Classical physical organic molecular descriptors, such as logP, Hammett, Taft, or Charton parameters are often used for elucidating reaction mechanisms, yet, cannot always account for the intricate molecular interactions invoked in modern synthetic chemistry. Comprehensive experimental inquiry, complemented by data-intensive physical organic analysis, can bridge this gap and enable the study and optimization of increasingly complex systems. The overarching goal of our research program is to understand structural effects at the origin of chemical reactivity, selectivity, and functionality. To this end, novel parameter systems and data analysis strategies will be applied and developed, allowing the prediction of chemical outcomes and the study of reaction mechanisms. These techniques will be employed in the context of functional organic materials as well as organo-, organometallic, and biomimetic catalytic systems. Of particular interest are chemical processes driven not by rigid covalent or dative bonds, but by weaker, non-covalent interactions. The ubiquity and diversity of such interactions provide seemingly endless approaches to rational catalyst or functional material design, yet controlling them remains an exciting challenge.