Because of the extensive use of methyl tert‐butyl ether (MTBE) as an additive to increase the
octane quality of gasoline, the environmental pollution by this compound has increased in recent
decades. Environmental release of MTBE may lead to its entry to the blood stream through inhalation or drinking of contaminated water, and its interactions with biological molecules such as proteins. The present study was proposed to comparatively investigate the interactions of MTBE with
hemoglobin (Hb) from diabetic and nondiabetic individuals using various spectroscopic methods
including UV‐visible, fluorescence, chemiluminescence, and circular dichroism. These results demonstrated the effects of MTBE on heme degradation of Hb and the reaction of these degradation
products with water generating reactive oxygen species. Interaction of Hb with MTBE enhanced
its aggregation rate and decreased lag time, indicating the antichaperone activity of MTBE upon
interaction with Hb. Furthermore, the diabetic Hb showed more severe effects of MTBE, including
heme degradation, reactive oxygen species production, unfolding, and antichaperone behavior
than the nondiabetic Hb. The results from molecular docking suggested that the special interaction
site of MTBE in the vicinity of Hb heme group is responsible for heme degradation.