Organic Chemistry, Physical Chemistry, Chemical Physics
Department of Chemistry and Supercomputer Institute, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455-0431
(Ph: 612-624-0859; Fax: 612-626-2006) email: cramer@maroon.tc.umn.edu
I began my career as a synthetic organic chemist and enjoyed the challenges offered by that particular art. However, I found myself increasingly interested in the fundamental questions of structure and reactivity underpinning the synthetic process. In order to address such issues, I had occasion to turn to the then rapidly expanding field of theoretical organic chemistry. My personal research interests naturally evolved in that direction, and as a result my group is now devoted to the development and application of computational chemistry for the purpose of investigating phenomena of organic, organometallic, bio-organic and environmental interest.
Solvation Effects. Moving computational chemistry from the gas-phase to solution is at the theoretical frontier. An alternative to approaches involving the explicit inclusion of hundreds of solvent molecules is to treat the solvent as a dielectric continuum with corrections for specific solvation effects. We have pioneered methods for accomplishing this using semiempirical molecular orbital theory. The two major advantages of this approach are (i) its great speed and (ii) its quantum mechanical treatment of the solute. Concomitant with continuing methods development (better theoretical models, implementation at ab initio levels of theory, extension to multiple solvents, etc.), we are also investigating processes of fundamental chemical and biological interest, e.g., conformational issues in sugars, aqueous acceleration of electrocyclic reactions, prediction of environmental fate constants, and bonding/stacking interactions as they affect DNA base-pairing.
One area that we perceive as particularly ripe for study is the use of calculated molecular properties, especially those derived from calculations which include solvent effects, in regression analyses. The goal of such analyses is to determine what microscopic factors are responsible for the observed range of properties, reactivities, toxicities, etc., within a series of compounds. In essence, this is then a computational analog of the quantized structure-activity relationship (QSAR) formalism that has long been used in biological and medicinal chemistry. The virtue of the computational approach is that it can be used very efficiently and economically, especially when applied in conjunction with the execution and design of additional experiments.
Open-Shell Organic Molecules. We are also currently fascinated by nitrenium ions; these species are implicated as carcinogenic products derived from aromatic amine catabolism. Being divalent, nitrenium ions may exist in either singlet or triplet spin states. Early theoretical work suggested arylnitrenium ions to be uniformly ground state singlets; however, our recent higher level calculations have indicated that in certain circumstances the triplet spin state may be preferred. This is quite important since the mechanisms for reaction of the singlet and triplet are distinct. Modeling the interaction of the reactive species with DNA provides a significant challenge.
In the materials venue, high-spin molecules may serve as useful building blocks for organic and organometallic bulk materials which exhibit ferromagnetic or conducting properties. From a theoretical standpoint, accurate analysis of orbital energies and spin multiplicities in the monomers is a first step towards understanding the important band structure and spin communication in the macroscopic materials. In this regard, non-Kekulé molecules have long fascinated theorists and experimentalists alike. We have found density functional theory (DFT) to be a very useful tool for the calculation of multiplet splittings in small- and medium-sized organic molecules. Ultimately, we plan to use this methodology to attack larger and more polar systems. DFT should be particularly appropriate for larger molecules and moreover we are incorporating a continuum dielectric model into DFT in order to account for macroscopic surroundings. Our preliminary results suggest that this should be of considerable importance for polarized and/or polarizable cases.
Phosphorus and Silicon Compounds--Structure, Spectroscopy and Reactivity. Additionally, we have been active in the investigation of factors influencing the stability of hypervalent phosphorus species. Describing such effects is of fundamental interest in elucidating the structural details of organophosphorus compounds; practical applications include modeling the biodegradation of pesticides and warfare agents. In this same subject area, the common use of chiral phosphorus stabilizing groups in organic synthesis provides rich opportunity for molecular engineering of these systems. By analysis of hyperconjugative and other effects on competing transition states, diastereomeric excesses may be predicted and analyzed. Our most recent efforts include moving into aqueous solution and examining the mechanistic details involved in the hydrolysis of biologically important phosphate esters.
The Electronic Structure of Singlet and Triplet Nitrenium
Ions From MCSCF and DFT Calculations
Predicting Regioselectivity in the Reduction of Polynitroaromatics in
Aqueous Solution
In addition to full-fledged posters, the Army High Performance Computing Research Center maintains précis of some of our ongoing projects for their Environmental Chemistry focus area. Presently available is Quantum Chemical Conformational Analysis of 1,3-Dimethylthiourea.
OMNISOL is a free (but licensed) program for the rapid (non-quantum-mechanical)
estimation of solvation free energies in water or organic solvents.
For more information see the
OMNISOL
Homepage.
We are grateful to the following for financial support:
Computational Chemistry (Chemistry 8003) is in the process of taking greater advantage of the Web. Comments are welcome.
Spring of 1997 (Chemistry 3301) also had a web page, and comments are welcome.
As of January 1, 1997, yours truly is past-chair of the Computers in Chemistry Division of the American Chemical Society
Associate Editor, Theoretical Chemistry Accounts
Associate Editor, Journal of Physical Organic Chemistry
My A.B. in Chemistry and Mathematics is from Washington University, my Ph.D. in Chemistry is from the University of Illinois, and my proactive attitude is from several years spent rolling along with those caissons.