1.    Application of Quantum Chemical Methods to Problems of Biochemical Relevance. We have a long standing interest in applying state-of-the-art computational modeling (DFT and ab initio methods) to elucidate the catalytic mechanisms in salient organic, organometallic and enzymatic systems. Two recent representative examples are:
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  • Computational Antioxidant Design. Oxidative damage to DNA and proteins is a primary cause of many chronic inflammatory diseases. In recent work,[1] we design highly-potent, bioinspired antioxidants targeted against HOCl-mediated oxidative damage. This research provides the knowledge base needed to explore possible treatments and drug development to obviate HOCl-mediated oxidative stress and its consequences in numerous chronic diseases.
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  • Modeling Biochemical Reactions. In a recent collaborative effort between theory and experiment we have elucidated the catalytic mechanism of the Peroxiredoxin enzyme (Prx3).[2] This research significantly extends the current understanding of structure-function relationships in the active site of Peroxiredoxins.
2.    Application of Quantum Chemical Methods to Graphene catalysis.
3.    Development of Ab Initio Composite Thermochemical Methods. Together with Jan M. L. Martin (Weizmann Institute of Science), we develop ab initio composite methods employing successively higher cluster expansion terms in conjunction with basis set extrapolation techniques and explicitly correlated methods (most notably, W1-F1[2,3] W3.2lite[4] and W4[5] theories). W1-F12 theory, which exploits the fast basis set convergence of explicitly-correlated methods, represents a major step forward as it is capable of unprecedented accuracy in thermochemical predictions for systems as large as corannulene and for systems of biological relevance (e.g., amino-acid residues and DNA bases).
References:

(1) Karton, A.; O’Reilly, R. J.;Pattison, D. I.; Davies, M. J.; Radom, L. J. Am. Chem. Soc. 2012, 134, 19240.

(2) Nagy, P.; Karton, A.; Betz, A.; Peskin, A. V.; Pace, P.; O’Reilly, R. J.; Hampton, M. B.; Radom, L.; Winterbourn, C. C. J. Biol. Chem. 2011, 286, 18048.

(3) Karton, A.; Martin, J. M. L. J. Chem. Phys. 2012, 136, 124114.

(4) Karton, A.; Kaminker, I.; Martin, J. M. L. J. Phys. Chem. A 2009, 113, 7610.

(5) Karton, A.; Rabinovich, E.; Martin, J. M. L.; Ruscic, B. J. Chem. Phys. 2006, 125, 144108.

(6) Karton, A.; O’Reilly, R. J.; Chan, B.; Radom, L. J. Chem. Theory Comput. 2012, 8, 3128.