Previous research on catechol chemistry has primarily examined its oxidation to o-quinones under harsh, non-physiological conditions, often requiring strong oxidants, metal catalysts, or extreme environmental factors such as high pH, elevated temperatures, or catechol concentrations exceeding 200 mM ; Yang . In contrast, physiological oxidation of catechols is typically mediated by polyphenol oxidases such as tyrosinase and catechol oxidase . This study reveals, however, that catechols undergo rapid, spontaneous reactions under physiologically-relevant conditions, even at micromolar concentrations, forming spectrally active products within minutes without enzymatic catalysis or cellular biotransformation. Our investigation began by demonstrating catechol browning in DMEM, a widely used cell culture medium cited in over 31,000 papers as of 2016 . Individual amino acids and proteins were then shown to play complex roles, likely facilitating catechol deprotonation and/or reacting with obenzoquinone intermediates . The amino acid concentration in human blood plasma is approximately 6.3 mM, with Pro and Lys among the most abundant , while intracellular levels in tissues such as muscle may reach as high as 35 mM . In comparison, DMEM used in this study contains 10.6 mM amino acids . Proteins are present at 60-80 mg/mL in plasma and up to 200 mg/mL intracellularly -though these exceed the optimal peak we identified for protein-enhanced catechol browning. Additionally, browning was shown to be pH-dependent, with higher rates at alkaline pH. Human physiological environments such as intracellular spaces, interstitial fluid, and arterial blood have pH ranges that can typically span from as low as 7.03 to as high as 7.60, even under normal healthy conditions , and DMEM equilibrates to pH 7.7 under 5% CO2 .