EDTA Titrations

Introduction

1.) Metal Chelate Complexes

 Any reagent which reacts with an analyte in a known ratio and with a large
equilibrium constant can potentially be used in a titration.

 Complexation Titrations are based on the reaction of a metal ion with a

chemical agent to form a metal-ligand complex.

Metal Ligand Metal-Ligand Complex

Note: multiple atoms from

EDTA are binding Mn2+

Metal – Lewis Acid or Electron-pair acceptor

Ligand – Lewis Base or Electron-pair donor
 EDTA Titrations

Introduction

1.) Metal Chelate Complexes

 Complexation Titrations are essentially a Lewis acid-base reaction, in which
an electron pair is donated from one chemical to another
 The ligands used in complexometric titrations are also known as chelating
agents.
- Ligand that attaches to a metal ion through more than one ligand atom
 Most chelating agents contain N or O
- Elements that contain free electron pairs that may be donated to a metal

Fe-DTPA Complex
 EDTA Titrations

Metal Chelation in Nature

1.) Potassium Ion Channels in Cell Membranes

 Electrical signals are essential for life
 Electrical signals are highly controlled by the selective passage of ions across
cellular membranes
- Ion channels control this function
- Potassium ion channels are the largest and most diverse group
- Used in brain, heart and nervous system
K+ is chelated by O
channel contains in channel
pore that only
allows K+ to pass

K+ channel spans membrane

Opening of potassium channel allows K+ to exit cell

and change the electrical potential across membrane Current Opinion in Structural Biology 2001, 11:408–414
http://www.bimcore.emory.edu/home/molmod/Wthiel/Kchannel.html
 EDTA Titrations

Metal –Chelate Complexes

1.) Formation Constant (Kf)

 The equilibrium constant for the reaction between a metal ion (M +n) and a
chelating agent (L-P) is known as a formation constant or stability constant.

 Applying different and specific names to the general equilibrium constant is a

common occurrence
- Solubility (Ksp), acid-base (Ka, Kb), water dissociation (Kw), etc

 Chelate effect: ability of multidentate ligands to form stronger metal

complexes compared to monodentate ligands.

Kf = 8x109 Kf = 4x109

2 ethylenediamine molecules binds tighter than 4 methylamine molecules

 EDTA Titrations

Metal –Chelate Complexes

2.) Chelate Effect

 Usually chelating agents with more than one electron pair to donate will form
stronger complexes with metal ions than chelating agents with only one
electron pair.
- Typically more than one O or N
- Larger Kf values

 Multidentate ligand: a chelating agent with more than one free electron pair
- Stoichiometry is 1:1 regardless of the ion charge

 Monodentate ligand: a chelating agent with only one pair of free electrons

Multidentate ligand that binds radioactive metal attached

to monoclonal antibody (mAb).

mAb is a protein that binds to a specific feature on a

tumor cell delivering toxic dose of radiation.
 EDTA Titrations

EDTA

1.) EDTA (Ethylenediaminetetraacetic acid)

 One of the most common chelating agents used for complexometric titrations
in analytical chemistry.

 EDTA has 6 nitrogens & oxygens in its structure giving it 6 free electron pairs
that it can donate to metal ions.
- High Kf values
- 6 acid-base sites in its structure
 EDTA Titrations

EDTA

2.) Acid-Base Forms

 EDTA exists in up to 7 different acid-base forms depending on the solution
pH.

 The most basic form (Y4-) is the one which primarily reacts with metal ions.

EDTA-Mn Complex
 EDTA Titrations

EDTA

2.) Acid-Base Forms

 Fraction () of the most basic form of EDTA (Y 4-) is defined by the H+
concentration and acid-base equilibrium constants
K1K 2 K 3 K 4 K5 K6
Y 4  
{[H ]  [H ] K1  [H ] K1K 2  [H ] K1K 2 K 3  [H  ]2 K1K 2 K 3 K 4  [H  ]K1K 2 K 3 K 4 K5  K1K 2 K 3 K 4 K5 K6 }
 6  5  4  3

Fraction () of EDTA in the form Y4-:

[Y 4  ]
Y 4  
[H6Y 2  ]  [H5Y  ]  [H 4Y ]  [H 3Y  ]  [H2Y 2  ]  [HY 3  ]  [Y 4  ]

[Y 4  ]
Y 4  
 EDTA
where [EDTA] is the total concentration of all free EDTA species in solution

Y4- is depended on the pH of the solution

 EDTA Titrations

EDTA

3.) EDTA Complexes

 The basic form of EDTA (Y4-) reacts with most metal ions to form a 1:1
complex.
- Other forms of EDTA will also chelate metal ions

[MY n- 4 ]
Kf 
[M n  ][Y 4  ]
Note: This reaction only involves Y4-, but not the other forms of EDTA

 Recall: the concentration of Y4- and the total concentration of EDTA is

solution [EDTA] are related as follows:

[Y 4  ]  Y 4   EDTA 
where Y4-is dependent on pH
 EDTA Titrations

EDTA

3.) EDTA Complexes

 The basic form of EDTA (Y4-) reacts with most metal ions to form a 1:1
complex.
 EDTA Titrations

EDTA

3.) EDTA Complexes

 Substitute [Y4-] into Kf equation

[Y 4
]  Y 4   EDTA 
[MY n- 4 ]
Kf 
[M n  ][Y 4  ]

[MY n- 4 ] where [EDTA] is the total

Kf  concentration of EDTA added
[M n  ] Y 4- [EDTA ] to the solution not bound to
metal ions

 If pH is fixed by a buffer, then Y4- is a constant that can be combined with Kf

[MY n- 4 ]
Conditional or effective formation constant: K 'f  K  K f  Y 4- 
(at a given pH) [M n  ][EDTA ]
 EDTA Titrations

EDTA

3.) EDTA Complexes

 Assumes the uncomplexed EDTA were all in one form

K 'f  K f  Y 4-

at any pH, we can find Y4- and evaluate Kf’

 EDTA Titrations

EDTA

4.) Example:
 What is the concentration of free Fe3+ in a solution of 0.10 M Fe(EDTA)- at pH
8.00?
 EDTA Titrations

EDTA

5.) pH Limitation
 Note that the metal –EDTA complex becomes less stable as pH decreases
- Kf decreases
- [Fe3+] = 5.4x10-7 at pH 2.0 -> [Fe3+] = 1.4x10-12 at pH 8.0

 In order to get a “complete” titration (Kf ≥106), EDTA requires a certain

minimum pH for the titration of each metal ion

End Point becomes less distinct as pH is

lowered, limiting the utility of EDTA as a titrant
 EDTA Titrations
Minimum pH for Effective
Titration of Metal Ions
EDTA

5.) pH Limitation
 By adjusting the pH of an EDTA
titration:
 one type of metal ion (e.g. Fe3+) can
be titrated without interference from
others (e.g. Ca2+)
 EDTA Titrations

EDTA Titration Curves

1.) Titration Curve

 The titration of a metal ion with EDTA is similar to the titration of a strong acid
(M+) with a weak base (EDTA)

K 'f  K f  Y 4-

 The Titration Curve has three distinct regions:

- Before the equivalence point (excess Mn+)

- At the equivalence point ([EDTA]=[Mn+]

- After the equivalence point (excess EDTA)

pM   log [M n  ]
 EDTA Titrations

EDTA Titration Curves

2.) Example
 What is the value of [Mn+] and pM for 50.0 ml of a 0.0500 M Mg2+ solution
buffered at pH 10.00 and titrated with 0.0500 m EDTA when (a) 5.0 mL, (b)
50.0 mL and (c) 51.0 mL EDTA is added?

Kf = 108.79 = 6.2x108

Y4- at pH 10.0 = 0.30

mL EDTA at equivalence point:

Ve ( mL )  0.0500 M    5.00 mL  ( 0.0500 M )  Ve  50.00 mL

mmol of EDTA mmol of Mg2+

 EDTA Titrations

EDTA Titration Curves

2.) Example
 (a) Before Equivalence Point ( 5.0 mL of EDTA)

Before the equivalence point, the [Mn+] is equal to the concentration of excess
unreacted Mn+. Dissociation of MYn-4 is negligible.

moles of Mg2+
originally present moles of EDTA added

2 [(0 .0500 M Mg 2  )(0 .0500 L) - (0 .0500 M EDTA )(0 .0050 L )]

[Mg ]
[0.0500 L  0.0050 L]

Original volume Volume titrant

Dilution effect
solution added

[Mg 2  ]  0.0409 M  pMg 2    log[Mg 2  ]  1.39

 EDTA Titrations

EDTA Titration Curves

2.) Example
 (b) At Equivalence Point ( 50.0 mL of EDTA)

Virtually all of the metal ion is now in the form MgY 2-

Original volume of
Original [Mn+] Mn+ solution Moles Mg+ ≡ moles MgY2-

(0 .0500 L)
[MgY 2  ]  (0 .0500 M )
(0.0500 L  0.0500 L)

Original volume Volume titrant

Dilution effect
solution added

[MgY 2  ]  0.0250 M
 EDTA Titrations

EDTA Titration Curves

2.) Example
 (b) At Equivalence Point ( 50.0 mL of EDTA)

The concentration of free Mg2+ is then calculated as follows:

Initial Concentration (M) 0 0 0.0250

Final Concentration (M) x x 0.0250 - x

[Mg ( EDTA )- 2 ]
K 'f  K f Y 4  
[Mg 2  ][EDTA ]
8 ( 0.0250  x )
 ( 6.2  10 )( 0.30 ) 
( x )( x )
Solve for x using the quadratic equation:

 x  [Mg 2  ]  [EDTA ]  1.16  10 5  pMg 2   4.94

 EDTA Titrations

EDTA Titration Curves

2.) Example
 (c) After the Equivalence Point ( 51.0 mL of EDTA)

Virtually all of the metal ion is now in the form MgY 2- and there is excess,
unreacted EDTA. A small amount of free M n+ exists in equilibrium with
MgY4- and EDTA.

Calculate excess [EDTA]: Volume excess

Original [EDTA] titrant Excess moles EDTA

(0 .0500 M )(0 .0010 L)

[EDTA ] 
(0.0500 L  0.0510 L )

Original volume Volume titrant

solution Dilution effect
added

[EDTA ]  4.95  10 4 M
 EDTA Titrations

EDTA Titration Curves

2.) Example
 (c) After the Equivalence Point ( 51.0 mL of EDTA)

Calculate [MgY2-]:
Original volume of
Original [Mn+] Mn+ solution Moles Mg+ ≡ moles MgY2-

(0 .0500 L) Only Difference

[MgY 2  ]  (0 .0500 M )
(0.0500 L  0.0510 L)

Original volume Volume titrant

Dilution effect
solution added

[MgY 2  ]  0.0248 M
 EDTA Titrations

EDTA Titration Curves

2.) Example
 (c) After the Equivalence Point ( 51.0 mL of EDTA)

[Mg2+-] is given by the equilibrium expression using [EDTA] and [MgY 2-]:

' [Mg ( EDTA )- 2 ]

K f  K f Y 4  
[Mg 2  ][EDTA ]

( 0.0248 M )
 ( 6.2  10 8 )( 0.30 ) 
( x )( 4.95  10  4 M )

 x  [Mg 2  ]  2.7  10 7  pMg 2   6.57

 EDTA Titrations

EDTA Titration Curves

2.) Example
 Final titration curve for 50.0 ml of 0.0500 M Mg 2+ with 0.0500 m EDTA at pH
10.00.
- Also shown is the titration of 50.0 mL of 0.0500 M Zn2+

Note: the equivalence point is sharper for Zn 2+

vs. Mg2+. This is due to Zn2+ having a larger
formation constant.

The completeness of these reactions is

dependent on Y4- and correspondingly pH.

pH is an important factor in setting the completeness

and selectivity of an EDTA titration
 EDTA Titrations

Auxiliary Complexing Agents

1.) Metal Hydroxide

 In general, as pH increases a titration of a metal ion with EDTA will have a
higher Kf.
- Larger change at the equivalence point.

 Exception: If Mn+ reacts with OH- to form an insoluble metal hydroxide

 Auxiliary Complexing Agents: a ligand can be added that complexes with M n+

strong enough to prevent hydroxide formation.
- Ammonia, tartrate, citrate or triethanolamine
- Binds metal weaker than EDTA

1
Fraction of free metal ion (M) depends on the M 
equilibrium constants () or cumulative formation 1  1 [ L ]   2 [ L ] 2    n [ L ] n
constants:

Use a new conditional formation constant that K'f'  Y 4   Zn2  K f

incorporates the fraction of free metal:
 EDTA Titrations

Auxiliary Complexing Agents

2.) Illustration:
 Titration of Cu+2 (CuSO4) with EDTA
 Addition of Ammonia Buffer results in a dark blue solution
- Cu(II)-ammonia complex is formed
 Addition of EDTA displaces ammonia with corresponding color change

CuSO4 Cu-ammonia Cu-EDTA

 EDTA Titrations

Metal Ion Indicators

1.) Determination of EDTA Titration End Point

 Four Methods:
1. Metal ion indicator
2. Mercury electrode Potential
3. pH electrode
4. Ion-selective electrode
Measurements

 Metal Ion Indicator: a compound that changes color when it binds to a metal
ion
- Similar to pH indicator, which changes color with pH or as the compound
binds H+

 For an EDTA titration, the indicator must bind the metal ion less strongly than
EDTA
- Similar in concept to Auxiliary Complexing Agents
- Needs to release metal ion to EDTA

End Point indicated by a color

change from red to blue
(red) (colorless) (colorless) (blue)
 EDTA Titrations

Metal Ion Indicators

2.) Illustration
 Titration of Mg2+ by EDTA
- Eriochrome Black T Indicator

Addition of EDTA

Before Near After

Equivalence point
 EDTA Titrations
Metal Ion Indicators

3.) Common Metal Ion Indicators

 Most are pH indicators and can only be used over a given pH range
 EDTA Titrations
Metal Ion Indicators

3.) Common Metal Ion Indicators

 Useful pH ranges
 EDTA Titrations

EDTA Titration Techniques

1.) Almost all elements can be determined by EDTA titration

 Needs to be present at sufficient concentrations

 Extensive Literature where techniques are listed in:

1) G. Schwarzenbach and H. Flaschka, “Complexometric Titrations”,
Methuen:London, 1969.
2) H.A. Flaschka, “EDTA Titrations”, Pergamon Press:New York, 1959
3) C.N. Reilley, A.J. Bernard, Jr., and R. Puschel, In: L. Meites (ed.) “Handbook
of Analytical Chemistry”, McGraw-Hill:New York, 1963; pp. 3-76 to 3-234.

 Some Common Techniques used in these titrations include:

a) Direct Titrations
b) Back Titrations
c) Displacement Titrations
d) Indirect Titrations
e) Masking Agents
 EDTA Titrations
EDTA Titration Techniques

2.) Direct Titrations

 Analyte is buffered to appropriate pH and is titrated directly with EDTA

 An auxiliary complexing agent may be required to prevent precipitation of

metal hydroxide.

3.) Back Titrations

 A known excess of EDTA is added to analyte
- Free EDTA left over after all metal ion is bound with EDTA

 The remaining excess of EDTA is then titrated with a standard solution of a

second metal ion

 Approach necessary if analyte:

- precipitates in the presence of EDTA
- Reacts slowly with EDTA
- Blocks the indicator

 Second metal ion must not displace analyte from EDTA

K f ( analyte )Y 4   K f (sec ond metal ion )Y 4 
 EDTA Titrations
EDTA Titration Techniques

4.) Displacement Titration

 Used for some analytes that don’t have satisfactory metal ion indicators

 Analyte (Mn+) is treated with excess Mg(EDTA)2-, causes release of Mg2+.

Requires: K f ( M n  )Y 4   K f ( Mg 2  )Y 4 

 Amount of Mg2+ released is then determined by titration with a standard EDTA

solution
- Concentration of released Mg2+ equals [Mn+]
 EDTA Titrations
EDTA Titration Techniques

5.) Indirect Titration

 Used to determine anions that precipitate with metal ions

 Anion is precipitated from solution by addition of excess metal ion

- ex. SO42- + excess Ba2+
- Precipitate is filtered & washed

 Precipitate is then reacted with excess EDTA to bring the metal ion back into
solution

 The excess EDTA is titrated with Mg2+ solution

[Total EDTA] = [MYn-4] + [Y4-]

complex free

Known determine Titrate

 EDTA Titrations
EDTA Titration Techniques

6.) Masking Agents

 A reagent added to prevent reaction of some metal ion with EDTA

Al3+ is not available to bind EDTA because of the complex with F-

Requires: K f ( AlF 3  )  K f ( Al ( EDTA ))

6

 Demasking: refers to the release of a metal ion from a masking agent