Molecular overlay as a tool to model biospecificity: A case study with mosquito repellents

AGRO 67

Ramanathan Natarajan, rnataraj@nrri.umn.edu1, Subhash C. Basak, sbasak@nrri.umn.edu1, Wieslaw Nowak2, and Przemyslaw Miszta, miszta@phys.uni.torun.pl3. (1) Center for Water and the Environment, Natural Resources Research Institute, University of Minnesota, 5013 Miller Trunk Highway, Duluth, MN 55811, (2) Institute of Physics, Molecular Biophysics Group, N.Copernicus University, Grudziadzka 5, 87100 Torun, Poland, (3) Institute of Physics, N. Copernicus University, Grudziadzka 5, 87-100 Torun, Poland
Enantiomers and diastereomers are important classes of stereoisomers. Enantiomers are isomers that are related such that the object and its mirror image are not superimposable. Diastereomers are stereoisomers that differ in 3-dimensional arrangement and do not have the mirror-image relation. Diastereomerism arises out of differences in configuration or conformation. Enantiomers have identical physical and chemical properties, while diastereomers differ in physiochemical properties. Molecular descriptors derived from adjacency and distance matrices of molecular graphs fail in differentiating enantiomers because they have identical scalar properties. The same is true in the case of diastereomers arising out of polychiral diastereomerism. In such cases, we have to come up with new strategies to differentiate the three dimensional disposition of atoms around chiral centers. Molecular overlay of optimized geometries of diastereomers was found to be one of the possible alternatives because it is a holistic approach where the entire structures are compared rather than parts or descriptors calculated by reductionistic approaches. In order to find the level of theory necessary to get reasonable predictions, we used the quantum chemical methods in a graduated manner from semiempirical AM1, to Hartree Fock (STO3G, 3-21G, 6-31G, and 6-311G) to Density Functional Theory (B3LYP/6-31G, B3LYP/6-311G). We were able to correctly order the repellency of diastereomeric insect repellents using the hierarchical molecular overlay approach.
 

New Developments and Issues in Agrochemical Sciences
8:00 AM-11:00 AM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Division of Agrochemicals

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007