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, 11:408414
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 (a) of the most basic form of EDTA (Y4-) is defined by the H+
concentration and acid-base equilibrium constants
K1K 2 K 3 K 4 K5 K6
aY 4 6 5 4 3
{[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 K 5 K1K 2 K 3 K 4 K5 K6 }

Fraction (a) of EDTA in the form Y4-:

[Y 4 ]
aY 4
[H6Y 2 ] [H5Y ] [H 4Y ] [H 3Y ] [H2Y 2 ] [HY 3 ] [Y 4 ]

[Y 4 ]
aY 4
EDTA
where [EDTA] is the total concentration of all free EDTA species in solution

aY4- 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 ] aY 4 EDTA
where aY4-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

4
] aY 4 EDTA
[MY n- 4 ]
[Y Kf
[M n ][Y 4 ]

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

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

If pH is fixed by a buffer, then aY4- is a constant that can be combined with Kf

[MY n- 4 ]
Conditional or effective formation constant: K'f K K f a 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 a Y 4-

at any pH, we can find aY4- 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 a 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

aY4- 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 Mg2 )(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 MgY2-

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 aY 4
[Mg2 ][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 MgY2- and there is excess,
unreacted EDTA. A small amount of free Mn+ 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 [MgY2-]:

[Mg( EDTA)- 2 ]
K f K f aY 4
'
[Mg2 ][EDTA]

8 ( 0.0248 M )
( 6.2 10 )( 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 Mg2+ 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 Zn2+

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

The completeness of these reactions is

dependent on aY4- 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 Mn+
strong enough to prevent hydroxide formation.
- Ammonia, tartrate, citrate or triethanolamine
- Binds metal weaker than EDTA

1
Fraction of free metal ion (aM) depends on the aM
equilibrium constants () or cumulative formation
constants:
1 1 [ L ] 2 [ L ] 2 n [ L ] n

Use a new conditional formation constant that K'f' aY 4 a Zn 2 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

Kf ( analyte )aY 4 Kf (sec ond metal ion )aY 4

 EDTA Titrations
EDTA Titration Techniques

4.) Displacement Titration

Used for some analytes that dont have satisfactory metal ion indicators

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

Requires: Kf ( M n )aY 4 Kf ( Mg2 )aY 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: Kf ( AlF 3 ) Kf ( Al ( EDTA ))

6

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