Complexometric Titrations - Pharmaceutical Analysis 1 B. Pharma 1st semester

Complexometric Titrations

CONTENTS

•       Complexometric Titrations

•       Terminology

•       Principle involved  in complexometric titrations

•       Titrations with EDTA

•       Chemistry of Indicators

•       Theory involved in indicators 

•       Types of complexometric titrations

            Direct titration

            Back titration

            Replacement of one complex by another

            Alkalimetric titration of metals (Indirect Titration)

•       Masking & Demasking agents 

OBJECTIVES

By the end of this lecture, students will be able to:

Ø  Explain the principle involved in Complexometric titrations

Ø  Describe complexing agents

Ø  Explain the method of complexometric titration with EDTA

Ø   Explain the mechanism of indicators used in complexometric titrations

Ø  Explain the role of masking and demasking agents

Ø  Brief the theory of metal ion indicators 

Complexometric Titrations 

•       Complexometric titration is a type of titration based on complex formation between the analyte (metal ions) and titrant (especially EDTA).

•       Complexometric titrations are particularly useful for determination of a mixture of different metal ions in solution

•       An indicator with a marked color change is usually used to detect the end-point of the titration

Terminology

•       Ligand – Electron donating species (should possess atleast  one electron pair to donate)

•       Central metal ion - The central atom (a metal ion or cation) accepts an electron pair from one or more ligands

•       Chelate - Multidentate ligands complexed to metal ions are called chelates. Chelates always have a "chelate ring." For example, the zinc-8-hydroxyquinolate complex.

•       Coordination number

•       Formation constant

Any complexation reaction can in theory be applied as a volumetric technique provided that :

•       Reaction reaches equilibrium rapidly following each addition of titrant.

•       Interfering situations do not arise such as stepwise formation of various complexes resulting in the presence of more than one complex in solution in significant concentration during the titration process

•       A complexometric indicator capable of locating equivalence point with fair accuracy is available

•       In practice, the use of EDTA as a titrant is well established.

General Principles of complexometry

Most metal ions form coordination compounds with electron-pair donors (ligands)

       Mⁿ⁺  +  qL^m- ßà ML_q^n-mq                     

          ^{Formation constant,}K_f = [ML_q^n-mq]/[Mⁿ⁺][L^m-]^q

The number of coordinate covalent bonds formed is called the “coordination number” (e.g. 2,4,6)

e.g., Cu²⁺ has coordination number of 4

Cu²⁺ + 4 NH₃ ßà Cu(NH₃)₄²⁺

Cu²⁺ + 4 Cl^-  ßà Cu(Cl)₄^2-

•       The most useful complex-formation reactions for titrimetry involve chelate formation

•       A chelate is formed when a metal ion coordinates with two of more donor groups of a single ligand

Types of Ligands

•       Ligands are classified regarding the number of donor groups available:

                    unidentate (one donor group)

                    Bidentate (two donor groups)    

                    Tridendate (three donor groups)

                    Tetradendate (four donor groups)

                    Pentadentate(five donor groups)

                    Hexadentate(six donor groups)

•       Multidentate ligands (especially with 4 and 6 donors) are preferred for titrimetry.

–      react more completely with metal ion

–      usually react in a single step

–      provide sharper end-points

Examples for Ligands

•       Unidendate or Monodendate

Anionic ligands such as halides, SCN^1-, CN^1-, OH^1-, RCOO^1-, S^2-, C₂O₄^2- (oxalate), etc.

Molecular ligands include water, ammonia, RNH₂ (amines) C₅H₅N (pyridine)

•       Bidendate ligands

Glycine complexed with copper(II).

Ethylene diamine complexed with zinc ion

Structure of EDTA

Properties of EDTA

•       Ethylenediamine tetraacetic acid, has four carboxyl groups and two amine groups (act as electron pair donors or Lewis bases)

•       EDTA has the ability to donate its six lone pairs of electrons for the formation of coordinate covalent bonds to metal cations (Makes EDTA a hexadentate ligand)

      In practice EDTA is usually only partially ionized, and

•       Thus forms fewer than six coordinate covalent bonds with metal cations

•       Disodium EDTA, commonly used in the standardization of aqueous solutions of transition metal cations

•       Only forms four coordinate covalent bonds to metal cations at pH values less than or equal to 12 as in this range of pH values the amine

•       Groups remain protonated and thus unable to donate electrons to the formation of coordinate covalent bonds

Complexometric Titration with EDTA

•       it is almost always necessary to use a complexometric indicator to carry out metal cation titrations using EDTA

•       Usually an organic dye such as Fast Sulphon Black, Eriochrome Black T, Eriochrome Red B or Murexide to determine when the end point has been reached

•       Dyes bind to the metal cations in solution to form colored complexes

•       EDTA binds to metal cations much more strongly than the dye used as an

•       indicator

•       EDTA will displace the dye from the metal cations as it is added to the solution of analyte

•       A color change in the solution being titrated indicates that all of the dye has been displaced from the metal cations in solution, End point has been reached

EDTA Titrations

•       General shape of titration curves obtained by titrating 10.0 mL of a 0.01M solution of a metal ion M with a 0.01 M EDTA solution

•       Apparent stability constants of various metal-EDTA complexes are indicated at the extreme right of the curves

•       It is evident that the greater the stability constant, the sharper is the end point provided the pH is maintained constant

•       In acid-base titrations the end point is generally detected by a pH-sensitive Indicator.

•       In the EDTA titration a metal ion sensitive indicator (metal indicator or metal-ion indicator) is often employed to detect changes of pM

Three Regions of EDTA Titration

 The curves are easily calculated by dividing the curve up into domains:

•          The pM before equivalence.

•           The pM at equivalence.

•          The pM after equivalence.

As the pH increases, the equilibrium shifts to the right.

Titration curves for 100 mL 0.1 M Ca²⁺  versus 0.1 M Na₂EDTA at pH 7 and 10.

Advantage of EDTA Titrations

•       Enables us to analyze ions in very small quantities.

•       Care should be taken on effects of pH on the titration method

•       Biological use of complexometric titration

•       Application on living cells.

Indicators

•       Indicators  form complexes with specific metal ions, which differ in colour from the free indicator and produce a sudden colour change at the equivalence point

•       Contain types of chelate groupings and generally possess resonance systems typical of dyestuffs

•       End point of the titration can also be evaluated by other methods including potentiometric, amperometric, and spectrophotometric techniques.

Types of complexometric titrations

•       Direct titration

•       Back titration

•       Replacement of one complex by another

•       Alkalimetric titration of metals (Indirect Titration)

Direct Titration

•       Solution containing the metal ion to be determined is buffered to the desired pH

•       Titrated directly with the standard EDTA solution

•       It may be necessary to prevent precipitation of the hydroxide of the metal (or a basic salt)

•       By the addition of some auxiliary complexing agent, such as tartrate or citrate or triethanolamine

•       At the equivalence point the magnitude of the concentration of the metal ion being determined decreases abruptly

•       This is generally determined by the change in colour of a metal indicator or by amperometric, spectrophotometric and potentiometric methods

•       Example: Magnesium sulphate directly titrated with EDTA solution using mordant black-II as an indicator.

Back Titration

•       Many metals cannot be titrated directly for various reasons, may precipitate from the solution in the pH range necessary for the titration or may form inert complexes or a suitable metal indicator is not available

•       In such cases an excess of standard EDTA solution is added, the resulting solution is buffered to the desired pH

•       Excess of the EDTA is back-titrated with a standard metal ion solution

•       A solution of zinc chloride or sulphate and magnesium chloride or sulphate is often used for this purpose

•       Example: Determination of Mn. This cannot be directly titrated with EDTA because of precipitation of Mn(OH)₂. An excess of known volume of EDTA added to an acidic solution of Mn salt and then ammonia buffer is used to adjust the PH to 10. Excess EDTA is back titrated with a standard Zn solution using Eriochrome black -T as indicator.

Replacement or Substitution Reaction

•       Substitution titrations may be used for metal ions that do not have sharp end point.

•       Metal may  be determined by  the displacement of an equivalent amount  from a less stable EDTA complex.

 Example: Titration of calcium

•       An excess Mg-EDTA chelate is added to ca solution. Ca quantitatively displaces Mg form Mg-EDTA chelate. This displacement takes place because ca forms a more stable complex with EDTA.

•       Free Mg metal is directly titrated with standard EDTA solution.

Alkalimetric Titration

•       It is used for the determination of ions such as anions ,which donot react with EDTA chelate

•       Protons from disodium EDTA are displaced by a heavy metal

•       Liberated protons  can be titrated with a standard solution of sodium hydroxide using an acid-base indicator or a potentiometric end point

•       Alternatively, an iodate-iodide mixture is added as well as the EDTA solution and

•       Liberated iodine is titrated with a standard thiosulphate solution using starch solution as indicator.

•       Solution of the metal to be determined must be accurately neutralized before titration

•       It is often a difficult to account on the hydrolysis of many salts and constitutes a weak feature of alkalimetric titration

Metal Ion Indicators

•       Success of an EDTA titration depends upon the precise determination of the end point

•       Most common procedure utilises metal ion indicators

Requisites of a metal ion indicator for use in the visual detection of end points include:

(a) Colour reaction must be before the end point, when nearly all the metal ion is complexed with EDTA, the solution is strongly coloured.

(b) Colour reaction should be specific or selective.

(c) Metal-indicator complex must possess sufficient stability,Otherwise, due to dissociation, a sharp colour change is not attained

(d)Metal-indicator complex must be less stable than the metal-EDTA complex to ensure that, at the end point EDTA removes metal ions from the metal indicator-complex

(e)Change in equilibrium from the metal indicator complex to the metal-EDTA complex should be sharp and rapid

(f) Colour contrast between the free indicator and the metal-indicator complex should be readily observed

(g) Indicator must be very sensitive to metal ions (i.e. to pM) so that the colour change occurs as near to equivalence point as possible

(h)Above requirements must be fulfilled within the pH range at which the titration is performed

Theory of Metal Ion Indicators

•       Use of a metal ion indicator in EDTA titration may be written as

M-In + EDTA -----------à  M-EDTA + In

•       This reaction will proceed if the metal-indicator complex M-In is less stable than the metal-EDTA complex M-EDTA

•       Former dissociates to a limited extent, andDuring the titration the free metal ions are progressively complexed by the EDTA until ultimately the metal is displaced from the complex M-In To leave the free indicator (In)

•       The stability of the metal-indicator complex may be expressed in terms of the formation constant (or indicator constant)

•       KI_n = (M-In)/(M)(In)

•       Indicator color change is effected by hydrogen ion concentration  

Masking and Demasking Agents

•       EDTA is a very unselective reagent because it complexes with numerous doubly, triply and quadruply charged cations

•       When a solution containing two cations which complex with EDTA is titrated without the addition of a complex-forming indicator 

•       Then ratio of the stability constants of the EDTA complexes of the two metals M and N must be such that K_M/K_N >10⁶  If N is not to interfere with the titration of M

•       Constants K_M and K_N considered in the above expression should be the apparent stability constants of the complexes

•       If complex-forming indicators are used, then for a similar titration error K_M/K_N > 10⁸

The following procedures will help to increase the selectivity:

(a) Suitable control of the pH of the solution

•       Makes use of the different stabilities of metal-EDTA complexes

•       Bismuth and thorium can be titrated in an acidic solution (pH = 2) with xylenol orange or methyl thymol blue as indicator and most divalent cations do not interfere

•       A mixture of bismuth and lead ions can be successfully titrated by first titrating the bismuth at pH 2 with xylenol orange as indicator, and then adding hexamine to raise the pH to about 5 and then titrating the lead.

(b) Use of masking agents

•       Masking may be defined as the process in which a substance, without physical separation of it or its reaction products, it is so transformed that it does not enter into a particular reaction

•       Demasking is the process in which the masked substance regains its ability to enter into a particular reaction

•       By the use of masking agents, some of the cations in a mixture can often be 'masked' so that they can no longer react with EDTA or with the indicator

•       An effective masking agent is the cyanide ion

•       This forms stable cyanide complexes with the cations of Cd, Zn, Hg(II), Cu, Co, Ni, Ag and platinum metals but not with the alkaline earth metals like manganese and lead.

(c) Selective demasking

•       Cyanide complexes of zinc and cadmium may be demasked with formaldehyde-acetic acid solution or better with chloral hydrate

•       Use of masking and selective demasking agents permits the successive titration of many metals

A solution containing Mg, Zn, and Cu can be titrated as follows:

1. Add excess of standard EDTA and back-titrate with standard Mg solution using solochrome black as indicator gives the sum of all the metals present

2. Treat an aliquot portion with excess of KCN (Poison !) and titrate as before

This gives Mg only

3. Add excess of chloral hydrate (or of formaldehyde-acetic acid solution, 3:1) To the titrated solution in order to liberate the Zn from the cyanide complex, and Titrate until the indicator turns blue. This gives the Zn only. Cu content may then be found by difference

SUMMARY

•       Complexometric titration is a type of titration based on complex formation between the analyte and titrant.

•       Complexometric titrations are particularly useful for determination of a mixture of different metal ions in solution

•       An indicator with a marked color change is usually used to detect the end-point of the titration

•       In practice, the use of EDTA as a titrant is well established

•       The most useful complex-formation reactions for titrimetry involve chelate formation

•       Ethylenediamine tetra acetic acid, has four carboxyl groups and two amine groups that can act as electron pair donors, or Lewis bases

•       Usually an organic dye such as Fast Sulphon Black, Eriochrome Black T, Eriochrome Red B or Murexide used as indicators.

•       Indicators form complexes with specific metal ions, which differ in colour from the free indicator and produce a sudden colour change at the equivalence point

•       Contain types of chelate groupings and generally possess resonance systems typical of dyestuffs

•       Types of complexometric titrations

               Direct titration

               Back titration

               Replacement of one complex by another

               Alkalimetric titration of metals

•       Masking may be defined as the process in which a substance, without physical separation of it or its reaction products.

•       Demasking is the process in which the masked substance regains its ability to enter into a particular reaction