1. BIOINORGANIC CHEMISTRY discipline at the interface between inorganic chemistry and biology

2. BIOINORGANIC CHEMISTRY discipline at the interface between inorganic chemistry and biology Resources Biological Inorganic Chemistry: Structure and Reactivity H. B. Gray, E. I. Stiefel, J. Selverstone Valentine, I. Bertini, Eds., University Science Books, 2006 The long history of iron in the Universe and in health and disease Biochim. Biophys. Acta, 2012, 1820, 161-187

3. THE ELEMENTS OF LIFE 24 elements are essential to life H through Zn – excluding He, Ne, Ar, Li, Be, Al, Sc, Ti Se, Mo, I 7 additional elements are essential to certain organisms Sr, Ba, W, As, Br, Cd, Sn

4. THE ELEMENTS OF LIFE bulk elements C, H, N, O, P, S macrominerals and ions Na, K, Mg, Ca, Cl, PO 4 3-, SO 4 2- trace elements Fe, Zn, Cu ultratrace nonmetals and metals F, I, Se, Si, As, B Mn, Mo, Co, Cr, V, Ni, Cd, Sn

5. ELEMENTAL FUNCTIONALITY charge carriers – Na, K, Cl structure and templating – Ca, Zn, Si, S signaling – Ca, B, N, O, Zn buffering – P, C catalysis – Zn, Fe, Ni, Mn, V, Co, Cu, W, S, Se electron transfer – Fe, Cu, Mo energy storage – H, P, S, Na, K, Fe biomineralization – Ca, Mg, Fe, Si, Sr, Cu, P

6. THE ELEMENTS OF LIFE bulk elements C, H, N, O, P, S macrominerals and ions Na, K, Mg, Ca, Cl, PO 4 3-, SO 4 2- trace elements Fe, Zn, Cu ultratrace nonmetals and metals F, I, Se, Si, As, B Mn, Mo, Co, Cr, V, Ni, Cd, Sn

7. ELEMENTAL MASS ABUNDANCE IN A 70 kg HUMAN

8. SYMPTOMS OF ELEMENTAL DEFICIENCY IN HUMANS

9. ELEMENTAL ABUNDANCE IN THE UNIVERSE

10. TERRESTRIAL ELEMENTAL ABUNDANCE

12. ELEMENTAL ABUNDANCE

13. TERRESTRIAL ELEMENTAL ABUNDANCE

15. ELEMENTAL MOLAR ABUNDANCE OF TRANSITION METALS

16. TRAPS FOR BIOLOGICAL ELEMENTS

17. CARRIERS IN BLOOD PLASMA

18. ELEMENTAL MOLAR ABUNDANCE OF TRANSITION METALS

19. ELEMENTAL ABUNDANCE IN THE UNIVERSE

20. EVOLUTIONARY TIMELINE

21. HYDROLYSIS REACTIONS OF Fe 3+

22. ELEMENTAL MASS ABUNDANCE IN A 70 kg HUMAN

23. AVERAGE IRON DISTRIBUTION IN HUMANS

24. BINDING OF O 2 BY MYOGLOBIN

25. HEME REDUCTION POTENTIALS Fe 3+ /Fe 2+

26. IRON REDUCTION POTENTIALS

27. PROTEINS – CLASSES AND FUNCTIONS dynamic catalysis enzymes transporthemoglobin protectionantibodies muscle contractionactin and myosin metabolic controlhormones gene transcriptionhistones storageferritin structural matrices for bone collagen and elastin and connective tissue

28. PROTEINS proteins are polymers of 20 different  -amino acids, known as the common amino acids, which have a specific codon in the DNA genetic code properties of 20 genetically coded amino acids  -amino group – except proline, which has an imino group  -carboxyl group unique R side chain and a hydrogen bound at the central  carbon possess at least one asymmetric carbon ( L form) except glycine HOOC – C – NH 2 H R

29. PROTEINS at neutral pH, the amino and carboxyl groups are ionized, and the amino acids thus exist as zwitterions proteins are produced by enzymatic polymerization of the 20 common amino acids, connected by peptide bonds formed by dehydration

30. AMINO ACIDS – ALIPHATIC

31. AMINO ACIDS – POLAR

32. AMINO ACIDS – AROMATIC

33. AMINO ACIDS – SULFUR OR SELENIUM H

34. AMINO ACIDS – SECONDARY AMINE

35. AMINO ACIDS – CHARGED

36. PROTEINS proteins are produced by enzymatic polymerization of the 20 common amino acids, connected by peptide bonds formed by dehydration the specific sequence of amino acids in the polypeptide chain is called the primary structure of the protein and is determined from the genetic information

37. PROTEINS apoprotein – amino acids only cofactors – small organic (e.g., vitamins, ATP, NAD, FAD) or inorganic molecules (particularly metal ions) that are required for activity; can be loosely bound (coenzymes) or tightly bound (prosthetic groups) prosthetic group – tightly bound group (e.g., heme) to apoprotein holoprotein – active protein with cofactors and prosthetic groups attached

38. COFACTORS may participate directly in catalytic processes or carry other small molecules; binding to proteins may be weak or strong are required in small quantities, may have to be supplied in diet and are either water or fat soluble functions metal ions maintain protein conformation through electrostatic interactions prosthetic groups like heme may bind to active site and change the conformation to control bonding may accept a substrate during reaction

39. METAL LIGATION metal ions are bound in mononuclear or polynuclear coordination units in which amino acid side chains function as endogenous multidentate chelating ligands (protein) often protein ligation does not coordinately saturate metals – catalysis common bridging ligands O 2-, OH -, -CH 2 S -, S 2-, -CH 2 CO 2 -, imidazole exogenous terminal ligands are also often bound to metals H 2 O, OH -, O 2-, HS -, S 2-

40. ENDOGENOUS METAL LIGATION Oxygen atoms of peptide carbonyls, nitrogen atoms of deprotonated backbone amides, and lysine side chains are also available for metal coordination. Protein residues as ligands for metal ions

41. ENDOGENOUS METAL LIGATION

43. PROTEINS apoprotein – amino acids only cofactors – small organic (e.g., vitamins, ATP, NAD, FAD) or inorganic molecules (particularly metal ions) that are required for activity; can be loosely bound (coenzymes) or tightly bound (prosthetic groups) prosthetic group – tightly bound group (e.g., heme) to apoprotein holoprotein – active protein with cofactors and prosthetic groups attached

44. PROSTHETIC GROUPS biosynthesized groups that may participate directly in catalytic processes or carry other small molecules; binding to proteins is strong functions bind metal cations tightly may accept a substrate may participate in electron transfer may bind to active site and change the conformation to control bonding

45. MACROCYCLIC LIGANDS tetrapyrroles most common, best known bioinorganic compounds study of structure/function and organic synthesis of these complexes led to several Nobel prizes 1915 – Willstätter (extraction of pigments, relationship between chlorophyll and heme) 1930 – Fischer (formula of heme and chlorophyll, first synthesis of tetrapyrroles) 1962 – Kendrew & Perutz (X-ray structure of hemoglobin and myoglobin) 1964 – Crowfoot Hodgkin (X-ray structure of vitamin B 12 ) 1965 – Woodward (total synthesis of vitamin B 12 and chlorophyll) 1988 – Deisenhofer, Huber, & Michel (X-ray structure of photosynthetic reaction centers containing heme and chlorophyll in bacteria)

46. TETRAPYRROLES partially unsaturated, tetradentate, macrocyclic ligands stable, rigid, planar or nearly planar ring system deprotonated forms bind metal ions tightly and size selectively extensive conjugation leads to very intense colors (pigments of life) and potentially to redox activity

47. PORPHYRINS

50. CHLORINS – CHLOROPHYLL a chlorophyll a

51. CORRINS – VITAMIN B 12

52. SPECIAL COFACTOR LIGANDS – PTERINS FOR Mo AND W M = Mo or W R = H or adenosine M = Mo or W R = H, adenosine, cytosine, guanosine, hypoxanthine

53. SPECIAL COFACTOR LIGANDS FOR Mo Mo NITROGENASE A few families of bacteria and archea are the only organisms that can produce nitrogen-containing compounds from atmospheric dinitrogen (N 2 fixation). All other fixed-nitrogen derives from abiological processes. Current nitrogen fixation : -Abiological natural processes (lightning, volcanic eruptions): ≈10% -Haber-Bosch process: ≈30% -Biological nitrogen fixation: ≈60% The most common nitrogen-fixing enzyme is Mo-nitrogenase

54. SPECIAL COFACTOR LIGANDS FOR Mo – NITROGENASE His homocitrate In fact, recent evidence indicates that there is a carbon in the middle of the FeMo cofactor of nitrogenase: Science 2011, 334, 940 Science 2011, 334, 974 Typical textbook drawing:

55. SPECIAL COFACTOR LIGANDS – IRON SULFUR CLUSTERS

57. Dark gray: Fe(III) Light gray: Fe(II) Dual color circle: Fe centers with +2.5 oxidation state Localized and delocalized charges possible Ferromagnetic and antiferromagnetic coupling possible

58. FERREDOXINS