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Key points from last lecture

Key points from last lecture. Many “inorganic” elements are essential for life Organisms make economic use of available resources, but also have developed mechanisms to accumulate certain elements

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Key points from last lecture

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  1. Key points from last lecture • Many “inorganic” elements are essential for life • Organisms make economic use of available resources, but also have developed mechanisms to accumulate certain elements • Despite the low amount of metal ions present in living systems, they are enormously important for virtually all life processes • Both deficiency and overload/excess lead to illness

  2. Bio-Inorganic Chemistry Lecture 2: Basic Principles and Concepts

  3. Synopsis of important properties of metal ions Geometries and electronic structures of metal ions in Biological System Thermodynamics: complex stability and site selectivity Stability constants Charge Ionic radii HSAB principle Irving-Williams Series Other effects pKa values and the competition of metals with protons Properties important for catalysis Lewis acidity Redox potentials and electron transfer rates Ligand exchange rates Effect of metal environment created by protein Overview

  4. General properties + + 2+ 2+ 2+ 2+ Characteristics Na , K Mg , Ca Zn , Ni Fe, Cu, Co, Mo, Mn Predominant +1 +2 + 2 see Table 4 oxidation state stability of very low low or high high (except 2+ complexes medium Fe and 2+ Mn , medium ) preferred O O N, S N, S donor atoms (sometimes O for high oxidation states) mobility in high medium low to low to biological medium(esp. medium 2+ systems Zn) (Fe and 2+ Mn )

  5. Geometries Causes: see Ligand-field theory and steric factors

  6. ¡ +7 l l ¡ +6 l l ¡ +5 l l ¡ ¡ +4 l l l ¡ ¡ ¡ ¡ ¡ +3 l l l ¡ ¡ ¡ ¡ ¡ ¡ ¡ + 2 l l ¡ ¡ +1 K Ca S c Ti V Cr Mn Fe C o Ni Cu Zn Oxidation states X X X X X X X ¡ X X X X ¡: common in chemistry : Less common in chemistry X : Not available to biology

  7. Common spin states for some metal ions

  8. Stability aspects: Thermodynamics of metal binding • Important for Understanding of: • Metal uptake and distribution • Specificity of metal binding (bio)molecules • Catalysis by metalloenzymes • Interactions of metals with nucleic acids

  9. Stability constants L + M LM [LM] = = K [L] [M] Often expressed as log K: e.g.: K = 1015 log K = 15 The dissociation constant Kd is K-1  log Kd = -15

  10. Stability constants - ranges Rough rule of thumb: • Strong complexes: log K > 10 • Weak complexes log K < 4

  11. Stability Aspects: What governs stability ?1. charge effects • Rule of thumb: The higher the charge of the cation, the more stable the complex • Biophysical reason: Charge recombination is favourable • But see later: HSAB principle

  12. 2. Ionic radii • Ionic radii are dependent on: • position in periodic system • charge (the higher, the smaller) • coordination number (the higher, the larger) • If covalence (due to differences in electronegativity), steric hindrance etc. would not operate, z/r (charge/radius) would dictate order of stabilities • In reality: seldom observed, only with very small ligands, e.g. F-

  13. Hard and Soft Acids and Bases • See Handout

  14. Hard and Soft Acids

  15. Stability Aspects: The Irving-Williams Series • Stability order for high-spin divalent metal ion complexes • Always peaks at Cu(II) • Mn(II) always the minimum • Underlying reasons:a) ionic radiib) LFSE Zn(II)

  16. X Y M Stability Aspects: Interplay between HSAB principle andthe Irving-Williams Series: • High-spin M(II) complexes • Bidentate ligands • Trend more pronounced the softer the ligand S,N log K O,O N,N N,O Figure from Sigel and McCormick, Acc. Chem. Res. 3, 201 (1970). Fe Cu

  17. Competition with protons • Both metal ions and H+ are positively charged and have an affinity for bases • The actual concentration of a complex ML therefore depends on [M], [L], and [H+] • Low pH  high [H+]: ML complexes dissociate  Effective (or apparent or conditional) stability constants

  18. Competition between protons and metal ions: Conditional stability constants of the four most common zinc ligands in proteins logK’ 10 Calculated with: logK’ = logK + logKa – log (Ka+[H+]) and values for logK for the 1:1 Zn(aa) complexes (taken from the IUPAC stability constants database). -logKa (= pKa): Cys: 8.5 His: 6-7 Asp/Glu: 4 Zn-Cys 9 Cys (S,N) 8 7 Zn-His His (N,N) Asp (N,O) 6 Glu (N,O) Zn-Asp and Zn-Glu 5 4 3 2 1 0 0 2 4 6 8 10 12 pH

  19. Other contributions to stability • Chelate effect • Preferred coordination geometry • Dielectric constant of the medium: Interiors of proteins can be very different from water – usually more hydrophobic  lower dielectric constant: Enhances charge recombination and therefore complex formation

  20. Catalysis in Metalloenzymes

  21. d- d+ Properties of metal ions exploited for enzymatic catalysis • Lewis acidity: affinity for electrons- polarisation of substrates:- facilitation of attack by external base - increasing attacking power of bound base- pKa values of coordinated ligands are lowered E.g.: aquo-ions: pKa usually 9-10 in zinc enzymes as low as 7. • Orienting the substrate and stabilising it in a conformation conducive to reaction • Redox activity

  22. Lewis acidity: Effect on pKa of bound ligands NB: Hydrolysis of aquocomplexes From Lippard and Berg

  23. Importance of redox chemistry in biological systems • Electron transfer reactions: Energy generation for life is based on flow of electrons - e.g. from “fuel” to O2 (respiration) http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter9/animations.html#

  24. Standard reduction potentials (pH 0) Oxidising powerincreases NB: Redox potentials of metal ions are highly dependent on environment and coordinated ligands Biology (ie chemistry in water) is limited to this range. H+/H2 (pH 7): -0.4 V O2/OH- (pH 7): +0.8 V

  25. Kinetic aspects Expressed as lifetime of complexes Useful to characterise reactivity in ligand exchange reactions • Water exchange rates labile inert

  26. Proteins tune the properties of metal ions • Co-ordination number: • The lower the higher the Lewis acidity • Co-ordination geometry • Proteins can dictate distortion • Distortion can change reactivity of metal ion • Weak interactions in the vicinity: second shell effects • Hydrogen bonds to bound ligands • Hydrophobic residues: dielectric constant can change stability of metal-ligand bonds • We’ll look at these in more detail later (lectures on zinc, copper, and iron enzymes)

  27. Summary • The behaviour of metal ions in biological systems can be understood by combining the principles of coordination chemistry with a knowledge of the special environment created by biomolecules

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