Hemin esterification was achieved Towards a green synthesis of hemin derivatives, its esterification reaction was performed in a solvent mixture of only CH3OH and H2SO4, obviating the use of THF previously employed . Accordingly, both the reaction volume and the amounts of ethyl acetate and chloroform for the aqueous two-phase purification decreased by 60 % compared to that of the THF-containing reactions. Moreover, this reaction proceeded for less than 30 min, and the time required for the solvent evaporation was reduced by 50 % producing a high yield of hemin dimethyl ester. From the liquid chromatography (LC) analysis, the ratio between the unreacted hemin, monoester and diester of hemin was calculated to be 1:5:16.86 and the yield of hemin diester from the first reaction was 70 % (Supplementary figs. 1-3). However, the overall yield could be increased by repeating the reaction on the resulting hemin monoester and unreacted hemin. Hemin esterification was confirmed via 1 H-NMR relative to that of pure hemin (Supplementary fig. ). The FTIR (3) ionized hemin/tyramine conjugate (m/z 854.2) (Supplementary fig. ). A comparison between the UV-vis and FTIR spectra of activated hemin, H-Tyra, H-Tyros, tyramine and tyrosine is in Supplementary figs. 13-15,17.