Complex

Introduction

1. COMPLEXATION
ShaikhSabina Meraj
Assistant Professor
Y.B. ChavanCollege of Pharmacy.
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2. DEFINITION
Complexcompoundsaredefinedasthose
moleculesinwhichmostofthebonding
structurescanbedescribedbyclassical
theoriesofvalencybetweenatoms,butoneormore
of these bonds are somewhat
anomalous(different).
Acomplexisaspeciesformedbythereversibleor
irreversibleassociationoftwoormoreinteracting
moleculesorions.
Complexeshavebeenusuallyreferredtoascoordination
compounds.
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3. INTRODUCTION
Intermolecularforcesinvolvedintheformationof
complexesare
Coordinatecovalenceisimportantinmetalcomplexes.
VanderWaalsforcesofdispersion
Hydrogenbonding:provideasignificantforceinsome
molecularcomplexes
Hydrophobicinteraction
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4. INTRODUCTION
Oncecomplexationoccurs,thephysicalandchemical
propertiesofthecomplexingspeciesarealtered
(solubility,stability,partitioning,energyabsorption,and
emissionandconductance)
Complexformationusuallyaltersthephysicaland
chemicalpropertiesofthedrug.Forexamples:
(1)chelatesoftetracyclinewithcalciumarelesswater
solubleandarepoorlyabsorbed.
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5. INTRODUCTION
(2)Theophyllinecomplexedwithethylenediaminetoform
aminophyllineismorewatersolubleandisusedfor
parenteralandrectaladministration.
Theophylline
Aminophylline
(Water-soluble)
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6. INTRODUCTION
(3)cyclodextrinsareusedtoformcomplexeswithmany
drugstoincreasetheirwatersolubility.
Hydrophilic
exterior
Hydrophobic
interior
Hydrophobic
drug
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7. INTRODUCTION:
Complexes,accordingtotheclassicdefinition,resultfroma
donor-acceptormechanismorLewisacid-basereaction
betweentwoormoredifferentchemicalconstituents.
ALewisacidisamoleculeorionthatacceptsanelectronpair
toformacovalentbond.Theacceptor,orconstituentthat
acceptsashareinthepairofelectrons,isfrequentlyametallic
ion,althoughitcanbeaneutralion.
ALewisbase(Ligand)isamoleculethatprovidesapairof
unsharedelectronsbywhichthebasecoordinateswiththe
acid.Anynonmetallicatomorion,whetherfreeorcontained
inaneutralmoleculeorinanioniccompound,thatcandonate
anelectronpairmayserveasthedonor. 7

8. 8

9. CLASSIFICATIONOFCOMPLEXES
Complexesmaybedividedbroadlyintotwoclasses
dependingonwhethertheacceptorcomponentisa
metallicionoranorganicmolecule;theseareclassified
accordingtoonepossiblearrangement.
Athirdclass,theinclusion/occlusioncompounds,
involvingtheentrapmentofonecompoundinthe
molecularframeworkofanother.
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10. CLASSIFICATIONOFCOMPLEXES
1. Metal Ion Complexes:
a. Inorganic Type
b. Chelates
c. Mental-olefins
2. Organic molecular Complexes
a. .Drug andcaffeinecomplexes
b. Polymertypes
c. Picricacidtypes
d. Quinhydronetypes
3. Inclusion/occlusion Complexes
a. channel lattice type
b. layer type
c. clathrates
d. monomolecular inclusion compounds
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11. METALCOMPLEXES
Inthistypeofcoordinationcomplexes,components
areorganicmoleculesandtheseareheldtogetherby
weakerforcesorhydrogenbonding.
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12. INORGANICCOMPLEXES
Theammoniamoleculesinhexamminecobalt(III)
chloride,asthecompound[Co(NH3)6]3+Cl3-is
called,astheligandsandaresaidtobecoordinatedto
thecobaltion.
Thecoordinationnumberofthecobaltion,ornumberof
ammoniagroupscoordinatedtothemetalions,issix.
Othercomplexionsbelongingtotheinorganicgroup
include[Ag(NH3)2]+,[Fe(CN)6]4-,and[Cr(H2O)6]
3+.
Eachliganddonatesapairofelectronstoforma
coordinatecovalentlinkbetweenitselfandthecentral
ionhavinganincompleteelectronshell.
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13. For example
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LigandssuchasH
2O:,H
3N:,NC:
-
,orCl:
-
donatea
pairofelectronsinformingacomplexwithametal
ion,andtheelectronpairentersoneoftheunfilled
orbitalsonthemetalion.

14. 14
Hybridizationplaysanimportantpartin
coordinationcompoundsinwhichsufficientbonding
orbital'sarenotordinarilyavailableinthemetalion.

15. CHELATES
Whenaligandprovidesonegroupforattachmenttothe
centralion,thenitscalledmonodentate.
Moleculeswithtwoorthreegroupsarecalledbidentateand
tridentaterespectively(multidentateorpolydentate).
Ifametalionbindstotwoormoresitesonamultidentate
ligand,acycliccomplexisformed;thiscycliccomplexis
knownasachelate.
Chelatesarecomplexesthattypicallyinvolvearing-like
structureformedbytheinteractionbetweenapartialringof
atomandametal.
Inchelates,ligandsareusuallyorganicmolecules,knownas
chelatingagents,chelators,chelantsorsequesteringagents.
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16. Someofthebondsinachelatemaybeionicorofthe
primarycovalenttype,whileothersarecoordinate
covalentlinks.
Theformationofchelatecomplexesiscontrolledby
stringentstericrequirementsonboththemetalionand
theligand.
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17. 17
Manybiologicallyimportantmolecules(e.g.
hemoglobin,insulin,cyanocobalamine,chlorophyll)are
chelates.
Otherbiologicalchelatesincludealbumin,themost
commonplasmaproteinwhichactsasacarrierof
variousmetalions(Cu2+andNi2+)andsmallmolecules
intheblood.

18. Hemoglobinalsocontainsaporphyrinchelatingagent
bondedtoanironIIion.
Inchlorophyllthecentralionismagnesium,andthe
largeorganicmoleculeisaporphyrin.Theporphyrin
containsfournitrogenatomsthatformbondsto
magnesiuminasquareplanararrangement.
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19. Ethylenediaminetetraaceticacid(EDTA)hassixpoints
forattachmenttothemetalionandaccordinglyis
hexadentate.
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20. EDTAisasyntheticchelatingagentusedtosequester
ions(ironandcopper)thatcatalyzesoxidative
degradationreactionsindrugpreparation.
EDTAisalsowidelyusedtosequesterandremove
calciumionsfromhardwater.
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21. Thechelatingpropertiesofprocainamide(Sodium
channelblocker,ClassIAantiarrhythmic)hasbeenused
asanassayforitscontentinpharmaceutical
preparations.
ComplexformationwithCu2+resultsinacolored
compoundthatcanbemeasuredbyvisible
spectrophotometry.
Thuscalorimetricmethodstoassayprocainamidein
injectablesolutionsisbasedontheformationofa1:1
complexofprocainamidewithcupricionatpH4to4.5.
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22. 22
Tetracyclineantibioticsarecapableofactingaschelating
agentsandbindingavarietyofpolyvalentmetalions
(Fe2+,Mg2+,Al3+,Bi3+).
Thecomplexationresultsinchangesinboththedrugs’
andthemetalions’physicalandchemicalproperties.
Thecomplexationbetweentetracyclineantibioticsand
metalionseitherinfood(cabbage)orinpharmaceutical
preparations(ironcontainingsupplements)hasbeen
foundtoreduceboththesolubilityandbioavailabilityof
theantibiotics.

23. 23
Tetracyclinesarecontraindicatedinpediatricpatients
sincetheyarepronetotetracyclinecomplexationof
calciuminteethandbonesresultinginteeth
discolorationandbonegrowthproblems.

24. OLEFINTYPES
Thesetypesofcomplexesareusedascatalystsinthe
manufactureofbulkdrugs,intermediatesand
intheanalysisofdrugs.
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25. ORGANICMOLECULARCOMPLEX
Inthistypeofcoordinationcomplexes,components
areorganicmoleculesandtheseareheldtogetherby
weakerforcesorhydrogenbonding.
Classification oforganicmolecularcomplex
a. Drug andcaffeinecomplexes
b. Polymertypes
c. Picricacidtypes
d. Quinhydronetypes
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26. ORGANICMOLECULARCOMPLEX
Hydrogenbonds-Heredipole-dipoleandlondontypeof
forcesareresponsibleforitsstability.
ThecompoundsN-dimethylanilineand2,4,6-
trinitroanisolereactinthecoldtogiveamolecular
complex:
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27. 27
Chargetransfercomplexes-Inthistypeonemolecule
polarizeother,resultinginelectrostaticinteraction
formingacomplexwithionictypeofinteraction.
Resonancemakethemaincontributionforstability.
For example, the polar nitro groups of trinitrobenzene
induce a dipole in the readily polarizablebenzene
molecule, and the electrostatic interaction that results
leads to complex formation:

28. 28
Electrondonor–acceptormechanism:-Thetypeof
bondingexistinginmolecularcomplexesinwhich
hydrogenbondingplaysnopartisnotfullyunderstood,
butitmaybeconsideredaselectrondonor–acceptor
mechanism.

29. A. DRUGANDCAFFEINECOMPLEXES
Caffeinecomplexingwithanumberofacidicdrugs,such
assulfonamideorbarbiturate.
Mechanism:a.dipole–dipoleforceorhydrogenbonding
betweenthepolarizedcarbonylgroupsofcaffeineand
thehydrogenatomoftheacid.
b.interactionprobablyoccursbetweenthe
nonpolarpartsofthemolecules,andtheresultant
complexis“squeezedout”oftheaqueousphaseowing
tothegreatinternalpressureofwater.
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30. IncaffinemoleculeNitrogenbecomesmorestrongly
electrophillicoracidduetowithdrawalofoxygenfrom
boththesides,formingapositivecenterwhichisoffered
forcomplexation.
Inbenzocainemoleculeesterbecomepolarizeinsucha
waythatcarboxyoxygenactsasneutrophillorbase.
Thecomplexresultinformationofdipoledipole
interactionbetweencarboxyoxygengroupofbenzocaine
andelectrophillicNitrogenofcaffine.
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31. Caffeineformscomplexeswithorganicacidanionsthat
aremoresolublethanthepurexanthine,butthe
complexesformedwithorganicacids,suchasgentisic
acid,arelesssolublethancaffeinealone.
Suchinsolublecomplexesprovidecaffeineinaformthat
masksitsnormallybittertasteandshouldserveasa
suitablestateforchewabletablets.
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32. B. POLYMERTYPES
Polyethyleneglycols,polystyrene,carboxymethylcellulose,
andsimilarpolymerscontainingnucleophilicoxygenscan
formcomplexeswithvariousdrugs.,canbeattributedtothese
interactions.Theinteractionsthatmayoccurinsuspensions,
emulsions,ointmentsandsuppositories.
Theincompatibilitiesofcertainpolyethers,suchasthe
Carbowaxes,Pluronics,andTweenswithtannicacid,salicylic
acid,andphenolmaybemanifestedasa
precipitate,
flocculate,
delayedbiologicabsorption,
lossofpreservativeaction,
undesirablephysical,chemical,andpharmacologiceffects.
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33. C. PICRICACIDTYPES
Picricacid,beingastrongacid,formsorganic
molecularcomplexeswithweakbases,whereasit
combineswithstrongbases(anestheticactivityof
butesin)toyieldsalts.
Picricacidcomplexes–suchasButesinpicratewhich
combinestheantisepticpropertyofpicricacidand
anestheticpropertyofButesinusedasa1%ointmentfor
burnsandpainfulskinabrasions.
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34. 34
2
Butesin Picric acid

35. Quinhydronecomplexes–quindronecomplexis
formedbymixingalcoholicsolutionsofbenzoquinone
andhydroquinoneforminggreencrystals.
Quinhydrone, the complex disassociates into equivalent
amounts of quinoneand hydroquinone in an Aqueous
Saturated solution.
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36. Thesecomplexesarealsocalledocclusion
compoundsinwhichoneofthecomponentsis
trappedintheopenlatticeorcagelikecrystal
structureoftheother.
A class of addition compounds where one of the
constituent of the complex is trapped in the theother to
yield a stable layout.
Type of Host-Guest compound.
Depends on the architecture arrangement rather than the
chemical affinity.
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37. CHANNELTYPES
Whenthepowder(host)crystallizesintheformof
channels,thesechannelshavespecificcharacteristicsand
stereochemistrythatallowsonlySpecifictypeofguest
moleculetofitin.
Averycommonexampleofsuchcomplexesistheone
formedbystarchandiodinewhereiodinemoleculesare
trappedwithinchannelsconsistingofspiralsofglucose
residuesofstarch;othermaterialscapableofforming
thesechannelsincludebileacids,ureaandtheorem.
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38. LAYERTYPE
Compoundssuchasclays,montomorillorite
(constituentofbentonite),canentraphydrocarbons,
alcoholsandglycols.
Theyformalternatemonomolecular(monoatomic)
layersofguestandhost.
Theirusesarecurrentlyquitelimited;howeverthese
maybeusefulforcatalysisonaccountofalarger
surfacearea.
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39. CLATHRATES
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Theclathratescrystallizeintheformofacagelikelattice
inwhichthecoordinatingcompoundisentrapped.
Chemicalbondsarenotinvolvedinthesecomplexes,and
onlythemolecularsizeoftheencagedcomponentisof
importance.
Thestabilityofaclathrateisduetothestrengthofthe
structure,thatis,tothehighenergythatmustbe
expendedtodecomposethecompound.

40. the highly toxic agent hydroquinone (quinol) crystallizes
in a cage like hydrogen-bonded structure.
The holes have a diameter of 4.2 A and permit the
entrapment of one small molecule to about every two
quinolmolecules. Small molecules such as methyl
alcohol, CO2, and HClmay be trapped in these cages,
But larger molecules such as ethanol cannot be
accommodated.
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41. 41
Cagelikestructureformedthroughhydrogenbondingofhydroquinonemolecules.
Smallmoleculessuchasmethanolaretrappedinthecagestoformtheclathrate

42. In this class of inclusion compounds, a single guest
molecule is entrapped in the cavity of one host molecule.
A representative example of such compounds is
cyclodextrins.
Cyclodextrinsare cyclic oligosaccharides containing a
minimum of six D (+) glucopyranoseunits attached by
an -1,4 linkage.
Cyclodextrinsare produced from starch by the action of
bacterial amylase.

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43. 43
Host molecule
Cavity for guest molecule
Hydrophobic interior
Hydrophilic entrance

44. TheinterioroftheCDcavityisusuallyhydrophobic
becauseoftheCH2groups,whiletheexteriorofthe
cavityishydrophilicbecauseofthepresenceofthe
hydroxylgroups.
ComplexationwithCDdoesnotordinarilyinvolvethe
formationofcovalentbonds.Moleculesofappropriate
sizeandstereochemistrycanbeincludedinthe
cyclodextrincavitybyhydrophobicinteraction.
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45. Thenaturallyoccurringα-CD,β-CDandγ-CDcontain6,
7and8unitsofglucoserespectively.
Thecyclodextrinsformaringandthemoleculeactually
existsasatruncatedconeinwhichguestmoleculescan
beaccommodatedtoformaninclusioncomplex.
Thesizeofthecavityincreasesbyincreasingthenumber
ofglucoseunits,α-CDbeingthesmallest,α-CDisnot
veryusefulforpharmaceuticalapplications,β-CDand
γ-CDaremoreusefulowingtothelargecavity.
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46. Thankyou
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