Transition metal oxides are an important class of materials that are valued for their catalytic, ferroelectric, superconducting, and optical properties, and hence they find uses in diverse applications such as heterogeneous catalysts, sensors, solar cells, and high temperature superconductors.  Such rich properties of metal oxide are partly enabled by their complex surface chemistry and the presence of lattice vacancies that significantly perturb the electronic structure of the material.  Hence, an in-depth understanding of the origin and nature of these defect states is important for further expanding the scope of oxide-based systems for various applications. The focus of this presentation is on elucidating the nature of interaction of various chemicals with defects in metal oxide.  The chemical-structure-property correlations developed in this work can enable rational engineering of a new type of nanoscale, low temperature catalysts having tailored functionality and selectivity that can significantly reduce the energy cost and carbon footprint of many important chemical reactions.