Overview

Question 1

Bioinorganic chemistry

Answer 1

The chemistry of metals in biological systems

Question 2

Bertrand diagram

Answer 2

Describes the physiological and toxic effects of metals

Question 3

Involvement of metals in biological systems as analytical probes

Answer 3

Heavy metals e.g. Hg, Pt for X-ray determination
Paramagnetic metals for NMR, EPR
Luminescent complexes

Question 4

Involvement of metals in biological systems in medicine

Answer 4

Diagnostics .g. 99mTc, Gd (MRI)
Chemotherapy drugs e.g. Pt, Au, Li
Toxicology e.g. Hg

Question 5

Biological functions of metals

Answer 5

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

Question 6

Examples of reactions catalysed by metals in biological systems

Answer 6

Non-redox reactions e.g. hydrolysis of CO2/amides/phosphates
Isomerases (sugars)
Reductases
Dehydrogenases

Question 7

Borderline metal ions

Answer 7

Fe2+, Co2+, Ni2+, Cu2+, Zn2+

Question 8

Entatic state

Answer 8

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

Question 9

Irving-Williams series

Answer 9

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

Question 10

Acidity of coordinated ligands

Answer 10

Acidity of XH (X = ligand) increases on coordination

Dependent on identity of metal ion

Question 11

Template effect

Answer 11

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

Question 12

Spectrochemical series

Answer 12

An list of ligands, ordered by the strength at which they induce crystal field splitting

Question 13

The redox potential vs M(H2O)6^n+ can be changed by…

Answer 13

…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

Question 14

Additional factors that can regulate redox potentials

Answer 14

Non-bonding interactions with biopolymer/biomolecule

Cooperativity effects in supramolecular interactions

Question 15

Biological systems depend on…

Answer 15

…fast exchange processes

Question 16

Ligand exchange reactions depend heavily on…

Answer 16

…the metal ion

Generally small, highly charged ions exchange slower

Question 17

Mechanism of substitution in octahedral complexes

Answer 17

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)

Question 18

Parallel beta-sheets

Answer 18

Both chains run in the same direction

Question 19

Anti-parallel beta-sheets

Answer 19

Chains running in opposite directions

Question 20

Forces responsible for protein folding

Answer 20

Hydrophobic interactions (reducing hydrophobic surface)
H bond bridges
S-S bonds between Cys residues
Coordination of metals

Question 21

Types of metal coordination in protein structures

Answer 21

1. Preorganised coordination sphere (i.e. even without the metal) - high selectivity for a specific metal
2. Well-defined structural change upon coordination of a metal e.g. Ca2+ - leads to change in function
3. Coordination of the metal leads to an unordered protein adopting a defined tertiary structure (becomes highly ordered) e.g. Zn finger

Question 22

Primary structure of DNA

Answer 22

Nucleic acid sequence

Question 23

Secondary structure of DNA

Answer 23

Base pairing between nucleic acids

Question 24

Tertiary structure of DNA

Answer 24

Folding into the double helix structure

Generates major and minor grooves (potential drug targets)

Question 25

Metal binding sites in DNA/RNA

Answer 25

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

Question 26

Most important amino acids as ligands for metals

Answer 26

Cys, His, Tyr, Asp, Glu