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1. Introduction

Understanding hydrogen-bond dynamics in methanol and other alcohols is important to energy-related research because these liquids are widely used as additives or alternatives to petroleum-derived fuels. My strategy to investigate hydrogen bond dynamics in methanol is to connect molecular dynamics (MD) simulations of dilute acetonitrile-methanol mixtures to novel chemical-exchange two-dimensional infrared (2D IR) measurements, where the CN stretch of acetonitrile serves as a vibrational probe of hydrogen-bond dynamics. Using 2D IR the Hochstrasser laboratory has measured the timescales of hydrogen bond formation and dissociation between acetonitrile and methanol. The results of these experiments present an unprecedented opportunity to assess directly the accuracy of hydrogen bond dynamics in existing empirical force fields and to guide the development of improved models—provided the 2D IR spectra can be calculated within MD simulations. My challenge has been to develop a robust protocol for the calculation of the CN stretch vibrational frequency of acetonitrile within a fluctuating methanol environment. Once this challenge is met, we will have the ability to make a direct connection to experiment by calculating the actual experimental observable, the 2D IR spectrum. In Section 2, I will discuss my progress toward computing accurate CN stretch vibrational frequencies in the condensed-phase, and in Section 3 I will enumerate some future directions.

2. Summary of Results

We have parameterized an accurate and transferable methodology for the calculation of CN stretch frequencies of acetonitrile in hydrogen bonding solvents, including water and methanol. Currently, we are utilizing our optimized quantum mechanics/molecular mechanics (OQM/MM) technique to compare systematically the infrared absorption spectrum for the CN stretch of acetonitrile in methanol for a series of commonly used classical force fields for both acetonitrile and methanol.  For methanol we are considering the popular J2 model developed by Jorgensen and coworkers and the transferable potential for phase equilibria (TraPPE) model of Siepmann et al.  For acetonitrile we are considering the TraPPE model and three permutations based on a model used previously in our work. The three modified acetonitrile models correspond to three different charge distributions across the acetonitrile molecule; a gas-phase CHelpG charge description, a solvated CHelpG charge description averaged from 200 clusters produced in a TraPPE simulation, and a charge distribution taken from the work of Kollman and coworkers. The result is the calculation of eight CN stretch spectra corresponding to the pairing of four acetonitrile models with two methanol models.  The model set encompasses the most commonly used potentials for rigid body simulation of methanol and acetonitrile, and includes some rational modifications to the acetonitrile model. Preliminary results show that minor changes in the force field can dramatically impact the resulting infrared absorption spectrum. This implies that experiments can be used in conjunction with the OQM/MM methodology to design and/or test the accuracy of classical models in describing complex condensed-phase environments.

3. Future Directions

With a robust and flexible methodology for computing nitrile vibrational frequencies now in hand thanks to the generous support of the American Chemical Society Petroleum Research Fund, I will turn my future attention to hydrogen bond dynamics at biomolecular interfaces. In particular, I will investigate the dynamics of major- and minor-groove water at the DNA interface through computational studies of the novel infrared probes, N-nitrile-deoxyuridine (CNdU) and N-nitrile-deoxyguanosine (CNdG). The CN bond in CNdU and CNdG can probe the dynamics of confined water within the grooves of DNA. Nitrile vibrational probes are significantly more local and less perturbative than other probes used to investigate biomolecular hydration dynamics. Control simulations will determine the degree to which the CNdU and CNdG probes disrupt the structure of the DNA strand and the dynamics of nearby water. These studies of CNdU and CNdG in DNA will establish the differences between water dynamics in the major- and minor-grooves of DNA with high spatial resolution. I will also generate important predictions and insight that will guide the development of future ultrafast vibrational experiments to probe the dynamics of water at biological interfaces.