Nitrite　reduction　to　nitric　oxide　by　heme　proteins　was　reported　as　a　protective　mechanism　to　hypoxic　injury　in　mammalian　physiology.　In　this　study,　the　pathways　of　nitrite　reduction　to　nitric　oxide　mediated　by　iron(II)　porphyrin　(P)　complexes,　which　were　generally　recognized　as　models　for　heme　proteins,　were　investigated　by　using　density　functional　theory　(DFT).　In　view　of　two　type　isomers　of　combination　of　nitrite　and　Fe(II)(P),　N-nitro-　and　O-nitrito-Fe(II)-porphyrin　complexes,　and　two　binding　sites　of　proton　to　the　different　O　atoms　of　nitrite　moiety,　four　main　pathways　for　the　conversion　of　nitrite　into　nitric　oxide　mediated　by　iron(II)　porphyrins　were　proposed.　The　results　indicate　that　the　pathway　of　N-bound　Fe(II)(P)(NO2)　isomer　into　Fe(III)(P)(NO)　and　water　is　similar　to　that　of　O-bound　isomer　into　nitric　oxide　and　Fe(III)(P)(OH)　in　both　thermodynamical　and　dynamical　aspects.　Based　on　the　initial　computational　studies　of　five-coordinate　nitrite　complexes,　the　conversion　of　nitrite　into　NO　mediated　by　Fe(II)(P)(L)　complexes　with　14　kinds　of　proximal　ligands　was　also　investigated.　Generally,　the　same　conclusion　that　the　pathways　of　N-bound　isomers　are　similar　to　those　of　O-bound　isomer　was　obtained　for　iron(II)　porphyrin　with　ligands.　Different　effects　of　ligands　on　the　reduction　reactions　were　also　found.　It　is　notable　that　the　negative　proximal　ligands　can　improve　reactive　abilities　of　N-nitro-iron(II)　porphyrins　in　the　conversion　of　nitrite　into　nitric　oxide　compared　to　neutral　ligands.　The　findings　will　be　helpful　to　expand　our　understanding　of　the　mechanism　of　nitrite　reduction　to　nitric　oxide　by　iron(II)　porphyrins.　(C)　2015　Elsevier　Inc.　All　rights　reserved.