Upper Rim Bifunctional cone-Calix[4]arenes Based on a Ligated Metal Ion and a Guanidinium Unit as DNAase and RNAase Mimics

The catalytic activity of an artificial phosphodiesterase that combines a ligated metal ion (CuII, ZnII) with a guanidinium unit connected by a 1,2-vicinal calix[4]arene spacer was investigated in the transesterification of RNA models HPNP and four diribonucleoside 3′,5′-monophosphates. Comparison with previous data related to the 1,3-distal regioisomeric metal complexes confirms the superiority of the CuII complexes over the ZnII analogs and shows that in the reactions of HPNP, GPU, and UpU, the catalytic efficiency depends very little on whether the substitution pattern is 1,2-vicinal or 1,3-distal. On the other hand, CpA turned out to be a good substrate for the CuII complex of the 1,2-vicinal catalyst and a bad substrate for the corresponding 1,3-distal regioisomer, whereas the opposite holds for GpA. Extension of the investigation to the cleavage of the DNA model BNPP showed that both ZnII and CuII complexes exhibit good catalytic efficiency, with a superiority of the 1,2-vicinal catalyst in both cases. The data reported in this work show that rate accelerations over background for the best catalyst-substrate combinations at 0.5 mM catalyst concentration are 3.6 × 105-fold for HPNP, 1.1 × 106-fold for BNPP, and range from 1.3 × 106- to 1.3 × 107-fold for diribonucleoside monophosphates.