Complexometric titrations- Pharmaceutical Analysis

Complex-formation reactions are widely used in analytical chemistry. One of the first uses of these reagents was for titrating cations. In addition, many complexes are colored or absorb ultraviolet radiation; the formation of these complexes is often the basis for spectrophotometric determinations. Some complexes are sparingly soluble and can be used in gravimetric analysis. Complexes are also widely used for extracting cations from one solvent to another and for dissolving insoluble precipitates. The most useful complex forming reagents are organic compounds that contain several electron donor groups that form multiple covalent bonds with metal ions.
FORMING COMPLEXES
Most metal ions react with electron-pair donors to form coordination compounds or complexes. The donor species, or ligand is an ion or a molecule that forms a covalent bond with a cation or a neutral metal atom by donating a pair of electrons that are then shared by the two.
The number of covalent bonds that a cation tends to form with electron donors is its coordination number. Typical values for coordination numbers are two, four, and six. The species formed as a result of coordination can be electrically positive, neutral, or negative.
A ligand that has a single donor group, such as ammonia, is called unidentate(single-toothed), whereas one such as glycine, which has two groups available for covalent bonding, is called bidenate. Tridentate, tetradentate, pentadentate, and hexadentate chelating agents are also known.
Another important type of complex, a macrocycle, is formed between a metal ion and a cyclic organic compound. The selectivity of a ligand for one metal ion over another relates to the stability of the complexes formed. The higher the formation constant of a metal-ligand complex, the better the selectivity of the ligand for the metal relative to similar complexes formed with other metals.

1. Complexometric
Titrations
By;-SANCHIT DHANKHAR

2. Complex-formationreactionsarewidelyusedin
analyticalchemistry.Oneofthefirstusesof
thesereagentswasfortitratingcations.In
addition,manycomplexesarecoloredorabsorb
ultravioletradiation;theformationofthese
complexes isoftenthebasisfor
spectrophotometricdeterminations.Some
complexesaresparinglysolubleandcanbeused
ingravimetricanalysis.Complexesarealso
widelyusedforextractingcationsfromone
solventtoanotherandfordissolvinginsoluble
precipitates.Themostusefulcomplexforming
reagentsareorganiccompoundsthatcontain
severalelectrondonorgroupsthatformmultiple
covalentbondswithmetalions.

3. FORMING COMPLEXES
Mostmetalionsreactwithelectron-pairdonorstoformcoordinationcompounds
orcomplexes.Thedonorspecies,orligandisanionoramoleculethatformsa
covalentbondwithacationoraneutralmetalatombydonatingapairof
electronsthatarethensharedbythetwo.
Thenumberofcovalentbondsthatacationtendstoformwithelectrondonorsis
itscoordinationnumber.Typicalvaluesforcoordinationnumbersaretwo,four,
andsix.Thespeciesformedasaresultofcoordinationcanbeelectrically
positive,neutral,ornegative.

4. Aligandthathasasingledonorgroup,suchasammonia,iscalled
unidentate(single-toothed),whereasonesuchasglycine,whichhastwogroups
availableforcovalentbonding,iscalledbidenate.Tridentate,tetradentate,
pentadentate,andhexadentatechelatingagentsarealsoknown.
Anotherimportanttypeofcomplex,amacrocycle,isformedbetweenametal
ionandacyclicorganiccompound.Theselectivityofaligandforonemetalion
overanotherrelatestothestabilityofthecomplexesformed.Thehigherthe
formationconstantofametal-ligandcomplex,thebettertheselectivityofthe
ligandforthemetalrelativetosimilarcomplexesformedwithothermetals.

7. Producing Soluble Compelxes
ComplexationreactionsinvolveametalionM
reactingwithaligandLtoformacomplexML.
M+L ML
Complexationreactionsoccurinastepwisefashion,
andthereactionaboveisoftenfollowedby
additionalreactions:
ML+L ML
2
ML
2+LML
3
ML
n-1+L ML
n
Unidentateligandsinvariablyaddinaseriesof
steps.Withmultidentateligands,themaximum
coordinationnumberofthecationmaybesatisfied
withonlyoneorafewaddedligands.

8. …continued…
Theequilibriumconstantsforcomplexformation
reactionsaregenerallywrittenasformation
constants.
M+2LML
2
M+3LML
3
M+nLML
n
Theoverallformationconstantsareproductsof
thestepwiseformationconstantsforthe
individualstepsleadingtotheproduct. 

2
2
12 
ML
ML
KK
 

3
3
123 
ML
ML
KKK
 

n
n
n
ML
ML
KKK 

12....
2
3
n

9. Forming Insoluble Species
Theadditionofligandstoametalionmayresultininsolublespecies,suchasthe
familiarnickel-dimethylglyoximeprecipitate.Inmanycases,theintermediate
unchargedcomplexesinthestepwiseformationschememaybesparingly
soluble,whereastheadditionofmoreligandmoleculesmayresultinsoluble
species.AgClisinsoluble,butadditionoflargeexcessofCl
-
producessoluble
AgCl
2
-
,AgCl
3
2-
,andAgCl
4
3-
.

10. …continued…
Incontrasttocomplexationequilibria,whichare
mostoftentreatedasformationreactions,
solubilityequilibriaareusuallytreatedas
dissociationreactions
M
xA
y(s)xM
y+
(aq)+yA
x-
(aq)
K
sp=[M
y+
]
x
[A
x-
]
y
where,K
sp=solubilityproduct.Hence,forBiI
3,
thesolubilityproductiswrittenK
sp=[Bi
3+
][I
-
]
3
.
Theformationofsolublecomplexescanbeusedto
controltheconcentrationoffreemetalionsin
solutionandthuscontroltheirreactivity.

11. TITRATION WITH INORGANIC COMPLEXING AGENTS
Complexationreactionshavemanyusesinanalyticalchemistry,buttheir
classicalapplicationisincomplexometrictitrations.Here,ametalionreacts
withasuitableligandtoformacomplex,andtheequivalencepointis
determinedbyanindicatororasuitableinstrumentalmethod.Theformationof
solubleinorganiccomplexesisnotwidelyusedfortitrationbuttheformationof
precipitatesisthebasisformanyimportantdeterminations.

12. Complexation Titrations
Theprogressofacomplexometrictitrationisgenerallyillustratedbyatitration
curve,whichisusuallyaplotofpM=-log[M]asafunctionofthevolumeof
titrantadded.Mostoftenincomplexometrictitrationstheligandisthetitrant
andthemetaliontheanalyte,althoughoccasionallythereverseistrue.Many
precipitationtitrationsusethemetalionasthetitrant.Mostsimpleinorganic
ligandsareunidentate,whichcanleadtolowcomplexstabilityandindistinct
titrationendpoints.

13. …continued…
Astitrants,multidentateligands,particularlythosehavingfourorsixdonor
groups,havetwoadvantagesovertheirunidentatecounterparts.First,they
generallyreactmorecompletelywithcationsandthusprovidesharperend
points.Second,theyordinarilyreactwithmetalionsinasingle-stepprocess,
whereascomplexformationwithunidentateligandsusuallyinvolvestwoormore
intermediatespecies.

15. Precipitation Titratons (Chapter 13)
Precipitationtitrimetry,whichisbasedonreactionsthatyieldioniccompounds
oflimitedsolubility,isoneoftheoldestanalyticaltechniques.Theslowrateof
formationofmostprecipitates,however,limitsthenumberofprecipitating
agentsthatcanbeusedintitrationstoahandful.Themostwidelyusedand
importantprecipitatingreagent,silvernitrate,whichisusedforthe
determinationofthehalogens,thehalogen-likeanions.Titrationswithsilver
nitratearesometimescalledargentometrictitrations.

16. The Shapes of Titration Curves
Titrationcurvesforprecipitationreactionsarederivedinacompletelyanalogous
waytothemethodsdescribedfortitrationsinvolvingstrongacidsandstrong
bases.P-functionsarederivedforthepreequivalence-pointregion,the
postequivalencepointregion,andtheequivalencepointforatypical
precipitationtitraton.
Mostindicatorsforargentometrictitrationsrespondtochangesinthe
concentrationofsilverions.Asaconsequence,titratoncurvesforprecipitation
reactionsusuallyconsistofaplotofpAgversusvolumeofAgNO
3.

19. End Point for Argentometric Titrations
Threetypesofendpointsare:(1)chemical,(2)
potentiometric, (3) amperometric.
Potentiometricendpointsareobtainedby
measuringthepotential.Toobtainan
amperometricendpoint,thecurrentgenerated
betweenapairofsilvermicroelectrodesis
measuredandplottedasafunctionofreagent
volume.Thechemicalendpointconsistsofa
colorchangeortheappearanceor
disappearanceofturbidity.Therequirements
are(1)thecolorchangeshouldoccurovera
limitedrangeinthep-function,and(2)the
colorchangeshouldtakeplacewithinthesteep
portionofthetitrationcurve.

20. Formation of a Colored Precipitate
The Mohr Method
Sodiumchromatecanserveasanindicatorforthe
argentometricdeterminationofchloride,bromide,and
cyanideionsbyreactingwithsilveriontoformabrick-
redsilverchromate(Ag
2CrO
4)precipitateinthe
equivalence-pointregion.Thereactionsinvolvedinthe
determinationofchlorideandbromide(X
-
)are
titrationreaction:Ag
+
+X
-
AgX
(s)[white]
indicatorreaction:2Ag
+
+CrO
4
2-
Ag
2CrO
4(s)[red]
Thesolubilityofsilverchromateisseveraltimesgrater
thanthatofsilverchlorideorsilverbromide.

21. Adsorption Indicators: The Fajans Method
Anadsorptionindicatorisanorganiccompoundthat
tendstobeadsorbedontothesurfaceofthesolid
inaprecipitationtitration.Ideally,theadsorption
occursneartheequivalencepointandresultsnot
onlyinacolorchangebutalsoinatransferofcolor
fromthesolutiontothesolid(orthereverse).
Fluoresceinisatypicaladsorptionindicatoruseful
forthetitrationofchlorideionwithsilvernitrate.
Inaqueoussolution,fluoresceinpartiallydissociates
intohydroniumionsandnegativelycharged
fluoresceinateionthatareyellow-green.The
fluoresceinateionformsanintenselyredsilversalt.
Titrationsinvolvingadsorptionindicatorsarerapid,
accurate,andreliable.

22. The Volhard Method (Colored Complex)
IntheVolhardmethod,silverionsaretitrated
withastandardsolutionofthiocyanateion:
Ag
+
+SCN
-
AgSCN(s)
Iron(III)servesastheindicator.Thesolutionturns
redwiththefirstslightexcessofthiocyanateion:
Fe
3+
+SCN
-
Fe(SCN)
2+
red
Thetitrationmustbecarriedoutinacidicsolution
topreventprecipitationofiron(III)asthe
hydratedoxide. 
  
K
FeSCN
FeSCN
f  
()
.


10510
3
-
2+
3+

23. …continued…
ThemostimportantapplicationoftheVolhardmethodisfortheindirect
determinationofhalideions.Ameasuredexcessofstandardsilvernitrate
solutionisaddedtothesample,andtheexcesssilverionisdeterminedby
back-titrationwithastandardthiocyanatesolution.

24. ORGANIC COMPLEXING AGENTS
(Chapter 17)
Manydifferentorganiccomplexing
agentshavebecomeimportantin
analyticalchemistrybecauseoftheir
inherentsensitivityandpotential
selectivityinreactingwithmetalions.
Suchreagentsareparticularlyusefulin
precipitatingmetalandinextracting
metalfromonesolventtoanother.The
mostusefulorganicreagentsform
chelatecomplexeswithmetalions.

25. Reagents for Precipitating Metals
Oneimportanttypeofreactioninvolvinganorganic
complexingagentisthatinwhichaninsoluble,
unchargedcomplexisformed.Usually,itisnecessaryto
considerstepwiseformationofsolublespeciesinaddition
totheformationoftheinsolublespecies.Thus,ametal
ionM
n+
reactswithacomplexingagentX
-
toformMX
(n-1)+
,
MX
2
(n-2)+
,MX
n-1
+
,andMX
n(soln).
M
n+
+nX
-
MX
n(soln)
MX
n(solid)MX
n(soln)K
eq=[MX
n]
Solubilityproductexpressionis:
K
sp=[M
n+
][X
-
]
n
=K
eq/
n 
 
n
n
n
MX
MX
KKK 

12....
n+
-
n

26. Forming Soluble Complexes for Extractions
Manyorganicreagentsareusefulinconvertingmetalionsintoformthatcanbe
readilyextractedfromwaterintoanimmiscibleorganicphase.Extractionare
widelyusedtoseparatemetalsofinterestfrompotentialinterferingionsandfor
achievingaconcentratingeffectbyextractingintoaphaseofsmallervolume.
Extractionsareapplicabletomuchsmalleramountsofmetalsthan
precipitations,andtheyavoidproblemsassociatedwithcoprecipitation.

28. Ethylenediaminetetraacetic Acid (EDTA)
Ethylenediaminetetraaceticacid[alsocalled
(ethylenedinitrilo)tetraaceticacid],whichis
commonlyshortenedtoEDTA,isthemostwidely
usedcomplexometrictitrant.FullyprotonatedEDTA
hasthestructure
TheEDTAmoleculehassixpotentialsitesfor
bondingametalion:thefourcarboxylgroupsand
thetwoaminogroups,eachofthelatterwithan
unsharedpairofelectrons.Thus,EDTAisa
hexadentateligand.

29. EDTA Is a Tetrabasic Acid
ThedissociationconstantsfortheacidicgroupsinEDTAareK
1=1.02X10
-2
,K
2=
2.14X10
-3
,K
3=6.92X10
-7
,andK
4=5.50X10
-11
.Itisofinterestthatthefirst
twoconstantsareofthesameorderofmagnitude,whichsuggeststhatthetwo
protonsinvolveddissociatefromoppositeendsofthelongmolecule.Asa
consequenceoftheirphysicalseparation,thenegativechargecreatedbythe
firstdissociationdoesnotgreatlyaffecttheremovalofthesecondproton.The
variousEDTAspeciesareoftenabbreviatedH
4Y,H
3Y
-
,H
2Y
2-
,HY
3-
,andY
4-
.

31. Reagents for EDTA Titrations
ThefreeacidH
4Yandthedihydrateofthesodiumsalt,Na
2H
2Y.2H
2O,are
commerciallyavailableinreagentquality.
Undernormalatmosphericconditions,thedihydrate,Na
2H
2Y.2H
2O,contains0.3%
moistureinexcessofthestoichiometricamount.Thisexcessissufficiently
reproducibletopermituseofacorrectedweightofthesaltinthedirect
preparationofastandardsolution.Thepuredihydratecanbepreparedbydrying
at80
o
Cforseveraldaysinanatmosphereof50%relativehumidity.

33. Nitrilotriacetic acid (NTA)

34. The Nature of EDTA Complexes with Metal Ions
SolutionsofEDTAarevaluableastitrantsbecausethe
reagentcombineswithmetalionsina1:1ratio
regardlessofthechargeonthecation.
Ag
+
+Y
4-
AgY
3-
Al
3+
+Y
4-
AlY
-
EDTAisaremarkablereagentnotonlybecauseit
formschelateswithallcationbutalsobecausemost
ofthesechelatesaresufficientlystablefor
titrations.Thisgreatstabilityundoubtedlyresults
fromtheseveralcomplexingsiteswithinthe
moleculethatgiverisetoacagelikestructurein
whichthecationiseffectivelysurroundedand
isolatedfromsolventmolecules.TheabilityofEDTA
tocomplexmetalsisresponsibleforitswidespread
useasapreservativeinfoodsandinbiological
samples.

37. Indicators for EDTA Titrations
Indicatorsareorganicdyesthatformcoloredchelates
withmetalionsinapMrangethatischaracteristicofthe
particularcationanddye.Thecomplexesareoften
intenselycoloredandarediscernibletotheeyeat
concentrationsintherangeof10
-6
to10
-7
M.
EriochromeBlackTisatypicalmetal-ionindicatorused
inthetitrationofseveralcommoncations.
H
2O+H
2In
-
HIn
2-
+H
3O
+
K
1=5X10
-7
red blue
H
2O+HIn
2-
In
3-
+H
3O
+
K
2=2.8X10
-12
blue orange
Theacidsandtheirconjugatebaseshavedifferent
colors.

38. …continued…
ThemetalcomplexesofEriochromeBlackTaregenerallyred,asisH
2In
-
.Thus,
formetal-iondetection,itisnecessarytoadjustthepHto7orabovesothatthe
blueformofthespecies,HIn
2-
,predominatesintheabsenceofametalion.Until
theequivalencepointinatitration,theindicatorcomplexestheexcessmetal
ionsothatthesolutionisred.WiththefirstslightexcessofEDTA,thesolution
turnsblueasaconsequenceofthereaction
MIn
-
+HY
3-
HIn
2-
+MY
2-
red blue

44. Titration Methods Employing EDTA
DirectTitration:Manyofthemetalsintheperiodictablecanbedeterminedby
titrationwithstandardEDTAsolution.Somemethodsarebasedonindicatorsthat
respondtotheanalyteitself,whereasothersarebasedonanaddedmetalion.
MethodsBasedonIndicatorsforanAddedmetalIon:Incasewhereagood,
directindicatorfortheanalyteisunavailable,asmallamountofametalionfor
whichagoodindicatorisavailablecanbeadded.Themetalionmustforma
complexthatislessstablethantheanalytecomplex.

45. …continued…
PotentionmetricMethods:Potentialmeasurementscanbeusedforend-point
detectionintheEDTAtitrationofthosemetalionforwhichspecificion
electrodesareavailable.
SpectrophotometricMethods:MeasurementofUV/visibleabsorptioncanalso
beusedtodeterminetheendpointsoftitrations.Inthesecases,an
instrumentrespondstothecolorchangeinthetitrationratherthanrelyingon
avisualdeterminationoftheendpoint.

46. …continued…
Back-TitrationMethods:Back-titrationsareusefulforthedeterminationof
cationsthatformstableEDTAcomplexesandforwhichasatisfactoryindicatoris
notavailable;thedeterminationofthalliumisanextremeexample.The
methodisalsousefulforcationssuchasCr(III)andCo(III)thatreactonlyslowly
withEDTA.AmeasuredexcessofstandardEDTAsolutionisaddedtotheanalyte
solution.Afterthereactionisjudgedcomplete,theexcessEDTAisback-titrated
withastandardmagnesiumorzincionsolutiontoanEriochromeBlackTor
Calmagiteendpoint.

47. …continued…
Displacementmethods:Indisplacementtitrations,anunmeasuredexcessofa
solutioncontainingthemagnesiumorzinccomplexofEDTAisintroducedintothe
analytesolution.Iftheanalyteformsamorestablecomplexthanthatof
magnesiumorzinc,thefollowingdisplacementreactionoccurs:
MgY
2-
+M
2+
MY
2-
+Mg
2+
whereM
2+
representstheanalytecation.TheliberatedMg
2+
or,insomecasesZn
2+
isthentitratedwithastandardEDTAsolution.Displacementtitrationsareused
whennoindicatorforananalyteisavailable.

48. THANKYOU