A principal technique of the project involves preparation of amorphous, microporous layers of M(Por) complexes (M = Fe(II), Mn(II) or other M(II); Por = meso-tetraarylporphyrinato dianion) by sublimation onto a substrate cooled by liquid nitrogen or helium closed cycle refrigeration system. The facile reactions of these layers with volatile reactants can be studied in detail using vibrational (FTIR, RRS) and optical spectroscopy. The power of this method draws from the ability to investigate such processes under carefully controlled and tunable conditions, especially temperature. Furthermore, the solvent-free medium gives relatively sharp bands in the FTIR spectra that, combined with isotopic labeling experiments, provide structural information to identify otherwise elusive intermediates and insight into key mechanistic steps. Examining the FTIR, RRS and optical spectra of complexes thus prepared allows one to identify the species initially formed and to characterize subsequent transformations upon changing temperature or adding reactants. For heme modeling iron-porphyrins, the dependence of vibrational frequencies on the iron oxidation and spin states is well-documented in both IR and RRS spectra [1]. Spectral studies will be carried out in the low-temperature solutions in specially designed device for evaluation of energetic parameters of complexation. For characterization of the products of catalytic transformations gas chromatography - mass-spectrometry and NMR methods will be widely used.

Typically, M(Por) containing proteins have one metal coordination site (the proximal side of the M(Por) plane) occupied by an electron donor ligand (N-, S- and O-) from an amino acid residue. It is at the other axial coordination site (the distal side) where biologically important transformations involving small molecules such as NO or nitrite occur. For this reason we will prepare 5-coordinate M(Por) complexes in our system with various donor ligands and investigate the interactions with various small molecules (O₂, CO, NO, NO₂, etc). Of crucial interest is how coordination of these molecules is perturbed by various trans ligands as reflected by equilibrium constants and thermodynamic parameters of binding, metal ion spin states, etc.

For example, we recently discovered that the reaction of Fe(Por) with nitrogen dioxide (NO₂) gave the O-bound 5-coordinate nitrito complex Fe(Por)(ONO) [2]; however, when this was exposed to several nitrogen bases (B) the N-bound 6-coordinate nitro isomer (B)Fe(Por)(NO₂) was formed [3]. Thus, the trans-ligand can markedly affect the nature of the nitrite ion binding. This is particularly relevant, since coordinated nitrite ions in these two forms are likely to have markedly different reactivities. Our recent studies also show that the nitrato complexes of iron-porphyrins have flexible coordination modes [4]. The bidentate symmetric ?²-coordination of nitrato ligand in 5-coordinate Fe(Por) complexes [5] transforms to the monodentate form when a ligand is present in the proximal site [4].

We will extend these studies by preparing 6-coordinate nitrosyl, nitro/nitrito and nitrato complexes of Co-, Mn- and Fe-porphyrins having N-, S- and O- axial ligands. The iron derivatives will closely model the heme proteins with such electron-donor proximal ligands. The mode of binding, the spin state of central metal ion and the reactions of these species with small molecules as NO, NO₂, O₂, C₂H₄ etc. will be the subject of detailed exploration by using mainly low-temperature spectral (FTIR, RRS, UV-Vis) technique, since many of these species will be thermally unstable as are the intermediates for which they are models. Of special interest will be the study of NO interaction with (1-MeIm)Fe^III(Por)(NO₂) recently obtained in our laboratory [2]. It has been proposed that an analogous interaction of Fe^IIIhemoglobin (metHb) leads to the formation of nitrogen trioxide (N₂O₃) which escapes from the red blood cell, thereby avoiding NO inactivation in the erythrocyte [6]. Our model studies will test the chemical validity of this hypothetical mechanism which has drawn considerable attention in the field of cardiovascular science as an explanation of therapeutic effects from added nitrite.

Another topic will be the O- and N-coordinated peroxynitrite complexes of heme proteins postulated by a numerous researchers [7]. However, these postulated intermediates in the reaction of NO with the oxygenated globins oxyHb and oxyMb have been seen only by optical spectroscopy in rapid mixing experiments [8] and by ESR data obtained using rapid-freezing techniques [8b]. Optical spectroscopy is far from definitive, especially with regard to the structures of such intermediates. Furthermore, the subsequent peroxynitrite-to-nitrate isomerization has not been elucidated, although it was suggested that a ferryl intermediate might be formed [8b]. Such questions would be addressed by obtaining the vibrational spectra. Thus, we will characterize the FTIR and UV-Vis of peroxynitrite complexes with the metal porphyrins M(Por) (M = Fe, Co, Mn) the low-temperature stabilization (to 10 K) and prepare analogous ¹⁵N- and ¹⁸O-containing compounds to aid the assignment of key bands. DFT calculations will also be carried out for realistic predictions of vibrational frequencies. Intermediates in the peroxynitrite to nitrate isomerization upon warming these systems will be characterized spectroscopically.

The formation of (oxo)iron(IV) porphyrin intermediates is a central theme in mechanisms for dioxygen activation by heme proteins and ferryl- and manganyl-porphyrin species (O=M^IV(Por) have been proposed for Fe- and Mn-porphyrins models of such reactions [9]. The present project will prepare the latter species and their 6-coordinate derivatives in thin amorphous layers and characterize the FTIR spectral changes upon oxidation of M^II(Por) species to O=M^IV(Por. These compounds will be stabilized at low-temperature, and reactions of these strong oxidants with various substrates will be elucidated.

Development of robust heterogeneous catalysts for activation of molecular oxygen is important for a wide range of applications including environmentally-benign synthesis and the oxygen reduction reaction in fuel-cell technology. The nitro and nitrato complexes of M(Por) in their 5- and 6-coordinate forms will be surveyed for their ability to participate in oxo-transfer reactions with appropriate O-atom acceptors that may be catalytic in presence of O₂ [10]. We will study mechanistic aspects of these processes for M(Por)s in their layered and electrostatically immobilized forms. Successful implementation of the project’s goals will not only help in understanding the oxidation and reduction processes performed by the M(Por) but also will provide guidelines for creation of effective biomimetic oxidation catalysts.

The research group of the Laboratory of Optical Spectroscopy of Molecule Structure Research Center of the Scientific Technological Center of Organic and Pharmaceutical Chemistry of the National Academy of Sciences, Republic of Armenia, has an excellent record of collaboration with foreign scientists. In this project we intend to collaborate with the scientists who have made prominent contributions in the fields of project activity. Collaboration will involve the information exchange in the course of project implementation, joint discussion of obtained results, publications and presentations at conferences as well as the use of certain facilities available in the collaborator’s research group.

The project team in Armenia consists of skillful researchers having extensive experience in the specified area with the prominent publications in leading scientific journals. MS and Ph.D. students are involved in the project and will perform their theses during project implementation

Working on the project will allow participants to redirect their talents to peaceful activities. It will also help to promote the further integration of scientists of the Republic of Armenia into the international scientific community.

References:

1. Oshio H. et al. Spectrochim. Acta. 1984, 40A, 863. (b) Burke J.M. et al. J.Amer. Chem. Soc. 1978, 100, 6083.
2. Kurtikyan T.S., Ford P.C. Angew. Chem. Intern. Edit. 2006, 45, 492.
3. Kurtikyan T.S., Hovhannisyan A.A., Gulyan G.M., Ford P.C. Inorg. Chemistry, 2007, 46, 7024. (b) Kurtikyan T. S., Hovhannisyan A.A. Hakobyan M.E., Patterson J., Iretskii A., Ford P.C. J. Amer. Chem. Soc. 2007, 129, 3576.
4. Kurtikyan T.S., Martirosyan G.G., Hakobyan M.E., Ford P.C. Chem. Comm., 2003, 1706. (b) Gulyan G. M., Kurtikyan T. S., Ford P.C. Inorganic Chemistry, 2008, 47, 787.
5. Wyllie G.R. A., Munro O.Q., Schulz Ch.E., Scheidt W.R. Polyhedron, 2007, 26, 4664.
6. Basu S. et al. Nature Chemical Biology, 2007, 3, 785.
7. Herold S., Koppenol W.H. Coord. Chem. Rev., 2005, 249, 499.
8. Herold S., Exner M., Nauser T. Biochemistry, 2001, 40, 3385. (b) Olson J.C. et al. Free Radical Biol. Med. 2004, 36, 685.
9. Chin D.H., Balch A.L., LaMar G.N. J Am. Chem. Soc.1980, 1446. (b) Groves G.T., Gross Z., Stern M.K. Inorg. Chem., 1994, 33, 5065.
10. Goodwin J. A. et al. Inorg. Chem. 2001, 40, 4217. (b) Goodwin J. A., Kurtikyan T. S. et al. Inorganic Chemistry. 2005, 44, 2215.