ApA cleavage promoted by oxa-aza macrocycles and their Zn(II) complexes. The role of pH and metal coordination in the hydrolytic mechanism

The thermodynamic parameters for protonation and Zn(ll) complex formation with ligand 1,4,7,16,19,22-hexaza-10,13,25,28-tetraoxacyclotriacontane (Ll) have been determined. Ll forms stable dizinc complexes from neutral to alkaline pH. The hydrolytic ability toward adenylyl(3 ' -5 ' )adenosine (ApA) of L1 and its dizinc(II) complexes have been analyzed by means of HPLC chromatography. Only partially protonated species of L promote ApA hydrolysis suggesting that the cleavage process is cooperatively promoted by a general base catalysis by neutral amine groups and a general acid catalysis by protonated ammonium functions. Concerning the Zn(II) complexes, the hydrolysis rates increase in the presence of the hydroxo complexes [Zn(2)L1(OH)](3+) and [Zn(2)L1(OH)(2)](2+). This indicates that Zn-OH functions play a crucial role in the hydrolytic process, assisting the deprotonation of the 2 ' -OH group of ApA, which may act as nucleophile in the cleavage process. Both binuclear Ll complexes are better catalysts than the mononuclear [ZnL2(OH)](+) complex (L2 = 1,4-Dioxa-7,10,13-triazacyclopentadecane), indicating a cooperative role of the two Zn(II) ions in ApA cleavage by [Zn(2)L1(OH)](3+) and [Zn(2)L1(OH)(2)](2+), probably due to a bridging coordination of the phosphate moiety of ApA to the two metal centers.