To summarize, a wide range of substituents can result in significant destructive interference effects in the transmission of Si and Ge cores. These are substituents based on carbon, such as alkyl and phenyl substituents, and we show that this substituent effect is systematic by correlating the transmission with different Hammett constants. However, we find that fluorination appears to be the only substituent that is likely to result in significant conductance-suppression in the carbonbased bicyclo[2.2.2]octane we have studied here. s-interference thus appears to be much more sensitive to chemical changes than the more well-established p-interference effect. Until recently, we may have thought that saturated molecules are some of the simplest and best understood systems in molecular electronics. Recent results by us and other groups suggest there is much more potential, 5, 66 which may be applied for novel chemical designs. This letter is a step in this direction, and future work must continue to build on the electron transport structure-property relationship of saturated carbon molecules and their heavier group 14 analogues.