Bioinorganic Flashcards
How does cis-platin work?
In blood plasma has 2x Cl ligands as high [Cl-]
In cytosol low [Cl-] so replaced by OH2 to make charged complex which can coordinate
What are the characteristics of Na+ and K+ complexes?
Weak interactions
Hard ligands
Selectivity from size match and hydrophobicity
No redox chemistry
How are Na+ and K+ used in cells?
Controlling osmotic pressured
Transported in and out of cells - weak, reversible coordination chemistry
What are the characteristics of Mg2+ and Ca2+ complexes?
Hard ligands
Strong ionic interactions - charge dense ions
Selectivity from size match and hydrophobicity
Ca - fast ligand exchange kinetics
No redox chemistry
How is Mg and Ca used in biology?
Mg - ATP catalysis, structural role in enzymes
Ca - signalling (as fast ligand exchange with hard ligands), and structural (Ca phosphates/carbonates are insoluble)
Define compartmentalisation
Distribution of elements in and out of a cell, between organelles
Barriers formed by lipid bilayers - impermeable to ions
What is the concentration of Na+ and K+ in and outside a cell?
Inside - high [K+] and low [Na+]
Outside - low [K+] and high [Na+]
Define passive transport
Channel or ionophore facilitates diffusion of ion down its conc gradient
No energy required
How do K+ protein channels function?
K+ conducted down electrochem gradient
Selective against Na+
What is a ionophore?
Small molecule with polar interior and lipophilic exterior
Allows for reversible binding of ions for membrane transport
What is the use of an ionophore?
Antibiotic targeting the K+ membrane transport
Selectively transports K+ and disrupts ion gradients to destroy bacteria
What is active transport?
Ion pump transports ions against conc gradient using energy from ATP hydrolysis
How do ion pumps work?
Free energy of ATP hydrolysis used to interconvert between two conformations of ion pump
Why is Ca2+ suitable for signalling?
Large & flexible coordination geometry
Intermediate binding constants
Fast ligand exchange kinetics
What is Calmodulin?
Ca2+ sensor - protein
Changes conformer upon 4x Ca2+ binding
How is iron often stored in animals and why?
Essential but difficult to obtain and v toxic in XS
Haemoglobin and myoglobin as Fe-porphyrins
How is Fe(III) transported in mammals?
Transferrin proteins
What are the properties of transferins?
Hard donors
Multi-dentate, chelate effect
High binding constant - to obtain Fe(III) at low conc
How can bacteria get a source of Fe?
Cannot absorb directly - precipitates as Fe(OH)3
Multi-dentate O-donor ligands called siderophores used to scavenge
Describe how myoglobin works
Fe protein that coordinates O2 reversibly
Protein has several alpha-helices, haem is between them
Helix E stabilises coordinated O2
Helix F provides proximal histidine ligand
What is haem?
Fe(II) - porphyrin
How does O2 bind to myoglobin?
Works as O2 is a strong field pi-acceptor ligand
Fe(II) LS has no e- in antibonding orbitals so small radiuseff and moves into porphyrin plane
How can the binding of O2 in myoglobin be shown as an MO diagram?
Where is myoglobin found?
Found in tissue
Controls [O2] in the tissue
What is haemoglobins purpose and basic structure?
O2 transport protein in RBCs
α2β2 Tetramer - each subunit being similar to myoglobin
How does the oxygen binding affinity of myoglobin and haemoglobin compare?
Why is myoglobin not used for oxygen transport?
Myoglobin - 98% saturated in lungs and 91% in tissue so only 7% of sites can be used for transport
Haem - 66 % of sites can be used for transport, due to cooperative binding and release
What does the basic term cooperativity of haem mean?
Change of shape of the haem structure as binding of oxygen changes
What is the model of allosteric cooperativity in haemoglobin?
What prevents the oxidation of haem to Fe(III)?
Steric bulk prevents this thermo tendency
What is hemocyanin?
Cu protein used in anthropods for O2 transport
In the blood plasma directly
Define energy in electrochem terms
Flow of e- from fuel to an oxidant
What are the three electron transfer centre classes?
All found in proteins, and adapted for long-range transfer
What factors affect reduction potentials of metals in proteins?
Coordination chem: ionisation energy, ligands
Influence of active site: relative permittivity, neighbouring charges on AA, H-bonding
How does the influence of the active site affect reduction potential?
Permittivity - stabilises low charge centres
H bonding - stabilise reduced states
What is Marcus’ theory on the rate of ET?
ET rate depends on:
ΔG0 - of reaction
ΔG - activation
λ - reorganization energy
HAD - overlap of electron donor and acceptors
Temperature
What is commonly seen in ET centres in proteins?
Redox active metal centres
Small r(M-L) change between oxn states
Close donor and acceptors
Ability to delocalise e-
How does ET work in Fe porphyrins?
(type of cytochromes)
6-coordinate and low spin
Cytochrome has edge exposed to solvent - can interact with other proteins to allow for e- transfer
How is Cu coordinated in transfer centres?
N imidazole (histidine)
Thiolate S (cysteine)
More oxidising by cytochromes
Why and when are cu centres blue?
Small e- transfer proteins
Ligand to metal charge transfer transitions
What is the entactic state?
State of an atom/group which has geometric or electronic condition adapted for function
Due to binding in a protein
How does ET occur in mono-Cu centred proteins?
Rigid coordination sphere from protein
Why is ET fast in Cu centred proteins?
Rigid coordination sphere prevents r(M-L) change
Small reorganisation energy
When are bi-nuclear Cu e- transfer centres used?
Long range e- transfer in some enzymes
Similar coordination environment to mono
e- delocalised which lowers reorganisation energy
What are the roles and abundance of metal-S/O clusters?
Found in nearly all organisms
Used for: ET, redox catalysis, acid-base catalysis, sensing
What is the structure of Fe-S centres?
Why are FeS centres good for doing fast ET?
Can delocalise the extra e-
Minimises bond length change
Decreased reorganisation energy
What are the structures of the three most common FeS centres?
What are the features of FeS structures wrt electronic factors?
Generally single ET
Reduced form is a good reducing agent (in general)
Fe atoms are high spin (tet. geometry of thiolate ligands)
What is the reduction half-equations for FeS?
What affects the redox potential of FeS clusters?
Ligands bonded to Fe: His coordination stabilises Fe(II) and raises reduction potential (more +ve)
Protein environment: proteins raise redox potential (more +ve) due to H-bonding and local dielectric environment
What is an electron relay?
Chain of FeS clusters in proteins
e- tunnels between clusters, to redox partners in mitochondrial membranes
Causes H+ pumping, O2 reduction to H2O
E.g. NADH-hydrogenase
What is a hydrogenase?
Metalloenzymes which catalyse interconversion of H2 and H+
High turnover enzymes
All contain Fe, some also contain Ni in active site
What does the active site of a hydrogenase look like?
Features: bi-metallic, coordinated to protein via cysteine S ligands, one CO or CN ligand
How is H2 oxidised by [FeFe] hydrogenase?
How is H2 oxidised by [NiFe] hydrogenase?
Arginine pockets acts as a base
How does H2 oxidation by hydrogenase compare with classical oxidation?
Classical: oxidative addition by TM complex
Hydrogenase: H2 split heterolytically by “Frustrated Lewis Pair”
How can catalysts working similar to hydrogenases be synthesised?
Frustrated lewis pair compounds synthesised
Compound has lewis acid and base that cannot combine to form an adduct
What is the structure of the Dubois catalyst?
Frustrated lewis pair catalyst
What is carbon monoxide dehydrogenase?
CO2 conversion to CO
Uses FeS clusters, with Ni
[Ni4Fe-4S] clusters
What is the shape of clusters in CO2 dehydrogenase?
What are nitrogenases?
Reduction of N2 to NH3
Found in nitrogen fixing bacteria on root nodules of legumes
Active process - uses ATP, but does at RTP which usually difficult as high activation cost
What is the overall equation of nitrogen fixation?
Uses nitrogenase
N2 + 8 H+ + 16 ATP → 2 NH3 + H2 + 16 PO3(OH)2- + 16 ADP
What is the structure of nitrogenase enzymes?
Two proteins: MoFe and Fe protein
What is the structure of the P cluster in nitrogenases?
What is the structure of the FeMo-cofactor in nitrogenases?
What does FeMo-cofactor (FeMoco) do in nitrogenase?
Site responsible for N2 to NH3
Mechanism not understood
What is the function of Cytochrome c peroxidase?
Reduction of H2O2 using e- from cytochrome c
Uses Ferryl complex
What is the structure of cytochrome c peroxidase?
Fe(III) cytochrome
What is the catalytic cycle for reduction using cytochrome c peroxidase?
What is a ferryl complex?
FeIV=O complex
oxide ligand stabilises high oxidation state
What is cytochrome P450?
Mono-oxygenase → catalyses regiospecific O-insertion into C-H bonds
Essential in biosynthesis
What is the mechanism of Cytochrome P450?
When are ferryl intermediates found in non-haem oxygenases?
Fe(II),coordinated by AA, reacts with O2 → ferryl species
Ferryl species used to oxidise organic compounds
Fe(II) low in Irving-Williams series, so ion not bound tightly and difficult to study spectroscopically
What is corrin?
Cobalt in a complex with macrocyclic ligand
Used as a cofactor
What is cobalamin?
When 5th ligand on corrin complex is benzimidazole
What is a cofactor?
Non-protein compound or metal ion required for enzyme’s activity as a catalyst
What is the structure of coenzyme B12?
What is the structure of coenzyme B12?
What oxidation states of cobalt can exist in macrocycles?
What is the mechanism of the methyl transfer by coenzyme B12?
What is the mechanism of radical-based rearrangements by coenzyme B12?
Co(II) is low spin and JT distortion occurs
Even powerful σ-donors not bound, so weak N- or O- donors do not bind to Co and inhibit catalysis
What are the steps in radical-based rearrangement by coenzyme B12?
Co(III) - C bond in resting state
Homolytic cleavage
C radical performs hydride abstraction
Radical rearrangement to form 1,2 transfer
What forms of radical rearrangements do coenzyme B12 catalyse?
Isomerisation by mutases
Dehydration or deamination by lyases
What is the name of enzymes which use FeS clusters for radical-based rearrangements?
Radical S-adenosylmethionines (radical SAMs)
Same as B12 - uses a 5’-deoxyadenosyl radical, but generated by reductive cleavage of SAM cation using [4Fe-4S] cluster
What is the mechanism for radical SAM production of 5’-deoxyadenosyl radical?
Learn the radical SAM rearrangement with lysine zwitterion?
What is the purpose of cytochrome c oxidase?
Proton pump reduces O2 to H2O
Found in mitochondrial membranes
What is the equation and mechanism of cytochrome c oxidase?
O2(g) + 4e- + 8H+ → 2H2O(l) + 4H+
Proton in reactants from inside, in products outside
Protons pumped across mitochondrial membrane against conc gradient
Gradient formed used to make ATP (via ATP synthase), so is an energy store
What is the structure of metal centres in cytochrome c oxidase?
What is the mechanism of cytochrome c oxidase?
O2 binding to Fe(II) porphyrin (like haemoglobin)
Radical formation (on nearby tyrosine – like cytochrome c peroxidase)
Formation of an Fe(IV) ferryl intermediate (like peroxidase and P450)
How is O2 produced in photosynthesis?
2H2O → 4H+ + 4e- + O2
2H2O → 2H2 + O2
Solar energy captures & stores energy as chemical bonds via oxidation, occurs in chloroplasts
H2 stored as NADPH
What metal is found in chloroplasts?
Manganese-oxo species
What is the cycle for photosynthesis?
What is the Mn complex structure in chloroplast?
What are the main mechanisms in enzyme catalysis?
Ferryl intermediates
Oxygen rebound mech - cytochrome P450
Radical - coenzyme B12
Radical SAM
How do metalloenzymes typically act as lewis acid-base catalyst?
Metal acts as lewis acid
Surrounding ligand (side chains) or water acts as lewis base
Often Zn as no accessible redox chem (high on IW series) and FeS clusters
What is the difference between structural or catalytic zinc?
Structural - coordinatively saturated (4 coordinate)
Catalytic - metal ion in active site (3 coordinate), coordinatively unsaturated
What are zinc fingers?
Small proteins using Zn(II) ions in a structural role
Many play roles in DNA recognition - regulates transcription and translation
What are some features of catalytic Zn?
3-coordinate, 4th is exchangeable with H2O
Fast H2O and ligand exchange rates
Flexible coordination geometry
Acts as a Lewis acid
How can Zn catalyse amide/ester hydrolysis?
Aided by coordinating ligand in proteins (His)
Large effective [OH-] in active site
What is the mono Zn-carbonyl mechanism for amide/ester hydrolysis?
What is the Zn-carbonyl mechanism for amide/ester hydrolysis with 2xZn?
What is the alcohol dehydrogenase mechanism using Zn-carbonyl?
What is the mechanism of carbonic anhydrase?
Hydrolysis of CO2
Produces carbonic acid
How are FeS centres used in lewis acid-base catalysis?
In aconitase which is included in the Krebs cycle
What does aconitase catalyse?
What is the cycle in aconitase catalysis of citrate?
