The primary objective of this research was to evaluate various factors that affect the reaction rate of oxidative coupling (OXC) reaction of phenolic estrogens catalyzed by horseradish peroxidase (HRP). Kinetic parameters were obtained for the conversion of phenol as well as natural and synthetic estrogens. estrone (E-1), 17 beta-estradiol (E-2), estriol (E-3), and 17 alpha-ethinylestradiol (EE2). Molecular orbital theory and Autodock software were employed to analyze chemical properties and substrate binding characteristics. Reactions were first order with respect to phenolic concentration and reaction rate constants (k(r)) were determined for phenol, E-3, E-1, E-2 and EE2 (in increasing order). Oxidative coupling was controlled by enzyme-substrate interactions, not collision frequency. Docking simulations show that higher binding energy and a shorter binding distance both promote more favorable kinetics. This research is the first to show that the OXC of phenolics is an entropy-driven and enthalpy-retarded process. Published by Elsevier Inc.