Mechanical stimuli can modify the energy landscape of chemical reactions and enable new pathways, offering a complementary synthetic strategy to conventional chemistry13. The mechanochemical mechanisms have been extensively studied in one-dimensional (1D) polymers under tensile stress49 using ring-opening10 and reorganization11, polymer unzipping6,12 and disulfide reduction13,14 as model reactions. In these systems, the pulling force stretches chemical bonds, initiating the reaction. Recently, it has also been shown that forces orthogonal to the chemical bonds can alter the rate of bond dissociation15. However, these bond activation mechanisms have not been possible with isotropic, compressive stress (i.e., hydrostatic pressure). Here we show that mechanochemistry through isotropic compression is possible by molecularly engineering structures that can translate macroscopic isotropic stress into molecular-level anisotropic strain. We engineer molecules with mechanically heterogeneous components consisting of a compressible (soft) mechanophore, and incompressible (hard) ligands, and term these molecular anvils. Metal organic chalcogenides16 incorporate molecular elements with heterogeneous compressibility, such that isotropic stress leads to relative motions of the rigid ligands, anisotropically deforming the compressible mechanophore and activating bonds. Conversely, rigid ligands in steric contact impede relative motion, blocking reactivity. We combine experiments and computations to demonstrate hydrostatic-pressure-driven redox reactions in metal-organic chalcogeni Show Partial Abstract