BIOINORGANIC CHEMISTRY

Homepage of University of Szeged Department of Inorganic

and Analytical Chemistry: www.sci.u-szeged.hu /inorg/oktatas

Recommended literature:

Robert R. Crichton:
Biological Inorganic Chemistry, An Introduction, Elsevier,
Amsterdam, 2007

S.J. Lippard, J.M. Berg:

Principles of Bioinorganic Chemistry, University Science
Book, California, 1994

W. Kaim, B. Schwederski:
Bioinorganic Chemistry: Inorganic Elements in the
Chemistry of Life, John Wiley & Sons, 1994
 The development and subject of bioinorganic chemistry

Subject: The exploration and modeling the biological role (absorption,

binding, transport, distribution, function, excertion) of inorganic
elements (essential or toxic), as well as the practical applications of
these findings in pharmacy, in agriculture, in environmental protection
etc.

Development: parallel with the development of other disciplines:

- biochemistry: coloured proteins, biological redox processes, etc.
- Increase of the sensitivity of analytical methods:
~ 50 70 chemical elements have been usually detected in real
biological samples.
- clinical observations: diseases due to metabolic disturbances of
-metal ions
-coordination chemistry: stability of metal ion bioligand interactions
Descriptive knowledge will be given primarily based on the
function of the metal ions and not on their position in the
periodic table.

- Distribution of the elements in biology and their evolution.

- Interactions of biomolecules and metal ions.
- Enzymes, metalloenzymes.
- Metabolism of metal ions, absorption, transport, storage.
- The role of metal ions in biological processes (unequal ion
distribution, electrontransfer, enzymes, activation of small
molecules).
- Complex physiological effects of metal ions (disfunctions in
metal ion homeostasis, toxic metal ions, medicinal applications)
- Appendicies: Basic coordination chemistry. Methods.
 Elemental composition of biological systems

Results of the chemical analysis of biological samples:

practically all elements of the periodic table (min. 50-70 element)
can be detected in real biological samples by up to date analytical
instruments.

Classification
Essential elements
occur in a given concentration range,
they excert positive biological effects for several different
species
- Impurity elements
their quantity is a function of environmental effects
types : indifferent elements
beneficial elements
toxic elements
 Biological effects of the elements

+ essential
normal
Physiological
response indifferent

-
toxic

Concentration in food
 Essential elements
(conditions for classification)

1. Positive physiological response can be ascribed to their

presence in the case of several species.

2. They occur in well defined concentration range in each species,

3. Deprival (from food) will results in reproducible and negative

physiological changes. These effects can be reversible reversed
or at least reduced by addition of the given element.

4. Their deficiency and excess is connected with well defined

diseseases.

5. The biological presence of the element is connected with well

defined biochemical processes.
 Essential elements

1. Organic skeleton components: (6 elements)

C, H, O, N, S, P

2. Inorganic skeleton and body-fluid components: (5 elements)

Na, K, Ca, Mg, Cl

3. Trace elements: (~14 elements)

- main group: Se, Si, Sn, F, I
- transition metal: Fe, Zn, Cu, Mn, Co, Ni, V, Cr, Mo

Non essential (impurity) elements:

- beneficial: B, Ti, W,... (As, Cd, Pb....)
- toxic: Hg, Cd, Pb, Tl, As, Pt metals, Be, Ba,..
 Biological functions of the elements

1) Elements forming the outer and inner skeleton: anion

formings: C,O,P,S,N,F,Si; cation formings: K, Ca, Mg;
2) Their biological functions are due to the unequal distribution:
K, Na, Ca, Mg, Cl, HPO4;
3) Lewis acid catalysts: Zn, Mg, (Fe, Mn), redox catalysts: Fe, Cu,
Mn, Mo, Co, Ni, (V, Se)
4) Metal ions for electrontransfer processes: Cu, Fe, Ni
5) Metal ions participating in activation of small biomolcules; O 2:
Fe, Cu, Mn; N2: Fe, Mo, V; CO2: Ni, Fe,
6) Metal ions with special functions: cobalamin coenzyme: Co;
chlorophyl: Mg; magnetic or gravity sensors: Fe, Ca, Si;
 Average amount of the various elements in a human organism
(70 kg body weight)

(m/m) (n/n) (m/m)

Element mass Element mass (n/n)%
% % %
O (kg) 45,55 65,1 26,0 Na (g) 70 0,10 0,03
C (kg) 12,59 18,0 9,6 Mg (g) 42 0,06 0,02
H (kg) 6,78 9,7 62,3 Fe (g) 4-4,5 0,007 0,0007
N (kg) 1,82 2,6 1,2 Zn (g) 2-3 0,0035 0,0004
P (g) 680 1,0 0,2 Cu (mg) 80-120 0,00014 0,00001
S (g) 100 0,15 0,03 Mn (mg) 12-20 0,00003 -
Ca (g) 1700 2,42 0,38 Mo (mg) 4-5 0,00001 -
K (g) 250 0,36 0,06 Se (mg) 20 0,00004 -
Cl (g) 115 0,16 0,03 I (mg) 30 0,00005 -

For comparison: Pb: 80 mg/70 kg, Al: 100 mg/70 kg, Sr: 140 mg/70 kg
 Factors affecting the selection of the trace elements

1. Priority of the C based life: C, H, O, N, S, P

may life be based on other element? (B, Si,...)
(not known and is not very likely)

2. Accumulation of the inorganic components

- composition of the todays and the prehistoric men
- environmental conditions of the origin of life
occurrance in the earth crust/sea water and their changes
- role of chemical factors: COMPLEX FORMATION
solubility factors
redox potential
hard-soft theory
Amount of the trace elements of the todays and prehistoric men (ppm)

Element Prehistoric man Todays man Accumulation

Fe 60 60 1,0
Zn 33 33 1,0
Cu 1,0 1,2 1,2
Mo 0,1 0,1 1,0

Al 0,4 0,9 2,3

Ti 0,4 0,4 1,0

Cd 0,001 0,7 700

Hg < 0,001 0,19 > 200
Pb 0,01 1,7 170
 Origin of life I.

Chemical evolution: formation of simple and later more

complex organic molecules from the chemical elements

Prebiological evolution: development of living cells from

biologically important organic molecules

Biological evolution: development of the living system

 Composition and changes of the atmosphere

Phase 1 (~ 4109 year) Phase 2 (~ 2109 year) Phase 3 (present)

Main components: (p > 10-2 bar)

CO2 (10 bar) N2 N2
N2 (1 bar) O2
CH4, CO

Low concentration components: (10-2 > p > 10-6 bar)

H2O H2O H2O
H2S CO2 CO2
NH3, Ar, H2(?) Ar, O2 Ar

Trace components: (p < 10-6 bar)

O2 (10-13 bar) CH4, NH3 CH4, CO
SO , NO, SO
 Composition and changes of sea water

Phase 1 (~ 4109 year) Phase 2 (~ 2109 year) Phase 3 (present)

pH ~ 2 ( 5.5), pH ~ 8.0 pH ~ 8.0

T ~ 80 oC T ~ 55 oC T ~ 25 oC

Source of acidity:
HCl (+ CO2, SO2)

Redox potential:
0,0 - 0,5 V 0,0 + 0,4 V ~ + 0,8V

Chemical constituents:
M+ and M2+ ions in increasing, while M3+ ions in decreasing
concentration
Elemental composition of earth crust and sea water (ppm)

Element Sea water Earth accumulation

crust (sea/earth)
Na 10050 28300 0,37
Cl 19000 130 146
Al 0,01 81300 10-7
Si 3,0 277000 10-5
Ti 0,001 4400 10-7
Cr 0,0005 100 10-6
Mo 0,01 1,5 0,01
Ln 10-7 1 100 10-8
Cu 0,003 55 10-5
 Development of organic compounds/life

4 billion years ago: solidification of the Earth crust

atmosphere of the Earth: reductive
H2, He elimination to the cosmos
the most stable C compounds: CH4, CO s CO2
further main components: H2O, SO2, N2

prehistoric ocean: H2O + N2 + NH3 + SO2 + CO2 + H2 + CO + ...

And from other simple inorganic compounds under the reactive
conditions (on the effects of UV, cosmic, radioactiv radiations and
electric discharges) abiogen formation of simple organic compounds
(e.g. amino acids, nucleic bases, etc.) development of the
anaerobic forms of life (3.5 billion years ago)
(Deeply in the ocean because of the strong UV radiation.)
 Development of oxygen atmosphere I.

H2O in the atmosphere UV-light, photodissociation H2, O2

- At the hight of 11 km: 60 C, vapour precipitates, H2 migrates
O2 is layered above the ice/water
- Conditions of anaerobic metabolism start to be exhausted.

Oxygen in the atmosphere decreses UV radiation; at a level of the

0.001 part of the todays level photodissociation stops and thus
further increase in the oxygen level is possible only in a biological
way.
- However, O2 is toxic for the anaerobic life forms development of
aerobic life forms starts:
photosynthesis

H2O + CO2 + h O2 + CH2O (carbohydrates)

 Development of oxygen atmosphere II.

2,5 3 billion years ago the O2 reaches 0.01 part of the

todays level perspiration instead of anaerobic
fermentation higher organisation at 30 cm depth of the
oceans
600 - 700 million years ago the O2 reaches 0.1 part of the
today s level; the ozone layer becomes thicker life could
leave the ocean and occurred on the earth

- 300 million years ago the todays atmosphere was formed

elementar composition of the biological systems becomes
stable (further changes occur only by human activity)
 Classification of the role of trace elements
1. Transport and storage of small biomolecules
e.g. O2 transport: hemoglobin (Fe) hemerythrin (Fe) hemocyanin (Cu)
O2 storage: myoglobin (Fe),....

2. Activation of molecules: metalloenzymes

a/ catalyses of redox processes:
FeIII/FeII s CuII/CuI redox systems (+ Mn, Co, Mo,....)
b/ catalyses of acid-base processes (hydrolitic reactions)
ZnII-complexes (+ Ca, Mg, (Mn,...))

3. Stabilisation of conformation of macromolecules

a/ metalloenzymes (the metal ion is not active centrum)
b/ zinc fingers (structure makers)

4. Transport and storage of trace elements:

e.g. ferritin, transferrin (Fe)
 Ellenrz krdsek
1. Mi a klnbsg a hasznos s a ltfontossg elemek
kztt?
2. Mennyire klnbz koncentrciban szksgesek a
ltfontossg elemek az emberi szervezet szmra?
3. Vltozott-e a ltfontossg elemek csoportja a kmiai
s biolgiai evolci sorn? Pldkkal igazolja
lltst!
4. Milyen kmiai illetve biolgiai folyamat vltoztatta meg
a redukl satmoszfrt oxidlv?
5. Hogyan vdekeztek az ssejtek a szmukra mrgez
oxign megjelense ellen?
Bioszervetlen kmia segdanyagok:

Kmia intzet honlapja:

http://www.chem.science.unideb.hu
Kurzusinformaciok
K3125 Bioszervetlen kmia
Bevezets
Koordincis kmia
Alklifmek s alklifldfmek
Rz
Vas I.
Vas II.
Cink
MoMnCoNiSe
Alkalmazsok
Vandium s p-mez elemei
Javasolt irodalom:

1. Kiss Tams, Gajda Tams, Gyurcsik Bla:

Bevezets a bioszervetlen kmiba (Nemzeti Tanknyvkiad)

2. Krs Endre: Bioszervetlen kmia (Gondolat Kiad)

3. S.J. Lippard, J.M. Berg:

Principles of Bioinorganic Chemistry (University Science Book)

4. W. Kaim, B. Schwederski:
Bioinorganic Chemistry: Inorganic Elements in the
Chemistry of Life, (John Wiley & Sons)
 Hard-soft (kemny-lgy) sav-bzis elmlet (HSAB)
Lewis sav: elektronpr akceptor Lewis bzis: elektronpr donor
Csoportosts: polarizlhatsg (ionmret + tlts) alapjn
Hard (kemny): nehezen polarizlhat = kis mret + nagy tlts
Soft (lgy): knnyen polarizlhat = nagy mret + kis tlts

sav bzis
hard (s2p6) Li+, Be2+, Al3+, Ln3+ F-, O2-,...
Ti(IV), Mn(VII)

soft ( d8- d10) Cu(I), Ag(I), Hg(II) I-, S2-, CN-,....

tbbszrs kts
szerves vegyletek
(tiolok, aroms-N)

kzbens (3dx) Cu(II), Zn(II),... Cl-, Br-, H2O,

(borderline) NH3,....