Metals in Medicines: Bioinorganics, Diagnostics and Therapeutics

Question 1

Discuss the metal centre, ligands, geometry, structure and function of Hb.

Answer 1

metal centre: Fe II/III

ligands: 4 N on plane, 1 N histidine below, 1 O₂ above
geometry: octahedral, when O₂ bound
structure: 4 subunits, each include a haeme group
function: oxygen transport, gases transport CO₂ NO

Question 2

What are examples of reactions in metal centres?

Answer 2

• substitution reactions (ligand exchange)
• addition reactions
• elimination reactions
• oxidative/reductive addition

Question 3

What are the two ways substitution reactions can occur?

Answer 3

step by step

• ML₅X -> ML₅ + X
• ML₅ + Y -> ML₅Y

one step process

• ML₅X -> ML₅XY -> ML₅Y

Question 4

What would a graph look like for a step by step substitution reaction?

Answer 4

• two transition states with an intermediate

Question 5

What would a graph look like for a one step substitution reaction?

Answer 5

• one transition state
• no intermediate

Question 6

What is the most common substitution reaction?

Answer 6

hydrolysis (Y is water)

Question 7

What are things to consider in metal reactions?

Answer 7

• changes in oxidation state
• changes in geometry
• charge of ligands

Question 8

How does UV VIS work?

Answer 8

electrons jump to unoccupied orbitals to higher energy states

Question 9

What do the three jumps on a UVVIS graph show?

Answer 9

• intra-ligand transitions; if ligand is a chromophore
• L-M or M-L charge transfer; always occurs
• metal d-d bands; if electrons present in d orbital

Question 10

What generates the colours on UV-VIS?

Answer 10

d-d transition bands

Question 11

How can you characterise metalloproteins?

Answer 11

• UV-Vis
• MS
• NMR - EPR
• IR - RAMAN

Question 12

What is EPR?

Answer 12

electronic paramagnetic resonance

need an uneven no. of electrons = uneven spin

unpaired electrons placed in magnetic field

can determine oxidation state and nature of ligands directly bound to metal centre

Question 13

What is RAMAN?

Answer 13

looks like a flipped IR spectra, less signals

Question 14

When is lithium carbonate used?

Answer 14

• acute treatment of mania
• prophylaxis in bipolar disorder
• augments antidepressants in treatment refractory recurrent depression

taken orally, mostly renal elimination

narrow TI

Question 15

How do you monitor metal levels in biological samples?

Answer 15

• molecular spectroscopy
  
  • broad
• atomic spectroscopy
  
  • thin, no overlap so intensity can be related to concentration

both show absorption and emission (at higher orbital)

Question 16

What are contrast agents for CT scan and MRI?

Answer 16

CT scan: xray based, usually iodine, barium, gallium based

MRI: NMR based, usually gallium based

Question 17

What are arthritis treatments and how are they administered?

Answer 17

myocrisin: IM inj
auranofin: orally - reduces inflammation

Question 18

How is auranofin metabolised? what is its mechanism of action?

Answer 18

phase I deacetylation - loses all groups that are protecting OHs in sugar unit

inhibits redox enzymes and induces enzyme with antiinflammatory properties