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Research Methodology Spring 2019 Metals in Biology

Research Methodology Spring 2019 Metals in Biology. 1. Not having the structure or organization of living bodies 2. Not characterized by vital processes 3. Not fundamental or related; extraneous 4. Pertaining to compounds that are not hydrocarbons 5. Mineral.

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Research Methodology Spring 2019 Metals in Biology

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  1. Research Methodology Spring 2019 Metals in Biology

  2. 1. Not having the structure or organization of living bodies 2. Not characterized by vital processes 3. Not fundamental or related; extraneous 4. Pertaining to compounds that are not hydrocarbons 5. Mineral 1. (Gr. “bios” ‘life, course or way of living’). In compounds formed in Greek itself, as biography; and in modern scientific words in which bio- is extended to mean ‘organic life.’ 2. A prefix meaning “life” Websters, OED Bio inorganic Chemistry

  3. Bio inorganic Chemistry Molybdenum Enzymes Hemoglobin (Fe) Zinc Enzymes (Zn) Vitamin B12 (Co) Iron enzymes Copper Enzymes (Cu) Manganese Enzymes Tungsten Enzymes V, Ti, Cr Therapeutics Auranofin (Au) arthritis Cis-platin (Pt) cancer

  4. Bio inorganic Chemistry Cis-platin (Pt) cancer Molybdenum Enzymes Hemoglobin (Fe) Zinc Enzymes (Zn) Vitamin B12 (Co) Iron enzymes Copper Enzymes (Cu) Manganese Enzymes Tungsten Enzymes V, Ti, Cr 3 Therapeutic s 4 Aurial (Au) arthritis

  5. What is the answer to Life, the Universe and Everything? 42 !! is the atomic number of Molybdenum

  6. in the beginning… 4.5 bya! 3.5 bya! 0.5 bya BANG! Archean 3.8 -2.5 bya Hadean 4.5 -3.8 bya Oldest rocks?

  7. Proterozoic Hadean Archean Paleozoic Mesozoic Cenozoic today in the beginning… Mar. 19 2019 4 bya 3 bya 2 bya 1 bya

  8. Cyanobacteria Need Mo in the Beginning of Life… 4 bya 3 bya 2 bya 1 bya Oldest fossils: stromatolites = Calcium carbonate deposits from blue-green algae or cyanobacteria. Most famous characteristic? Nitrogen “fixing” bacteria: N2 + 3 H2 --> 2 NH3

  9. What do we find deep within cyanobacteria’s amazing N2-fixing machinery?

  10. (Greek ‘molybdos’ ) lead-like # 42 Mo Molybdenum “Moly” The Answer to Life, the Universe, and Everything (?)

  11. Cyanobacteria Need Mo Plants Need Mo in the Beginning of Life… 4 bya 3 bya 2 bya 1 bya

  12. Grown with Mo Grown without Mo

  13. Tobacco plants (Arabidopsis thaliana) Healthy (wild type) Sick (mutant) Nitrate  Nitrite  Proteins nitrate nitrite All plants require the molybdoenzyme Nitrate Reductase

  14. Cenozoic 65 mya - today! quagga Mesozoic 2.5 -0.6 mya Paleozoic 540 - 250 mya “age of dinosaurs” Plants!! Animals!! Global catastrophe! Another extinction!! 250 mya 65 mya 540 mya “age of mammals” Did evolution moved on without #42 - Mo?

  15. What about the animals?

  16. enzyme in mammalian milk xanthine oxidase Got Mo? two enzymes in livers of mammals and avians sulfite oxidase aldehyde oxidase

  17. Why the correct oxidation state matters

  18. MRI of brain of deceased baby with Sulfite Oxidase Deficiency MRI of healthy brain

  19. The baby died because this reaction didn’t happen: SO32- + H2O ---> SO42- + 2H+ + 2e- Sulfite Sulfate S4+ S6+ The baby has a genetic defect in the enzyme that catalyzes this reaction. Babies with this genetic disease die within hours. The enzyme is Sulfite Oxidase. You have it in your liver. Cali

  20. Review the terms: Oxidation SO32- + H2O ---> SO42- + 2H+ + 2e- half reactionS4+ in Sulfite S6+ in Sulfate Reduction Mo6+ + 2e- ---> Mo4+ half reaction Net redox reaction SO32- + H2O + Mo6+ ---> SO42- + 2H+ + Mo4+

  21. xanthine dehydrogenase xanthine uric acid sulfite sulfate hypoxanthine xanthine sulfite oxidase aldehyde oxidase Human Molybdenum Cofactor Disorder: Combined Oxidase Deficiency • xanthinuria • (gout) • Mental/motor retardation • Epileptic seizures • Brain atrophy • Dislocated ocular lens • death • No detoxification of heterocycles

  22. defectivemolybdoenzymes Not repaired by adding Mo alone + Mo Non-functionalenzyme Human Molybdoenzyme Deficiencies: Cured with more Mo?

  23. The Molybdenum Cofactor: Moco Early experiments indicated a common cofactor … but it wasn’t entirely correct.

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

  25. 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?

  26. Project 1. Mo Chemistry 1. Oxidation states Mo occurs in mulitple oxidation states from 0  +6 Project 1 will generate Mo complexes in states +4 – 6, the same as in Mo enzymes

  27. Project 1. Mo Chemistry 2. Geometries: Mo complexes have Coordination Numbers from CN 4  8 Project 1 uses reagents or makes products with CN 4  7

  28. Project 1. Mo Chemistry 3. Reaction Chemistry Mo S use the dithiocarbamate, dtc, ligand Mo O Use Mo=O ligands

  29. The Mo Compounds + HCl MoO2detc2 - H2O MoOCl2detc2 + PPh3 - 0=PPh3 Mo Cl + MoO2detc2 S O N C H MoOdetc2 + 2 “S” Mo2O3detc4 MoO(S2)detc2

  30. Molybdenum, atomic # 42: is it the answer to Life, the Universe and Everything? Sure looks like it! What’s the Ultimate Question? Douglas Adams speculates in “The Restaurant at the End of the Universe”: What do you get if you multiply nine by six?

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