A detailed listing of research interests and accomplishments, cross-referenced with abstracts from relevant publications, is available on the Research portion of my Group Web Page. A much abbreviated list of current interests follows here:

Mono- and Polynuclear Metalloenzyme Models and Small-molecule Analogs. The active sites of a number of metalloenzymes contain one or more metal atoms and are noteworthy for their use of molecular oxygen as a source of oxidizing power. Tyrosinase, for example, has an active side containing two copper atoms and carries out the oxidation of phenols (in the biological form of tyrosine) to catechols. Besides the economic interest in the actual reactions of tyrosinase, the enzyme is of fundamental interest to the extent that it sheds light on related systems, including the photosynthetic active site (which activates molecular oxygen in a similar way, albeit with manganese metal atoms) and organometallic catalysts for C-H bond activation. Moreover, to the extent that the active site breaks (or in reverse makes) the O-O bond in molecular oxygen, there is a fascinating potential for water splitting catalysts to be developed from suitably supported architectures. Calculations on such systems are extraordinarily demanding because the electronic states of the dinuclear systems are best described as weakly antiferromagnetically coupled low-spin systems, and this poses significant challenges to single-determinantal models like Hartree-Fock theory or Kohn-Sham density functional theory (although it may prove possible to systematically develop the latter to be more useful in this context, and we are examining this point actively). Through careful comparisons of completely renormalized coupled-cluster theory, as well as multiconfigurational approaches, we are learning more about how ligands and other factors influence the structure and reactivity of these inorganic cores. Other systems of interest include galactose oxidase, catecholase, peptidylglycine α-hydroxylating monooxygenase, and the better characterization of small-molecule analogs that may prove useful as catalysts for carrying out reactions identical to those accomplished by their enzymatic congeners. For full-scale enzymatic studies, QM/MM modeling efforts are likely to be required, and another motivation for studying smaller model systems is to validate levels of electronic structure theory for use in this context. In addition to copper-based catalysts, we are also actively working on iron-based oxygen activation in heme- and non-heme-based species (e.g., horseradish peroxidase) and on ruthenium based water-splitting catalysts, the improved development of which may significantly advance fuel cell technology.

Calculations of Accurate Electronic Structures and State Energies in Open-Shell Systems. There are a large number of interesting organic and inorganic reactive intermediates whose reactivities are dominated by 2-electron-in-2-orbital considerations. For example, carbenes, nitrenium ions (implicated as carcinogenic products from aromatic amine catabolism), nitrenes, phosphinidenes, silylenes, and non-Kekulé systems. We have been particularly active in validating theoretical models appropriate for the study of these systems, and in subsequently applying those models to gain further insights into their reactivities and potential design opportunities. Stable high-spin states offer possibilities for the construction of organic ferromagnets while reactive states, whether high- or low-spin, can be exploited for targeted reactivity. Some of our ongoing efforts include characterization of the uni- and bimolecular pathways by which nitrenium ions react, to include their covalent modification of nucleic acid bases (requiring a quantum mechanical/molecular mechanical (QM/MM) modeling approach when the nucleic acid bases are assembled in a full DNA structure). We are also studying how substitution and diradical positioning affects the structure and reactivity of arynes (didehydro-aromatic biradicals). Much of our work is collaborative with various experimental groups, e.g., Falvey at Maryland, Kenttämaa at Purdue, and Phillips at Hong Kong. This work is technically demanding in the sense that many of the electronic states in which we are interested are multideterminantal, and models that are rigorously well defined for such cases (e.g., CASPT2, MRCI) are not very practical for any but the smallest of systems. Density functional models can be useful, but tend to be somewhat capricious, particularly with respect to their sensitivity to the inclusion of Hartree-Fock exchange in the functional. We are actively examining how to improve DFT or still simpler levels of theory, like neglect-of-diatomic-differential-overlap and tight-binding semiempirical theories, to permit their specific application to problems like hydrogen-atom abstraction from DNA sugar backbones by aryne biradicals.

Solvation and Other Condensed Phase Phenomena. The development of theoretical chemistry methods that are as robust for condensed phases as those already available for the gas phase continues to be at the theoretical frontier. An alternative to approaches involving the explicit inclusion of hundreds to thousands of surrounding atoms/molecules is to treat the embedding medium as a dielectric continuum with additional terms to account for non-electrostatic interactions between explicit and implicit regions. We have pioneered methods for accomplishing this using classical and quantal theories. We have moreover developed the methodology to handle equilibrium and non-equilibrium solvation regimes, the latter being particularly relevant for spectroscopy and reaction dynamics. Concomitant with continuing methods development, particularly with extensions to mixed quantal/classical treatments and to non-homogeneous condensed phase environments, we are also investigating phenomena of fundamental biological, chemical, and environmental interest, e.g. conformational issues in sugars, solvent effects on uni- and bimolecular chemical reactions, partitioning of organic molecules between unlike media, and fate constants of environmental contaminants in aqueous media.

Experimental/Theoretical Synergy. Through many collaborations with experimental colleagues, we have contributed to the better understanding of a variety of issues associated with organic and inorganic structure and reactivity. The areas where we continue to have key interests include elucidating the mechanistic and stereochemical course of electrocyclic organic reactions, characterizing processes by which various classes of contaminants are degraded in the environment, and the nature of inter- and intramolecular interactions governing crystal morphology, molecular recognition, etc.

The Electronic Structure of Singlet and Triplet Nitrenium Ions From MCSCF and DFT Calculations

Predicting Regioselectivity in the Reduction of Polynitroaromatics in Aqueous Solution

Substituent Effects on the Structure and Reactivity of Aromatic Nitrenes

On the GAMESSPLUS homepage you can obtain modules that, when added to the free electronic strucure program GAMESS, allow for the inclusion of solvation effects at the ab initio and density functional SCRF levels. The HONDOPLUS homepage provides details on analogous free, stand-alone code having the same functionality.

More information on similar modules available for the Gaussian series of programs can be found on the MN-GSM homepage.

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.

For a complete comparison of available codes and solvation modules, see http://comp.chem.umn.edu/solvation/comparison.htm.