Kinetics of interaction of the thione unit in 4-thio-2′-deoxyuridine and 4-thiouridine 5′-monophosphate with rapidly reacting gold(III) complexes‡

Abstract

Reactions of 4-thio-2′-deoxyuridine d(^s4U) and 4-thiouridine 5′-monophosphate ^s4UMP with trans-[AuY₂Cl₂]^+/– (Y = CN^– or NH₃) have been investigated by conventional and high-pressure stopped-flow spectrophotometry in aqueous solution with 2.9 ⩽ pH ⩽ 7.0. For a given combination of metal complex and sulfur donor the observed second-order rate constants decreased with increasing pH. In the pH range 2.9 to 5.5 this decrease is mainly due to displacement of the pH-dependent equilibrium trans-[AuY₂Cl₂]^+/–+H₂O⇌trans-[AuY₂Cl(OH)]^+/–+Cl^–+H⁺ and formation of an increasing fraction of the less reactive gold(III) hydroxo complex. The activation parameters ΔH ^‡, ΔS ^‡ and ΔV ^‡ at pH 4.0 for substitution of chloride for thione at trans-[AuY₂Cl₂]^+/– indicate an associative interchange process. When the thione-containing nucleotide reacts with the cation, steric and electrostatic interactions between the metal complex and the phosphate group oppose each other and the rate of the reaction of trans-[Au(NH₃)₂Cl₂]⁺ with ^s4UMP is approximately the same as with d(^s4U). Thus, the electrostatic outer-sphere interaction with a single phosphate group adjacent to the kinetically preferred binding site is not sufficient to induce a reactivity that significantly exceeds that of direct interaction between the thione and the rapidly reacting gold(III) centre. In contrast, reaction of trans-[Au(CN)₂Cl₂]^– with ^s4UMP is significantly slower than with d(^s4U), most likely due to the combined effect of electrostatic repulsion and steric blocking.