Polarizability in Substituted Oxazoles : A PC-Model Data Analysis

A systematic investigation of various Oxazole derivatives has been subjected to a Polarized Continuums Model (PCM) for evaluation of their physicochemical parameters. The data thus obtained have been used to discuss the effect of substituents on polarizability of the oxazole aromatic ring and its possible dependence on the lipophilicity. In view of their biological activity a quantitative dependence of the physico-chemical parameters of the oxazole derivatives with the π – lipophilicity distributive parameter [8] with respect to substituents on the oxazole aromatic ring, have been attempted. These physico-chemical parameters showed a dependence with respect to their X1, X2 and X3 substituents as H, H, H < H, H, Ph < H, Ph, Ph < Ph, Ph, Ph The variations thus obtained have been discussed in light of substitutions and their effect on the polarizability of the oxazole ring.


Introduction
Molecule may visualized as the Mechanics originating out of Orientations and Location of Entities Connected Using Levi-able Electrons.The entities include atoms, groups and molecular fragments.The location of such entities is decided by the affinity of the sites and electro negativity of the incoming substituents.In addition to this respective responses of entities with respect to their neighbors give rise to steric adaptations or conformations called as orientations.These orientations develop a mechanics in the molecule, which is the sole cause for their detection using electromagnetic radiations.
Keeping this idea in mind a systematic investigation of various Oxazole derivatives 1,2 have been subjected to a Polarized Continuums Model (PCM) for evaluation of their physico-chemical parameters.The data thus obtained have been used to discuss the effect of substituents on polarizability of the oxazole aromatic ring and its possible dependence on the lipophilicity.Similar such reports are cited in literature [3][4][5] .

Experimental
Serena Software 6 Ver 5.13 based on evaluation of molecular mechanics energy (energy closely related to internal energy of molecule) and its breakup into molecular force fields viz., E MM = E bn + E an + E vdw + E tor + E ch + E misc The package provides a minimization of E MM over various possible conformations giving rise to the breakup of the force field where Ebn corresponds the bond energy, E an energy of angle, E vdw correspond to Vander Waals forces, Etor torsion, Ech charges and Emisc.Constitute the miscellaneous forces other than mentioned above.
The package is able to produce window compatible output with the help of Quantum Chemistry Program Exchange (QCPE) ver 5.04.The physico-chemical properties calculated by the package include; the dipole moments, Vander Waal forces, molar volume ( • A) and the Z-matrices (Cartesian coordinates) for the hypothetical molecule.Five of these molecules have been synthesized and characterized from our laboratories.The computational out puts thus obtained have been recorded with respect to the substituents in Table-1.X1, X2 and X3 are the positions for substitution on the oxazole aromatic ring whereas H, -CH 3 (Me), -C 2 H 5 (Et) and -C 6 H 5 (Ph) are the substituents.Several such compounds have been reported 7,8 as anti malarial agents.In view of their biological activity a quantitative dependence of the physico-chemical parameters of the oxazole derivatives with the π -lipophilicity distributive parameter 9 with respect to substituents on the oxazole aromatic ring, have been attempted.The z-matrix obtained after several iterations have been used to express the relative distances in bond lengths with added substituents.The values of the bond lengths are recorded in Table 3.

Results and Discussion
Table records the magnitudes of physico-chemical constants viz., dipole moments, van der Waal forces and the molar volumes.The partial charges (in esu) values for oxygen and nitrogen atoms have also been recorded in their adjacent columns.
A perusal of the values, in general, shows a marked dependence of the physicochemical parameters on their respective substitutions.Dipole moment value, which is indirectly, related to the molecular des-symmetry of charges show a marked increase with bulkier substituents.These physico-chemical parameters showed dependence with respect to their X 1 , X 2 and X 3 substituents as: H   To observe the role of these physico-chemical parameters on the biological activities, an attempt has been made to observe the variation in these physico-chemical parameters with respect to the lipophilicity coefficient π * * (as reveled by Hansch 9 ).The individual variations of these parameters with π -parameter though fail to show any significant dependence ( R, R2 and slope values) Table 2 section-A.Similarly a multi-component variation of these parameters with π -values have been attempted (both with and without molar volumes.The interdependence of these parameters (matrix) Table 3 show a poor relationship in all the values except the molar volumes.The two multi-component equations express that the dipole moment and the molar volumes are the significant parameters in affecting the lipophilicity values and thus in turn the biological activities.
The effect of the X 1 , X2 substituents as polarizability properties of the ring may also be observed from the changes in their respective bond-length values of the ring structure.Table 4 records the relative variation in the bond -length values as evaluated using the Cartesian coordinates for different molecules.

Table 1
Variation in the Physico-chemical properties for substituted Oxazoles as obtained using PC-Model software.

< Et, H, Ph < Et, Ph, Ph < Ph, Ph, Ph
2and slope values (Table2, Section B), however, the general trend for the variations are almost same.

Table - 2
Variation in the Lipophilicity Distributive parameters and The Dipole Moment values with Dependable parameters with their Slope Values, Intercepts, R and R

Table 3
Variation in the inter-dependence of the correlation parameters in the multiple four

Table 4
The bond length values for the X1, X2 and X3 Positions as obtained from the Z-matrix parameters developed by PC-Model * * π is the lipophilicity coefficient or distributive parameters used for the evaluation of hydro-phobicity values by Hansch