An ab-initio study of pyrrole and imidazole arylamides

Arylamide foldamers have been shown to have a number of biological and medicinal applications. For example, a class of pyrrole-imidazole polyamide foldamers is capable of binding specific DNA sequences and preventing development of various gene disorders, most importantly cancer. Molecular dynamics (MD) simulations can provide crucial details in understanding the atomic level events related to foldamer/DNA binding. An important first step in the accurate simulation of these foldamer/DNA systems is the reparametrization of force field parameters for torsion around the aryl-amide bonds. Herein, the density functional theory (DFT) potential energy profiles and the derived force field parameters for four types of aryl-amide bonds for pyrrole and imidazole building blocks, which have been extensively employed in foldamer design for DNA-binding polyamides, will be highlighted. These results contribute to the development of computational tools for an appropriate molecular modeling of pyrrole-imidazole polyamide/DNA binding, and provide an insight into the chemical factors that influence the flexibility of pyrrole-imidazole polyamides and their binding to DNA.