Overview Flashcards
Bioinorganic chemistry
The chemistry of metals in biological systems
Bertrand diagram
Describes the physiological and toxic effects of metals
Involvement of metals in biological systems as analytical probes
Heavy metals e.g. Hg, Pt for X-ray determination
Paramagnetic metals for NMR, EPR
Luminescent complexes
Involvement of metals in biological systems in medicine
Diagnostics .g. 99mTc, Gd (MRI)
Chemotherapy drugs e.g. Pt, Au, Li
Toxicology e.g. Hg
Biological functions of metals
Structural - the coordination geometry around the metal leads to the surrounding protein adopting specific conformations
Communication - information transfer via concentration gradients
Electron reservoir e.g. Fe2S2 clusters
Oxygen transports e.g. Fe, Cu
Catalysts with high selectivity
Examples of reactions catalysed by metals in biological systems
Non-redox reactions e.g. hydrolysis of CO2/amides/phosphates
Isomerases (sugars)
Reductases
Dehydrogenases
Borderline metal ions
Fe2+, Co2+, Ni2+, Cu2+, Zn2+
Entatic state
The active sites of enzymes are held by the protein in a geometry that approaches the structure of the transition state for the reaction that the enzyme catalyses
Ligands with their donor atoms pre-arranged in the same position as in the final metal complex will bind the metal much stronger
Irving-Williams series
Refers to the relative stabilities of complexes formed by transition metals (+2 oxidation state)
Can be explained by electrostatic effects (ionic radius decreases) and LFSEs
Acidity of coordinated ligands
Acidity of XH (X = ligand) increases on coordination
Dependent on identity of metal ion
Template effect
The presence of the metal ion in the reaction mixture directs the formation of the ligand due to the pre-organisation of the coordination sphere
Different products are formed from the same organic reactants in the absence of the metal
Spectrochemical series
An list of ligands, ordered by the strength at which they induce crystal field splitting
The redox potential vs M(H2O)6^n+ can be changed by…
…stabilisation of one oxidation state by ligands
e.g. Cu2+ + e- Cu+ = 0.153 V
Ligands higher in the spectrochemical series (hard donors) stabilise Cu(II), therefore = -1.21 V
Ligands lower in the spectrochemical series (soft donors) stabilise Cu(I) = -0.83 V
…also by strain of the preferred square-planar Cu(II) geometry towards the preferred tetrahedral Cu(I) geometry
Additional factors that can regulate redox potentials
Non-bonding interactions with biopolymer/biomolecule
Cooperativity effects in supramolecular interactions
Biological systems depend on…
…fast exchange processes
Ligand exchange reactions depend heavily on…
…the metal ion
Generally small, highly charged ions exchange slower
Mechanism of substitution in octahedral complexes
Generally a dissociative mechanism via CN5
High stabilisation of CN5 c.f. CN6 leads to faster exchange (d4 and d9 ions)
High stabilisation of CN6 c.f. CN5 leads to slower exchange (d3 and d6 low spin ions)
Parallel beta-sheets
Both chains run in the same direction
Anti-parallel beta-sheets
Chains running in opposite directions
Forces responsible for protein folding
Hydrophobic interactions (reducing hydrophobic surface)
H bond bridges
S-S bonds between Cys residues
Coordination of metals
Types of metal coordination in protein structures
- Preorganised coordination sphere (i.e. even without the metal) - high selectivity for a specific metal
- Well-defined structural change upon coordination of a metal e.g. Ca2+ - leads to change in function
- Coordination of the metal leads to an unordered protein adopting a defined tertiary structure (becomes highly ordered) e.g. Zn finger
Primary structure of DNA
Nucleic acid sequence
Secondary structure of DNA
Base pairing between nucleic acids
Tertiary structure of DNA
Folding into the double helix structure
Generates major and minor grooves (potential drug targets)
Metal binding sites in DNA/RNA
Endocyclic N in the bases favoured by heavy metals e.g. Pt, Cu(II), Cr(III)
OH groups in sugar can be bound by Os(VI) (but rare)
O in phosphate can bind to hard metals e.g. Mg
Most important amino acids as ligands for metals
Cys, His, Tyr, Asp, Glu
