It is noted that the mercapto substituent (attractor effect) lowers the energies of HOMO and LUMO. Its influence on the energy of the LUMO is more important (Table-5). Study of structure and physico-chemical properties re- lationship for thiazoles derivatives: We have studied six physico-chemical proprieties of thiazole derivatives using HyperChem. We will continue this work in the future by a quantitative calculation. These properties are van der Waals- surface-bounded molecular volume, the log of the octanol- water partition coefficient (log p), polarizability, solvent- accessible surface bounded molecular volume and molecular mass (M). Calculation of log p is carried out using atomic parameters derived by Ghose and coworkers 20 . Computation of molar refractivity was made via the same method as log p. Ghose and Crippen presented atomic contri- butions to the refractivity 21 . Solvent-accessible surface bounded molecular volume and van der Waals-surface-bounded mole- cular volume calculations are based on a grid method derived by Bodor et al . 22 , using the atomic radii of Gavezzotti 23 . Polarizability was estimated from an additivity scheme given by Miller 24 with a 3 % in precision for the calculation, where different increments are associated with different atom types. Hydration energy is a key factor determining the stability of different molecular conformations 25 . The calculation is based on exposed surface area and employs the surface area as computed by the approximate method (above), weighted by atom type. Structural comparison of thiazole derivatives: Based on our conclusions on the effect of substitution on the thiazole molecule, we chose a series of thiazole derivatives (thiazolopyridines); some of them have a biological activity. This series of thiazole derivatives which, have been synthe- sized and characterized by Anthosen et al . 26 . Initially, we performed a structural comparison of this series (Fig. 3). Fig. 4 shows the favoured conformation in 3D of the compound 3 . These molecules have a weak conformational flexibility, with regard to the other macrocycles of macrolide type 27-33 . In a window of 2 kcal/mol (MM), only one favoured conformations is found, for each structure. Fig. 4. 3D Conformation of compound 3 (HyperChem 8.03) Structure and physico-chemical properties relation- ship: Polarizability values are generally proportional to surfaces and of volumes. The decreasing order of polarizability for these studied thiazoles is: 5, 7, 4, 6, 8, 3, 2 and 1 (Table-8). The order of polarizability is the same one for volumes, but it is a little different for surfaces. This is due primarily to the folding up of surfaces of some structures compared to the majority of the extended structures. This is also explained by the relation between polarizability and volume for the relatively non polar molecules.
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- dr. ahmed