The Molybdenum Cofactor: Moco

1. The Molybdenum Cofactor: Moco What early experiments indicated: … but it wasn’t entirely correct.

2. Now we know that there is not just one Moco, but a family of related Moco structures in molybdenum enzymes:

3. Questions asked of molybdoenzymes and their model compounds: • What is the redox potential ( energy of) Mo • redox reactions? • What are the structural details? What is bond • order? (angles, bond distances) • How well do models mimic reactions of Mo • in enzymes? in structure? in reactivity?

4. A “second generation” Moco model: the Holm-Berg model

5. Sulfite Oxidase Berg-Holm Model Mimicking the Catalytic Reactions of Moco

6. What would the Berg-Holm model system suggest? • a 2 e- process between Mo(6+) and Mo(4+), and only • the Mo(6+) and Mo(4+) ox. states are required. • BUT, it was known that Mo(5+) plays a role (by EPR)

7. A proposed mechanism for Moco Catalysis of Sulfite Oxidation: OAT and CEPT

8. Why such a BIG Ligand on Mo?

9. Typical Mo-oxo Chemistry Step 1: Step 2: • Mo(5+)- Mo(5+) dimer • CN = 6 • Terminal vs bridging Mo-O

10. Except… it didn’t!!! Later researchers showed formation of BIG Ligand is intended to prevent dimerization

11. What is the sulfur donor ligand for the family of related Moco structures in molybdenum enzymes? From X-ray diffraction of protein crystals, ~1994

12. dithiolene pterin The Ligand is called Molybdopterin nucleotide Mo

13. This week’s reactions: MoO2(detc)2 + excess PPh3 --> RED RED + propylene sulfide --> BLUE Chromatography to separate:

14. Technique: Column Chromatography • Review: • chromatographic separations are based on: • dipolar interaction of molecules with solid support (SiO2) • partitioning of molecule between support and solvent • In practice: • Silica gel column chromatography elutes most non-polar • first, most polar last. • Different species may be selectively eluted with increasing • the polarity of solvents, e.g., • CH2Cl2, then acetone, then methanol

15. Related to the Blue Reaction: Propylene Sulfide - C3H6S Expected reactivity?? Purpose?? Source of sulfur, formally S0

16. Elemental form: S8 vs. O=O As ligands: M=S M(S2) M(S3) M(S4) M(S5) disulfide trisulfide tetrasulfide pentasulfide Sulfur is strange!!!! That’s why the alchemists loved it. They thought that everything, every substance could be made from the “proper” mixture of sulfur, mercury and salt. Sulfur does not behave like its smaller cousin, O. As ions: S2- & [S2]2-O2- &[O2]2- &[O2] - polysulfides [S3]2- & [S5]2-

17. Technique: Infrared Spectroscopy • Application to Berg-Holm model and Mo-dimer: • detection of Mo=O groups • number of absorption related to number Mo=O • frequency related to Mo oxidation state • frequency also reveals Mo-O-Mo Infrared Spectroscopy helps assign sulfur ligand type: M=S has nM=S ~ 450-500 cm-1 M(S2) has nM-S ~ 500-550 cm-1 M(S3), M(S4) has nM-S < 480 cm-1 Let’s try it …

18. [Tp*Mo(X)(S4)]— What is X?

19. B-H C-H C=N O-H ring Mo=S compound was determined to be [Tp*Mo(S)(S4)]—

20. Product was determined to be a mixture of both [Tp*Mo(S)(S4)]— and [Tp*Mo(O)(S4)]— Mo=S Mo=O

21. What happens in reactions with Mo complexes? ? + S • characteristics: • Mo(4+): could be oxidized or reduced • open (vacant) coordination site • Mo loves S • characteristics: • Mo(6+): • filled coordination sphere • Mo loves S • Seems OK but is it right? How could we know for sure?????