INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Iron (III) porphyrinates in the formation of nitrosative species: theoretical results and experimental approach
Autor/es:
PERISSINOTTI, LAURA L.; LEVIN, NATALIA; ESTRIN, DARÍO A.; BARI, SARA E.
Lugar:
New Mexico, USA
Reunión:
Conferencia; Sixth International Conference on Porphyrins and Phthalocyanines (ICPP-6); 2010
Resumen:
<!-- /* Font Definitions */ @font-face {font-family:Wingdings; panose-1:5 0 0 0 0 0 0 0 0 0; mso-font-charset:2; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:0 268435456 0 0 -2147483648 0;} @font-face {font-family:Times; panose-1:2 2 6 3 5 4 5 2 3 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:536902279 -2147483648 8 0 511 0;} @font-face {font-family:HelveticaNeue-LightCondObl; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-format:other; mso-font-pitch:auto; mso-font-signature:3 0 0 0 1 0;} @font-face {font-family:HelveticaNeue-MediumCond; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-format:other; mso-font-pitch:auto; mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin-top:12.0pt; margin-right:0cm; margin-bottom:12.0pt; margin-left:0cm; text-align:justify; mso-pagination:widow-orphan; mso-hyphenate:none; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:Arial; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:FR; mso-fareast-language:AR-SA;} p.MsoHeader, li.MsoHeader, div.MsoHeader {mso-style-noshow:yes; margin-top:12.0pt; margin-right:0cm; margin-bottom:12.0pt; margin-left:0cm; text-align:justify; mso-pagination:widow-orphan; mso-hyphenate:none; tab-stops:center 207.65pt right 415.3pt; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:Arial; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:FR; mso-fareast-language:AR-SA;} span.WW8Num8z0 {mso-style-name:WW8Num8z0; mso-style-parent:""; font-family:Symbol; mso-ascii-font-family:Symbol; mso-hansi-font-family:Symbol;} p.Abstract, li.Abstract, div.Abstract {mso-style-name:Abstract; margin:0cm; margin-bottom:.0001pt; text-align:justify; mso-pagination:widow-orphan; mso-hyphenate:none; font-size:10.0pt; font-family:Times; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:FR; mso-fareast-language:AR-SA;} p.References, li.References, div.References {mso-style-name:References; mso-style-parent:Abstract; margin-top:0cm; margin-right:0cm; margin-bottom:0cm; margin-left:14.4pt; margin-bottom:.0001pt; text-align:justify; text-indent:-14.4pt; mso-pagination:widow-orphan; mso-hyphenate:none; tab-stops:28.8pt; font-size:10.0pt; font-family:Times; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:FR; mso-fareast-language:AR-SA;} p.Bib-RefTitle, li.Bib-RefTitle, div.Bib-RefTitle {mso-style-name:Bib-Ref_Title; margin-top:8.0pt; margin-right:0cm; margin-bottom:4.0pt; margin-left:0cm; mso-pagination:widow-orphan; page-break-after:avoid; mso-hyphenate:none; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:Times; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; text-transform:uppercase; mso-font-kerning:.5pt; mso-ansi-language:EN-US; mso-fareast-language:AR-SA; font-weight:bold; mso-bidi-font-weight:normal;} @page Section1 {size:595.25pt 841.85pt; margin:164.15pt 68.3pt 122.45pt 68.3pt; mso-header-margin:35.45pt; mso-footer-margin:57.0pt; mso-paper-source:0;} div.Section1 {page:Section1; mso-footnote-position:beneath-text;} --> The anhydride of nitrous acid, N2O3, is a highly unstable gas molecule that homolitically decomposes into nitric oxide and nitrogen dioxide (NO and NO2, respectively). This set of NOx products has been shown to play a key role in reactions of biochemical significance such as tyrosine nitration, or the formation of S-nitrosothiols and N-nitrosamines (nitrosative stress).[1][2] N2O3 can be produced by the reaction of NO and superoxide, or by the auto-oxidation of NO.[3] In anaerobic conditions, where the production of NO from the NO2- pool provides a compensative mechanism for hypoxia, the reaction of haemoglobin (PFeII) with NO2- also produces N2O3, through a stepwise, metal catalyzed reaction involving both NO2- and NO. [4] PFeII  +  NO2- + 2 H+  ó   PFeIII  + NO + H2O PFeIII  + NO2- + NO   ó   PFeII  + N2O3 We focused in the formation of the species N2O3 catalyzed by iron(III) porphyrinate model systems, from a theoretical and experimental perspective, to understand the interplay between nitrosative stress and heme systems. To explore this reaction we have performed density functional calculations with the SIESTA code. The starting model system was an iron(III) porphine coordinated to imidazole, with a N- or O- bound nitrite,[5]  as sixth ligand ((Im)FeIII(NO2-) ó (Im)FeII(NO2.)). Further reaction with NO points to an intermediate species which consists on a N- bound (Im)FeII(N2O3) complex, among other considered geometries; the formation of such species is thermodynamically favored by 12 kcal/mol. The dissociation of the nitrogenated ligand, yielding the iron(II) porphine and N2O3 takes 29 kcal/mol. We also performed IR frequency calculations for all optimized structures in the gas phase; the calculated IR spectra envisage an unequivocal assignment for future experimental results. The sequential additions of NO2- (10-3M) and NO(g) (10-3M) to buffered solutions (PO43-, pH=5.8, 25ºC) of TPPSFeIII or microperoxidase 11 (10-5M) were followed spectroscopically. The presence of only one axial site available for coordination in microperoxidase 11 precludes trans- coordination of both NO2- and NO, and hence the formation of FeII(N2O3) probably explains the spectroscopic changes (lmax=398, 525, 558, 620 à 414, 528, 561 nm). TPPSFeIII offers several coordination possibilities to explain the observed incomplete spectroscopic shift (lmax=393 à 417nm): TPPSFeII(NO2)(NO), TPPSFeII(N2O3), TPPSFeIII(NO2-). Excess quantities of NO(g) lead to TPPSFeII(NO) as final product. For both model systems, the specific, efficient trapping with 2,3-diaminonaphtalene of the decomposition products of N2O3 was followed by fluorescence spectroscopy.[3] In order to complete the coordinated N2O3 characterization, hybrid QM-MM calculations and further experimental work are presently carried out. References 1.    J Heinecke, PC Ford, Coord. Chem. Rev. 2010, 254, 235-247. 2.    MT Gladwin, R Grubina, MP Doyle, Acc. Chem. Res. 2009, 42, 157-167. 3.   A Daiber, S Schilknecht, J Müller, J Kamuf, Mm Bachschmid, V Ullrich, Free. Rad. Biol. Med. 2009, 47, 458-467. 4.    SBasu, R Grubina, J  Huang, J Conradie, Z  Huang, A Jeffers, A  Jiang, X  He, I Azarov, R Seibert, A Mehta, R Patel, SB King, N Hogg, A Ghosh, MT Gladwin, DB Kim-Shapiro, Nat. Chem. Biol. 2007, 3, 785-794. 5.   J Yi, MK Safo, GB Richter-Addo, Biochemistry 2008, 47, 8247-9.
rds']