Christopher J. Cramer, Fellow

Computational Chemistry

These researchers are involved in a wide variety of modeling studies. Focus areas include:

• Molecular modeling of transfer ribonucleic acid (tRNA)
• Predicting the dynamical properties of RNA and deoxyribonucleic acid (DNA) tetraloops
• Including solvation effects in quantum chemical calculations
• Calculation of accurate multiple splittings in open-shell systems
• Understanding the structure and reactivity of phosphorus-containing molecules
• Characterization of organometallic systems with respect to structure and reactivity

In the first of these they addressed the atomic mutagenesis of tRNA tetraloop analogs. These can be used to better understand the properties of charging RNA with appropriate amino acid. Mutagenesis of a tRNAAla tetraloop analog structure (solved by nuclear magnetic resonance [NMR], Varani) to C1:G70 does not charge the RNA with alanine. The dynamic behavior of the wild type and the mutant in simulations were compared to better understand their different biological activity. These simulations included the full environment (water, counterions, etc.), taking advantage of recently developed simulation technology (parallel simulation code, Particle Mesh Ewald accounting for long-range electrostatics, etc.).

The group developed a number of new studies in this research period. Among them was a method of quantum chemical characterization of cycloaddition reactions between 1,3-butadiene and oxyallyl cations of varying electrophilicity. Hydroxyallyl cation and lithium and sodium oxyallyl cations were predicted to react with 1,3-butadiene both in a stepwise fashion and via concerted [4 + 3] cycloaddition with so-called extended stereochemistry. With hydroxyallyl cation, the stepwise process is preferred and subsequent second bond closures generate products equivalent to those that would arise from concerted [4 + 3] or [3 + 2] cycloadditions. For lithium and sodium oxyallyl cations, concerted, asynchronous processes were predicted to be preferred over stepwise processes, with [3 + 2] cycloaddition to generate a 3H-dihydrofuran followed by Claisen rearrangement of that intermediate being the lowest energy pathway for formation of a seven-membered ring. In the case of uncharged 2-oxyallyl, only transition state structures for concerted cycloadditions appeared to exist. The researchers inferred that for [4 + 3] cycloadditions, concerted pathways are preferred over stepwise pathways provided that the separation between the electrophilicity of the allyl component and the electrofugacity of the 4p component is not too large. The Hammond postulate was shown to rationalize variations in free energies of activation for different processes as a function of allyl electrophilicity. The researchers also studied the factors influencing the stereochemical outcome of different cycloadditions.

A further area of study by these researchers concerned perspective sugar anomerism. This work presented the first conformational analysis of the anomeric effect within the context of molecular orbital theory, discussed the utility of Fourier decomposition of a torsional co-ordinate as a method for analyzing disparate electronic influences on that coordinate, and helped settle debate on the nature of anomeric stabilization.

In another study, the researchers demonstrated the feasibility of computational electrochemistry, specifically the calculation of the aqueous one-electron oxidation potentials of substituted anilines. Here, the emphasis was on semiempirical molecular orbital theory and density functional theory as used to compute one-electron oxidation potentials for aniline and a set of 21 mono- and di-substituted anilines in aqueous solution. Linear relationships between theoretical predictions and experiment were constructed, providing mean unsigned errors as low as 0.02 V over a training set of 13 anilines; the error rises to 0.09 V over a test set of eight additional anilines. A good correlation was also found between oxidation potential and a simple computed property, namely the energy of the highest occupied molecular orbital for neutral anilines in aqueous solution. For the particular case of the substituted anilines, a strong correlation between oxidation potential and pKa was found, in conjunction with a still stronger correlation between oxidation potential and physical organic descriptors for aromatic substituents, albeit over a reduced data set.

Another project involved the prediction of soil sorption coefficients using a universal solvation model. Using a database of 440 molecules, the researchers developed a set of effective solvent descriptors that characterize the organic carbon component of soil and thereby allow quantum mechanical SM5 universal solvation models to be applied to partitioning of solutes between soil and air. Combining this set of effective solvent descriptors with solute atomic surface tension parameters already developed for water/air and organic solvent/air partitioning allows one to predict the partitioning of any solutes composed of H, C, N, O, F, P, S, Cl, Br, and I between soil and water. The researchers also presented linear correlations of soil/water partitioning with 1-octanol/water partition coefficients using the same database. The quantum mechanical calculations have the advantages that they require no experimental input and should be robust for a wide range of solute functionality. The quantitative effective solvent descriptors can be used for a better understanding (than with previously available models) of the sources of different partitioning phenomena in cases where the results exhibit significant fragment interactions. From this work, the researchers anticipated that the model would be useful for understanding the partitioning of organic chemicals in the environment between water and soil or, more generally, between water and soil or sediments (geosorbents). A measure of partitioning between soil organic matter and water, normalized to organic carbon content, was taken for analysis. The availability of measured values of KOC for a large number of organic compounds has prompted many efforts to develop predictive models for this quantity. Such models are useful in providing estimates that may avoid the need for experimental measurements or assist in optimizing the methodology employed for those measurements as well as for environmental modeling. Linear correlations between KOC and other measured solute properties (and nonlinear correlations between KOC and PO/W or other solute properties) were also developed.

Research Group and Collaborators

Chrissy Brown, Undergraduate Student Researcher
Robert Hanson, Chemistry Department, St. Olaf College,
Northfield, Minnesota
William Johnson, Research Associate
Christopher Kinsinger, Graduate Student Researcher
Bethany Kormos, Graduate Student Researcher
Junseok Lee, Graduate Student Researcher
Jiabo Li, Molecular Simulations Inc., San Diego, California
Bing Luo, Graduate Student Researcher
Maria C. Nagan, Graduate Student Researcher
Youngshang Pak, Department of Chemistry, Pusan
National University, College of Natural Sciences,
Kumjeong-ku, Pusan, Korea
Eric Patterson, Division of Science, Truman State
University, Kirksville, Maryland
Mark Seierstad, Researcher Associate
Edward C. Sherer, Graduate Student Researcher
Michael B. Sullivan, Research School of Chemistry,
Australian National University
Jason Thompson, Graduate Student Researcher
Donald G. Truhlar, Faculty Collaborator
Paul Winget, Graduate Student Researcher