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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 1 Bio-Inorganic Chemistry Lecture 2: Basic Principles and Concepts 2 Overview a) Synopsis of important properties of metal ions b) Geometries and electronic structures of metal ions in Biological System c) 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 d) Properties important for catalysis • • • Lewis acidity Redox potentials and electron transfer rates Ligand exchange rates e) Effect of metal environment created by protein 3 General properties Characteristics Na+, K+ Mg2+, Ca2+ Zn2+, Ni 2+ Predominant +1 oxidation state stability of very low complexes +2 +2 low or medium high preferred donor atoms O O mobility in biological systems high medium Fe, Cu, Co, Mo, Mn see Table 4 high (except Fe2+ and Mn2+, medium ) N, S N, S (sometimes O for high oxidation states) low to low to medium(esp. medium Zn) (Fe2+ and Mn2+) 4 Geometries Preferred geometries in small high- Metal ion spin complexes with O and N donors Cu(II), d9 Mn(III) d4 Cu(I) d10 linear, trigonal planar, or tetrahedral Co(II) d7 octahedral > tetrahedral>others Zn(II) d10 tetrahedral > octahedral > 5-coord. Fe(III), d5 Co(III), d6 Cr(III), d3 Mn(II), d5 Ni(II) d8 tetragonal > 5-coord. > tetrahedral octahedral > others Causes: see Ligand-field theory and steric factors 5 Oxidation states +7 +6 +5 +4 +3 +2 +1 X l X l K Ca Sc Ti X l X X l X X l l X l X l l X l l X V Cr Mn Fe l l l Co Ni Cu Zn : common in chemistry l: Less common in chemistry X : Not available to biology 6 Common spin states for some metal ions Table: Common spin states for some metal ions Metal M2+ M3+ Mn high-spin d5 high-spin d4 Fe low-spin or high-spin d5 Co Ni high-spin d 6 high-spin d 7 high-spin d 6 low-spin d 6 low-spin d 7 7 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 8 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 9 Stability constants - ranges Rough rule of thumb: • Strong complexes: log K > 10 • Weak complexes log K < 4 10 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 11 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. F12 Hard and Soft Acids and Bases Hard Borderline Soft Acids: Fe2+, Co2+, Ni2+, H+, Na+, K+, Mg2+, Cu2+, Zn2+ Ca2+, Cr3+, Fe3+, Co3+ Cu+, Ag+, Au+, Pt2+, Pb2+, Hg2+, Cd2+ Bases: Ar-NH2, Imidazole NH3, RNH2, H2O, OH, O2-, ROH, RO-, RCO2-, PO43- RS-, RSR 13 • See Handout Hard and Soft Acids 14 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 radii b) LFSE Zn(II) 15 Stability Aspects: Interplay between HSAB principle and the IrvingWilliams Series: • High-spin M(II) complexes • Bidentate ligands log K S,N X Y M • Trend more pronounced the softer the ligand O,O N,O N,N Fe Cu Figure from Sigel and McCormick, Acc. Chem. Res. 3, 201 (1970). 16 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 17 Competition between protons and metal ions: Conditional stability constants of the four most common zinc logK’ ligands in proteins 10 Zn-Cys 9 Calculated with: Cys (S,N) logK’ = logK + logKa – log (Ka+[H+]) 8 7 6 5 Zn-His His (N,N) Asp (N,O) Glu (N,O) Zn-Asp and and values for logK for the 1:1 Zn-Glu Zn(aa) complexes (taken from the IUPAC stability constants database). 4 3 -logKa (= pKa): Cys: 8.5 His: 6-7 Asp/Glu: 4 2 1 00 2 4 6 pH 8 10 12 18 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 19 Catalysis in Metalloenzymes 20 Properties of metal ions exploited for enzymatic catalysis • Lewis acidity: affinity for electrons - polarisation of substrates: Zn 2+ - facilitation of attack by external base - increasing attacking power of bound base dO OR' d+ + OHR - 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 21 Lewis acidity: Effect on pKa of bound ligands NB: Hydrolysis of aquocomplexes 22 From Lippard and Berg 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.h 23 Standard reduction potentials (pH 0) Species E0 (V) Cu2+/Cu+ +0.153 Fe3+/Fe2+ +0.771 Mn3+/Mn2+ +1.51 Co3+/Co2+ +1.842 O2 /O2– – 0.33 O2 + H+/ HO2 – 0.13 O2 + 2H+ / H2O2 +0.281 O2 + 4H+ / 2H2O +0.815 O2– + 2H+ / H2O2 +0.89 OH + H+ / H2O +2.31 H+/H2 (pH 7): -0.4 V O2/OH- (pH 7): +0.8 V Oxidising power increases NB: Redox potentials of metal ions are highly dependent on environment and coordinated ligands Biology (ie chemistry in water) is limited to this range. 24 Kinetic aspects • Water exchange rates Expressed as lifetime of complexes Useful to characterise reactivity in ligand exchange reactions inert labile 25 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) 26 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 27