We found that absolute hardness-absolute electronegativity (eta-chi) activity diagrams play an important role as a new coordinate of bioactivity in structure-activity relationships. In this paper, the eta-chi activity diagram, focusing on the molecular mechanism of bioactive compounds is used to discuss two major problems. First, the potency of bioactivities for xenobiotics such as polychlorinated dibenzo-p-dioxins (PCDDs) 3 and polychlorinated biphenyls (PCBs) 4, were found to be strongly related to their absolute hardness (eta). Second, the antibacterial activity of new quinolones such as norfloxacin 1 and enoxacin 2, was found to be strongly related to their absolute electronegativity (chi). These findings predict at least two chemical properties for a hardness-controlled or electronegativity-controlled enzyme.