants, and the deprotonation constant (pK(a)) of the coordinated water molecules in (1), the active species were confirmed to be {HL(1)Zn(OH)/L(1)Zn(H(2)O)} at pH 8.5. The trizinc complex (3) effects hydrolysis of parathion, with three times rate enhancement over the mononuclear (1), indicating that cooperative action of the three zinc centers is limited.