KINETICS OF INTERACTION OF THE THIONE UNIT IN 4-THIO-2'-DEOXYURIDINE AND 4-THIOURIDINE 5'-MONOPHOSPHATE WITH RAPIDLY REACTING GOLD(III) COMPLEXES

Reactions of 4-thio-2'-deoxyuridine d(U-s4) and 4-thiouridine 5'-monop hosphate (UMP)-U-s4 with trans-[AuY2Cl2](+/-) (Y = CN- or NH3) have be en investigated by conventional and high-pressure stopped-flow spectro photometry in aqueous solution with 2.9 less than or equal to pH less than or equal to 7.0. For a given combination of metal complex and sul fur donor the observed second-order rate constants decreased with incr easing pH. In the pH range 2.9 to 5.5 this decrease is mainly due to d isplacement of the pH-dependent equilibrium trans-[AuY2Cl2](+/-) + H2O reversible arrow trans-[AuY2Cl(OH)](+/-) + Cl- + H+ and formation of an increasing fraction of the less reactive gold(In) hydroxo complex. The activation parameters Delta H double dagger, Delta S double dagger and Delta V double dagger at pH 4.0 for substitution of chloride for thione at trans-[AuY2Cl2](+/-) indicate an associative interchange pro cess. When the thione-containing nucleotide reacts with the cation, st eric and electrostatic interactions between the metal complex and the phosphate group oppose each other and the rate of the reaction of tran s-[Au(NH3)(2)Cl-2](+) with (UMP)-U-s4 is approximately the same as wit h d(U-s4). Thus, the electrostatic outer-sphere interaction with a sin gle phosphate group adjacent to the kinetically preferred binding site is not sufficient to induce a reactivity that significantly exceeds t hat of direct interaction between the thione and the rapidly reacting gold(In) centre. In contrast, reaction of trans-[Au(CN)(2)Cl-2](-) wit h (UMP)-U-s4 is significantly slower than with d(U-s4), most likely du e to the combined effect of electrostatic repulsion and steric blockin g.