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Quantum Chemical Study of Molecular Similarity and Dissimilarity : Development of DFT Based Similarity Indices and Study of Enantiomers

Monday, 26 June, 2006 - 17:00
Campus: Brussels Humanities, Sciences & Engineering campus
Faculty: Science and Bio-engineering Sciences
Greet Boon
phd defence

Quantum Molecular Similarity (QMS), for which the first measures were introduced
by Carbó in the early 1980's, has been shown to be an important concept when
comparing properties and reactivity of different, albeit mostly related, molecules.
As an application of Conceptual DFT, a similarity index constructed via a DFT based
local reactivity descriptor, namely the local softness, is proposed and used in this
doctoral thesis to probe the "similarity of reactivity" of a series of peptide isosteres
after which the use of the autocorrelation function for condensed indices is
investigated, turning out to be a valuable technique to circumvent the orientationtranslation
dependence of similarity indices.

When establishing a link between the Fundamental(s) of DFT and QMS the role of
the shape function turns out to be predominant and an extension of Mezey's
Holographic Electron Density Theorem for ρ(r) to the shape function σ(r) is
presented. On this basis similarity in shape is the fundamental issue to be looked at,
both globally and locally. As an application, global and local similarity measures were
evaluated using the Hirshfeld partitioning technique for the enantiomers of CHFClBr
and the amino acids Alanine and Leucine, giving numerical evidence for Mezey’s
Holographic Electron Density Theorem.

Furthermore, QMS is evaluated for enantiomers in the case of molecules showing
conformational flexibility, proposing the use of a Boltzmann weighted similarity
index. The conformers of the enantiomers of the amino acids Alanine, Asparagine,
Cysteine, Leucine, Serine and Valine were examined. Finally, QMS is evaluated for
enantiomers in the case of molecules possessing a chiral axis, as an extension of our
previous studies on molecules possessing one single asymmetric carbon atom. As a
case study, the enantiomers of substituted allenes are examined.

Next to studying global indices, local similarity is evaluated using our earlier
proposed local similarity index based on the Hirshfeld partitioning, in order to further
investigate Mezey’s Holographic Electron Density Theorem in chiral systems and to
quantify dissimilarity of enantiomers. Furthermore, the relation between the optical
activity and the dissimilarity is studied for these chiral systems.