Transition Metals
Periodic Table
bulk elements
for some species
trace elements
General roles of metal ions in
biology
Na, K:
Charge carriers
Osmotic and electrochemical gradients
Nerve function
Mg, Ca:
Enzyme activators
Structure promoters
Lewis acids
Mg2+: chlorophyll, photosynthesis
Ca2+: insoluble phosphates
Fe, Cu, Mo:
Electron-transfer
Redox proteins and enzymes
Oxygen carrying proteins
Nitrogen fixation
Zn:
Metalloenzymes
Structure promoters
Lewis acid
Not a redox catalyst!
Other metal ions: less well defined and more
obscure roles
Biochemical Reactivity







Promotion of Appropriate Geometry
Change acid/base character
Change Redox potentials
Change ionic concentration
Formation of Unique species
Formation of structural materials
Activation of small molecules (NO)
Fe(II), Fe(III):

Essential for ALL organisms

In plants: iron deficiency

In human body: 4-5 g

Uptake: ~ 1 mg/day
In human body
75% Hem-iron




Hemoglobin
Myoglobin
Cytochromes
Oxidases, P-450
25% Non-hem-iron


Rubredoxins
Ferredoxins
Porphyrins

Fe

Oxygen Transport

Hemoglobin




4 Fe containing globin units (2-alpha and 2-beta)
K increases with each O2 added
Fe(II) does not oxidize to Fe(III)
 Non-aqueous or simultaneous Oxygen to two hemes.
Oxygen Storage

Myoglobin

1 heme group
Porphyrin
Hemoglobin
Fe
Iron Environment in Myoglobin
Cytochromes, Peroxidases, and
Catalases

Cytochrome P-450


Oxidation catalyst
Peroxidases/Catalases

Decomposition of organic peroxides.
Electron Transfer Chains
Other Fe Compounds

Ferritin / Transferrin

Iron storage in spleen, liver and marrow.

Mw  445,000 (4,300 Fe atoms)
Periodic Table
bulk elements
for some species
trace elements
Cu(I), Cu(II)
Plants
Animals
Electron transfer
O2-carrying
Protection of DNA
from O2-
Cu-proteins and enzymes

Cytochrome oxidase
O2
H2O

Tyrosinase, phenol oxidase
ox. of phenols

Ceruloplasmin
Fe(II)

Blue proteins
Electron transfer

Superoxide dismutase
Elimination of O2-

Hemocyanin
O2 transport
Fe(III)
Superoxide Dismutase
SOD-Cu2+ + O2.-  SOD-Cu1+ + O2
SOD-Cu1+ + O2.- + 2H+  SOD-Cu2+ + H2O2
Oxygen hemocyanin
mollusks and arthropods
Copper-related Pathological Disorders
1. Wilson’s disease:
Hereditary disfunction of ceruloplasmin
Cu2+ accumulates in liver, brain: dementia, liver failure
Administration: Cu-specific chelate
2. Menke’s „kinky hair” syndrome:
Hereditary disfunction of intracellular copper transport
Copper deficiency symptoms: disturbances in the mental and
physical development
Therapy: intravenously administered copper compounds
3. Acute copper deficiency
Insufficient oxygen utilization in brain
4. Mutations in the copper dependent superoxide dismutase
Ni(II)

Ni-containing enzymes of bacteria

Urease

CO-dehydrogenase

Hydrogenases
(Vesicle)
Membranes
Mo
HPO42-
Uptake :
MoO42SO42-
Molybdenium enzymes

Nitrogenase
N2  NH3

Aldehyde oxidases
-CHO  -COOH

Nitrate reductase
NO3-  NO2-

Sulfide oxidase
SO32-  SO42-

Xanthin oxidase
purin catabolism

Formate dehydrogenase
H-COO-  CO2
Platinum Complexes in Cancer
Therapy
Cl
NH3
NH3
Pt
Cl
Cl
Pt
NH3
Cis-dichlorodiammineplatinum (II)
Blocking cell division
Cl
NH3
Trans-dichlorodiammineplatinum (II)
inactive
Cl
Cl
Cl
Cl
NH3
Pt
Pt
Cl
NH3
Cl
Cis-tetrachlorodiammineplatinum (IV)
biologically active
NH3
NH3
Cl
Cl
Trans-tetrachlorodiammineplatinum (IV)
inactive
Platinum Complexes in Cancer Therapy
NH3
NH
N H33
Cl
Pt
NH3
NH
N
H33
PPtt
Cl
Cisplatin
NN
O
N H2
N
N
N
HN
HN
N
N
O
N H2
NH
2
N
Platinum Complexes in Cancer Therapy
Protein
P rot ein
Pt
Pt
G
NNH
H 33
Pt
Pt
G
NNH
H 33
a
G
N H3
NH
3
b
NNH
H 33
Injection
Blood
Toxic side effect
Cytostatic effect
Plasma proteins
Blood stream
Kidney
Other organs
Liver
Excretion
Tumor cells
Activity of Pt(NH3)2X2 complexes
X
Activity
NO3-
toxic
H2O
toxic
Cl-
antitumor
Br-
antitumor
I-
inactive
SCN-
inactive
NO2-
inactive
CN-
inactive
(X = ligand)
O
C
O
Pt
C
O
N H3
N H3
O
a Pt-chelate complex
(considerable antitumor activity)