Anatase TiO 2 , a widely used semiconductor metal oxide support, was tested for biomimetic carbonic anhydrase activity catalyzing the reversible hydration of CO 2 to bicarbonate ions. Owing to superior photocatalytic response of nanoclusters of TiO 2 and its apparent role in catalyzing CO 2 hydration, (TiO 2) 15 nanocluster was tested for the reaction using density functional theory calculations. Free energy landscape of the reaction was developed following the biological mechanism consisting of H 2 O adsorption, deprotonation, CO 2 complexation, CO 2 bending, intramolecular proton transfer, and bicarbonate ion displacement. The identity of the intermediates of the mechanistic cycle was further confirmed by computational nuclear magnetic resonance and infrared spectroscopic studies. A close correspondence of the computational and reported experimental spectroscopic analyses confirmed the identity of the intermediates and the presence of biomimesis over the TiO 2 cluster. K E Y W O R D S biomimetic catalyst, carbonic anhydrase enzyme, CO 2 hydration, density functional theory, (TiO 2) 15 cluster