COORDINATION CHEMISTRY OF HYDROXYUREA ON CYANOFER

ANDREA C. MONTENEGRO,† SARA E. BARI,† JOSÉ A. OLABE,† MARÍA M. GUTIÉRREZ§ AND VALENTÍN T. AMOREBIETA§

Sudafrica

Conferencia; 37th International Conference of Coordination Chemistry; 2006

COORDINATION CHEMISTRY OF HYDROXYUREA ON CYANOFERRATES   Andrea C. Montenegro,† Sara E. Bari,† José A. Olabe,† María M. Gutiérrez§ and Valentín T. Amorebieta§   †Departamento de Química Inorgánica, Analítica y Química Física, INQUIMAE, FCEyN, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, C1428EHA, Argentina and §Departamento de Química, FCE, Universidad Nacional de Mar del Plata, Mar del Plata, B7602AYL, Argentina. e-mail: olabe@qi.fcen.uba.ar   Hydroxyurea (HU) is currently used in the treatment of sickle cell, neoplasic and HIV diseases. Side effects of HU are known to be related to the formation of reactive nitrogen and oxygen species (RNOS). The in vivo reaction mechanisms are unknown, but hemeproteins and non heme ferric compounds probably act as catalysers of drug activation and as potential targets. 1 By taking advantage of the labile site and redox versatility of the iron center, we explored the coordination of HU on the aquapentacyanoferrate(II) and (III) ions. HU forms a red compound (lmax = 468 nm; e = 3000 M-1 cm-1) with [FeIII(CN)5H2O]2- or with [FeII(CN)5H2O]3- in aerated medium. Isolation of a solid from methanol/ diethylether solutions allowed its tentative characterization as a C-nitroso derivative, Na3[FeII(CN)5H2NCONO].2H2O (I), supported by chemical analysis and FTIR spectroscopy. Uncontrolled reaction conditions lead to the formation of sodium nitroprusside, Na2[Fe(CN)5NO].2H2O (NP), probably as a final product of oxidation. EPR measurements in solution showed a stable triplet signal, assignable to [Fe(CN)5NO·]3- as a probable intermediate in the formation of NP. The chemical reactivity of (I) towards soluble FeIII- and MnIII-porphyrins is also currently being explored. The MnIII compounds, efficient traps for the nitroxyl species  (HNO/NO-), showed a quantitative, hypsochromic shift of the Soret band, suggesting the formation of a Mn(RNOS) derivative. The hemins only showed mild reactivity. These preliminary results channel our work to gain a mechanistic insight into how transition metal ions are able to bind HU and promote its oxidative reactivity, in the context of the presence of potential biochemical targets.   1 S. Bruce King, Curr. Topics Med. Chem. 5, 665 (2005).