1. Synthesis and Characterization of Iron Dinitrosyl Complexes with Ligands that Mimic Histidine Chaitali Sheth Chaitali Sheth California State University, Long Beach

2. Nitric Oxide Active molecule in biological systemsActive molecule in biological systems Plays a vital role in giving men erections, lowering blood pressure, arming the immune system, and preventing premature birth and memory lossPlays a vital role in giving men erections, lowering blood pressure, arming the immune system, and preventing premature birth and memory loss Forms complexes with transition metals, such as FeForms complexes with transition metals, such as Fe

3. Dinitrosyl Iron Complexes Non-heme iron dinitrosyl complexes store and release NONon-heme iron dinitrosyl complexes store and release NO Rhodococcus Sp contains a light-sensitive nitrile hydratase, which stores NO at its non-heme iron centerRhodococcus Sp contains a light-sensitive nitrile hydratase, which stores NO at its non-heme iron center NO is released upon irradiation of the enzymeNO is released upon irradiation of the enzyme It is difficult to isolate and characterize such enzymesIt is difficult to isolate and characterize such enzymes

4. Objectives Synthesize iron dinitrosyl complexes using dinitrosyl dicarbonyl iron, Fe(NO) 2 (CO) 2, with ligands that mimic biologically active compoundsSynthesize iron dinitrosyl complexes using dinitrosyl dicarbonyl iron, Fe(NO) 2 (CO) 2, with ligands that mimic biologically active compoundsHistidine Characterize the compounds with FT-IR, UV-Vis, Electron Paramagnetic Resonance (EPR), Nuclear Magnetic Resonance (NMR), and electrochemical techniquesCharacterize the compounds with FT-IR, UV-Vis, Electron Paramagnetic Resonance (EPR), Nuclear Magnetic Resonance (NMR), and electrochemical techniques Study the NO releasing kinetics of the compoundsStudy the NO releasing kinetics of the compounds Such compounds can be incorporated in potential drugs for medicinal useSuch compounds can be incorporated in potential drugs for medicinal use

5. Previous Studies Reactions of Fe(NO) 2 (CO) 2 with 1- methylimidazole (1-MeIm) and imidazole (Im) have been carried outReactions of Fe(NO) 2 (CO) 2 with 1- methylimidazole (1-MeIm) and imidazole (Im) have been carried out Reaction conditions:Reaction conditions: –Temperature: 25°C –Solvents: ether and methylene chloride –Environment: N 2 purged Im 1-MeIm

6. X-ray Crystallographic Structures Fe(NO) 2 (1-MeIm) 2 [Fe(NO) 2 (Im)] 4

7. IR frequencies of nitrosyls in Fe(NO) 2 (CO) 2 (1810 and 1767 cm -1 ) shifted upon the addition of Im (1796 and 1726 cm -1 ), suggesting the role of Im as a σ-donor.IR frequencies of nitrosyls in Fe(NO) 2 (CO) 2 (1810 and 1767 cm -1 ) shifted upon the addition of Im (1796 and 1726 cm -1 ), suggesting the role of Im as a σ-donor.

8. Cyclic Voltammetry Cyclic voltammetry of the complex at a Pt electrode in THF and 0.1 M Tetrabutylammonium perchlorate showed a reversible one-electron reduction at E1/2 = -0.875 V with a scan rate of 0.1 V/s.Cyclic voltammetry of the complex at a Pt electrode in THF and 0.1 M Tetrabutylammonium perchlorate showed a reversible one-electron reduction at E1/2 = -0.875 V with a scan rate of 0.1 V/s.

9. EPR EPR spectra of the complex were recorded at 170K in THF. The hyperfine, nine-line structure was a result of the coupling of two equivalent 14 N nuclei from the nitrosyl and one 14 N from the imidazole ligand.EPR spectra of the complex were recorded at 170K in THF. The hyperfine, nine-line structure was a result of the coupling of two equivalent 14 N nuclei from the nitrosyl and one 14 N from the imidazole ligand. EPR in THF g = 2.035 Preliminary EPR Simulation

10. UV-Vis Spectroscopy The UV-Vis spectrum in THF showed three peaks at 759 (from d-d transition), 519 (metal-ligand charge transfer, MLCT), and 342 nm (from imidazole ligand).The UV-Vis spectrum in THF showed three peaks at 759 (from d-d transition), 519 (metal-ligand charge transfer, MLCT), and 342 nm (from imidazole ligand). Probable MLCT

11. Fe(NO) 2 (1-MeIm) 2 Fe(NO) 2 (1-MeIm) 2 has been characterized by FT-IR and EPR spectroscopy.Fe(NO) 2 (1-MeIm) 2 has been characterized by FT-IR and EPR spectroscopy. IR frequencies of nitrosyls in Fe(NO) 2 (CO) 2 (1810 and 1767 cm -1 ) shifted upon the addition of 1-MeIm (1673 and 1616 cm -1 ), suggesting the role of 1-MeIm as a σ-donor.IR frequencies of nitrosyls in Fe(NO) 2 (CO) 2 (1810 and 1767 cm -1 ) shifted upon the addition of 1-MeIm (1673 and 1616 cm -1 ), suggesting the role of 1-MeIm as a σ-donor. Fe(NO) 2 (CO) 2 gave a broad peak with g = 2.0275 at 298 K. The addition of 1-MeIm gave a signal at g = 2.0151 at 240 KFe(NO) 2 (CO) 2 gave a broad peak with g = 2.0275 at 298 K. The addition of 1-MeIm gave a signal at g = 2.0151 at 240 K

12. EPR This signal was further resolved to a well-split, nine-line spectrum yielding a structure of Fe(NO) 2 (1-MeIm) 2 +.This signal was further resolved to a well-split, nine-line spectrum yielding a structure of Fe(NO) 2 (1-MeIm) 2 +.

13. Synthesis Synthesize iron dinitrosyl complexes with 5,6- dimethylbenzimidazole (Me 2 BzIm) and 4- methylimidazole (4-MeIm) with similar reaction conditionsSynthesize iron dinitrosyl complexes with 5,6- dimethylbenzimidazole (Me 2 BzIm) and 4- methylimidazole (4-MeIm) with similar reaction conditions

14. Fe(NO) 2 (L) 2 Reactions Reaction SchemeReaction Scheme

15. Characterization FT-IR: To prove the carbonyl substitution by ligandsFT-IR: To prove the carbonyl substitution by ligands UV-Vis: To study the electronic behaviorUV-Vis: To study the electronic behavior NMR: To decipher the structure in the absence of a crystal structureNMR: To decipher the structure in the absence of a crystal structure EPR: To examine the biological non-heme relevanceEPR: To examine the biological non-heme relevance Cyclic Voltammetry: To study the redox behaviorCyclic Voltammetry: To study the redox behavior NO Releasing Kinetics: By photolysis of productsNO Releasing Kinetics: By photolysis of products

16. Cyclic Voltammetry Can be used to study the binding mechanism of Fe to the ligandsCan be used to study the binding mechanism of Fe to the ligands React constant number of moles of Fe(NO) 2 (CO) 2 with varying moles of the ligandsReact constant number of moles of Fe(NO) 2 (CO) 2 with varying moles of the ligands http://nanonet.rice.edu/research/CVtutorial2/sld011.htm

17. Recrystallization Use a soluble solvent to dissolve the productUse a soluble solvent to dissolve the product Filter through gravity filtrationFilter through gravity filtration Collect filtrate in a vial and add a few drops of a non-soluble solventCollect filtrate in a vial and add a few drops of a non-soluble solvent Place the vial at considerably low temperaturePlace the vial at considerably low temperature Vapor diffusion techniques may be usedVapor diffusion techniques may be used

18. Conclusions From the preliminary data, it is established that the reaction of dinitrosyl dicarbonyl iron with ligands containing the imidazole moiety gives Fe(NO) 2 (L) 2 or [Fe(NO) 2 (L)] 4 type complexesFrom the preliminary data, it is established that the reaction of dinitrosyl dicarbonyl iron with ligands containing the imidazole moiety gives Fe(NO) 2 (L) 2 or [Fe(NO) 2 (L)] 4 type complexes These complexes are easy to characterize to study their electronic and binding behaviorThese complexes are easy to characterize to study their electronic and binding behavior NO releasing kinetics can be easily studied from these complexesNO releasing kinetics can be easily studied from these complexes

19. Acknowledgements Dr. Lijuan Li Dr. Ximeng Wang Howard Hughes Medical Institute