Metal Ion Complexes of Macrocyclic Polyamines Enhance Both the Phosphate Hydrolysis and Imidazole Ring Opening of RNA 5′‐ cap Structure

The cleavage of P 1 ‐(7‐methylguanosyl‐5′) P 3 ‐(guanosyl‐5′) triphosphate, a RNA 5′‐ cap model, by 2‐hydroxyethyl‐ ( 6a – 6c ) and 2‐aminoethyl‐ ( 7a – 7c ) substituted macrocycles in the presence and absence of Zn 2+ and Cu 2+ ions has been studied at pH 7.2 and 60°. In the presence of the metal ions, hydrolysis of the phosphate group is enhanced. The mono‐ and dinuclear Zn 2+ complexes promote solely the phosphate hydrolysis, whereas the corresponding Cu 2+ complexes accelerate both the phosphate hydrolysis and the imidazole ring opening of the 7‐methylguanine base. In the absence of the metal ions, the macrocycles mainly promote breakdown of the 7‐methylguanine base, most probably by enhancing the nucleophilic attack of hydroxide ion on the C(8)‐atom by shielding the repulsive negative charge on the phosphate moiety. The 2‐hydroxyethyl and 2‐aminoethyl side arms exhibit a two‐ to three‐fold rate acceleration. Opening of the imidazole ring eventually results in cleavage of the triphosphate bridge.