A chemical mechanism to explain the observed anisotropy in the shock wave initiation of pentaerythritol tetranitrate (PETN) single crystals is proposed on the basis of semiempirical quantum chemical calculations. Building on the previously proposed model of steric hindrance to shear, the molecular mechanics of shear deformation at the lattice level is correlated with rotational conformations of PETN. The numerous stable conformations of PETN differ in symmetry and dipole moment values. The initial conformation belongs to the S-4 molecular point group and possesses no dipole moment. Because of shear deformations, the molecules change conformations. The [110] shocks result in sterically hindered shear and generate polar conformations. In contrast, the [100] shooks result in little or no polarization. Because the decomposition chemistry of PETN at 5-10 GPa is likely dominated by ionic reactions, local polarity of the lattice plays a crucial role in reactivity. The polar lattice stabilizes the transition state due to dipole-dipole interactions and, thus, facilitates the ionic dissociation. In contrast, the nonpolar lattice results in no stabilization and low reaction rates. Plausible ionic reactions are briefly discussed and experiments are suggested to verify the mechanism proposed.