Ring Around the Cobalt: Vitamin B12

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Presentation transcript:

Ring Around the Cobalt: Vitamin B12 “VitaminB12,the beautiful: excitement will not cease!” -Albert Eschenmoser Ring Around the Cobalt: Vitamin B12 Cassie Gates Advanced Bioinorganic Dr. Sharon Burgmayer

Getting to Know Your Cobalamins R- Group Name CN Cyanocobalamin CH3 Methylcobalamin 5’-deoxyadenosyl Adenosylcobalamin OH Hydroxycobalamin D C

Making a State-ment Co–C bond for Cyanocobalamin (1.86 Å) is short MeCbl and AdoCbl the Co–C bond is longer ( 1.98 Å and 2.0 Å) Homolytically - Co(II) and an alkyl free radical R Heterolytically – either Co(I) and R+ or Co(III) and R– http://www.neurology.org/content/58/9/1395/F2.expansion.html

Enzyme Time +1 +3 +2

B12, what is it good for? Absolutely, nothing everything

Go with your Gut

The Anti-Villian of Vitamins

Gray: C atoms of the corrin unit Yellow: C atoms of the phenyl ligands Dark red: Co atom Blue: N atoms Light red: O atoms Two projections of a model of the structure of EtPhCbl derived from X‐ray crystal‐structure analysis. Gray: C atoms of the corrin unit, yellow: C atoms of the phenyl ligands, dark red: Co atom, blue: N atoms, light red: O atoms. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. Angewandte Chemie International Edition Volume 52, Issue 9, pages 2606-2610, 13 FEB 2013 DOI: 10.1002/anie.201209651 http://onlinelibrary.wiley.com/doi/10.1002/anie.201209651/full#fig1

Equilibrium Dissociation Constant of EtPhCbl IF (k+=7.9×107 M−1 s−1) TC (k+=9.3×107 M−1 s−1) TC (k−<4×10−6 s−1) IF (k−<5×10−6 s−1) Equilibrium Dissociation Constant of EtPhCbl Kd≈2×10−14 M

Got it on Lock! So where from here?

Questions to Consider Why cobalt? Why DMB? What else could be used as a good R-group for an anti-vitamin B12? (characteristics should it have?) Why is this useful? + CN - 

Bibliography Kroner, Zina (2011). Vitamins and Minerals. Vitamin B12. Retrieved from http://www.eblib.com Perry, C., Marques, H. (2004), Fifty years of X-ray crystallography of vitamin B12 and its derivatives. South African Journal of Science. July/August. 100 Ruetz, M., Gherasim, C., Gruber, K., Fedosov, S., Banerjee, R. and Kräutler, B. (2013), Access to Organometallic Arylcobaltcorrins through Radical Synthesis: 4- Ethylphenylcobalamin, a Potential “Antivitamin B12” . Angew. Chem. Int. Ed., 52: 2606–2610. doi:10.1002/anie.201209651