1. Principles of Bioinorganic Chemistry You should have your paper topic approved by Prof. Lippard this week, if you have not done so already (by 10/12 please). The oral presentations will be held in research conference style at MIT's Endicott House estate in Dedham, MA, on Saturday, October 18. WEB SITE: web.mit.edu/5.062/www/

2. Structural and Spin State Changes upon Binding of Dioxygen to an Iron Porphyrin Center High-spin ferrous Low-spin ferric Deoxy Hb (T state) Oxy Hb (R state). Hb binds 4 O 2 molecules. When 2 are bound, T switches to R and makes the next ones easier to bind.

3. Model Chemistry for Oxy Hb and Oxy Mb The problem: Fe II P + O 2 Fe III P–O 2 - PFe III –O O–Fe III P.. 2PFe IV =O: PFe III –O–Fe III P.. Fe II P  -oxo, “dimer” The solutions: Attach the porphyrin to a solid support to avoid the bimolecular reaction; or, use low T, non-aqueous solvents, and py or 1-MeIm complexes, but stability is lost at - 45 °C or above. The best solution was the construction of a sterically hindered cavity for dioxygen binding to avoid the intemolecular chemistry leading to the thermodynamic sink of the system, the (  - oxo)diiron(III) species. Fe II P ferryl

4. Synthetic Models for OxyHb and OxyMb (Collman)(Baldwin)

5. The Cytochrome P-450 Reaction Cycle When an axial site is available on the iron porphyrin, dioxygen can bind and/or be activated there. With proton- mediated reductive activation of the O 2 molecule, a peroxo intermediate forms that converts to an Fe IV =O species, the ferryl ion. The ferryl can oxidize hydrocarbons to alcohols, epoxidize olefins, oxidize amines to amine oxides and do related chemistry. P-450’s are liver enzymes necessary for metabolism and used to convert pro-drugs and pro-carcinogens to their active forms.

6. Protoctechuate 3,4-Dioxygenase Notes: dioxygenase vs. monooxygenase; iron oxidation state does not change; iron acts as a Lewis acid; semiradical character of the catecholate ligand activates it for direct attack by the dioxygen molecule.

7. Hemerythrins - Diiron Dioxygen Carriers Properties: Mono- (myo Hr) and multi- (Hr) subunit proteins. Found in marine invertebrates. Easily isolated protein; crystallizes after one step!! Deoxy Hr, colorless, diiron(II) Oxy Hr, red, diiron(III) peroxo O–O, 844 cm -1 in the terminally bound peroxide region. Fe–O–Fe, 486 cm -1, resonance enhanced symmetric stretch. The asymmetric stretch occurs at 757 cm -1. Mixed-valent, semimet Hr, Fe(II)Fe(III): inactive.

8. Structure of Azidomethemerythrin Contains a (  -oxo)diiron(III) core. Met, artificially oxidized. An inactive form of the protein. The azido anion occupies the place of the hydroperoxo anion in oxyHr. The structure was encountered for the first time when the protein crystallographers found it in azidometmyoHr. Myo, single subunit. The electronic spectrum is characteristic and a consequence of antiferromagnetic spin exchange between the two high-spin Fe(III) centers.

9. Note proton-coupled electron transfer Evidence for proton transfer comes from resonance Raman work

10. Early Structural Models for Methemerythrin These and related complexes have no site for binding of azide or dioxygen related species such as hydroperoxide. The syntheses exemplify spontaneous self-assembly. The challenges are to make a site available, allow redox chemistry to occur, and avoid polymerization to rust or molecular ferric wheels and related complexes.

12. None does the chemistry of the protein!

13. Properties of Oxy Hr, Deoxy Hr, and Models

14. Structure and Chemistry of Class I Ribonucleotide Reductase R2 Protein Reaction of the reduced diiron(II) form of the R2 protein with dioxygen affords a high valent, Fe(III)Fe(IV) intermediate designated as X. Intermediate X is kinetically competent to oxidize the tyrosyl residue to afford a tyrosyl radical. This radical in turn transfers electrons to the R1 subunit of the enzyme where a Cys-S–S- Cys cation radical forms. This radical in turn initiates chemistry to convert ribo- to deoxyribonucleotides.

15. Hemocyanins - Dicopper Dioxygen Carriers Properties: Multi-subunit proteins, ranging in size up to 460 kDa. Found in spiny lobsters, crayfish, and arachnids. Deoxy Hc, colorless, dicopper(I) Oxy Hc, blue, dicopper(II) peroxide O–O, 745-750 cm -1 in the peroxide region, but low. Unusual structure, first established by model chemistry: O Cu O

16. Schematic Views of Deoxy and Oxy Hc Note, Type III copper

17. Structure of Deoxyhemocyanin The two Cu atoms are held by six terminal histidine residues, the Cu Cu distance being 3.7 Å. There is no obvious bridging ligand....

18. Monooxygenase Activity in Synthetic Cu 2 Models The dinuclear complex mediates insertion into the C–H bond. The chemistry mimics that of tyrosinase.

19. Important Relationships Reversible O 2 binding Iron porphyrin, Hb/Mb Iron porphyrin, P-450 Dicopper center, Hc Dicopper center, tyrosinase Diiron center, Hr Diiron center, R2, MMO O 2 Activation WHAT CONTROLS THE FUNCTION??

20. Principles Illustrated by these Cases Substrate binding and redox changes occur: In all three cases, O 2 binding is accompanied by electron transfer from one or two metal ions to dioxygen. Coupled proton-electron transfer steps set the potentials: In oxyHr a proton transfers from the bridging hydroxide to the peroxo ligand; this step appears to block further conversion to high-valent iron oxidase center(s). Metal center used to create or destroy radical species: Occurs in ribonucleotide reductase R2 protein. Catechol dioxygenase - Fe(III) coordination favors semiquinone form of a bound ligand without redox reaction occurring. Changes in metal coordination sphere facilitate allostery: Explains the cooperativity of O 2 binding in Hb.

22. Plants recruit oil-detoxifying microbes, as discovered by scientists analyzing the recovery of the environment in the Persian Gulf region following the 1991 Gulf War. " In the root zone was a rich reservoir of well-known oil eating microbes... one family of which (Arthrobacter) accounted for fully 95 percent..." Science News, 148, 84 (August 5, 1995) Methanotrophs are Used in Bioremediation of the Environment Prince William Sound, Alaska: After the Exxon Valdez oil spill, fertilizers were spread on the beaches and natural methanotrophs restored their pristine beauty.

23. The Mineral Springs in Bath, England, Source of Methylococcus capsulatus (Bath) The Restutive Contents of the WATER’s Concoctive Power: Solution of gaffes, chaos of Salts and mineral effluvia of subterranean expiration. It cleanses the body from all blotches, scurvicial itchings and BREAKING OUTS WHATSOEVER!

25. Structures of the sMMO Components