Cleavage of an RNA Model Catalyzed by Dinuclear Zn(II) Complexes Containing Rate-Accelerating Pendants. Comparison of the Catalytic Benefits of H-Bonding and Hydrophobic Substituents

The transesterification of a simple RNA model, 2-hydroxypropyl p-nitrophenyl phosphate (2, HpNPP) promoted by seven dinuclear Zn(II) catalysts (3,4,5,6,7,8,9:Zn(II)2:(-OCH3)) based on the bis[bis(2-substituted-pyridinyl-6-methyl)]amine ligand system was investigated in methanol under s spH-controlled conditions at 25.0 ± 0.1 °C. The two metal complexing ligands were joined together via the amino N connected to a m-xylyl linker (3, 4, 5, 6, 7) where the 2-pyridinyl substituent = H, CH3, (CH)4, NH2, and NH(CO)CH3, respectively, and a propyl linker (8, 9) where the ring substituent = H and CH3. All of the dinuclear complexes except 8:Zn(II)2 exhibit saturation kinetics for the k obs versus [catalyst] plots from which one can determine catalyst:substrate binding constants (K M), the catalytic rate constants for their decomposition (k cat), and the second order catalytic rate constants (k 2 cat = k cat/K M). In the case of 8:Zn(II)2, the plots of k obs versus [catalyst] as a function of s spH are linear, and the catalytic rate constants (k 2 cat) are defined as the gradients of the plots. Analysis of all of the data at the s spH optimum for each reaction indicates that the presence of the amino and acetamido H-bonding groups and the CH3 group provides similar increases of the k cat terms of 25−50 times that exhibited by the parent complex 3:Zn(II)2. However, in terms of substrate catalyst binding (K M), there is no clear trend that H-bonding groups or the CH3 group provides stronger binding than the parent complex. In terms of the overall second order catalytic rate constant, the CH3, amino, and NH(CO)CH3 groups provide 20, 10, and 68 times the k 2 cat observed for the parent complex. In the case of 9:Zn(II)2, the presence of the methyl groups provides a 1000-fold increase in activity (judged by k 2 cat) over the parent complex 8:Zn(II)2. The results are interpreted to indicate that H-bonding effects may be important for catalysis and less so for substrate binding, but the steric effect and impact on the local polarity provided by a methyl substituent is just as effective and in fact may form part of the acceleratory effect attributed to H-bonding in related systems.