BIOINORGANIC CHEMISTRY

1. 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

2. The development and subject of bioinorganicchemistry • Subject: The exploration and modelingthebiologicalrole (absorption, binding, transport, distribution, function, excertion) of inorganicelements (essentialortoxic), aswellasthepracticalapplications of thesefindingsinpharmacy, inagriculture, inenvironmentalprotection etc. • Development: parallel withthedevelopment of otherdisciplines: • - biochemistry:colouredproteins, biologicalredoxprocesses, etc. • - Increase of thesensitivityofanalyticalmethods: • ~ 50 – 70 chemicalelementshavebeenusuallydetectedinreal • biologicalsamples. • clinicalobservations: diseasesduetometabolicdisturbances of • metal ions • coordinationchemistry: stability of metal ion – bioligandinteractions

3. 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.

4. Elementalcomposition of biologicalsystems • 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

5. Biological effects of the elements + essential normal Physiological response indifferent - toxic Concentration in food

6. Essentialelements (conditionsforclassification) • 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.

7. 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,..

8. Biological functions of the elements • 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; • Lewis acid catalysts: Zn, Mg, (Fe, Mn), redox catalysts: Fe, Cu, Mn, Mo, Co, Ni, (V, Se) • 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, • Metal ions with special functions: cobalamin coenzyme: Co; chlorophyl: Mg; magnetic or gravity sensors: Fe, Ca, Si;

9. Average amount of the various elements in a human organism (70 kg body weight) For comparison: Pb: 80 mg/70 kg, Al: 100 mg/70 kg, Sr: 140 mg/70 kg

10. 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

11. Amount of the trace elements of the today’s and prehistoric men (ppm)

12. Origin of life I. Chemicalevolution: formation of simple and later more complexorganicmoleculesfromthechemicalelements Prebiologicalevolution: development of livingcellsfrombiologicallyimportantorganicmolecules Biologicalevolution:development of thelivingsystem

13. 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 H2O H2S 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

14. 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

15. Elemental composition of earth crust and sea water (ppm)

16. 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, COés 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.)

17. Development of oxygen atmosphere I. UV-light, photodissociation – H2O in the atmosphere 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 → development of aerobic life forms starts: photosynthesis H2O + CO2 + h O2 + CH2O (carbohydrates)

18. Development of oxygen atmosphereII. – 2,5 – 3 billion years ago the O2reaches 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 theO2reaches 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)

19. Classification of the role of trace elements • Transport and storage of small biomoleculese.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)

22. Ellenőrző kérdések • 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?

23. 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

24. Javasolt irodalom: • 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)

25. 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 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 kötésű szerves vegyületek (tiolok, aromás-N) közbenső (3dx)Cu(II), Zn(II),...Cl-, Br-, H2O,(borderline) NH3,....