Tuesday, 27 August 2013
Stability,chelation and chelate effect in coordination compounds
Stability, Chelation and the Chelate Effect
A metal ion in solution does not exist in isolation, but in combination with ligands (such as solvent molecules or simple ions) or chelating groups, giving rise to complex ions or coordination compounds.
These complexes contain a central atom or ion, often a transition metal, and a cluster of ions or neutral molecules surrounding it. Many complexes are relatively unreactive species remaining unchanged throughout a sequence of chemical or physical operations and can often be isolated as stable solids or liquid compounds.
Other complexes have a much more transient existence and may exist only in solution or be highly reactive and easily converted to other species.
All metals form complexes, although the extent of formation and nature of these depend very largely on the electronic structure of the metal.
The concept of a metal complex originated in the work of Alfred Werner, who in 1913 was awarded the first Nobel Prize in Inorganic chemistry. A description of his life and the influence his work played in the development of coordination chemistry is given by G.B. Kauffman in "Inorganic Coordination Compounds", Heyden & Son Ltd, 1981.
Complexes may be non-ionic (neutral) or cationic or anionic, depending on the charges carried by the central metal ion and the coordinated groups. The total number of points of attachment to the central element is termed the coordination number and this can vary from 2 to greater than 12, but is usually 6.
The term ligand (ligare [Latin], to bind) was first used by Alfred Stock in 1916 in relation to silicon chemistry. The first use of the term in a British journal was by H. Irving and R.J.P. Williams in Nature, 1948, 162, 746 in their paper describing what is now called the Irving-Williams series.
For a fascinating review of the origin and dissemination of the term 'ligand' in chemistry see: W.H. Brock, K.A Jensen, C.K. Jorgensen and G.B. Kauffman, Polyhedron, 2, 1983, 1-7.
Ligands can be further characterised as monodentate, bidentate, tridentate etc. where the concept of teeth (dent) is introduced, hence the idea of bite angle etc.
The term chelate was first applied in 1920 by Sir Gilbert T. Morgan and H.D.K. Drew [J. Chem. Soc., 1920, 117, 1456], who stated:
"The adjective chelate, derived from the great claw or chela (from the Greek χηλη) of the lobster or other crustaceans, is suggested for the caliperlike groups which function as two associating units and fasten to the central atom so as to produce heterocyclic rings."
Metal complexation is of widespread interest. It is studied not only by inorganic chemists, but by physical and organic chemists and by biochemists, pharmacologists, molecular biologists and environmentalists.
Thermodynamic Stability
In the laboratory course, it will have been pointed out that the "stability of a complex in solution" refers to the degree of association between the two species involved in the state of equilibrium. Qualitatively, the greater the association, the greater the stability of the compound. The magnitude of the (stability or formation) equilibrium constant for the association, quantitatively expresses the stability. Thus, if we have a reaction of the type:
M + 4L → ML4
then the larger the stability constant, the higher the proportion of ML4 that exists in the solution. Free metal ions rarely exist in solution so that M, will usually be surrounded by solvent molecules which will compete with the ligand molecules, L, and be successively replaced by them. For simplicity, we generally ignore these solvent molecules and write four stability constants as follows:
l. M + L → ML K1 = [ML] / [M] [L]2. ML + L → ML2 K2 = [ML2] / [ML] [L]3. ML2 + L → ML3 K3 = [ML3] / [ML2] [L]4. ML3 + L → ML4 K4 = [ML4] / [ML3] [L]
where K1, K2 etc. are referred to as "stepwise stability constants".
Alternatively, we can write the "Overall Stability Constant" thus:
M + 4L → ML4 β4 = [ML4]/ [M] [L]4
The stepwise and overall stability constants are therefore related as follows:
β4 =K1.K2.K3.K4 or more generally,βn =K1.K2.K3.K4--------------K n
If we take as an example, the steps involved in the formation of the cuprammonium ion, we have the following:
Cu2+ + NH3 ↔ Cu(NH3)2+ K1 = [Cu(NH3)2+]/[Cu2+] [NH3]CuNH32+ + NH3 ↔ Cu(NH3)22+ K2 = [Cu(NH3)22+]/[Cu(NH3)2+] [NH3]
etc. where K1, K2 are the stepwise stability constants.
Also:
β4 = [Cu(NH3)42+]/[Cu2+] [NH3]4
The addition of the four ammine groups to copper shows a pattern found for most formation constants, in that the successive stability constants decrease. In this case, the four constants are:
logK1 =4.0, logK2 =3.2, logK3 =2.7, logK4 =2.0 or logβ4 =11.9
A number of texts refer to the instability constant or the dissociation constant of coordination complexes. This value corresponds to the reciprocalof the formation constant, since the reactions referred to are those where fully formed complexes break down to the aqua ion and free ligands.
This should be compared with the equation for the formation constant given earlier.
It is usual to represent the metal-binding process by a series of stepwise equilibria which lead to stability constants that may vary numerically from hundreds to enormous values such as 1035 and more.
That is 100,000,000,000,000,000,000,000,000,000,000,000.0
For this reason, they are commonly reported as logarithms.
so log10 (β) = log10 (1035) = 35.
It is additionally useful to use logarithms, since log(K) is directly proportional to the free energy of the reaction.
ΔG° = -RTln(β)
ΔG° = -2.303 RTlog10(β)
ΔG° = ΔH° - TΔS°
For a problem relating to metal complex formation and calculations of free metal ions concentrations, try your hand at CALCULATION # ONE. Other problems can be found in the Tutorial paper for this course.
The Chelate Effect
The chelate effect can be seen by comparing the reaction of a chelating ligand and a metal ion with the corresponding reaction involving comparable monodentate ligands. For example, comparison of the binding of 2,2'-bipyridine with pyridine or 1,2-diaminoethane (ethylenediamine=en) with ammonia.
It has been known for many years that a comparison of this type always shows that the complex resulting from coordination with the chelating ligand is much more thermodynamically stable. This can be seen by looking at the values for adding two monodentates compared with adding one bidentate, or adding four monodentates compared to two bidentates, or adding six monodentates compared to three bidentates.
Some tables of thermodynamic data
| # of ligands | ΔG° (kJmol-1) | ΔH° (kJmol-1) | ΔS° (JK-1mol-1) | log β |
| 2 NH3(1 en) | -28.24 (-33.30) | -29.79 (-29.41) | -5.19 (+13.05) | 4.95 (5.84) |
| 4 NH3(2 en) | -42.51 (-60.67) | -53.14 (-56.48) | -35.50 (+13.75) | 7.44 (10.62) |
| # of ligands | log β | ΔG° (kJmol-1) |
| 2 py (1 bipy) | 3.5 (6.9) | -20 (-39) |
| 4 py (2 bipy) | 5.6 (13.6) | -32 (-78) |
| 6 py (3 bipy) | 9.8 (19.3) | -56 (-110) |
| # of ligands | log β | ΔG° (kJmol-1) |
| 1 NH3 | 2.8 | -16 |
| 2 NH3 (1 en) | 5.0 (7.51) | -28.5 (-42.8) |
| 3 NH3 | 6.6 | -37.7 |
| 4 NH3 (2 en) | 7.87 (13.86) | -44.9 (-79.1) |
| 5 NH3 | 8.6 | -49.1 |
| 6 NH3 (3 en) | 8.61 (18.28) | -49.2 (-104.4) |
A number of points should be highlighted from this data.
In the first table, it can be seen that the ΔH° values for the formation steps are almost identical, that is, heat is evolved to about the same extent whether forming a complex involving monodentate ligands or bidentate ligands.
What is seen to vary significantly is the ΔS° term which changes from negative (unfavourable) to positive (favourable). Note as well that there is a dramatic increase in the size of the ΔS° term for adding two compared to adding four monodentate ligands. (-5 to -35 JK-1mol-1).
What does this imply, if we consider ΔS° to give a measure of disorder?
In the case of complex formation of Ni2+ with ammonia or 1,2-diaminoethane, by rewriting the equilibria, the following equations are produced.
Using the equilibrium constant for the reaction (3 above) where the three bidentates replace the six monodentates, we find that at a temperature of 25C:
ΔG° = -2.303 RT log10 (K)= -2.303 R T (18.28 - 8.61)= -54 kJ mol-1
Based on measurements made over a range of temperatures, it is possible to break down the ΔG° term into the enthalpy and entropy components. ΔG° = ΔH° - TΔS°
The result is that:
ΔH° = -29 kJ mol-1- TΔS° = -25 kJ mol-1and at 25C (298K)ΔS° = +88 J K-1 mol-1
Note that for many years, these numbers have been incorrectly recorded in textbooks.
For example, the third edition of "Basic Inorganic Chemistry" by F.A. Cotton, G. Wilkinson and P.L. Gaus, John Wiley & Sons, Inc, 1995, on page 186 gives the values as:
ΔG° = -67 kJ mol-1ΔH° = -12 kJ mol-1- TΔS° = -55 kJ mol-1
The conclusion they drew from these incorrect numbers was that the chelate effect was essentially an entropy effect, since the TΔS° contribution was nearly 5 times bigger than ΔH°.
In fact, the breakdown of the ΔG° into ΔH° and TΔS° shows that the two terms are nearly equal (-29 cf. -25 kJ mol-1) with the ΔH° term a little bigger! The entropy term found is still much larger than for reactions involving a non-chelating ligand substitution at a metal ion.
How can we explain this enhanced contribution from entropy? One explanation is to count the number of species on the left and right hand side of the equation above.
It will be seen that on the left-hand-side there are 4 species, whereas on the right-hand-side there are 7 species, that is a net gain of 3 species occurs as the reaction proceeds. This can account for the increase in entropy since it represents an increase in the disorder of the system.
An alternative view comes from trying to understand how the reactions might proceed. To form a complex with 6 monodentates requires 6 separate favourable collisions between the metal ion and the ligand molecules. To form the tris-bidentate metal complex requires an initial collision for the first ligand to attach by one arm but remember that the other arm is always going to be nearby and only requires a rotation of the other end to enable the ligand to form the chelate ring.
If you consider dissociation steps, then when a monodentate group is displaced, it is lost into the bulk of the solution. On the other hand, if one end of a bidentate group is displaced the other arm is still attached and it is only a matter of the arm rotating around and it can be reattached again.
Both sets of conditions favour the formation of the complex with bidentate groups rather than monodentate groups.
Factors governing polarization and polarisability in Fazans Rule
FACTORS GOVERNING POLARIZATION AND POLARISABILITY (FAJAN’S RULE)
Cation Size: Smaller is the cation more is the value of charge density (Φ) and hence more its polarising power. As a result more covalent character will develop. Let us take the example of the chlorides of the alkaline earth metals. As we go down from Be to Ba the cation size increases and the value of Φ decreases which indicates that BaCl2 is less covalent i.e. more ionic. This is well reflected in their melting points. Melting points of BeCl2 = 405°C and BaCl2 = 960°C.
Cationic Charge: More is the charge on the cation, the higher is the value of Φ and higher is the polarising power. This can be well illustrated by the example already given, NaBr and AlBr3. Here the charge on Na is +1 while that on Al in +3, hence polarising power of Al is higher which in turn means a higher degree of covalency resulting in a lowering of melting point of AlBr3 as compared to NaBr.
Noble Gas vs Pseudo Noble Gas Cation:A Pseudo noble gas cation consists of a noble gas core surrounded by electron cloud due to filled d-subshell. Since d-electrons provide inadequate shielding from the nuclei charge due to relatively less penetration of orbitals into the inner electron core, the effective nuclear charge (ENC) is relatively larger than that of a noble gas cation of the same period. NaCl has got a melting point of 800°C while CuCl has got melting point of 425°C. The configuration of Cu+ = [Ar] 3d10 while that of Na+ = [Ne]. Due to presence of d electrons ENC is more and therefore Cl– is more polarised in CuCl leading to a higher degree of covalency and lower melting point.
Anion Size:Larger is the anion, more is the polarisability and hence more covalent character is expected. An e.g. of this is CaF2 and CaI2, the former has melting point of 1400°C and latter has 575°C. The larger size of I– ion compared to F– causes more polarization of the molecule leading to a lowering of covalency and increasing in melting point.
Anionic Charge:Larger is the anionic charge, the more is the polarisability. A well illustrated example is the much higher degree of covalency in magnesium nitride (3Mg++ 2N3–) compared to magnesium fluoride (Mg++ 2F—). This is due to higher charge of nitride compare to fluoride. These five factors are collectively known as Fajan’s Rule.
Example:
The melting point of KCl is higher than that of AgCl though the crystal radii of Ag+and K+ ions are almost same.
Solution:
Now whenever any comparison is asked about the melting point of the compounds which are fully ionic from the electron transfer concept it means that the compound having lower melting point has got lesser amount of ionic character than the other one. To analyse such a question first find out the difference between the 2 given compounds. Here in both the compounds the anion is the same. So the deciding factor would be the cation. Now if the cation is different, then the answer should be from the variation of the cation. Now in the above example, the difference of the cation is their electronic configuration. K+ = [Ar]; Ag+ = [Kr] 4d10. This is now a comparison between a noble gas core and pseudo noble gas core, the analysis of which we have already done. So try to finish off this answer.
Example: AlF3 is ionic while AlCl3 is covalent.
Solution: Since F– is smaller in size, its polarisability is less and therefore it is having more ionic character. Whereas Cl being larger in size is having more polarisability and hence more covalent character.
Example:
Which compound from each of the following pairs is more covalent and why?
(a) CuO or CuS (b) AgCl or AgI
(c) PbCl2 or PbCl4 (d) BeCl2 or MgCl2
Solution:
(a) CuS (b) AgI
(c) PbCl4 (d) BeCl2
Monday, 26 August 2013
Thursday, 22 August 2013
Wednesday, 21 August 2013
Cytochrome P450
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| Figure 1 The fold of cytochrome P450s is highly conserved and shown in a ribbon representation (distal face). Substrate recognition sequence (SRS) regions are shown in black and labeled. α-Helixes mentioned in the text are labeled with capital letters. |
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| P450 catalyti cycle |
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| Figure 3 Crystal structure of the oxy complex of wild-type CYP101 (pdb code 1dz8) that catalyzes the 5-exo hydroxylation of camphor. Oxygen binding induces a rotation of the amide of Asp251, which ensues binding of two new water molecules, Wat901 and Wat902. |
- P450 catalytic mech focuses on state of heme iron and O
- Steps:
- Oxygen binds reduced heme iron. Formation of oxygenated heme Fe2+-OO or Fe3+-OO-
- One-electron reduction of complex to a ferric peroxo state Fe3+-OO2-, which is earily protonated to form hydroperoxo Fe3+-OOH-
- 2nd protonation of latter Fe3+-OOH- complex at distal oxygen atom to form unstable transient Fe-OOH2. Followed by heterolytic scission of O-O bond. Water mol released
- Reactions of remaining higher valent pophyrin metal-oxo complex, a ferryl-oxo ð-cation porphyrin radical and referred to as “Compound I"
- intmts formed in reactions 2 to 4 have common features in all cytochrome P450s
- similar iron-oxygen states are thought to be important in non-heme oxygen activation
2. Active-Site Structure of P450 Enzymes
- P450 share common overall fold and topology
- Conserved P450 strucural core formed by a four-helix bundle composed of 3 parallel helices D,L, and I and 1 antiparallel helix E.51
- Prosthetic heme group is confined between distal I helix and proximal L helix and boung to adj Cysheme-ligand loop containing P450 signature aa seq.
- Absolutely conserved Cys is proximal or 5th ligand to heme iron
- This sulfur ligand is thiolate 52
- Prximal Cys forms 2 H bonds with neighbouring backbone amides
- Further interaction with a side chain in some P450s, with Gln in CYP 152A1 or Trp in nitric oxide synthase
- Mutations of these affect reduction potential or catalytic activity and stability of bond between heme iron and its 5th or 6th ligand in NOS
- Long I helix forms a wall of heme pocket and contains signature aa seq (A/G)-Gx(E/D)T which is centred at a kink in middle of helix
- Highly conserved thr preceded by an acidic residue is positioned in active site
- may be involved in catalysis
- SRS predetermine P450 substrate spec
- Point mutations in SRSs affect substrate spec
- SRSs are flesible protein regions
- move on substrate binding in induced fit mech to favour substrate binding
3. Enzymatic Reaction Cycle of Cytochrome P450
- Substrate binds to resting state of low spin (LS) ferric enzyme
- perturbs water coordinated as 6th ligand of hene iron
- change spin state to high spin (HS) substrate-bound complex
- HS F3+ has more positive reduction potential
- In CYO101 much easier reduced to ferrous state
- In other systems, spin shift is not obligatory part of cycle
- Oxygen binding ---> oxy-450 complex
- last relatively stable intmt in cycle
- Complex reduced
- formation of peroxo-ferric intmt
- formation of its protonated form, hydroperoxo-ferric intmt
- 2nd protonation of distal oxygen atom with heterolysis of O=O bond and formation of Compound I and water
- Oxygenation of substrate to form product complex
- P450 reaction cycle has at least 3 branch points
- multiple side reactions can occur under physiological conditions
- 3 major abortive reaction are
- autoxidation of oxy-ferrous enzyme with concomitant production of a superoxide anion and return of enz to resting state
- peroxide shunt. Coordinted peroxide or hydroperoxide anion dissoc from iron forming H2O2,completing unproductive 2-electron reduction of oxygen
- oxidase uncoupling. Ferry=oxo intmt is oxidised to water instead of oxygenation of substrate. Results in 4-electron reduction of O2 mol. Net formation of 2 mols of water.
- These procseses are uncoupling
3.1. Substrate Binding
- In general substrates for cyt P450 metabolism are hydrophobic
- Substrate binding triggers change of spin state from LS to HS in heme iron
- induce change in reduction potential from ca. -300 to ca. 100 mV more opsitive
- In resting state, or in quilibrium with aerobic media, cyt P450 appear in ferric Fe3+ form
- due to low reduction potential of Fe3+/Fe2+ couple
- -400 to -170mV
- Low redox potential is maintained by prsence of negatively charged proximal thiolate ligand
- same negative shift of reduction potential can be induced in other heme proteins eg myoglobin 85 by replacing proximal His by Cys
- LS-HS thermodynamis equilibria for Fe3+ and Fe2+ states of enz are coupled with 6th ligand binding equilibrium
- Experimentally measured mitpoint potential of heme enz depends on substrate's ability to change heme ligand binding equilibria in ferric and ferrous enz
- In purifies _450 systems, in absence of other stronger ligands, water coordination at 6th distal position can stabilise LS state of ferric iron
- Reduced ferrous cyt P450s are predominantly in HS 5-coordinated state
- water is much weaker ligand for Fe2+ heme
- Difference in ligation state of ferric and ferrous P450 in absence of substrates causes add. stabiliosation of ferric state and lower midpoint potentials of substrate-free cyt P450s.
- Substrate binding causes water mol coordinated to Fe 3+ to be usually displaced
- indicated by shift of spin state of 5-coordinated heme iron to HS
- Loss of 6th ligand of heme iron thermodynamically destabilises ferric state of cyt P450 with respect to Fe2+ state
- midpoint potential of heme shifts to positive values
- Stronger ability of substrate to perturb water ligation of ferric heme, more pronounced resulting positive shift of redox potential
- Same factors affect reduced enz
- In presence of CO or O2 which do not bind ferric iron porphyrins but are strong ligands for Fe2+ heme, reduction potential shifts to more positive values compared to those measured under inert atmosphere.
- Coupling between substrate binding and change in reduction potential is indicated by diff in substrate binding free energy in ferric and ferrous state
- caused by closed thermodynamic cycle.
- Temperature and pH and presence of cosolvents may change parameters of ovserved high-spin-low-spin equilibrium
- via perturbation of 6th ligand binding
- change reduction potential of cyt P450
- In most P450 systems ultimate reducing agent for catalytic cycle is NADPH, which has midpoint potential of -320 mV
- reduction potentials of protein's redox partners are roughly in same range
- cyt P450 should be reduced slowly before substrate binds
- Prevents unproductive turnover of enz with waste of NADPH and formatio nof toxic superoxides and peroxides which is rendered more likely due to fast autooxidation of thiolate ligated heme proteins
- Mammalian cytochrome CYP3A4 can bind 2 or 3 substrates mols
- In this system spin shift caused by cooperative substrate binding can serve as allosteric switch
- from slow turnowever at low [S] to faster turnover at high [S]
- Observed cooperativity of product formation may be higher than cooperativity of substrate binding
- Many of cyt P450s have broad spectrum of substrates
- Induced fit model
- Large str rearrangements induced by substrate binding observed by comparing Sray crystal st of cyt P450s
- Subsrate recognition sites are flexible and procide substrate access to heme
- HEme otherwise buried in protein globule
- In absence of charged and H bonding grps on substrate mols and in the active sites of most P450 enz. such binding mechs stabilise substrate in active centre
- In many cases diff substrate analogues bind tightly to P450 enz because of poor solubility in water
- not because of strong interactions at active site
- Wired substrates bind CYP101 more tightly than natural substrate camphor
- Camphor is tethered to fluorescent reporter grp by hydrophobic links of diff length
- Hydrocarbon tether is dehydrated ---> favourable effect
- Long hydrophobic tail is extended thru binding channel in protein globule up to surface, where fluoresecent grp is partly exposed to solvent
- Same conform changes observed with substrates linked to a Ru complex
- These tethered modified substrates do not dusplace water coordinated to heme iron
- do not shift spin state to high spin, as camphor does
- Spin shift reg mech is sensitive to str of bound substrate or analogue
- enz recognises optimcal substrates this way when there are almost no spec functional grps at active cetnre to control substrate binding spec
3.2. Iron Spin Shift and the Heme Redox Potential
- Some substrates of cyt P450s bind with very high affinity but do not display marked shirt in spin state of ferric he,e
- A crystal str shows no water at 6th ligand position for wired substrate but contains water for another analogue
- Redox potential as Fe3+/Fe2+ equilibrium is perturbed by changes in ligation state
- or changes in ligation strength in course of reduction or oxidation
- In presence of strong ligands for ferric heme redox potential is lower
- Strong ligands for ferrous state will increase redox potential of heme enz
- This concept is valid even without great change in spin state caused by ligand replacement
- equilibrium constants for spin state equilibrium change for diff ligands
- Interaction with other proteins may change heme reduction potential in cyt P450
- In ferric CYP101 studies, spec conform changes of heme, proximal thiolate and key distal pocket residues caused by formation of complex with putidaredoxin
- Interaction with adrenodoxin induces high spin shift in CYP11A1.
- Spin state of heme iron in CYP101 in complex with Pdr coupled with spec change in ESR spectrum of reduced Pdr
- may help function
- Perturb CO stretch band in Fe-CO complex in CYP 101
- promote e donation to heme iron from axial sulphur ligand of Cys357
- Conform hcange in P450 reductase important in reductase catalysis
- Shift of heme iron spin state from low to high spin
- Ligand concentration or temp can change position of thermodynamic equilibrium with coupled microscopic equilibria
- Redox potential is thermodynamic measure of equilibrium between diff oxidation states
- does not solely determine rate of heme reduction
- Kinetics of reduction depends on spin state change
- reorganisation energy diff involved in changes from a 6-coorfinated to 5-coordinated state
- If reduction is accompanied by changes in coordination state and spin state
=== activation barrier is higher
---- rate of reaction is lower
- Eg spni shift alone caused 200-fold increase of reduction rate in substrate-bound wildtpye CYP102 compared to substrate-free mutatns F393A and F393H of same protein
- all 3 enz have similar reduction potentials
- Catalytic turnover is higher in wt enz
- kinetic control of later steps in kinetic cycle, mainly 2nd ET to ferrous-exy complex
- Using resonance raman spectroscopic studies large changes of heme iron reduction potential attributed to conform changes of proponiate and vinyl grps
- Spec conform change caused by substrate binding and formation of complex with ET partners important in reduction kinetics
- Tight binding of steriodal P450 with its redox partner adrenodoxin increase rate of P450 reduction and product formation
- Substrate binding may be rate-limiting step in some P450 systems
--- low [S]
3.3. Oxygen Complex
- Oxygen binding reduced P450 gives Fe2+-OO complex or Fe3+-OO- complex
- Gross str of oxy-P450 similar to analogous xomplezes in Mb and Hb and heme enzymes, HRP, HO
- In P450 this complex is diamagnetic and EPR silent like Fe2+-OO complex
- only partial electron density transfer from iron to oxygen
- Active proton delivery to bound oxygen or peroxide ligand in P450 mech of oxygen activation
- Autoxidation rate depends strongly on reduction potential in mutants of CYP102
- X-ray crustal str of Fe2+-OO complex of CYP101 was similar to analogous complexes of other heme enz
- O is coordinated in bent end-on mode with angle Fe-O-O 142 degrees
- no steric conflict with bound substrate mol
3.4. Formation of the Peroxo/Hydroperoxo Complex
- Stability of peroxo state Fe3+-OO(H)- is marginal in heme enz
- Prsence of strong proximal ligand (His, Cys or Tyr) and aq sol near neutral pH defines str of most of these complexes as end-on and low-spin state
- Such complexes obtained in reactions with H2O2 with heme enz have low stability
- convert fast to ferryl-oxo-species
- Reactions of peroxide dianion with free Fe3+ porphyrins afford high spin Fe3+-OO2- complexes
--- with side-on-bound peroxide and iron displaced out of porphyrin plane towards bound ligand
- To realise this str in heme protein must break proximal ligand bond to iron
- Presence of strong proximal ligand favours low spin state in 6-coordinate Fe3+-OOH- comlexes
--- important restirction on chem of oxygen activation
--- characteristic of heme enz
- if system fails to do 2nd protonation at distal oxygen site to promote O-O cleavage
---> uncoupling reacion
--- transition from 5b to resting state of enz
3.5. Peroxoferric Intermediates in Heme
- Enzymes : role of protein transfer
- In heme enz porpyrin and proximal ligand provide heme with 5 coordination sites
- Predent side on of peroxide
--- common in non-heme metalloenz
--- very rare in model metalloporphyrin complezes
- Porphyrin donates e for O-O bond cleavage in peroxide ligated to heme iron
- Porphyrin donates 1 e to peroxide ligand
----> heterolytic scission of O=O bond
----> cation radical forms on pophyrin ring
- Oxyegn activation begins when O2 binds as an axial ligand to Fe2+ heme iron or H2O2 binding Fe3+ heme iron
- Diff between oxidase/ oxygenase pathway an peroxidase/peroxygenase pathway
--- diff in redox state of oxygen vs peroxide
--- former pathway needs 2 add reduction steps (1 e reductions by exogenous e donor)
--- must provide 2 protons delivered to peroxide dianion heme ligand
- Reultant equivalent of rearranged H2O2, iron-coordinated peroxo-water (Fe-O-OH2) is precursor to heterolytic O-O bond cleavage to form ferryl-oxo porphyrin complex and H2O product
- H bond stabilised network of watre mols is important
- uncoupling of cyt P450 CYP101 mutants with native substrate camphor and wt CYP101 when metabolising other substrates can be conceptualised via operation of distal pocket proton relay system
- Relay composed of water mols stabilised in active centre of enz and 2 residues conserved in P450 systems
- Famous acid-alcohol pair is Asp251-Thr252 in CYP101
- Peroxidase and oxygenase enz use high valent ferryl-oxo pophyrin caton radical as catalyst of oxidative transformation of substrates
- In P450 catalysis O2 binds reduced heme iron
- ferrous-oxygen or ferric-superoxide complex accepts one more e fr protein redox partner
- form peroxo ferric intmt
- protonated to hydroperoxo-ferric intermediate
- contrary to P450 and HO in peroxidases natural formation of active intmt involves HH2O2 as O donor
- H2O2 binds ferrric heme
- brings 2 e and 2 protons for Compound I generation
- Key step: proton transfer from proximal (closest to iron centre) to distal O atom of bound hydrogen peroxide
- Induce formation of oxo-water by heterolytic splitting of O-O bond
- may be promoted by ET from porphyrin to Fe-O bond
- Water mol and ferryl-ozo porphyrin cation radical are formed
- no other external source of e or protins
- Imidazole side chain of distal His may be intmt catalyst
- accept a proton from proximal oxygen on 1st step
- donates proton to distal oxygen at 2nd step
- pKa of Fe-coordinated Hoo(H) is 3.6-4.0 for HRP and CcP
- Iron-coordinated peroxide is anion at neutral and alkaline pH
- Unstable complex
- Hydroperoxide is weak ligand
- experimentally observed kcat is 10^7 M-1 s-1
- Dissociation rate of HOO(H) may be as high as 10^3-10^4s-1
- Typical for dissoc kinetics of diatomic ligands in heme proteins
- lower than rates of water replacement as a ligand in octahedral porphyrin complexes at room temp
- Protein redox partner reduces heme iron
- P450 enz must catalyse transfer of 2 protons to distal O atom of bound peroxide anion
- thru str arrangement and reulgation of proton relay system
- involves water mols
- stabilised in active centre thru H bonded network interacting with conserved acid-alchohol pair
- Mutating residues in network shows enz kinetics and coupling ratio are sensitive to H bonding properties of sites
- In absence of add catalysis of heterolytic scission thru 2nd protonation of distal O atom hetereolysis or homlysis of O=O bond is governed by thermodynamic stability of reactant and product
- If iron peroxide complex is mainly in high spin state in non heme metal enz with weak or moderate ligand field
--- favourable homolysis of O--O bond
--- spin state of transition state and product state is high spin
- For heterolytic O-O scission with 2nd protonation of leaving O atom and foramtion of water mol
--- 2nd e supplied to peroxide ligand by porphyrin moiety
--- porhphyrin cation radical is formed
- determine behaviour of actualy systems in heterolysis/homolysis ratio and product distribution
- Parameters, pH of solvent, ligation of metal, str, redox properties of porphyrin and peroxide may play important roles
- may favour spec catalytic pathway
- by shifting HS-LS equilbrium
- provide protonation of coordinated peroxide
- weak O=O bond
- homolytic decomposition of H2O2 favoured for HS and LS states
- Porphyrin important as e donor for heterolytic scission of O-O bond in coordinated hydroperoxide to form
Metathesis reactions in chemistry
Metathesis Reactions
A reaction such as
in which the cations and anions exchange partners is called metathesis. In actual fact, the chemistry takes place in several steps. When the chemicals (sodium chloride and silver nitrate) are dissolved, they become hydrated ions:
NaCl(s) + 12 H2O ® [Na(H2O)6]+ + [Cl(H2O)6]-
AgNO3(s) + 12 H2O ® [Ag(H2O)6]+ + [NO3(H2O)6]-
When the silver ions and chloride ions meet in solution, they combine and form a solid, which appears as a white precipitate:
The above equation shows the net ionic reaction, whereas the bystander ions Na+ and NO3- are not shown. Bystander ions are also called spectator ions. A sound movie is available from the Journal of Chemical Education page on sodium chloride and silver nitrate reactions. This movie plays fine on Polaris computers, but ear phones are required for sound movies.
Metathesis reactions not only take place among ionic compounds, they occur among other compounds such as Sigma Bond Metathesis and Olifin Metathesis. Metathesis reaction is a type of chemical reactions, which include combination, decomposition, and displacement.
Types of metathesis reactions
What happens when you pour two solutions of different electrolytes together? The mixture will have all ions from the two electrolytes. Ions of the same charge usually repel each other, but ions of opposite charge may form a stable molecule or solid. When a solid is formed such as AgCl, aprecipitate is formed. From the observation point of view, metathesis reactions can be further divided into three classes:
- Precipitation reaction: products formed are not soluble, forming solids which we call precipitates. The solid silver chloride AgCl(s) mentioned above is a precipitate. Since the solid can be collected and dried, precipitation reactions are often used in gravimetric analysis, chemical analysis by mass or weight.
- Neutralization reaction: Products formed are neutral water molecules, and the net ionic reaction is actually
H+ + OH- = H2O. With proper indicators or pH monitoring, equivalence points are easily detected. Thus, neutralization reactions are used for volumetric analysis, quantitative determination by volume measurement. - Gas formation reaction: methesis reaction may lead to the formation of a neutral molecule that has low boiling point as well as low solubility in water. Thus, a gas is formed. For example:
2 H+ + CO32- = H2O + CO2(g)
Why do ions exchange partners?
Cations are always attracted to anions, but the hydration and hydrogen bonding keep the ions of electrolytes in solution. When two solutions are mixed, cations of one electrolyte meat anions of the other. If they form a more stable substance such as a solid or neutral molecules, exchange or metathesis reaction takes place. The new couples form a precipitation, gas, or neutral molecules. These reactions can be employed for gravimetric or volumetric analysis (determine the quantities present in a sample).
What substances are soluble?
You have to work with these materials to know them well. Here are two basic rules regarding solubility:
- Most nitrates are soluble. So are alkali and ammonium halides.
- Most carbonates, phosphates, sulfites, sulfides, Ca(OH)2, and AgCl are some of the substances that are only sparingly soluble (less than 0.1 g per 100-mL water).
Gravimetric Analysis
The quantitative determination of a component by measuring the mass of a compound formed with the component using a chemical reaction is called gravimetric analysis. Some examples are given here to show how gravimetric analysis are carried out.
Example 1:
To determine % of MgSO4 in epsom salts, you treat it with BaCl2, because of the following reaction:
You can dry the substance BaSO4 formed and weigh the resulting solid to determine the quantity of MgSO4 (mol. wt. 120.37) formed. Suppose you started with 1.0000 g of epsom salts, and got 0.5000 g of BaSO4 (mol. wt. 233.39). Calculate the percentage of MgSO4 in the sample.
Hint -
Use the following one-line method to do the conversion quickly.
1 mol BaSO4 1 mol MgSO4 120.37 g MgSO40.500 g BaSO4 -------------- ----------- --------------233.39 g BaSO4 1 mol BaSO4 1 mol MgSO4= 0.2579 g MgSO4he sample is 0.2579 g / 1.0000 g * 100 % = 25.79 % MgSO4.T
The numerators and denominators of the factors are equivalent under the condition of the problem. Thus, these are conversion factors, and the factors convert the weight of BaSO4 to that of MgSO4.
Note the strategy of the analysis, and the methods of calculation for study purposes.
Skill learned
Perform quantitative analysis is an important skill, and this link gives the procedures.
Example 2:
A sample weighing 3.77 g containing CaCl2 and AlCl3 dissolved in water was treated with AgNO3, and the dry AgCl collected weighs 13.07 g. Calculate the weight and mole percentages of CaCl2 in the sample.
Formula wt: CaCl2, 111.1; AlCl3, 133.5; AgCl, 163.4.
Hint -
Since both compounds contain Cl-, this problem required some thinking. Consider all quantities in moles.
1 mol AgCl13.07 g AgCl ---------- = 0.080 mol AgCl or Cl in the sample.163.4 g
Here is a place for the application of the skills learned in algebra. You can assume x be the weight (g) of CaCl2, then (3.77 - x) g must be AlCl3. Converting these into moles, and the sum of the moles of Cl- ions from both salt must equal to the (0.080) moles observed. Thus, we have
x g CaCl2 2 mol Cl (3.77 - x) g AlCl3 3 mol Cl----------------- ----------- + ------------------ -----------111.1 g/mol CaCl2 1 mol CaCl2 133.5 g/mol AlCl3 1 mol AlCl3
= 0.080 mol Cl-
Simplifying the above equation to give
0.0180 x + 0.0847 - 0.0225 x = 0.080
The solution gives
x = 1.04 g CaCl2, and
3.77 - 1.04 = 2.73 g AlCl3.
By definition, the weight percent of CaCl2 = 1.04/3.77 = 27.59 %
In order to calculate mole percent, the quantities are converted into moles
1 mol CaCl21.04 g CaCl2 -------------- = 0.0094 mol CaCl2111.1 g CaCl2
2.73 g / (133.5 g/mol) = 0.0204 mol AlCl3
Thus, the mole percentage of CaCl2 = 0.0094 / (0.0294) = 31.5 %
Skill learned:
Determine the weight and mole percentages of a mixture.
Confidence Building Problems
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© CChieh@UWaterloo.ca
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