An equal terms comparison of the proficiency of artificial phosphodiesterases by using simple models of RNA or DNA as benchmarks–the takeaway to design next generation supramolecular catalysts

This comprehensive review aims at identifying the structural features and general rules governing the design of enzyme mimics and supramolecular catalysts having the ability to hydrolytically cleave the phosphodiester bonds. Rate and binding constants of the artificial phosphodiesterases so far proposed and tested by using the model compounds, bis (p-nitrophenyl) phosphate (BNPP) and 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) as widely recognized model substrates have been collected, elaborated and compared. These substrates have been extensively used over time to evaluate the performance of artificial phosphodiesterases, providing consistent and unique bases for comparing different catalysts. Notably, no other substrates have been tested as extensively and over such a prolonged period. A wide variety of supramolecular phosphodiesterases have been considered, comprising metal-free- and metallocatalysts, acyclic, macrocyclic or even nanostructured ones. The scope and limits of the use of Effective Molarity to evaluate the enhanced reactivity of some of these supramolecular catalysts are also discussed. The information collected allows to give the reader a take-home message for the design of next generation artificial phosphodiesterases.