{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:15:58Z","timestamp":1783566958693,"version":"3.55.0"},"reference-count":71,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T00:00:00Z","timestamp":1517961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerul Educa\u021biei \u0219i Cercet\u0103rii \u0218tiin\u021bifice","award":["PCCE 140\/2008 and 488\/2012, Sectorial Operational Program for Human Resources Development 2007-2013, co-financed by the European Social Fund: POSDRU\/159\/1.5\/S\/132400"],"award-info":[{"award-number":["PCCE 140\/2008 and 488\/2012, Sectorial Operational Program for Human Resources Development 2007-2013, co-financed by the European Social Fund: POSDRU\/159\/1.5\/S\/132400"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The autocatalytic reaction between nitrite and the oxy form of globins involves free radicals. For myoglobin (Mb), an initial binding of nitrite to the iron-coordinated oxygen molecule was proposed; the resulting ferrous-peroxynitrate species was not detected, but its decay product, the high-valent ferryl form, was demonstrated in stopped-flow experiments. Reported here are the stopped flow spectra recorded upon mixing oxy Hb (native, as well as chemically-derivatized in the form of several candidates of blood substitutes) with a supraphysiological concentration of nitrite. The data may be fitted to a simple kinetic model involving a transient met-aqua form, in contrast to the ferryl detected in the case of Mb in a similar reaction sequence. These data are in line with a previous observation of a transient accumulation of ferryl Hb under auto-catalytic conditions at much lower concentrations of nitrite (Grubina, R. et al. J. Biol. Chem. 2007, 282, 12916). The simple model for fitting the stopped-flow data leaves a small part of the absorbance changes unaccounted for, unless a fourth species is invoked displaying features similar to the oxy and tentatively assigned as ferrous-peroxynitrate. Density functional theory (DFT) calculations support this latter assignment. The reaction allows for differentiating between the reactivities of various chemically modified hemoglobins, including candidates for blood substitutes. Polymerization of hemoglobin slows the nitrite-induced oxidation, in sharp contrast to oxidative-stress type reactions which are generally accelerated, not inhibited. Sheep hemoglobin is found to be distinctly more resistant to reaction with nitrite compared to bovine Hb, at large nitrite concentrations (stopped-flow experiments directly observing the oxy + nitrite reaction) as well as under auto-catalytic conditions. Copolymerization of Hb with bovine serum albumin (BSA) using glutaraldehyde leads to a distinct increase of the lag time compared to native Hb as well as to any other form of derivatization examined in the present study. The Hb-BSA copolymer also displays a slower initial reaction with nitrite under stopped-flow conditions, compared to native Hb.<\/jats:p>","DOI":"10.3390\/molecules23020350","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T12:20:29Z","timestamp":1518006029000},"page":"350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The Reaction of Oxy Hemoglobin with Nitrite: Mechanism, Antioxidant-Modulated Effect, and Implications for Blood Substitute Evaluation"],"prefix":"10.3390","volume":"23","author":[{"given":"Denisa","family":"Hathazi","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babe\u015f-Bolyai University, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florina","family":"Scurtu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babe\u015f-Bolyai University, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bischin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babe\u015f-Bolyai University, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustin","family":"Mot","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babe\u015f-Bolyai University, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Attia","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babe\u015f-Bolyai University, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania"},{"name":"Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Kongsted","sequence":"additional","affiliation":[{"name":"Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3038-7747","authenticated-orcid":false,"given":"Radu","family":"Silaghi-Dumitrescu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babe\u015f-Bolyai University, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1042\/BJ20061421","article-title":"Ferryl haem protonation gates peroxidatic reactivity in globins","volume":"403","author":"Reeder","year":"2007","journal-title":"Biochem. 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