This study investigates the spontaneous transformations of catechols under physiologically relevant conditions, focusing on their pH-and temperature-dependence, and interactions with biological amines (primarily amino acids and proteins). We demonstrate here that catechol undergoes rapid, spontaneous reactions in cell culture media and simple buffers at neutral or mildly-alkaline pH, forming spectrally-active products. These reactions, enhanced by amino acids and proteins, suggest that catecholic compounds may undergo transformations prior to cellular uptake, potentially influencing their bioactivity and therapeutic efficacy. Understanding these spontaneous transformations not only informs in vitro experimental design but also provides valuable insights into the structural-functional activities of catecholic compounds in biological systems.