Mechanochemical reactions of ¯uorides with hemin Armando Paneque a,b , Edilso Reguera a,c,* , Jose  Ferna Ândez-Bertra Ân a,b , H. Yee-Madeira d a Center of Applied Science and Advanced Technology, Legaria 694, Colonia Irrigacio Ân, C.P. 11500, Me Âxico, D.F., Mexico b Center of Pharmaeutical Chemistry, Havana, Cuba c Institute of Materials and Reagents, University of Havana, Havana 10400, Cuba d School of Physics and Mathematics, Col. Lindavista, IPN, Me Âxico, D.F., Mexico Received 09 February 2001; accepted 16 March 2001 Abstract Hemin has two potential sites to react with ¯uorides, the peripheral acid groups and the central Fe III cation. The mechanochemical reactions of hemin with ¯uorides LiF, NaF, KF, CsF, NH 4 F and AgF) were monitored using X-ray diffraction XRD), and IR and Mo Èssbauer spectroscopies. LiF and NaF were found inert when milled with hemin, however KF, CsF, NH 4 F and AgF react at both hemin sites. At the iron site Cl  is replaced by F  with formation of KCl, CsCl, NH 4 Cl, and AgCl, as detected by XRD, while with the peripheral acid groups, ¯uorides collect the acidic protons to form KHF 2 , CsHF 2 , NH 4 HF and AgHF 2 . The reactions of hemin with the reactive ¯uorides take place ®rst at the iron site and then at the propionic acid groups. # 2002 Elsevier Science B.V. All rights reserved. Keywords: Mechanochemical reactions; Hemin with ¯uorides; Hemoglobin 1. Introduction Hemoglobin, the oxygen carrier of blood, is composed of a large protein moiety, globin, linked to a Fe III -porphyrin IX center, the heme, by the coordination of Fe to a histidine residue. The hemin molecule, depicted in Fig. 1a, has been used as a simple model to understand hemoglobin chemistry and as a starting reagent in the synthesis of pharmaceutical products for the treatment of anemia [1,2]. It has the Fe III atom coordinated to the porphyrin IX ring. According to the crystallographic studies [3] the Fe III atom is slightly out the plane formed by the porphyrin ring Fig. 1b). The ®fth ligand in axial position is loosely coordinated to a Cl  anion, while the sixth axial position is vacant for coordination to oxygen and other nucleophylic ligands. Hemin has two potential sites to participate in reactions with basic substances, the two peripheral acid groups and the central Fe III cation. These reactions are important in the study of hemoglobin biochemistry as well as in the synthesis of complexes with pharmaceutical properties in the treat- ment of anemia [4,5]. The two propionic acid residues can interact by hydrogen bonding with other OH groups and Fe atoms in neighbor molecules leading to dimeric and poly- meric structures [6]. The modi®cation of these interactions is paramount in the synthesis of pharmaceuticals capable to be transported by the blood and assimilated by the cells [7]. The studies of bonding properties of iron at the sixth axial position with a wide variety of ligands have been related with its role as oxygen carrier in biological systems [8]. The absolute majority of reactions with hemin have been carried out in solutions with only a minimum in the solid state [8]. However, the reactions in solid state can shed light on some particularities of hemin complexes of biological importance [8]. In this communication we report reactions of hemin with ¯uorides by milling together the solid reagents. As refer- ence, the reactions were also carried out in methanolic solutions. The reactions products were characterized by IR, XRD and Mo Èssbauer techniques. 2. Experimental Li, NaF, KF, CsF, NH 4 F, AgF and hemin were commercial reagents of analytical grade from Sigma) and methanol absolute from Merck). For IR measurement KBr of spectro- scopic grade also from Sigma) was used. As reference compounds, LiFHF 2 , NaHF 2 and KHF 2 were prepared from HCl and the corresponding ¯uorides and then puri®ed from methanolic solutions. Their nature and purity were estab- lished using IR spectroscopy and XRD. Journal of Fluorine Chemistry 113 2002) 1±5 * Corresponding author. E-mail address: edilso@esfm.ipn.mx E. Reguera). 0022-1139/02/$ ± see front matter # 2002 Elsevier Science B.V. All rights reserved. PII:S0022-113901)00398-0