Published: December 21, 2011 r2011 American Chemical Society 1283 dx.doi.org/10.1021/jp210208m | J. Phys. Chem. A 2012, 116, 1283–1288 ARTICLE pubs.acs.org/JPCA Modeling Nonaqueous Proton Wires Built from Helical Peptides: Biased Proton Transfer Driven by Helical Dipoles Gustavo E. L opez,* ,†,‡ Inara Col on-Díaz, † Anthony Cruz, †,‡ Sumana Ghosh, § Samantha B. Nicholls, § Usha Viswanathan, § Jeanne A. Hardy, § and Scott M. Auerbach § † Department of Chemistry, University of Puerto Rico at Mayag€ uez, Mayag€ uez, Puerto Rico 00681 ‡ Department of Chemistry, Lehman College-CUNY, Bronx, New York 10034, United States § Department of Chemistry, University of Massachusetts at Amherst, Amherst, Massachusetts 01003, United States ABSTRACT: We report gas-phase electronic structure calculations on helical peptides that act as scaffolds for imidazole-based hydrogen-bonding networks (proton wires). We have modeled various 21-residue polyalanine peptides substituted at regular intervals with histidines (imidazole-bearing amino acids), using a hybrid approach with a semiempirical method (AM1) for peptide scaffolds and density functional theory (B3LYP) for proton wires. We have computed energy landscapes including barriers for Grotthuss-shuttling-type proton motions though wires supported on 3 10 -, α- and π-helical structures, showing the 3 10 - and α-helices to be attractive targets in terms of high proton affinities, low Grotthuss shuttling barriers, and high stabilities. Moreover, bias forces provided by the helical dipole moments were found to promote unidirectional proton translocation. I. INTRODUCTION The promise of hydrogen-based energy has generated renewed interest in rationally designed proton exchange membranes that can function in hydrogen fuel cells. 1 Ideal properties for new proton exchange membrane materials include the ability to function through nonsolvent-mediated mechanisms, thus avoiding the problem of dehydration due to electro-osmotic drag. Some promising new proton exchange membrane materials use tethered imidazoles as the primary proton translocating functionality. 2 Because imidazoles can both donate and accept hydrogen bonds, they are capable of forming extended hydrogen- bonding networks, i.e., proton wires that act as proton transpor- ters through the Grotthuss shuttling mechanism. Imidazoles are also used as proton translocating moieties in a number of native biological systems, inspiring biomimetic applications for this functional group. 3,4 Our previous calculations on nonpeptide proton wires show that backbone repeat distances in the range of 56 Å are required for continuous hydrogen-bond networks of imidazoles and triazoles, making helical peptides excellent can- didates for such scaffolds. 5 In addition to their geometrical properties, helical peptides exhibit electric dipoles that may promote unidirectional proton motion. In this article, we report electronic structure calculations on helical-peptide-based proton wires, predicting for the first time the utility of these systems for solvent-free proton conduction. Three major helical conformations of polypeptide chains can be formed from α-amino acids: 3 10 -, α-, and π-helices (Figure 1). In the present study, we consider 21-residue peptides with 3 10 -, α-, and π-helical structures substituted with histidine (an imidazole- bearing amino acid) at regular intervals so that all imidazoles decorate a single face of the helix. In particular, we have examined the designed 3 10 -, α-, and π-helical sequences Ala 3 (His-Ala 2 ) 6 , Ala 2 (His-Ala 3 ) 4 HisAla 2 , and Ala 2 (His-Ala 4 ) 3 HisAla 3 , respectively, using starting conformations of idealized 3 10 -, α-, and π-structures. These particular peptide sequences were designed as polyalanine- substituted scaffolds because polyalanine has been well studied from both theoretical and experimental perspectives. 612 In particular, recent experimental studies 13,14 have shown that α-helical polyalanine peptides are stable due to enthalpic factors that include cooperative H-bonding. The propensity of the helical conformation depends strongly on the terminal caps, length of the peptide, and temperature. These stabilization effects have been corroborated by electronic structure calculations. 15,16 Within the concept of a proton wire, the helices can be viewed as having two distinct regions: one consists of all the alanine residues plus the C-α atoms of the histidine backbone (denoted Received: October 24, 2011 Revised: December 19, 2011