BIOINORGANIC CHEMISTRY Homepage of University of Szeged Department
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;
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 Mo 0, 1 1, 0 Al 0, 4 0, 9 2, 3 Ti 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 (~ 4· 109 year) Phase 2 (~ 2· 109 year) Phase 3 (present) Main components: (p > 10 -2 bar) CO 2 (10 bar) N 2 (1 bar) CH 4, CO N 2 O 2 Low concentration components: (10 -2 > p > 10 -6 bar) H 2 O H 2 S CO 2 NH 3, Ar, H 2(? ) Ar, O 2 H 2 O CO 2 Ar Trace components: (p < 10 -6 bar) O 2 (10 -13 bar) CH 4, NH 3 SO 2, CH 4, CO NO, SO 2
Composition and changes of sea water Phase 1 (~ 4· 109 year) p. H ~ 2 (→ 5. 5), T ~ 80 o. C Phase 2 (~ 2· 109 year) Phase 3 (present) p. H ~ 8. 0 T ~ 55 o. C p. H ~ 8. 0 T ~ 25 o. C 0, 0 – + 0, 4 V ~ + 0, 8 V Source of acidity: HCl (+ CO 2, SO 2) Redox potential: 0, 0 – - 0, 5 V Chemical constituents: M+ and M 2+ ions in increasing, while M 3+ ions in decreasing concentration
Elemental composition of earth crust and sea water (ppm) Element Sea water Na Cl 10050 19000 Earth crust 28300 130 accumulation (sea/earth) 0, 37 146 Al Si Ti 0, 01 3, 0 0, 001 81300 277000 4400 10 -7 10 -5 10 -7 Cr Mo Ln Cu 0, 0005 0, 01 10 -7 0, 003 100 1, 5 1 – 100 55 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 H 2, He elimination to the cosmos the most stable C compounds: CH 4, CO és CO 2 further main components: H 2 O, SO 2, N 2 – prehistoric ocean: H 2 O + N 2 + NH 3 + SO 2 + CO 2 + H 2 + 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. – H 2 O in the atmosphere UV-light, photodissociation H 2, O 2 - At the hight of 11 km: – 60 ºC, vapour precipitates, H 2 „migrates” O 2 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, O 2 is toxic for the anaerobic life forms starts: → development of photosynthesis H 2 O + CO 2 + h O 2 + CH 2 O (carbohydrates)
Development of oxygen atmosphere II. – 2, 5 – 3 billion years ago the O 2 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 O 2 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. O 2 transport: hemoglobin (Fe) hemerythrin (Fe) hemocyanin (Cu) O 2 storage: myoglobin (Fe), . . 2. Activation of molecules: metalloenzymes a/ catalyses of redox processes: Fe. III/Fe. II és Cu. II/Cu. I redox systems (+ Mn, Co, Mo, . . ) b/ catalyses of acid-base processes (hydrolitic reactions) Zn. II-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 K 3125 Bioszervetlen kémia Bevezetés Koordinációs kémia Alkálifémek és alkáliföldfémek Réz Vas II. Cink Mo. Mn. Co. Ni. Se 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 (s 2 p 6) Li+, Be 2+, Al 3+, Ln 3+ Ti(IV), Mn(VII) bázis F-, O 2 -, . . . soft ( d 8 - d 10) Cu(I), Ag(I), Hg(II) I-, S 2 -, CN-, . . többszörös kötésű szerves vegyületek (tiolok, aromás-N) közbenső (3 dx) (borderline) Cu(II), Zn(II), . . . Cl-, Br-, H 2 O, NH 3, . .
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