Transition MetalsTransition MetalsTransition MetalsTransition Metals

bulk elements

trace elements

for some species

Periodic Table

General roles of metal ions in biologyNa, K:Na, K: Charge carriers

Osmotic and electrochemical gradients

Nerve function

Mg, Ca:Mg, Ca: Enzyme activators

Structure promoters

Lewis acids

Mg2+: chlorophyll, photosynthesis

Ca2+: insoluble phosphates

Other metal ions: less well defined and Other metal ions: less well defined and more more

obscure rolesobscure roles

Zn:Zn: Metalloenzymes

Structure promoters

Lewis acid

Not a redox catalyst!

Fe, Cu, Mo:Fe, Cu, Mo: Electron-transfer

Redox proteins and enzymes

Oxygen carrying proteins

Nitrogen fixation

Biochemical ReactivityBiochemical 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):Fe(II), Fe(III):

Essential for ALL organisms

In plants: iron deficiency

In human body: 4-5 g

Uptake: ~ 1 mg/day

In human bodyIn human body

75% Hem-iron75% Hem-iron

Hemoglobin Myoglobin Cytochromes Oxidases, P-450

25% Non-hem-iron25% Non-hem-iron

Rubredoxins Ferredoxins

PorphyrinsPorphyrins

FeFe Oxygen TransportOxygen 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 StorageOxygen Storage Myoglobin

1 heme group

Porphyrin

HemoglobinHemoglobin

FeFe

Iron Environment in Iron Environment in MyoglobinMyoglobin

Cytochromes, Peroxidases, Cytochromes, Peroxidases, and Catalasesand Catalases

Cytochrome P-450Cytochrome P-450

Oxidation catalyst

Peroxidases/CatalasesPeroxidases/Catalases

Decomposition of organic peroxides.

Electron Transfer ChainsElectron Transfer Chains

Other Fe CompoundsOther Fe Compounds

Ferritin / TransferrinFerritin / Transferrin

Iron storage in spleen, liver and marrow.

Mw 445,000 (4,300 Fe atoms)

bulk elements

trace elements

for some species

Periodic Table

Cu(I), Cu(II)Cu(I), Cu(II)

PlantsPlants Electron transfer

AnimalsAnimals O2-carrying

Protection of DNA

from O2-

Cu-proteins and enzymesCu-proteins and enzymes

Cytochrome oxidase O2 H2O

Tyrosinase, phenol oxidase ox. of phenols

Ceruloplasmin Fe(II) Fe(III)

Blue proteins Electron transfer

Superoxide dismutase Elimination of O2-

Hemocyanin O2 transport

Superoxide DismutaseSuperoxide Dismutase

SOD-Cu2+ + O2.- SOD-Cu1+ + O2

SOD-Cu1+ + O2.- + 2H+ SOD-Cu2+ + H2O2

Oxygen hemocyaninOxygen hemocyaninmollusks and arthropodsmollusks and arthropods

1. Wilson’s disease:

Hereditary disfunction of ceruloplasminCu2+ accumulates in liver, brain: dementia, liver failureAdministration: Cu-specific chelate

2. Menke’s „kinky hair” syndrome:

Hereditary disfunction of intracellular copper transportCopper deficiency symptoms: disturbances in the mental and physical developmentTherapy: intravenously administered copper compounds

3. Acute copper deficiency

Insufficient oxygen utilization in brain

4. Mutations in the copper dependent superoxide dismutase

Copper-related Pathological Disorders

Ni(II)Ni(II)

Ni-containing enzymes of bacteria

Urease (Vesicle)

CO-dehydrogenase

Hydrogenases Membranes

MoMoHPO4

2-

Uptake : MoOMoO442-2-

SO42-

Molybdenium enzymesMolybdenium enzymes

Nitrogenase N2 NH3

Aldehyde oxidases -CHO -COOH

Nitrate reductase NO3- NO2

-

Sulfide oxidase SO32- SO4

2-

Xanthin oxidase purin catabolism

Formate dehydrogenase H-COO- CO2

Platinum Complexes in Cancer Therapy

NH3

NH3Cl

Cl

Pt

Cis-dichlorodiammineplatinum (II)

Blocking cell division

NH3

NH3Cl

Cl

Pt

Trans-dichlorodiammineplatinum (II)inactive

Cis-tetrachlorodiammineplatinum (IV)

biologically active

NH3

NH3Cl

Cl

Pt

Cl

ClTrans-tetrachlorodiammineplatinum (IV)

inactive

NH3

NH3 Cl

Cl

Pt

Cl

Cl

NN

NH2

O

NH N

N

N

NH2

O

NH3

NH3

Pt

NN HN

NH2

N

N

N

Pt

NH3

NH3

Cisplatin

NH3

NH3 Cl

Cl

Pt

Platinum Complexes in Cancer Therapy

a b

G

G

NH3

NH3

Protein

NH3

G NH3

Pt

Pt

Pt

NH3

NH3

PtNH3

NH3

Protein

Platinum Complexes in Cancer Therapy

Injection

Blood

Toxic side effect Cytostatic effect

Plasma proteins Blood stream

Kidney Tumor cellsOther organs

Liver

Excretion

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)

C

C

OO

OO

Pt NH3

NH3

a Pt-chelate complex(considerable antitumor activity)