We have engineered and analyzed oligo(phenylene-ethynylene) (OPE) derivatives to understand and to control the bistable conductance switching exhibited by these molecules when inserted into saturated alkanethiolate and amidecontaining alkanethiolate self-assembled monolayers (SAMs) on Au{111}. By engineering the structures of the OPE derivatives, we have shown conductance switching to depend on hybridization changes at the molecule–substrate interface. In addition, we have demonstrated bias-dependent switching controlled by interactions between the dipole of the OPEs and the electric field applied between the scanning tunneling microscope tip and the substrate. These interactions are stabilized via intermolecular hydrogen bonding between the OPEs and host amide-containing SAMs.