Molecular computations for reactions and phase transitions: applications to protein stabilization, hydrates and catalysis

In this work we have made significant contributions in three different areas of interest: therapeutic protein stabilization, thermodynamics of natural gas clathrate-hydrates, and zeolite catalysis. In all three fields, using our various computational techniques, we have been able to elucidate phenomena that are difficult or impossible to explain experimentally. More specifically, in mixed solvent systems for proteins we developed a statistical-mechanical method to model the thermodynamic effects of additives in molecular-level detail. It was the first method demonstrated to have truly predictive (no adjustable parameters) capability for real protein systems. We also describe a novel mechanism that slows protein association reactions, called the “gap effect.” We developed a comprehensive picture of methioine oxidation by hydrogen peroxide that allows for accurate prediction of protein oxidation and provides a rationale for developing strategies to control oxidation. The method of solvent accessible area (SAA) was shown not to correlate well with oxidation rates. A new property, averaged two-shell water coordination number (2SWCN) was identified and shown to correlate well with oxidation rates. Reference parameters for the van der Waals Platteeuw model of clathrate-hydrates were found for structure I and structure II. These reference parameters are independent of the potential form (unlike the commonly used parameters) and have been validated by calculating phase behavior and structural transitions for mixed hydrate systems. These calculations are validated with experimental data for both structures and for systems that undergo transitions from one structure to another. This is the first method of calculating hydrate thermodynamics to demonstrate predictive capability for phase equilibria, structural changes, and occupancy in pure and mixed hydrate systems. We have computed a new mechanism for the methanol coupling reaction to form ethanol and water in the zeolite chabazite. The mechanism at 400°C proceeds via stable intermediates of water, methane, and protonated formaldehyde.

Kinetics and dynamics measured using IntraCavity Laser Absorption Spectroscopy

IntraCavity Laser Absorption Spectroscopy (ICLAS) is a high-resolution, high sensitivity spectroscopic method capable of measuring line positions, linewidths, lineshapes, and absolute line intensities with a sensitivity that far exceeds that of a traditional multiple pass absorption cell or Fourier Transform spectrometer. From the fundamental knowledge obtained through these measurements, information about the underlying spectroscopy, dynamics, and kinetics of the species interrogated can be derived. The construction of an ICLA Spectrometer will be detailed, and the measurements utilizing ICLAS will be discussed, as well as the theory of operation and modifications of the experimental apparatus. Results include: i) Line intensities and collision-broadening coefficients of the A band of oxygen and previously unobserved, high J, rotational transitions of the A band, hot-band transitions, and transitions of isotopically substituted species. ii) High-resolution (0.013 cm-1) spectra of the second overtone of the OH stretch of trans-nitrous acid recorded between 10,230 and 10,350 cm-1. The spectra were analyzed to yield a complete set of rotational parameters and an absolute band intensity, and two groups of anharmonic perturbations were observed and analyzed. These findings are discussed in the context of the contribution of overtone-mediated processes to OH radical production in the lower atmosphere.