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

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

The development and subject of bioinorganic chemistry

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.

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.

ClassificationEssential elements

occur in a given concentration range,they excert positive biological effects for several different

species

- Impurity elementstheir quantity is a function of environmental effects

types : „indifferent” elements„beneficial” elementstoxic elements

Elemental composition of biological systems

Biological effects of the elements

Concentration in food

Physiologicalresponse

-

+ essential

toxic

indifferent

normal

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 (conditions for classification)

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)

Element 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

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

Origin of life I.

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

N2 (1 bar) O2

CH4, CO

Low concentration components: (10-2 > p > 10-6 bar) H2O H2O H2OH2S CO2 CO2

NH3, Ar, H2(?) Ar, O2 Ar

Trace components: (p < 10-6 bar)O2 (10-13 bar) CH4, NH3 CH4, CO

SO2, NO, SO2

Composition and changes of sea water

Phase 1 (~ 4·109 year) Phase 2 (~ 2·109 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 crust

accumulation (sea/earth)

Na

Cl

10050

19000

28300

130

0,37

146

Al

Si

Ti

0,01

3,0

0,001

81300

277000

4400

10-7

10-5

10-7

Cr

Mo

0,0005

0,01

100

1,5

10-6

0,01

Ln

Cu

10-7

0,003

1 – 100

55

10-8

10-5

Development of organic compounds/life

– 4 billion years ago: solidification of the Earth’ crustatmosphere 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.)

– H2O in the atmosphere H2, O2

Development of oxygen atmosphere I.

- 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 → development of aerobic life forms starts: photosynthesis

H2O + CO2 + h O2 + CH2O (carbohydrates)

UV-light, photodissociation

– 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)

Development of oxygen atmosphere II.

Classification of the role of trace elements

1. Transport and storage of small biomoleculese.g. O2 transport: hemoglobin (Fe) hemerythrin (Fe) hemocyanin (Cu) O2 storage: myoglobin (Fe),....

2. Activation of molecules: metalloenzymesa/ 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 macromoleculesa/ 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. Mi a különbség a hasznos és a létfontosságú elemek között?

2. Mennyire különböző koncentrációban szükségesek a létfontosságú elemek az emberi szervezet számára?

3. Változott-e a létfontosságú elemek csoportja a kémiai és biológiai evolúció során? Példákkal igazolja állítását!

4. Milyen kémiai illetve biológiai folyamat változtatta meg a redukáló ősatmoszférát oxidálóvá?

5. Hogyan védekeztek az őssejtek a számukra mérgező oxigén megjelenése ellen?

Bioszervetlen kémia segédanyagok:

Kémia intézet honlapja:http://www.chem.science.unideb.huKurzusinformaciokK3125 Bioszervetlen kémia

BevezetésKoordinációs kémiaAlkálifémek és alkáliföldfémekRézVas I.Vas II.CinkMoMnCoNiSeAlkalmazásokVanádium 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 donorCsoportosítás: polarizálhatóság (ionméret + töltés) alapjánHard (kemény): nehezen polarizálható = kis méret + nagy töltésSoft (lágy): könnyen polarizálható = nagy méret + kis töltés

sav bázis

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

soft (d8- d10) Cu(I), Ag(I), Hg(II) I-, S2-, CN-,....többszörös kötésűszerves vegyületek(tiolok, aromás-N)

közbenső (3dx) Cu(II), Zn(II),... Cl-, Br-, H2O, (borderline) NH3,....