CONFORMATIONAL ANALYSIS AND FORMATION ENTHALPY OF (3R,5S,6R)-6-ACETYLAMIDOPENICILLANIC ACID CALCULATED BY THE PM3, PM6 AND PM7 SEMIEMPIRICAL MO METHODS

摘要

Thirty conformers of the (3R,5S,6R)-6- acetylamidopenicillanic acid were obtained by PM3 Conformational Search performed with HyperChem7.52 software. By energy minimization with the PM3, PM6 and PM7 semiempirical MO methods included in the M0PAC12 software, thirty, eight, and nine conformers respectively were obtained. The difference ΔΔ_fH~0 between the lowest and the highest standard formation enthalpy of conformers is 7.6934 kcal·mol~(-1), 3.6541 kcalmol~(-1) and 4.8064 kcal·mol~(-1) for PM3, PM6, and PM7 semiempirical MO methods, respectively. For all the conformers cubic interpolation relations of functional dependence of formation enthalpy on temperature (Δ_fH(T) = a_0 + a_1T + a_2T~2 + a_3T~3, T∈[100K,1000K]) were established: for PM3 Δ_fH(T) = -153.681(+2.132) + 0.0079(+0.0004)T + 1.1622(±0.006)T~2·10~(-4) - 3.437(+0.027) T~3·10~(-8); for PM6 Δ_fH(T) = -179.965(+1.233) + 0.008(±0.001)T + 1.174(±0.007)T~2·10~(-4) - 3.399 (±0.033) T~3·10~(-8) and PM7 respectively Δ_fH(T) = -165.517(11.589) + 0.009(±0.001)T + 1.150(±0.008)T~2·10~(-4) - 3.273(+0.037) T~3·10~(-8). The a_1, a_2 and a_3 values are neither dependent on the method of calculation, or on the conformer geometry. The a_0 free term is the only one which depends on the conformer geometry. It increases with the decreasing of the thermodynamic stability of conformers. These interpolation relations allow the calculation of molar fraction of each conformer in the mixture at a certain temperature in the interpolation range of Ts[100K,1000K].