A Mutagen Acts as a Potent Reducing Agent of Glycated Hemoglobin: a Combined Ultrafast Electron Transfer and Computational Studies

Glycated hemoglobin (GHb) found in mammals undergoes irreversible damage when exposed to external redox agents, which is much more vulnerable than its normal counterpart hemoglobin (Hb). Besides the oxygen regulation throughout the body, Hb plays a vital role in balancing immunological health and the redox cycle. Photoinduced ultra-fast electron transfer phenomena actively participate in regulation of various kind of homeostasis involved in such biomacromolecules. In the present study we have shown that a well-known mutagen Ethidium Bromide (EtBr) reduces GHb in femtosecond time scale (efficiently) upon photoexcitation after efficient recognition in the biomolecule. We have performed similar experiment by colocalizing EtBr and Iron (Fe(III)) on the micellar surface as Hb mimic in order to study the excited state EtBr dynamics to rationalize the time scale obtained from EtBr in GHb and Hb. While other experimental techniques including Dynamic Light Scattering (DLS), Zeta potential, absorbance and emission spectroscopy have been employed for the confirmation of structural perturbation of GHb compared to Hb, a detailed computational studies involving molecular docking and density functional theory (DFT) have been employed for the explanation of the experimental observations. Reduction of Glycated Hemoglobin (GHb): Ethidium bromide (EtBr) in its excited state behaves as a potential reducing agent for hemoglobin (Hb). EtBr transfers its excited state electron to the iron (Fe(III)) residing inside the heme-group of Hb and reduces it to its lower ionic state. Due to structural modification and electrostatic interaction between GHb and EtBr, this ultrafast reduction increases. image