Group for Quantum Organic Chemistry
The Group for Quantum Organic Chemistry (GQOC) is concerned with the application of state-of-the-art theoretical approaches to important problems in organic chemistry and biochemistry. Particular focus is devoted to understanding of the structure and function of proteins and the properties and design of functional molecules such as (super) acids and bases.
Relevant expertise: All staff members have extensive experience with the application of quantum chemical techniques to chemical and biochemical questions. More specifically, this refers to the use ofmethodologies such asab initio molecular orbital theory, density functional theory, and continuum approaches to the inclusion of solvent effects. These approaches can be considered to form the broad foundation of the group’s expertise.
Beyond this common knowledge base, there exists a host of more specialized skills within the group. This knowledge includes high-competency in classical molecular dynamics simulations, which is applicable to the explicit representation of various solvents as well as the structure and dynamical properties of large molecular systems, such as peptides, proteins and nucleic acids. The group is also well-versed in the application of hybrid quantum-mechanical/classical-mechanical (QM/MM) techniques, which are essential for investigating chemical events in macromolecular systems, such as enzyme catalysis. We have recently begun investigations using first-principles molecular dynamics, such as the Car-Parinello approach. The group also has expertise in programming and system administration.
Competitive Areas: The broad skill base present in GQOC, combined with an inherent flexibility, means that the group is capable of solving a large range of problems, even in the absence of direct, specific experience in a given application. Despite this diversity and adaptability, the group has two main areas where it is acknowledged as being competitive on the international scene.
The first such field is that of radical enzymes. These are enzymes that involve some form of free-radical intermediate in their operative mechanism. Because of the short-lived reactive nature of these experimentally elusive intermediates, this rapidly expanding field has a strong need for high-quality computational studies in order to understand the mechanistic complexities. The fact that GQOC has extensive experience in this field [e.g. 1, 4, 5], as well as established ties to the leading experimental groups, means that this is an area where GQOC has a significant competitive edge.
The other field where GQOC is particularly competitive is that of the computational design of organic superacids and superbases. The synthesis of compounds with the potential to be either superacids or superbases is an expensive endeavour. Prior establishment of their acidities (and/or basicities) by computational investigation is therefore an attractive way to significantly reduce the number of experimental targets. In analogy to the strength in radical enzymes mentioned above, the GQOC’s proven track record in the area of superbases and superacids and its excellent connections to the relevant experimental groups [e.g. 2, 3] is what makes the group highly competent in this field.
Significant past achievements: The Group was established in the mid nineties by Professor Zvonimir Maksić, who passed away unexpectedly in March of 2011. Since 2002, the members of GQOC have co-authored 91 papers indexed in CC, with a cumulative impact factor of 349. Early achievements were related to the understanding of cyclic (anti)aromatic hydrocarbons and, in particular, the nature of the Mills-Nixon effect and bond-stretch isomers. Progress was also made in terms of describing the correlation energy of molecules and its additivity. In the late nineties, the group began with the computational design of superbases and subsequently extended its activities to encompass superacids and the acidity of bio-molecules such as amino acids. This period bore witness to a significant number of publications, including 14 inJ. Phys. Chem. A (IF=2.899), 10 inNew. J. Chem. (IF=3.006), 10 inEur. J. Org. Chem. (IF=3.096), 2 inChem. Eur. J. (IF=5.382), and 2 inJ. Am. Chem. Soc. (IF=8.805).
The beginning of the group’s achievements in the field of enzyme mechanisms can be traced back to Dr. Smith’s PhD, when he began working on reactions dependent on coenzyme B12. Subsequent activities in this and related areas have resulted in a number of high-impact publications, including 2 inJ. Comput. Chem. (IF=3.769), 1 inJ. Chem. Theory Comput. (IF=4.804), 2 inChem. Eur. J. (IF=5.382), 17 inJ. Am. Chem. Soc. (IF=8.805),1 in Angew. Chem.(IF=11.829) and recently resulted in an invited contribution inAcc. Chem. Res.(IF=18.203) and a chapter on theoretical studies of radical enzymes in a 4 volume Handbook of Radical Chemistry and Biology, which will be published by Wiley in the near future.
Infrastructure/equipment:GQOC is equipped with numerous stand-alone workstations, one 20-processor computing cluster acquired from the Alexander von Humboldt Foundation and one 50-processor cluster purchased through an FP6 project. In addition to the local resources, the members of GQOC make extensive use of the Croatian National Grid Infrastructure.
Top 5 publications over the last 10 years:
1. Smith, D. M.; Buckel, W.; Zipse, H. Enhanced Acidity of Enoxy Radicals: Theoretical Validation of a 50 Year Old Mechanistic Proposal. Angew. Chem. Int. Ed. Eng. 42, (2003), 1867-1870. (IF=11.829).
2. Raab, V.; Gauchenova, E.; Merkoulov, A.; Harms, K.; Sundermeyer, J.; Kovačević, B.; Maksić, Z. 1, 8-Bis(hexamethyl-triamino-phosphazenyl) naphthalene, HMPN: A Superbasic Bisphosphazene "Proton Sponge". J. Am. Chem. Soc. 127, (2005), 15738-15743. (IF=8.805).
3. Coles, M. P.; Aragon-Saez, P. J.; Oakley, S. H.; Hitchcock, P. B.; Davidson, M. G.; Maksić, Z.; Vianello, R.; Leito, I.; Kaljurand, I.; Apperley, D. C.. Superbasicity of a Bis-guanidino Compound with a Flexible Linker: A Theoretical and Experimental Study. J. Am. Chem. Soc., 131, (2009), 16858-16868. (IF=8.805).
4. Sandala, G. M.; Kovačević, B.; Barić, D.; Smith, D. M.; Radom, L. On the Reaction of Glycerol Dehydratase with But-3-ene-1,2-diol. Chem. Eur. J. 15, (2009), 4865-4873. (IF= 5.382).
5. Sandala, G. M.; Smith, D. M.; Radom, L. Modeling the Reactions Catalyzed by Coenzyme B12 Dependent Enzymes. Acc. Chem. Res. 43, (2010), 642-651. (IF= 18.203).
A combined computational chemistry and mass spectrometry approach for improved detection of endogenous metabolites in living organisms
The project is aimed at the development of novel tools for structural elucidation of bioactive metabolites in biological samples, in order to improve understanding of experimental results from mass spectrometry measurements of biological metabolites by tools of computational chemistry. Specifically, the study has two main objectives:
- Structural characterization of vitamin D metabolites and structural epimers in chronic liver disease.
- Determination of new variants of toxic microcystin secondary metabolites from cyanobacteria.
Expected results of this project are a new techniques developed for structural elucidation and confirmation of unknown, bioactive molecules.more »