Molecular Design of Functionalized m-Poly(phenylene ethynylene) Foldamers: from Simulation to Synthesis

Abstract

m-Poly(phenylene ethynylene)s (mPPEs) are a class of synthetic molecules being used for biocide coatings, catalysis, as well as chemical and biomolecule sensing because they exhibit a propensity to form a helical secondary structure in solution. Additionally, the folding of mPPEs into such helical arrangements may generally be controlled by varying the primary structure of the mPPE and/or the nature of the solvent. As such, several attempts have been made at developing heuristics for predicting a priori whether a particular mPPE will fold into a helix in a given solvent based on energetic and structural considerations. However, the experimental evidence shows that the formation of helical structures by mPPEs cannot be reliably predicted using such simple models. In this work, we demonstrate that replica-exchange molecular dynamics (REMD) simulations provide excellent agreement with experimental observations. We have simulated 20 different mPPE variations in five different solvent environments. Experimental results are available for eight of these one hundred systems, and in all eight of these cases the REMD results were in agreement with the experiments. Additionally, we simulated and then synthesized two previously unreported mPPEs having both ester and nitrile functional groups. After studying their folding behaviors in chloroform and acetonitrile, it was found that experimental results were in agreement with our predictions. This illustrates how REMD simulations, which are easily carried out with publicly available software on most modern computing systems, can be used to guide synthesis efforts focused on the formation of macromolecules with specific secondary structures.