Redox titrations

Concepts to review

Oxidation-Reduction equilibrium. Half-reactions

• Reaction of oxidation and reduction: When a transfer of electrons is

involved
• In the reaction Zn + Cu2+ ⇌ Zn2+ + Cu
– Half-reaction of oxidation
• Zn ⇢ Zn2+ + 2 e-
• Zn gives electrons; becomes oxidized; reducing agent.
– Half-reaction of reduction
• Cu2+ + 2 e- ⇢ Cu
• Cu takes electrons; becomes reduced; oxidizing agent.
– 2 redox conjugated pairs
• Zn2+/Zn
• Cu2+/Cu

2
Concepts to review

Oxidation state (oxidation number)

• Number of charges of an atom after full • The oxidation number of a monoatomic ion =
transfer of electrons. charge of the monatomic ion.
–
• The oxidation number for an atom in its Examples:
• Oxidation number of S2- is -2.
elemental form is always zero.
• Oxidation number of Al3+ is +3.
– A substance is elemental if both of the following are true:
• only one kind of atom is present
• The oxidation number of all Group 1A metals
• charge = 0 = +1 (unless elemental).
– Examples:
• The oxidation number of all Group 2A metals
• S8: The oxidation number of S = 0
= +2 (unless elemental).
• Fe: The oxidation number of Fe = 0

• The sum of the oxidation numbers of all • Hydrogen (H) has two possible oxidation
atoms (or ions) in a neutral compound = 0. numbers:
– +1 when bonded to a nonmetal
• The sum of the oxidation numbers of all – -1 when bonded to a metal
atoms in a polyatomic ion = charge on the • Oxygen (O) has two possible oxidation
polyatomic ion numbers:
– -1 in peroxides (O22-)....pretty uncommon
– -2 in all other compounds...most common

• The oxidation number of fluorine (F) is

always -1

3
 Concepts to review
Study of redox reactions: Electrochemical
systems

• Electrochemical systems: Those where electron-transfer reactions occur

• The exchange of electrons between oxidazing and reducing agents can be
performed either in direct contact or through a conductor
• Direct contact:
– The electron transfer equilibrium is attained directly by the mix of two solutions
– One with the oxidized form of a redox pair and the other with the reduced
– There is NOT electric current
• Through a conductor:
– oxidazing and reducing agents are physically separated, and there is electric
current through an external circuit.
– This system is an electrochemical cell.
– Components:
• Two electrodes
• Solutions of oxidant and reducer in the adequate reactions media
• Salt bridge: Allows electric conection but not chemical exchange
• Electric device
Zn + Cu2+ → Zn2+ + Cu

4
Concepts to review

Electrochemical cells

• Galvanic or Voltaic cell (Battery)

– An electric current (flow of e- through a circuit) is generated
due to an spontaneous redox reaction
– Electric device: Voltmeter to determine the difference of
potential between two electrodes
• Electrolytic cell:
– Electric current is used to carry on a non-spontaneous redox
reaction
– Electric device: External electric energy supply to modify the
direction of the redox reaction

PILA ELETTRICA VOLTA (1800)

5
Concepts to review

Electromotive force
Daniell cell

• Electromotive force (emf, ΔE):

Difference of potential between two
electrodes (volts, V)
• Depends on the specific
reactions in anode and cathode,
on the concentration of the
reagents and on the temperature
• ΔEº: standard emf (298K, 1M, 1
atm)
• Cell emf:
– ΔEº = Eº(cathode) -
Eº(anode)
OXIDATION REDUCTION
– Spontaneous if ΔEº>0.
– ΔEº is intensive.
Zn (s) | Zn2+ (1 M) || Cu2+ (1 M) | Cu (s)

6
Concepts to review
Electrolysis

• By means of electric energy non spontaneous redox reactions can

be carried on
• Electrolytic reactions in electrolytic cells

7
Spontaneity of reactions

• The variation in the Gibbs free energy in a cell is equal to the

maximum electric energy (electric work) that can be obtained from
the chemical reaction
– ΔG = Wele = - q·ΔE = - nFΔE *
• Spontaneity:
– Spontaneous reaction: ΔG < 0  ΔE > 0
– Non-spontaneous reaction: ΔG > 0  ΔE < 0
• (Inverted are opposite)
– Equilibrium: ΔG = 0  ΔE = 0
• (There is no electric energy, the cell is exhausted)

* (1F= 1 Faraday, amount of charge of 1 mole of electrons, 96487 ≈ 96500 C/mol)

8
Nernst equation. Equilibrium constant

• For any chemical reaction,

• ΔG = ΔGº + RT·lnQ *
• In a cell,
• ΔG = -nFΔE and ΔGº = -nFΔEº
• -nFΔE = -nFΔEº + RT·lnQ
• Nernst equation:
• ΔE = ΔEº - RT/nF ·lnQ
• ΔE = ΔEº - 0.0592/n·logQ (at 25ºC)
• In equilibrium,
∆𝑬𝟎 ·𝒏
• ΔEº = 0.0592/n·logK (𝑲 = 𝟏𝟎 𝟎.𝟎𝟓𝟗𝟐 )

* R = 8.314472 J/(mol·K)

9
 Electrode potentials
• The potential of an electrode (therefore, a half-reaction) cannot be directly determined.
• Only versus a reference electrode of known potential
• Standard Hydrogen Electrode (SHE)
– Sheet of Pt into a ccontainer saturated in gas hydrogen at 1 atm and submerged into a
solution of H+ with activity equal to one.
– 2H+ (aq) + 2e- ⇌ H2 (g) Eº = 0 V
• Cells with one SHE and other unknown potential electrode, emf of the cell = emf of the unknown
electrode
• Normal or standard electrode potential (ΔEº): Electromotive force of the cell constituted by the
electrode submerged in a solution which is 1M for its ions (activity=1), and SHE, at 25 ºC and 1 atm

10
Electrode potentials

• In practice, versus Ag/AgCl or calomel reference electrodes

– Saturated calomel electrode (SCE):
• Hg electrode in contact with Hg2Cl2 (non-soluble)
into a solution of known concentration of KCl
(usually saturated).
– SCE: Hg/Hg2Cl2/KCl(sat) E0 = 0.242 V
– Ag/AgCl electrode
• Ag wire inserted in AgCl(s), into a solution of known
concentration of KCl
– Ag/AgCl: Ag/AgCl/KCl (1 M) E0 = 0.222 V

11
Scale of potentials

• Sorted table of standard

reduction potentials (Eº)
• The higher Eº
– The higher tendency to be
reduced
– The more oxidant

• Zn2+ + 2e- → Zn Eº = -0.76 V

• Cu2+ + 2e- → Cu Eº = +0.34 V
• Which one oxidizes and which
one is reduced?

12
Standard
reduction
potentials

13
Reduction potentials and emf of the reaction
• Example:
– Ag+ + 1 e- → Ag E0 = + 0.7996 V
• The oxidant of the redox pair (Ag+) shows higher tendency to become reduced than H+,
versus SHE the reaction proceeds as written.
•Ag electrode behaves as cathode versus SHE.
– Cd2+ + 2 e- → Cd E0 = - 0.402 V
• The reducer of the pair shows higher tendency to become oxidized than H2, versus SHE
the reaction goes in the opposite way
• Cd electrode behaves as anode versus SHE.

– If the cell is made: Cd│Cd2+ ║ Ag+│Ag

• Cell emf (asuming all activities equal to one)
– Ag+ + 1 e- → Ag E0 = + 0.7996 V
– Cd2+ + 2 e- → Cd E0 = - 0.402 V
• ────────────────────────────────────
– 2 Ag+ + Cd → Cd2+ + 2 Ag E0 = 0.7996 – (-0.402) = 1.2016 V

• For suming equations: number of given electrons equal to gained

electrons (multiply every half-reaction by the number of exchanged
electrons in the opposite half-reaction).
• The value of E0 is not multiplied.Intensive property
14
Potential in solutions

• Many redox pairs are ionic species in solution, e.g. Fe3+/Fe2+

• Redox potential cannot be measured using as electrode one of the species
• It can be measured by an inert electrode (Au, Pt) which will adopt the
potential of the pair, according to Nernst´s equation:
0.0592 a 2+
E = E0 − ·log Fe
n aFe3+
• In general, for a reaction
– aA + bB + ne- ⇌ cC + dD

E=E −00.0592 aCc ·aDd

·log a b = E 0 −
0.0592 C  D
c
·log a b
d

n1  n2 a A·aB n1  n2 A B 
• Formal potential or Standard electrode potential:
– Redox potential with solutes at an effective concentration of 1 mol/L,
and gases at a pressure of 1 atm

15
 Redox Titrations
Shape of a Redox Titration Curve

1.) Voltage Change as a Function of Added Titrant

➢ Consider the Titration Reaction (essentially goes to completion):
K ≈ 1016
➢ Ce4+ is added with a buret to a solution of Fe2+
➢ Pt electrode responds to relative concentration
of Fe3+/Fe2+ & Ce4+/Ce3+
➢ Calomel electrode used as reference
Indicator half-reactions at Pt electrode:
Eo = 0.767 V

Eo = 1.70 V

16
 Redox Titrations
Shape of a Redox Titration Curve

2.) Titration Curve has Three Regions

➢ Before the Equivalence Point
➢ At the Equivalence Point
➢ After the Equivalence Point

3.) Region 1: Before the Equivalence Point

➢ Each aliquot of Ce4+ creates an equal
number of moles of Ce3+ and Fe3+

➢ Excess unreacted Fe2+ remains in solution

➢ Amounts of Fe2+ and Fe3+ are known, use

to determine cell voltage.

➢ Residual amount of Ce4+ is unknown

17
 Redox Titrations
Shape of a Redox Titration Curve

3.) Region 1: Before the Equivalence Point

➢ Another special point, when [Ce4+]=0

➢ Voltage can not be calculated

➢ [Fe3+] is unknown

➢ If [Fe3+] = 0, Voltage = -∞
- Must be some Fe3+ from impurity
or Fe2+ oxidation

➢ Voltage can never be lower than value need

to reduce the solvent

Eo = -0.828 V

18
 Redox Titrations
Shape of a Redox Titration Curve

3.) Region 1: Before the Equivalence Point

Use iron half-reaction relative to calomel reference electrode:

Eo = 0.767 V
E = E + ( indicator electrode ) − E − ( reference electrode )
Potential of
calomel
electrode
 [ Fe 2 + ] 
E = 0.767 − 0.05916 log  − 0.241
3+
 [ Fe ] 
Simplify

 [ Fe 2 + ] 
E = 0.526 − 0.05916 log  
 [ Fe 3 + ] 
 
19
 Redox Titrations
Shape of a Redox Titration Curve

3.) Region 1: Before the Equivalence Point

➢ Special point when V = 1/2 Ve
3+ 2+
[ Fe ] = [ Fe ]

 [ Fe 2 + ] 
E = 0.526 − 0.05916 log  
 [ Fe 3 + ] 
 
Log term is zero

E = 0.526  E + = E o = 0.767V

The point at which V= ½ Ve is analogous to the

point at which pH = pKa in an acid base titration

20
 Redox Titrations
Shape of a Redox Titration Curve

4.) Region 2: At the Equivalence Point

➢ Enough Ce4+ has been added to react with all Fe2+
- Primarily only Ce3+ and Fe3+ present
- Tiny amounts of Ce4+ and Fe2+ from equilibrium

➢ From Reaction:

- [Ce3+] = [Fe3+]
- [Ce4+] = [Fe2+]

➢ Both Reactions are in Equilibrium at the

Pt electrode

 [ Fe 2 + ] 
E + = 0.767 − 0.05916 log  
 [ Fe 3 + ] 
 

 [Ce 3 + ] 
E + = 1.70 − 0.05916 log  
 [Ce ] 
4 +
 
21
 Redox Titrations
Shape of a Redox Titration Curve

4.) Region 2: At the Equivalence Point

➢ Don’t know the Concentration of either Fe2+ or Ce4+
➢ Can’t solve either equation independently to determine E+
➢ Instead ADD both equations together
 [ Fe 2 + ]   [Ce 3 + ] 
E + = 0.767 − 0.05916 log   E + = 1.70 − 0.05916 log  
 [ Fe 3 + ]   [Ce 4 + ] 
   
Add

 [ Fe 2 + ]   [Ce 3 + ] 
2 E + = 0.767 + 1.70 − 0.05916 log   − 0.05916 log  
 [ Fe 3 + ]   [Ce 4 + ] 
   

Rearrange

 [ Fe 2 + ] [Ce 3 + ] 
2 E + = 2.47 − 0.05916 log  
 [ Fe 3 + ] [Ce 4 + ] 
 
22
 Redox Titrations
Shape of a Redox Titration Curve

4.) Region 2: At the Equivalence Point

➢ Instead ADD both equations together
 [ Fe 2 + ] [Ce 3 + ] 
2 E + = 2.47 − 0.05916 log  
 [ Fe 3 + ] [Ce 4 + ] 
 
[Ce 3 + ] = [ Fe 3 + ]
[Ce 4 + ] = [ Fe 2 + ]
Log term is zero

2 E + = 2.47V  E + = 1.23V

Cell voltage

E = E + − E ( calomel ) = 1.23 − 0.241 = 0.99V

Equivalence-point voltage is independent of the

concentrations and volumes of the reactants

23
 Redox Titrations
Shape of a Redox Titration Curve

5.) Region 3: After the Equivalence Point

➢ Opposite Situation Compared to Before

the Equivalence Point

➢ Equal number of moles of Ce3+ and Fe3+

➢ Excess unreacted Ce4+ remains in solution

➢ Amounts of Ce3+ and Ce4+ are known, use

to determine cell voltage.

➢ Residual amount of Fe2+ is unknown

24
 Redox Titrations
Shape of a Redox Titration Curve

5.) Region 3: After the Equivalence Point

Use cerium half-reaction relative to calomel reference electrode:

Eo = 1.70 V

E = E + ( indicator electrode ) − E − ( reference electrode )

Potential of
calomel
electrode

 [Ce 3 + ] 
E = 1.70 − 0.05916 log  − 0.241
4+
 [Ce ] 
Simplify

 [Ce 3 + ] 
E = 1.46 − 0.05916 log  
 [Ce 4 + ] 
 
25
 Redox Titrations
Finding the End Point

1.) Indicators or Electrodes

➢ Similar to Acid-Base Titrations
➢ Electrochemical measurements (current or potential) can be used to
determine the endpoint of a redox titration

➢ Redox Indicator is a chemical compound that undergoes a color

change as it goes from its oxidized form to its reduced form
- Similar to acid-base indicators that change color with a change in protonation state

26
 Redox Titrations
Finding the End Point

2.) Redox Indicators

➢ Color Change for a Redox Indicator occurs mostly over the
range:

 0.05916 
E =  Eo  volts
 n 

where Eo is the standard reduction potential for the indicator

and n is the number of electrons involved in the reduction

27
 Redox Titrations
Finding the End Point

2.) Redox Indicators

➢ Color Change for a Redox Indicator occurs over a potential range
➢ Illustration:
For Ferroin with Eo = 1.147V, the range of color change
relative to SHE:
 0.05916 
E =  1.147  volts = 1.088 to 1.206 V
 1 

Relative to SCE is:

 0.05916 
E =  1.147   − E ( calomel ) = (1.088 to 1.206 V ) − ( 0.241 ) = 0.847 to 0.965V
 1 

28
 Redox Titrations
Finding the End Point

2.) Redox Indicators

➢ In order to be useful in endpoint detection, a redox indicator’s range of color
change should match the potential range expected at the end of the titration.

Relative to calomel electrode (-0.241V)

29
 Redox Titrations
Common Redox Reagents

1.) Starch
➢ Commonly used as an indicator in redox titrations involving iodine

➢ Reacts with iodine to form an intensely blue colored complex

➢ Starch is not a redox indicator

- Does not undergo a change in redox potential

I3- bound in center of starch helix

Repeating unit

30
 Redox Titrations
Common Redox Reagents

2.) Adjustment of Analyte Oxidation State

➢ Before many compounds can be determined by Redox Titrations, must
be converted into a known oxidation state
- This step in the procedure is known as prereduction or preoxidation

➢ Reagents for prereduction or preoxidation must:

- Totally convert analyte into desired form
- Be easy to remove from the reaction mixture
- Avoid interfering in the titration

➢ Examples:
- Preoxidation:
a) Peroxydisulfate or persulfate (S2O82-) with Ag+ catalyst

Powerful oxidants

Oxidizes Mn2+, Ce3+, Cr3+, VO2+

excess S2O82- and Ag+ removed by boiling the solution

31
 Redox Titrations
Common Redox Reagents

2.) Adjustment of Analyte Oxidation State

➢ Examples:
- Preoxidation:
b) Silver(II) oxide (AgO) in concentrated mineral acids also yields Ag2+
excess removed by boiling

c) Hydrogen peroxide (H2O2) is a good oxidant to use in basic solutions

Oxidizes Co2+, Fe2+, Mn2+
Reduces Cr2O72-, MnO4-
excess removed by boiling

- Prereduction:
a) Stannous chloride (SnCl2) in hot HCl
Reduce Fe3+ to Fe2+
excess removed by adding HgCl2
b) Jones reductor (Zn + Zn amalgam – anything in mercury)

32
 Redox Titrations
Common Redox Reagents

3.) Common Titrants for Oxidation Reactions

➢ Potassium Permanganate (KMnO4)
- Strong oxidant
- Self-indicator

pH ≤ 1
Titration of VO2+ with KMnO4
Eo = 1.507 V
Violet colorless

pH neutral or alkaline
Eo = 1.692 V
Violet brown

Before Near After pH strongly alkaline

Equivalence point Eo = 0.56 V
Violet green

33
 Redox Titrations
Common Redox Reagents

3.) Common Titrants for Oxidation Reactions

➢ Potassium Permanganate (KMnO4)
- Application of KMnO4 in Redox Titrations

34
 Redox Titrations
Common Redox Reagents

3.) Common Titrants for Oxidation Reactions

➢ Cerium (IV) (Ce4+)
- Commonly used in place of KMnO4
- Works best in acidic solution
- Can be used in most applications in previous table
- Used to analyze some organic compounds
- Color change not distinct to be its own indicator

Yellow colorless

Ce4+ binds anions very strongly results in variation of formal potential

1.70V in 1 F HClO4
Formal potential 1.61V in 1 F HNO3 Measure activity
1.47V in 1 F HCl not concentration
1.44V in 1 F H2SO4

35
 Redox Titrations
Common Redox Reagents

3.) Common Titrants for Oxidation Reactions

➢ Potassium Dichromate (K2Cr2O7)
- Powerful oxidant in strong acid
- Not as Strong as KMnO4 or Ce4+
- Primarily used for the determination of Fe2+
- Not an oxidant in basic solution
- Color change not distinct to be its own indicator

Eo = 1.36 V
orange green to violet

36
 Redox Titrations
Common Redox Reagents

3.) Common Titrants for Oxidation Reactions

➢ Iodine (Solution of I2 + I-)
- I3- is actual species used in titrations with iodine

K = 7 x 102
- Either starch of Sodium Thiosulfate (Na2S2O3) are used as indicator

I3 - I3 -+ S2O3 2- I3- + Starch

Before Before At
endpoint endpoint endpoint

37
 Redox Titrations
Common Redox Reagents

3.) Common Titrants for Oxidation Reactions

➢ Iodine (Solution of I2 + I-)
- Application of Iodine in Redox Titrations

38
 Redox Titrations
Common Redox Reagents

3.) Common Titrants for Oxidation Reactions

➢ Iodine (Solution of I2 + I-)
- Application for Redox Titrations that Produce I3-

39
 Redox Titrations
Common Redox Reagents

3.) Common Titrants for Oxidation Reactions

➢ Periodic Acid (HIO4)
- Commonly used in titration of organic compounds (especially carbohydrates)

4.) Titrations with Reducing Agents

➢ Not as common as titrations using oxidizing agents
- Available titrants are not very stable in the presence of atmospheric O2

➢ Reagents can be generated directly in solution by means of chemical or

electrochemical reactions

40
 PRIMARY STANDARDS REDOX

PS FOR REDOX TITRATIONS

NON-PS PR REACTION

KMnO4 As2O3 5H3AsO3 + 2MnO4- + 6H+ 2Mn2+ + 5H3AsO4 + 3H2O

KMnO4 Na2C2O4 5C2O42–+ 2MnO4-+6H+ 2Mn2+ + 10CO2 + 8H2O
Fe2+ Ce(SO4)2 Fe2++Ce4+ Fe3++Ce3+
(NH4)2Ce(NO3)6
Na2S2O3 K2Cr2O7 Cr2O72 –+6I – +14H+ 2 Cr3++3 I2+7 H2O
I2+ 2S2O32 – 2 I – +S4O62 –
Na2S2O3 KH(IO3)2 IO3- + 5I- + 6H+ 3I2 + 3H2O
Mg(IO3)2•4H2O I2+ 2S2O32 – 2I – + S4O62 –

I2 As2O3 HAsO2+I2+2H2O H3AsO4+2I – +2H+

41
 Redox Titrations
Common Redox Reagents

5.) Example
A 50.00 mL sample containing La3+ was titrated with sodium oxalate to
precipitate La2(C2O4)3, which was washed, dissolved in acid, and titrated
with 18.0 mL of 0.006363 M KMnO4.

Calculate the molarity of La3+ in the unknown.

42
SOME READING

How can we use redox reactions/titrations?

• Concentration of analytes
– Karl-Fischer Moisture Titration
– …
• Mechanisms of Reaction
– Basic Research
• Electron Transport Chain
• …
– Phase I Metabolism of Drugs
• Changes in Bioavailability
• …

43
Karl-Fischer Moisture Titration

• Water analysis is one of the most frequently performed laboratory

analyses in pharmaceutical industries.
• At every stage of the manufacturing process. The quality and the
preservation of the final product depend on the amount of water present.
• Excess levels of moisture will,
– allow bacterial growth
– decrease the performance of oils and lubricants
– modify the density and the viscosity
– disturb the texture of powdered products by forming conglomerates
• Rapidity, accuracy and ease of use: Karl-Fischer titration.

44
 Karl-Fischer Moisture Titration

• The sample into the titration dissolved by an appropriate solvent is titrated to complete dryness
with a solution containing iodine.
• Based on the oxidation of sulphur dioxide by iodine in the presence of water:
– I2 + SO2 + 2H2O ⇌ 2HI + H2SO4
– I2 + SO2 + 2H2O + 3 Base + 3 CH3OH ⇌ 2 Base·HI + Base·HSO4CH3

⚫ Volumetric Karl Fischer

determination covers the
range of 1 to 100 mg of
water in the sample taken

45
Karl-Fischer Moisture Titration

• The solvent

– Iodine and sulphur dioxide are dissolved in methanol.

– Ensure the stoichiometry of the Karl Fischer reaction (Methanol always present,
not lower than 25%)

– Dissolve the sample and the products of the reaction.

– Enable the detection of the end point.

– Other solvents (chloroform, formamide) to liberate the water more efficiently.

• The indicator electrode

– A double platinum electrode is used

– End point of the titration: detection of an excess of iodine (yellow colouring of

the working media)

46
Electron transport and oxidative phosphorylation

• Final step of energy generation

from glucose catabolism
– Oxidation of glucose to CO2
– 12 electron pairs stored as 10
NADH and 2 FADH2
– Glycolysis & citric acid cycle
(including PDH)
– To reduce oxygen to form water:
– 6O2 + 24H+ + 24e– → 12H2O

47
FAD+/FADH2 & NAD+/NADH+H+

48
Some reduction potentials in biochemistry

49
Electron transport of NADH

• Electrons are passed through a

chain of protein based redox
centers
• Goes downhill: from lower to
higher standard reduction
potentials
• NADH and FADH2 enter the
electron transport chain at
different places

50
Thermodynamics of electron transport

51
Redox reactions in the electron transport chain

52
Metabolism of drugs

• Phase I reactions (nonsynthetic) by oxidation, reduction, hydrolysis,

cyclization, and decyclization reactions.
– Oxidation: enzymatic addition of oxygen or removal of hydrogen
– Mixed function oxidases (liver).
– Cytochrome P450 haemoprotein, NADPH and oxygen.
– Phenothiazines, paracetamol, steroids...
• Phase II reactions (conjugation)
– with glucuronic acid, sulfonates, glutathione, amino acids…
– detoxication in nature (involve polar functional groups of phase I
metabolites)

53
Cytochrome P450 and Phase I metabolism

• CYPs are the major enzymes involved in drug metabolism, accounting for ≈75% of
the total metabolism.
• Cytochrome P450 is the most important element of oxidative metabolism
• Drug interaction

– Many drugs may increase or decrease the activity of various CYP isozymes

– Adverse drug interactions, due to different metabolism and clearance of various

drugs.

• if one drug inhibits the CYP-mediated metabolism of another drug, the

second drug may accumulate (overdose)

• if one drug induces the CYP-mediated metabolism of another drug, the

second drug may be too quickly metabolised (underdose)

– Hence, these drug interactions may necessitate dosage adjustments or

choosing drugs which do not interact with the CYP system.

54
 The P450 catalytic cycle

(…) In CYP3A4 the coordination of water at the sixth distal ligand position can stabilize the Low
Spin hexa-coordinated state of the ferric heme. As water is a weak ligand for the ferrous heme,
the reduced ferrous CYP3A4 is predominantly in the High Spin five-coordinated state (…). This
makes it easier for the substrate bound protein to be reduced (…) and is manifested in an
increase in the redox potential of CYP3A4 on binding substrates (…)

55
 Furanocoumarins from grapefruit against Cyt P450

• Medications that should be avoided – cisapride (Propulsid, Prepulsid) – sildenafil (Viagra)

with grapefruit – colchicine – simvastatin (Zocor)
– amiodarone (Cordarone) – eletriptan (Relpax) – sirolimus (Rapamune)
– astemizole (Hismanal) – etoposide (Vepesid) – terfenadine (Seldane)
– atorvastatin (Lipitor) – halofantrine (Halfan) – ziprasidone (Geodon)
– budesonide (Entocort)
– buspirone (BuSpar) – lovastatin (Mevacor)
– cerivastatin (Baycol) – mifepristone (Mifeprex)
– cilostazol (Pletal) – pimozide (Orap)
– quinidine (Quinaglute, Quinidex)

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