Transition Metals

Periodic Table bulk elements trace elements for some species

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 Mg

2+

: chlorophyll, photosynthesis Ca

2+

: 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

75% Hem-iron

    Hemoglobin Myoglobin Cytochromes Oxidases, P-450

In human body

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 O 2 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 trace elements for some species

Cu(I), Cu(II) Plants Animals

Electron transfer O 2 -carrying

Cu-proteins and enzymes

 Cytochrome oxidase  Tyrosinase, phenol oxidase  Ceruloplasmin  Blue proteins  Superoxide dismutase  Hemocyanin Protection of DNA from O 2 O 2 H 2 O ox. of phenols Fe(II) Fe(III) Electron transfer Elimination of O 2 O 2 transport

Superoxide Dismutase

SOD-Cu 2+ + O 2 .-



SOD-Cu 1+ + O 2 SOD-Cu 1+ + O 2 . + 2H +



SOD-Cu 2+ + H 2 O 2

Oxygen hemocyanin mollusks and arthropods

Copper-related Pathological Disorders 1.

Wilson’s disease: Hereditary disfunction of ceruloplasmin Cu 2+ 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 (Vesicle)  Hydrogenases Membranes

Mo

Uptake :

MoO 4 2 Molybdenium enzymes

 Nitrogenase  Aldehyde oxidases  Nitrate reductase  Sulfide oxidase  Xanthin oxidase  Formate dehydrogenase HPO 4 2 SO 4 2 N 2  NH 3 -CHO  -COOH NO 3 SO 3 2   NO 2 SO 4 2 purin catabolism H-COO  CO 2

Platinum Complexes in Cancer Therapy

Cl NH 3 Pt Cl NH 3

Cis-dichlorodiammineplatinum (II) Blocking cell division

Cl Cl NH 3 Pt Cl NH 3 Cl

Cis-tetrachlorodiammineplatinum (IV) biologically active

NH 3 Cl Pt Cl NH 3

Trans-dichlorodiammineplatinum (II) inactive

Cl Cl NH 3 Pt NH 3 Cl Cl

Trans-tetrachlorodiammineplatinum (IV) inactive

Platinum Complexes in Cancer Therapy

NH

3

3 NH 3 Cl Pt NH 3 Cl NH 3

Cisplatin

O NH 2 H N O NH

2

2

Platinum Complexes in Cancer Therapy

G G NH 3 NH 3

3

a G NH

3

3 NH 3

3

b

Toxic side effect Plasma proteins Kidney Injection Blood Other organs Liver Excretion Cytostatic effect Blood stream Tumor cells

Activity of Pt(NH 3 ) 2 X2 complexes

X NO

3 -

H

2

O Cl

-

Br

-

I

-

SCN

-

NO

2 -

CN

-

Activity toxic toxic antitumor antitumor inactive inactive inactive inactive (X = ligand)

O C C O O O Pt NH 3 NH 3

a Pt-chelate complex (considerable antitumor activity)