While biological catecholic transformations have been extensively studied, and novel controlled chemical reactions continue to emerge, the possibility of spontaneous enzyme-and cell-free reactions in physiologically-relevant conditions remains underexplored. Specifically, the pharmacokinetics and chemical transformations of catecholic compounds during extended residence or transit in physiological environments -such as cell culture media, biocompatible buffers, or within cell-free lumens -are still poorly understood. Addressing these gaps is essential for optimizing the therapeutic applications of catecholic compounds, including assessing their bioavailability, regulating their disposition and target delivery, and predicting potential off-target effects.