What is the answer to Life, the Universe and Everything?

HadeanArchean Proterozoic Mesozoic Cenozoic Paleozoic in the beginning… Nov today 1 bya2 bya3 bya4 bya

3.5 bya! Oldest fossils: stromatolites = Calcium carbonate deposits from blue-green algae or cyanobacteria.blue-green algae 0.5 bya N H 2 --> 2 NH 3 BANG! Hadean bya Archean bya Oldest rocks? Most famous characteristic? Nitrogen “fixing” bacteria: 4.5 bya!

What do we find deep within cyanobacteria’s amazing N 2 -fixing machinery?

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

540 mya Mesozoic mya Global catastrophe! Cenozoic 65 mya - today! “age of mammals” “age of dinosaurs” quagga Paleozoic mya 250 mya65 mya Plants!! Animals!! Another extinction!! Has evolution moved on without #42 - Mo?

Grown without Mo Grown with Mo

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

in the Beginning of Life… 1 bya2 bya3 bya4 bya Cyanobacteria Need Mo Plants Need Mo

What about the animals?

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

Why the correct oxidation state matters

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

The baby died because this reaction didn’t happen: SO H 2 O ---> SO H + + 2e- Sulfite Sulfate S 4+ S 6+ 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.

Oxidation SO H 2 O ---> SO H + + 2e- half reaction S 4+ in Sulfite S 6+ in Sulfate Reduction Mo e- ---> Mo 4+ half reaction Net redox reaction SO H 2 O + Mo > SO H + + Mo 4+ Review the terms:

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

+ Mo defective molybdoenzymes Human Molybdoenzyme Deficiencies: Cured with more Mo? Not repaired by adding Mo alone Non-functional enzyme

BioinorganicChemistry 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

BioinorganicChemistry Molybdenum EnzymesHemoglobin (Fe) Manganese Enzymes Zinc Enzymes (Zn) Auranofin (Au) arthritis Cis-platin (Pt) cancer Copper Enzymes (Cu) Vitamin B12 (Co) Iron enzymes Tungsten Enzymes Therapeutics V, Ti, Cr

BioinorganicChemistry Molybdenum EnzymesHemoglobin (Fe) Manganese Enzymes Zinc Enzymes (Zn) Aurial (Au) arthritis Cis-platin (Pt) cancer Copper Enzymes (Cu) Vitamin B12 (Co) Iron enzymes Tungsten Enzymes  Therapeutic s  V, Ti, Cr

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

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

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

3. Reaction ChemistryMo S; dtc ligand Mo O; Mo=O ligands Mo Chemistry

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

A proposed catalytic cycle for how Mo oxidizes SO 3 2-

Mo molybdopterin pterin dithiolene

Mo Ball and stick diagram Chemical structure diagram

   Protein structure destroyed Mo compound released (isolated) rapid decomposition