Single-molecule electronics is a sub-field of nanoelectronics in which individual devices are formed from single molecules placed between source and drain electrodes. During the past few years, scientists have demonstrated that the flow of electricity through these devices is controlled by quantum interference (QI) between electrons passing from source to drain. Their future development, however, is hampered by difficulties in controlling interference effects. Herein, we demonstrate that electron transport in tetracationic cyclophane circuits is mediated by QI between channels formed from two lowest unoccupied molecular orbitals (LUMOs), while their highest occupied molecular orbitals (HOMOs) play no significant role. Energy differences between these two LUMO channels induce constructive interference, leading to high conductance. By contrast, phase differences between these LUMO channels result in destructive interference and a suppression in overall conductance. Such a design of single-molecule circuits enables the construction of single-molecule conductors and insulators based on a single cyclophane platform.