pubs.acs.org/Macromolecules Published on Web 12/13/2010 r 2010 American Chemical Society 60 Macromolecules 2011, 44, 60–67 DOI: 10.1021/ma101514c Controlling the m-Poly(phenylene ethynylene) Helical Cavity Environment: Hydrogen Bond Stabilized Helical Structures Ha H. Nguyen, James H. McAliley, and David A. Bruce* Department of Chemical and Biomolecular Engineering, Clemson University Clemson, South Carolina 29634-0909, United States Received July 7, 2010; Revised Manuscript Received November 26, 2010 ABSTRACT: Replica exchange molecular dynamics (REMD) simulations using explicit solvents were used to study the folding behaviors of a group of m-poly(phenylene ethynylene)s (mPPEs), which are being actively investigated for a variety of biological and catalysis applications. The mPPEs considered in this study have different endohelix functional groups, which in the helical conformation of the polymer are localized within the helical cavity. The results showed that, for mPPEs with ester functional groups arranged on the exohelix of the helical polymer, altering the endohelix functional groups did not significantly affect folding behaviors in acetonitrile. This result is consistent with experimental data and indicates that the properties of the helical cavity may be tailored for certain applications without destabilizing the helix conformation, so long as the exohelix functional groups are esters. We also present simulation results for a set of mPPEs with endohelix functional groups that enhance the stability of the helical conformation via the formation of intra- and interturn hydrogen bonds (HBs). If mPPE folding is viewed as a nucleation/growth process, intraturn HB interactions facilitate both nucleation events and growth, while interturn HBs and π-stacking interactions affect only the growth process. These mPPEs, which lack exohelix functional groups, were shown to fold into stable helical secondary structures in acetonitrile, methanol, and even chloroform, although chlorinated solvents have previously been known to denature mPPE helical structures. Our results predict that this stabilization occurs to the extent that a variety of exohelix functional groups can be incorporated into mPPE backbones, while maintaining a stable helical secondary structure, including many functional groups that are known to destabilize the helix in non-hydrogen-bonded mPPEs. Introduction m-Poly(phenylene ethynylene)s or mPPEs are a class of poly- mers known for their ability to form helical secondary structure in suitable solvent conditions. 1 This special ability not only invites the opportunity for many different applications but also provides a simple and interesting platform for studying the conformational behavior of macromolecules. Thus, understanding and control- ling the factors that affect their folding behavior is crucial in designing an effective functionalized mPPE for a given application. It is especially important to understand the impact of functional groups on the polymer backbone, as such knowledge is extremely useful in studying secondary structure formation of macromolecules in general. Primarily, two types of functional groups can be employed to modify the properties of a given mPPE, as shown in Figure 1. On the basis of their locations on the expected helical structures, we refer to those in position R 1 as exohelix functional groups. These groups are at meta positions to the ethynylene linkages and arranged on the outer wall of the helical conformation. Similarly, we refer to groups at position R 2 as endohelix functional groups. These are located at the position that is ortho to both ethynylene linkages on a phenyl ring, and they are encased inside the cavity of the mPPE in its helical conformation. The exohelix functional groups of mPPEs have been shown by many experimental and modeling studies to directly affect the solubility and folding behaviors of their respective mPPEs. 1-10 The endohelix functional groups, on the other hand, have been employed mostly to control the environment inside the helix cavity. For example, Tanatani et al. 11 employed methyl func- tional groups to reduce the size of the helix cavity of an mPPE, effectively blocking the entrance of small molecules into the cavity. In another study, Prince et al. 12 used nitrile endohelix functional groups to form a silver ion complex within the helix cavity. The bonds between the ion and the nitrile functional groups of the complex provided an additional stabilizing effect for the helical structure in tetrahydrofuran solution. Aside from their ability to change the environment inside the mPPE helix cavity, endohelix functional groups may also influ- ence helix stability by enhancing the π-stacking of overlapping aromatic rings. This effect is brought about because, in general, substituted benzyl rings have stronger π-stacking interactions in comparison to benzene. 13,14 On the other hand, they could also inhibit helical formation through steric interactions. The steric effect was shown by Arnt and Tew 2 with an mPPE having large ether endohelix functional groups and by Adisa and Bruce 4 in a modeling study with similar mPPE structures. Steric interactions of course depend on the size of the functional groups, and in our previous study, 10 the folding behavior of an mPPE having small endohelix functional groups was found to be similar to that of an mPPE with only hydrogen endohelix functional groups. In this study, we examine how the stability of the mPPE helical structure is affected by endohelix functional groups, including those that are capable of forming hydrogen bonds. The idea of incorporating hydrogen bonds into an mPPE structure was previously explored by Cary and Moore, 15 by placing suitable functional groups at the position that is ortho to the ethynylene *Corresponding author. Address: Department of Chemical & Biomolecular Engineering, Clemson University, 127 Earle Hall, Clemson, SC 29634-0909. E-mail: dbruce@clemson.edu.