What is the
answer
to Life, the
Universe and
Everything?
Nov. 9
2005
in
the
beginning…
4 bya
Hadean
3 bya
Archean
2 bya
1 bya
Proterozoic
today
Hadean
4.5 -3.8 bya
Archean
3.8 -2.5 bya
Oldest rocks?
4.5 bya!
BANG!
3.5 bya!
0.5 bya
Oldest fossils: stromatolites = Calcium carbonate deposits
from blue-green algae or cyanobacteria.
Most famous characteristic?
Nitrogen “fixing” bacteria:
N2 + 3 H2 --> 2 NH3
What do we find
deep within
cyanobacteria’s
amazing
N2-fixing machinery?
# 42
Mo
Molybdenum
(Greek ‘molybdos’ ) lead-like
“Moly”
The Answer to Life,
the Universe,
and Everything (?)
Paleozoic
540 - 250 mya
Mesozoic
2.5 -0.6 mya
“age of dinosaurs”
Plants!!
Cenozoic
65 mya
- today!
Animals!!
Another
extinction!!
540 mya
250 mya
65 mya
“age of
mammals”
quagga
Has evolution moved on without #42 - Mo?
Grown with Mo
Grown without Mo
Tobacco plants (Arabidopsis thaliana)
Healthy
(wild type)
Sick
(mutant)
Nitrate
Nitrite
Proteins
All plants require
the molybdoenzyme
Nitrate Reductase
nitrate
nitrite
Cyanobacteria
Need
Mo
Plants
Need
Mo
in
the
Beginning
of
Life…
4 bya
3 bya
2 bya
1 bya
What about the animals?
Got Mo?
enzyme in mammalian milk
xanthine oxidase
two enzymes in livers
of mammals and avians
aldehyde oxidase
sulfite oxidase
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:
SO32- +
Sulfite
S4+
H 2O
--->
SO42- + 2H+ + 2eSulfate
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.
Review the terms:
Oxidation
SO32- + H2O --->
half reaction
S4+ in Sulfite
Reduction
Mo6+ +
half reaction
Net redox reaction
SO32- + H2O +
2e- --->
Mo6+ --->
SO42- + 2H+ + 2eS6+ in Sulfate
Mo4+
SO42- + 2H+ +
Mo4+
Human Molybdenum Cofactor Disorder: Combined Oxidase Deficiency
xanthine dehydrogenase
xanthine
uric acid
•xanthinuria
•(gout)
sulfite oxidase
aldehyde oxidase
hypoxanthine
xanthine
•No detoxification
of heterocycles
sulfite
sulfate
•Mental/motor retardation
•Epileptic seizures
•Brain atrophy
•Dislocated ocular lens
•death
Human Molybdoenzyme Deficiencies: Cured with more Mo?
defective molybdoenzymes
Not repaired by adding Mo alone
+ Mo
Non-functional enzyme
Bioinorganic Chemistry
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
Bioinorganic Chemistry
Molybdenum Enzymes
Vitamin B12 (Co)
Tungsten Enzymes
Cis-platin (Pt) cancer
Hemoglobin (Fe)
Iron enzymes
V, Ti, Cr
Therapeutics
Zinc Enzymes (Zn)
Copper Enzymes (Cu)
Manganese Enzymes
Auranofin (Au) arthritis
Bioinorganic Chemistry
Molybdenum Enzymes
Vitamin B12 (Co)
Tungsten Enzymes
Cis-platin (Pt) cancer
Hemoglobin (Fe)
Iron enzymes
V, Ti, Cr
Zinc Enzymes (Zn)
Copper Enzymes (Cu)
Manganese Enzymes
3 Therapeutic s 4
Aurial (Au) arthritis
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
Mo Chemistry
3. Reaction ChemistryMo
S; dtc ligand
Mo
O; Mo=O ligands
Molybdenum, atomic # 42: is it the answer
to Life, the Universe and Everything?
Sure looks like it!
What’s the Ultimate Question?
Adams speculates in “The Restaurant at the End of the Universe”:
What do you get
if you multiply nine by six?
A proposed catalytic cycle for how Mo oxidizes SO32coupled
oxygen
electron
proton
transfer
atom
+ SO3 2-
O
transfer
S
Mo+6
S
O
O
S
O
- H+, - e-
O
S
O
O
Mo+5
OH
O
- H+, - e- SO42-
S
S
O
O
S
S
a
S
Mo
S
S
O
S
Mo+4
O H
H
S
+ H2O
Mo+4
O O
Mo+4 S
O
O
dithiolene
Mo
pterin
molybdopterin
O O
P O
P O
O O
NH2
O
Mo
S
Mo
O
S
HN
HO
O
N
N
O
OH
NH
N
O
HN
NH2
Ball and stick diagram
Chemical structure diagram
O O
O
P O
P O
O O
S
Mo
O
S
& HN
O
NH
N
HN
&
O
HO
N
S
Mo
NH2
N
O
HN
OH
NH2
O
N
N
O
HO
O
S
O
&
O O
O
P O
P O
O O
OH
NH
N
HN
Mo compound
released (isolated)
NH2
NH2
rapid decomposition
Protein structure
destroyed
O
HN
Mo
H2N
N
HS
H
N
N HO
H
SH
O
O
O
N
HN
H2N
S
N
N
S
CHOHCH2OH
P
O
O