BIOINORGANIC CHEMISTRY
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Homepage of University of Szeged Department of Inorganic
and Analytical Chemistry: www.sci.u-szeged.hu/inorg/oktatas
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Recommended literature:
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Robert R. Crichton:
Biological Inorganic Chemistry, An Introduction, Elsevier,
Amsterdam, 2007
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S.J. Lippard, J.M. Berg:
Principles of Bioinorganic Chemistry, University Science
Book, California, 1994
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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; O2:
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)
Element
mass
(m/m)
%
(n/n)
%
Element
mass
(m/m)
%
(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 today’s 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 today’s and prehistoric men (ppm)
Prehistoric man
Today’s 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
Element
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 (~ 4·109 year)
Phase 2 (~ 2·109 year)
Phase 3 (present)
Main components: (p > 10-2 bar)
CO2 (10 bar)
N2
N2 (1 bar)
CH4, CO
N2
O2
Low concentration components: (10-2 > p > 10-6 bar)
H2O
H2O
H2S
CO2
NH3, Ar, H2(?)
Ar, O2
H2O
CO2
Ar
Trace components: (p < 10-6 bar)
O2 (10-13 bar)
CH4, NH3
SO2,
CH4, CO
NO, SO2
Composition and changes of sea water
Phase 1 (~ 4·109 year)
pH ~ 2 (→ 5.5),
T ~ 80 oC
Phase 2 (~ 2·109 year)
Phase 3 (present)
pH ~ 8.0
T ~ 55 oC
pH ~ 8.0
T ~ 25 oC
0,0 – + 0,4 V
~ + 0,8V
Source of acidity:
HCl (+ CO2, SO2)
Redox potential:
0,0 – - 0,5 V
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
Na
Cl
10050
19000
Earth
crust
28300
130
Al
Si
Ti
Cr
Mo
Ln
Cu
0,01
3,0
0,001
0,0005
0,01
10-7
0,003
81300
277000
4400
100
1,5
1 – 100
55
accumulation
(sea/earth)
0,37
146
10-7
10-5
10-7
10-6
0,01
10-8
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 és 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 ºC, 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 today’s 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
aerobic life forms starts:
→ development of
 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
today’s 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 today’s 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 és 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)
Ellenőrző kérdések
1.
2.
3.
4.
5.
Mi a különbség a hasznos és a létfontosságú elemek
között?
Mennyire különböző koncentrációban szükségesek a
létfontosságú elemek az emberi szervezet számára?
Változott-e a létfontosságú elemek csoportja a kémiai
és biológiai evolúció során? Példákkal igazolja
állítását!
Milyen kémiai illetve biológiai folyamat változtatta meg
a redukáló ősatmoszférát oxidálóvá?
Hogyan védekeztek az őssejtek a számukra mérgező
oxigén megjelenése ellen?
Bioszervetlen kémia segédanyagok:
Kémia intézet honlapja:
http://www.chem.science.unideb.hu
Kurzusinformaciok
K3125 Bioszervetlen kémia
Bevezetés
Koordinációs kémia
Alkálifémek és alkáliföldfémek
Réz
Vas I.
Vas II.
Cink
MoMnCoNiSe
Alkalmazások
Vanádium és p-mező elemei
Javasolt irodalom:
1. Kiss Tamás, Gajda Tamás, Gyurcsik Béla:
Bevezetés a bioszervetlen kémiába (Nemzeti Tankönyvkiadó)
2. Kőrös Endre: Bioszervetlen kémia (Gondolat Kiadó)
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 (kemény-lágy) sav-bázis elmélet (HSAB)
Lewis sav: elektronpár akceptor
Lewis bázis: elektronpár donor
Csoportosítás: polarizálhatóság (ionméret + töltés) alapján
Hard (kemény): nehezen polarizálható = kis méret + nagy töltés
Soft (lágy): könnyen polarizálható = nagy méret + kis töltés
sav
hard (s2p6)
Li+, Be2+, Al3+, Ln3+
Ti(IV), Mn(VII)
bázis
F-, O2-,...
soft (d8- d10)
Cu(I), Ag(I), Hg(II)
I-, S2-, CN-,....
többszörös kötésű
szerves vegyületek
(tiolok, aromás-N)
közbenső (3dx)
(borderline)
Cu(II), Zn(II),...
Cl-, Br-, H2O,
NH3,....