The peroxidative reactions of hemoglobin (Hb) and myoglobin (Mb) with hydrogen peroxide (H2O2) produce porphyrin /r-cation radical ferryl compound I (Fe'v=O Por*+) and ferryl compound II (Felv=O Por), which are very reactive and detrimental to red cells. At the same time, hydrogen sulfide (H2S) entering the blood stream, by environmental exposure or bacterial infections, can interact with these species leading to the formation of sulfhemoglobin (sulfHb) and sulfmyoglobin (sulfMb) with the subsequent disruption of Hb and Mb function. These inactive proteins, whose specific heme intermediates and reaction mechanism are still unknown, are characterized by a protoheme IX chlorin derivative with an absorption band at the 620 nm region, bearing the saturated 4-vinyl group with a H2S covalently bound across the¿-¿ double bond of the pyrrole "C". Our latest data show that under the same experimental conditions, of H202 and H2S, the hemoglobins I, II and III, (Hbl and Hbll/Hblll, respectively), from Lucina pectinata do not form these sulfheme derivatives. Hbl delivers H2S, while Hbll and Hblll transport 02 to symbiotic bacteria, despite the diversity in function and chemical structure no sulfheme-proteins derivatives have been detected in the L pectinata clam. This discrimination is not understood and will be used as a model to comprehend the mechanism toward sulfHb and sulfMb since the formation sulfHbl and sulfHbll/sulfHblll should proceed via the same high valent heme intermediates generated by the reaction with H2O2and H2S according to: H2S [Hbl (Fem) or Hbl (Fe"-O2) ] + H2O2~-* (Fe'v=O Por¿+) + (Felv=O Por) > SulfHbl (A) Compound I Compound II O2 Other notable difference between Hbl and Mb is that the ferryl compound I is near one thousand times more stable in the former than in the latter. Thus, our hypothesis suggests that the mechanism of sulfhemeprotein formation may depends on (1) the amino acid environment surrounding the heme center, (2) the life time of the ferryl species (compound I and II), and (3) the orientation and structure of the peripheral heme substituents. To explore these alternatives, we will monitor the bands at 648 nm, 620 nm, and 419 nm characteristic of Hbl compound I, sulfHbl, and compound II, respectively, by UV-Vis and stopped flow, upon the reaction (A) of hemeproteins (Mb, Hbl, Hbl mutants, and Hbll/Hblll). The intermediate and final structures will be pursued by resonance Raman, NMR and X-ray spectroscopy. The data will allow commenting on (i) the role of compound I and II in the formation of human sulfHb and sulfMb, (ii) unravel the selectivity of H2S for the pyrrole "C" reaction , and (iii) contribute to the development of direct strategies for the treatment and reversibility of sulfHb or sulfMb to the biological active human Hb and Mb.