AmericanChemicalSociety.com

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. Provided 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 briefly enumerate some broader impacts that have resulted from this project.

2. Summary of Results

Computing 2D IR spectra of acetonitrile in methanol requires an accurate and computationally efficient methodology to calculate the CN stretch vibrational frequency of acetonitrile in a complex solvent environment millions of times during the course of an MD simulation. My strategy has been to develop an optimized quantum mechanics/molecular mechanics (OQM/MM) method specifically for the purpose of calculating CN stretch vibrational frequencies in the condensed-phase. The OQM/MM procedure begins with a MD simulation of dilute acetonitrile in methanol from which several hundred acetonitrile/methanol clusters are extracted. Each cluster contains a single acetonitrile molecule and approximately two methanol solvation shells. These clusters form a training set for the OQM/MM method. For each cluster, the anharmonic CN stretch vibrational frequency of acetonitrile was computed with density functional theory (DFT), an accurate quantum mechanical method that is tractable for the acetonitrile/methanol clusters, but too computationally expensive to apply to the entire acetonitrile/methanol liquid simulation. Next, the CN stretch vibrational frequencies of the clusters were calculated with QM/MM, where the acetonitrile molecule was treated quantum mechanically with a semiempirical quantum chemical method called PM3, and the methanol was treated classically with a molecular mechanics force field. While this calculation was efficient, it was not sufficiently accurate. Therefore, the 18 independent parameters for nitrogen present in PM3 were optimized via a genetic algorithm to reproduce as closely as possible the DFT benchmark results for the CN stretch frequency of the acetonitrile/methanol clusters. After optimization, PM3 could be used as the efficient QM method to compute accurate QM/MM vibrational frequencies for acetonitrile in methanol.

Using the OQM/MM methodology, we have calculated the room temperature infrared absorption spectrum for the CN stretch of dilute acetonitrile in methanol with encouraging results. The spectrum exhibits a peak and a shoulder, just as in the experiment. The shoulder has been interpreted in the literature as a population of acetonitrile molecules that are engaged in hydrogen-bonds with methanol. The calculated spectrum slightly underestimates the intensity of the shoulder relative to the main absorption. We are currently extending our theoretical methodology to incorporate non-Condon effects, whereby the efficiency of infrared absorption depends on the local solvent environment in the vicinity of the CN vibrational probe. I anticipate that this correction will result in a spectrum that more closely matches the experiment. Two studies are then planned. First, we will investigate the temperature dependence of the infrared absorption spectrum. Experimentally, the shoulder in the spectrum is observed to sharpen and intensify at lower temperature as hydrogen-bonding between acetonitrile and methanol is increasingly favored thermodynamically. It will be an important validation of our computational methods if the temperature dependence of the spectrum is captured. Finally, we will calculate the 2D IR spectrum of dilute acetonitrile in methanol as a function of temperature, and we will attempt to relate the growth in off-diagonal intensity to hydrogen-bond dynamics.

3. Broader Impacts

The support of the American Chemical Society Petroleum Research Fund (ACS-PRF) for this project has resulted in a number of broader impacts. ACS-PRF funds have helped to support the training of one postdoctoral research associate (Dr. Kristina Furse), two graduate students (Ryan Haws and Laura Kinnaman), and one undergraduate (Lauren Schilling) student in theoretical and computational chemistry. With the support of the ACS-PRF the PI and Dr. Furse were afforded the opportunity to attend the American Chemical Society national meeting in Philadelphia (August 17-21, 2008) to disseminate results from this project and to further their professional development. Preliminary results from this project were essential in a successful grant application by the PI to the National Science Foundation: "CAREER: Computational Studies of Water Dynamics at DNA Interfaces." This project has generated new scientific initiatives within my research program that have resulted in several recent publications and new scientific collaborations. For example, in collaboration with the Brewer and Fenlon laboratories at Franklin and Marshall College I am currently utilizing the same theoretical methods developed in this project to investigate hydration dynamics of nitrile-labeled DNA probed with infrared spectroscopy. I am also using similar methodology as that developed with the support of the ACS-PRF to study peptide conformational structure and dynamics, as well as the protonation state of titratable amino acids with carbon-deuterium vibrational probes.