CHEMISTRY OF PHOSPHODIESTERS, DNA AND MODELS .2. THE HYDROLYSIS OF BIS(8-HYDROXYQUINOLINE) PHOSPHATE IN THE ABSENCE AND PRESENCE OF METAL-IONS

The pH dependence of the hydrolysis of bis(8-hydroxyquinoline) phosphate and bis(6-hydroxyquinoline) phosphate has been studied in the absence and presence of varying concentrations of Ni2+, Co2+, Zn2+, and Mn2+. Since both diesters are characterized by having two quinoline nitrogens as basic centers and a negative phosphate, they exist, depending upon pH, as unprotonated, mono-, di-, and triprotonated species {IV-, IVH, IVH2+, and IVH32+ for bis(8-hydroxyquinoline) phosphate; V-, VH, VH2+, and VH32+ for bis(6-hydroxyquinoline) phosphate}. The partial charges and basicity of the hydroxyl groups of 6- and 8-hydroxyquinoline are comparable. The electronic effect on the rate of hydrolysis brought about by protonation or metal ion complexing to the quinoline nitrogens should be the same for both bis(6-hydroxyquinoline) phosphate and bis(8-hydroxyquinoline) phosphate. Electronic effects upon hydrolytic rates can, therefore, be differentiated from proximity effects by comparison of the hydrolytic rate constants of the two diesters. The bis(6-hydroxyquinoline) phosphate hydrolysis is (i) quite slow (10(-7) s-1), (ii) pH independent from slightly acidic to neutral pH, and (iii) not catalyzed by the metal ions employed. On the other hand, hydrolysis of bis(8-hydroxyquinoline) phosphate proceeds through rapid spontaneous breakdown of IVH and through HO- catalyzed hydrolysis of IV-. The hydrolysis of IVH is not subject to buffer catalysis nor does it exhibit a deuterium solvent kinetic isotope effect. Arguments are presented in support of a mechanism for hydrolytic breakdown of IVH which involves quinoline nitrogen nucleophilic displacement on phosphorus with departure of N-protonated 8-hydroxyquinoline zwitterion. This mechanism provides a rate enhancement over the hydrolysis of the bis(6-hydroxyquinoline) phosphate of 1.1 X 10(3). Metal ion catalysis of the hydrolysis of the bis(8-hydroxyquinoline) phosphate involves a bimolecular reaction of Ni2+, Co2+, or Zn2+ (Mn2+ is not reactive) with the IV- species. Arguments support a mechanism of nucleophilic displacement by a quinoline nitrogen with assistance to departure of the leaving 8-hydroxyquinoline moiety by interaction of its quinoline nitrogen and the developing negative charge on its oxygen with a metal ion. This mechanism provides, at 1 M in metal ion, a rate enhancement over the spontaneous hydrolysis of IVH of 4.7 x 10(4) for Ni2+, 1.2 x 10(4) for Co2+, and 1.3 x 10(4) for Zn2+. The rate enhancement brought about by the concerted nucleophilic attack of quinoline nitrogen and metal ion assistance to departure of the leaving group in the hydrolysis of IV- is ca. 1-5 x 10(7) at 1 M metal ion.