What is the answer to Life, the

Universe and

Everything?

Hadean Archean Proterozoic

Mesozoic

Cenozo

ic

Paleozoic

inthe beginning…

Nov. 9 2005

today1 bya2 bya3 bya4 bya

3.5 bya!

Oldest fossils: stromatolites = Calcium carbonate deposits from blue-green algae or cyanobacteria.

0.5 bya

N2 + 3 H2 --> 2 NH3

BANG!

Hadean4.5 -3.8 bya

Archean3.8 -2.5 bya

Oldest rocks?

Most famous characteristic?Nitrogen “fixing” bacteria:

4.5 bya!

What do we find deep withincyanobacteria’samazing N2-fixing machinery?

MoMolybdenum

(Greek ‘molybdos’ ) lead-like

“Moly”

# 42

The Answer to Life, the Universe, and Everything (?)

540 mya

Mesozoic2.5 -0.6 mya

Global catastrophe!

Cenozoic65 mya - today!

“age of mammals”

“age of dinosaurs”

quagga

Paleozoic540 - 250 mya

250 mya 65 mya

Plants!!

Animals!!Anotherextinction!!

Has evolution moved on without #42 - Mo?

Grown without MoGrown with Mo

Tobacco plants (Arabidopsis thaliana)

Healthy(wild type)

Sick(mutant)

All plants requirethe molybdoenzymeNitrate Reductase

nitrate nitrite

Nitrate

Nitrite

Proteins

inthe Beginningof Life…

1 bya2 bya3 bya4 bya

CyanobacteriaNeed

Mo

PlantsNeed

Mo

What about the animals?

sulfite oxidase

xanthine oxidase

enzyme in mammalian milk

Got Mo?

aldehyde oxidase

two enzymes in liversof mammals and avians

Why the correct oxidation state matters

MRI of brain of deceased babywith Sulfite Oxidase Deficiency MRI of healthy brain

The baby died because this reaction didn’t happen:

SO32- + H2O ---> SO4

2- + 2H+ + 2e- Sulfite SulfateS4+ 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.

Oxidation SO32- + H2O ---> SO4

2- + 2H+ + 2e- half reaction S4+ in Sulfite S6+ in Sulfate

Reduction Mo6+ + 2e- ---> Mo4+ half reaction

Net redox reactionSO3

2- + H2O + Mo6+ ---> SO42- + 2H+ + Mo4+

Review the terms:

aldehyde oxidase sulfite oxidasexanthine 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

Bioinorganic Chemistry

1. Not having the structure or organization of living bodies2. Not characterized by vital processes3. Not fundamental or related; extraneous 4. Pertaining to compounds that are not hydrocarbons5. Mineral

1. (Gr. “bios” ‘life, course or way of living’). In compounds formed in Greek itself, as biography; and in modernscientific words in which bio- is extended to mean ‘organic life.’

2. A prefix meaning “life” Websters, OED

Bioinorganic ChemistryMolybdenum Enzymes Hemoglobin (Fe)

Manganese Enzymes

Zinc Enzymes (Zn)

Auranofin (Au) arthritisCis-platin (Pt) cancer

Copper Enzymes (Cu)Vitamin B12 (Co) Iron enzymes

Tungsten Enzymes

Therapeutics

V, Ti, Cr

Bioinorganic ChemistryMolybdenum Enzymes Hemoglobin (Fe)

Manganese Enzymes

Zinc Enzymes (Zn)

Aurial (Au) arthritisCis-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 Chemistry1.Oxidation states

Mo occurs in oxidation states from 0 +6Project 1 will generate complexes in states +4 –

6, same as enzymes

Mo Chemistry2. Geometries: Mo complexes have Coordination Numbers

from CN 4 8 Project 1 uses reagents or makes products

with CN 4 7

3. Reaction Chemistry Mo 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!

O

Mo+6

OS

S

O

MoOS

S

O

Mo+4

S

S

O

Mo+4OS

S

SO

OO

OSO

OO

O

Mo+4

S

SH

H

O

Mo+5OHS

S

a

- H+, - e -

- H+, - e -

+ SO32-

- SO42-

+ H2O

oxygen

atom

transfer

coupled

proton

electron

transfer

A proposed catalytic cycle for how Mo oxidizes SO32-

Mo

molybdopterinpterin

dithiolene

Mo

Ball and stick diagram Chemical structure diagram

S

S

O

HN NH

HNNO

O

NH2

MoO NN

NH2

O

HO

P OP O

O

O

OO

OH

S

S

O

HN NH

HNNO

O

NH2

MoO NN

NH2

O

HO

P OP O

O

O

OO

OH

S

S

O

HN NH

HNNO

O

NH2

MoO NN

NH2

O

HO

P OP O

O

O

OO

OH

Protein structuredestroyed

Mo compoundreleased (isolated)

rapid decomposition

HS

SH

HO

HN

NH

HN

N

O

O

H2N

Mo

P

O

O

O

N

N

HN

N

O

H2N S

S

CHOHCH2OH