CHAPTER - I
INTRODUCTION
The medical importance of chelating agents hinges on the fact that metals
play many critical roles in the life of living organisms. In the human body, metabolism
depends not only on sodium, potassium, magnesium and calcium but also to a
considerable degree on trace amounts of iron, cobalt, copper, zinc, manganese and
molybdenum. On the other hand, certain other metals like mercury, lead and cadmium,
even in trace amounts, are highly toxic to the body. The dependence of living
organisms on metals is well exemplified by the observation that one third of all
enzymes have a metal ion as an essential component.(1) Also it has been reported that
all most all globular proteins bind a wide range of metal ions.(2)
Many reviews on chelating agents in medicine have been published during the
period of last forty years.(317) In general, these reviews have dealt with the use of
chelating agents as therapeutic countermeasures to either the uptake of toxic metal
ions or the buildup and accumulation of essential metal ions to levels where they
become toxic. The symptomatology may be related to an imbalance of polyvalent
cations and an associated blocking effect on various metalloenzymes.
Current applications of chelating agents in medicine include:
(1) Mobilization of toxic metals like arsenic, cadmium lead, mercury, nickel,
aluminium and radionuclides originating from the nuclear fission process.(18)
(2) Mobilization of essential elements elevated to toxic levels such as iron and
copper in Cooley’s anemia(19) and Wilson’s disease(16), respectively.
(3) Regulation of metal ions at physiologically desirable levels, for example,
copper in the case of Menkes’ disease.(20)
(4) NonInvasive Diagnostic Medicine (NIDM) featured by radioactive isotopes
such as 99Tc (t0.5 6.02 h, arising as a daughter product of 99Mo (t0.5 66 h),
2
radionuclides of gallium(III), indium(III) and a few other polyvalent
cations(21) for imaging tumours and bones.
(5) Antiinflammatory agents comprised mainly of copper complexes.(2225)
(6) Antineoplasial, Antiviral, Antimicrobial and Antiparasitic Agents the
chelating agents coming under this category, with notable exceptions (e.g.
cisplatin) are inhibiting cellular function by inactivating metalloenzymes, and
(7) Metal chelation therapy in limiting tissue damage due to the manifestations of
oxygen toxicity through oxygen radicals.(2628)
The fact that the pharmacological action of certain drugs was due to the
formation of chelates with essential or trace metal ions of biological significance
prompted many research workers all over the world to investigate the structural
features of the metal chelates of drug substances both in solid state and in solution.
1.1 Antimicrobial Metal Complexes(17,29)
The antimicrobial action of 8hydroxyquinoline was due to the formation of
1:1 complex with either iron(II)(30) or copper(II)(31) ions. Similar observations were
made in the case of 2mercaptopyridineNoxide (a disinfectant)(32) and the salts of
dimethyldithiocarbamic acid (fungicide).(33) In recent years, 2,2|bipyridyls and the
structurally related 1,10phenanthrolines were being studied with interest. The mode
of antimicrobial action of 2,9dimethyl1,10phenanthroline and 2,2|bipyridyl
analogues has been attributed to their uptake of copper into the cell membranes.
3,4,7,8Tetramethyl1,10phenanthrolinatenickel(II) has been used as a disinfectant
in the cleansing of newborn babies.(34)
Scandium and indium chelates of enterobactin, a cyclic trilactone of
2,3dihydroxyNbenzoylLserine, have been shown to have antimetabolite
properties. The molluscidal action of 5,2|dichloro4|nitrosalicylanilide has been
attributed to the chelation of iron(III). Dimeric aryloxyacetatocopper(II) complexes
with antipyrine of the type, [Cu2(RCOO)4(Apy)2] were reported. Among the various
3
substituted phenoxyacetate complexes studied, the copper complex of phenoxyacetate
was found to be the most efficient compound of antimicrobial activity.(35)
The antimicrobial effects of copper(II) carboxylates showed an activity
increase in the order, Cu(FCH2COO)2< Cu(ClCH2COO)2 < Cu(BrCH2COO)2 <
Cu(ICH2COO)2. Similarly, arylcarboxylates were also studied.(36)
Metronidazole, an antitrichomonias drug was shown to form metal
complexes with copper(II)(37) rhodium(III)(38) and platinum(II)(39) salts. Synthesis and
bacteriostatic activities of some metal complexes of nitrofurazone and its sulfur
analogue have been reported.(40,41)
Metal complexes of antimalarial drugs, Primaquine and amodiaquine have
been synthesized and tested for their activity against microorganisms.(42,43) Complexes
studied include those formed by VO(II), Cr(III), Fe(III), Cu(II), Co(II), Ni(II), Zn(II),
Cd(II), Mg(II), Rh(III), Pd(II), Au(II), Ag(I), Mn(II), Sn(II) and Pt(II). Amodiaquine
was shown to form 1:1 metal complexes with chlorides and nitrate of these metals of
the type [M(L)yXm] nH2O where y = 2 or 3, m = 1, 2 or 3 and n = 0, 1 or 2. Primaquine
was shown to form 1:2 or 1:3 metal complexes of the type [M(L)yXm]nH2O where y
= 2 or 3, m = 1, 2 or 3 and n = 0, 1 or 2. Only the complexes of heavy metals like
cadmium and mercury were shown to have strong antimicrobial activity.
Isoniazid, a common antituberculosis drug, was shown to form complexes
with metal ions like, Fe2+, Co2+, Ni2+, Cu2+ and Zn2+.(44) Divalent iron and copper were
supposed to be essential for isoniazid to act against tubercule organisms. Isoniazid was
shown to form both 1:1 and 1:2 complexes with copper, binding through oxygen and
amino nitrogen.(45,46)
Pyrazinamide, another antituberculosis drug was reported to form metal
complexes of the type MX2, 4L where M= Co(II), Ni(II), Cu(II) and X = Cl1, Br, I.
Besides thermal and spectral studies of these complexes, ESR spectral study was also
made for the copper complex.(47) Complexes of the type ML2X2 for manganese(II),
4
iron(II), cobalt(II) and nickel(II) have also been reported.(48,49) Nickel was also shown
to form neutral 1:2 complex with pyrazinamide.
Since the discovery by Domagk of the antitubercular activity of
thiosemicarbazones, many of these compounds were reported to be of
pharmacological interest. Thiosemicarbazones have also been found to be active
against influenza, protozoa, small pox and certain kinds of tumour and have been
suggested as possible pesticides and fungicides. Liebermeister showed that copper
ions enhanced the antitubercular activity of pacetamidobenzaldehyde
thiosemicarbazone (thiacetazone).(50) Peter and coworkers showed that the active
intermediate in the antitumour activity of 3ethoxy2oxobutyraldehyde bis
(thiosemicarbazone), H2KTS was the chelate Cu(KTS).(51)
The copper complex of pacetamidobenzaldehyde thiosemicarbazone
(thiacetazone) was reported by Kuhn and Zilliken in 1954.(52) Gingras et al have
studied copper(I) complexes of many substituted aliphatic and aromatic
carboxaldehyde or ketone thiosemicarbazones.(53) Based on infrared spectral studies,
these ligands were shown to coordinate through sulfur and imine nitrogen of the
thiosemicarbazone moiety.
The literature on the metal complexes of thiosemicarbazones was surveyed by
Campbell,(54) and Padhye and Kauffman.(55) Recent studies were dealing with the
metal complexes of 2,6diacetylpyridine bis (thiosemicarbazone),(56) N(pyridyl)
furfural2aldehyde thiosemicarbazone and N(pyridyl)thiophene2aldehyde
thiosemicarbazone(57). Evidently, heterocylic thiosemicarbazones have been shown to
behave as tridentate or tetradentate ligands. Square planar complexes of 4methoxy
benzaldehyde4phenyl3thiosemicarbazone with copper(I) and a few platinum
group metals were reported.(58)
1.2 Metal Complexes of Sulfanilamides and Antibiotics
Sulfanilamides were the first effective chemotherapeutic agents to be
employed systematically for the prevention and cure of bacterial infections especially
5
of ophthalmic, urinary tract and gastrointestinal tract. The interest in sulfanilamides
was renewed by reason of the application of their metal compounds in topical burn
theraphy.
Four different types of metal compounds of sulfanilamides are described in
the literature.(59)
Type A M(HL)mXn, where the sulfanilamide (HL) is present as a neutral ligand
and X is present as counter ion (NO3) or coordinated to M(Cl, I, SCN,
acetate), and M= Ag(I)(60), Bi(III)(61), (Hg)(62,63), Cu(II)(64), [Cd(II), Co(II),
Mn(II), Ni(II), Zn(II)].(65,66)
Type B MLm, where the sulfanilamide is an anion(L) and M= Ag(I),(67,68)
Cu(II),(69) [Cd(II), Co(II), Mn(II), Fe(III), Ni(II), Zn(II)],(70,71) [As(III),
Bi(III), Sb(III), Sn(II)],(72) Hg(II).(73)
Type C (H2L)2 [MCl4], where the sulfanilamide is protonated (H2L+) and
M=[Cu(II), Co(II), Cd(II), Ni(II)].(65,70,71)
Type D MLmYn, where Y = NH3, morpholine, imidazole, pyridine, n = 2, 3 or 4
and M = Ag(I),(74) [Cd(II), Co(II), Mn(II), Ni(II), Zn(II)](65,70)
A review on the synthesis of metal sulfanilamide compounds was published
by Bult.(75) The following sulfanilamides were so far employed in preparing metal
compounds. 5Methylsulfadiazine, 5methoxysulfadiazine, phthalylsulfathiazole,
succinylsulfathiazole, sulfacetamide, sulfadiazine, sulfadimidine, sulfamethoxy-
pyridazine, sulfadimethoxine, sulfafurazole, sulfaguanidine, sulfaisomidine,
sulfamerazine, sulframethizole, sulfanilamide, sulfapyridine and sulfathiazole.
Ag(I), Zn(II) and Ce(III) compounds of sulfadiazone seemed to be suitable
for the treatment of burns. Recently organomercury,(76) Sb(III)(77), Cu(II) and Hg(II),(78)
compound of few sulfanilamides were reported. Binuclear copper(II) complexes of the
nitrogen containing heterocyclic derivatives of sulfanilamides have also been
reported.(79)
6
Antibiotics belong to a class of compounds of biosynthetic or semisynthetic in
nature. Most of them are produced by various species of microorganisms and other
living systems and are capable in small concentrations of inhibiting the growth of or
killing bacteria and other microorganisms.
An extensive review on the metal complexes of various antibiotics was
published.(80) It included complexes of tetracycline and daunorubicin, streptonigrin,
bleomycin, valinomycin, beauvericin and other enniatins, gramicidins, nactins,
lasalcid, monensin, calcimycin and related antibiotics, Deycloserine and related
aminoacids with antibiotic properties and ironcontaining antibiotics.
Chlorotetracycline (aureomycin) and oxytetracycline (terramycin) were
shown to have high affinity for the cations of heavy metals.(81) The avidity of
tetracycline towards first row transition metal ions and the corresponding stability
constants of the metal complexes have been reported.(82) The stoichiometries and
concentrations of the different metal complexes formed by tetracyclines in vivo could
be assessed on a quantitative basis by using high speed computer programmes to
simulate large equilibrium systems like plasma.(8385)
Metal complexes of Dcycloserine (D4amino3isoxazolidinone), used to
treat mycobacterial infections, with Pt(II), Pd(II), Rh(III), Ir(III), Hg(II), Cd(II) and
first row transition metal ions have been reported.(8688) Amikacin, a semisynthetic
aminoglycoside produced by chemical modification of Kanamycin, was reported to
form copper(II) complex of 1:1 stoichiometry.(89) Nalidixic acid, a quinolone
antibacterial agent was shown to form complexes with calcium, magnesium,
cadmium, mercury, palladium and first row transition metal ions.(90)
Thiadiazole derivatives have been reported to be biologically versatile
compounds, possessing antiviral, antibacterial, antipyretic, fungicidal and
analgesic activities. Complexes of 4acetyl2(acetylamino)5dimethyl21,3,4
thiadiazole with cadmium, mercury and first row transition metals have been
described.(91,92)
7
1.3 Metal Complexes as Antiinflammatory Agents
Many copper complexes have been studied as antiinflammatory agents. The
results of these studies confirm as well as extend the original observations that copper
complexes of inactive ligands and active antiinflammatory drugs are more active
than the parent drug or inorganic copper.(24)
Copper complexes of well known antiarthritic drugs include salicylic acid,
aspirin, niflumic acid, Dpenicillamine, hydrocortisone, dexamethasone,
dimethylsulfoxide, clopirar, ketoprofen, (+)naproxen, indomethacin and mefenamic
acid.
In 1960, Hanie and Michalov reported the synthesis and Xray analysis of
copper(II) salicylate tetrahydrate.(93) This study showed that the compound is
monomeric, containing only one copper ion per molecule. Inoue and coworkers
subsequently reported the synthesis of two distinct forms of anhydrous copper(II)
salicylate.(94) In each case, one form of the complex had a normal magnetic moment
and the other had a subnormal magnetic moment. These results indicated that
copper(II) complexes of salicylic acid may be monomeric, dimeric or polymeric,
depending on the reaction conditions.
ManojlovicMuir reported the synthesis and Xray crystallographic data for
copper(II) aspirinate.(95) The crystal structure contains binuclear units, [Cu(C9H7O4)]2
interconnected by CuO bonds to form a polymeric system. The coordination of the
copper atom is octahedral and the stereochemistry of the binuclear unit resembles that
found in the case of copper(II) acetate monohydrate. Lewis et.al studied the spectral
and magnetic properties of many copper(II) carboxylates including the
acetylsalicylate.(96)
The synthesis of bis(4aminosalicylato)copper(II) with no analytical data was
reported in 1978.(97) Trans and cis forms of bis(4aminosalicylato)copper(II)
monohydrate were synthesized and characterized by means of IR, UVVisible NMR,
ESR and magnetic susceptibility studies.(98) This work suggested monomeric structure
8
with square planar environment for both types of complexes. The metastable
ciscopper(II) complex which rearranges in solution was reported to be stabilized
through hydrogen bonding of the hydroxyl groups on the same side of the benzene
rings. Both of these complexes were studied spectrophotometrically for their viability
as a copper oxidase enzyme model.
Salicylate complexes of cobalt(II), nickel(II), zinc(II) and cadmium(II) with
the general formula [M(HSal)2]nH2O were prepared and characterized by Kharitonov
and Tuebakhova.(99) Salicylamide complexes with copper(II), nickel(II), cobalt(II),
zinc(II), cadmium(II), mercury(II) and iron(III) have been reported.(100102) Spectral
and magnetic properties of these complexes suggested that salicylamide coordinates to
the metal ion through phenolate oxygen and carbonyl oxygen or amide nitrogen.
Salicylamide was also shown to form adducts with vanadyl and other first row
transition metal salts of the composition [VO(SA)SO4], [VO(SA)Cl2],
[VO(SAH)(acac)], [M(SAH)2] and [M(SA)Cl2(H2O)] where M = Mn(II), Co(II),
Ni(II), Cu(II) and Zn(II)] and SAH deprotonated salicylamide.(103)
The preparation and properties of the copper(II) halide complexes, of
nictindole CuX2(NIDOL)2 (where X = Cl, Br) were reported.(104) The diffuse
reflectance spectra, magnetic moments and electron spin resonance spectra were
shown to be consistent with a tetragonally distorted pseudooctahedral environment
around the copper(II) ions. The infrared spectra indicated monodentate coordination of
the neutral drug to the central metal ion via the nitrogen atom of the pyridine ring. The
copper(II) complex, Cu(MKH)2.2H2O had been synthesized with the anti
inflammatory drug, 2aminomethyl4(1,1dimethylethyl)6iodophenol
(MK.447).(105) The structural investigation showed the monoanionic ligand with
coordination involving phenolate oxygen atom and the nitrogen atom of the
aminomethyl group. This copper complex was shown to have dismutase activity.
Metal complexes of other antiinflammatory drugs like isoxicam,(106)
tenoxicam(107) and meclofenamic acid(108) with few first row transition metal ions like
9
Mn2+, Fe3+, Co2+, Ni2+, Cu2+ and Zn2+ were reported. All these drugs behaved as a
monoanionic bidentate ligand with the general formula of the metal complexes
M(L)x.nH2O, where X = 2 or 3 and n = 0 to 5. Manganese(II) and copper(II)
complexes of meclofenamic acid and tenoxicam exhibited marked superoxide
dismutase activitiy in the nitro blue tetrazolium assay.
The copper(II) complex of indomethacin [1(pchlorobenzoyl)5methoxy
2methylindoleacetate] was prepared and characterized by Weser and
Coworkers.(109) The total yield was shown to be only 2% possibily due to high kinetic
stability of the complex. Crystallographic study revealed the dimeric form of the 1:2
complex Cu2 (indomethacin)4. Binary and ternary copper(II) complexes of
2,3diaminopropionic acid have been suggested to be important as possible
therapeutic agents to treat rheumatoid arthritis.(110)
1.4 Metal Complexes as AntiTumour Agents(111)
The discovery of cisplatin, cis[Pt(NH3)2Cl2] prompted the search for novel
potent antitumour agents among metallic compounds. Purely inorganic compounds,
coordination complexes and organometallic compounds, coordination complexes and
organometallic compounds are now extensively and systematically screened as
antitumour agents.
The antitumour properties and the mechanism of action of platinum(II) and
platinum(IV) complexes have been the subjects of many detailed review and books. A
series of second generation antitumour agents include carboplatin, spiroplatin,
oxoplatin and iproplatin. Among other metal compounds, bis(1phenyl1,3butane
dionato)diethoxytitanium(IV), auranofin (a gold(I) compound), bleomycin (a copper
containing antibiotic), copper(II) complex of 3ethoxy2oxobutyraldehyde
bis(thiosemicarbazone) and trans[Pd(NH3)2Cl2] are important antitumour agents.
10
1.5 Metal Complexes as AntiViral Agents(112)
The existence of virusspecific metalloenzymes and the differential toxicity
of free metal ions for viral proteins continue to hold out some promise that metal ions
and substance that chelate them might have useful applications as antiviral agents.
Some copper and zinc complexes of isatinthiosemicarbazones with an alkyl
substituent at the side chain sulfur atom have been prepared and complexation has
been claimed to be important for their biological activity.
(N)Heterocylic thiosemicarbazones chelate through ring nitrogen, the
iminonitrogen and the sulfur atoms. Complexes with iron, cobalt, nickel and copper
have been synthesized. Stability constants for the 2acetyl and 2formylpyridine
thiosemicarbzone complexes of copper and zinc are available. The anitviral activity
of 2acetylpyridine thiosemicarbazone might be due to chelation of the zinc ion in the
enzyme of the influenza virus.
Other compounds of interest include phosphonic acetic and phosphoformic
acids, diketones, quinolones and flavanoids. 1.6 Metal Complexes of Hallucinogenic Drugs(113)
Hallucinogenic drugs are substances that have fundamental effects upon the
sensory perception and the mind, above all colourful optical hallucinations, less often
illusions of the other senses. Mishra et.al(113) reported on the preparation of mercury
complexes of amphetamine, methamphetamine and ephedrine having the general
formula HgCl2L2.
A major number of well defined copper complexes could be isolated by
reacting the free bases with copper(II) chloride in an anhydrous solvent. The infrared,
and electronic spectra of copper complexes of escaline, methamphetamine and
phenylethylamine were examined in the solid state and in solution.
Diazepam was shown to form well defined metal complexes having the
composition M2L3X4 (M =Co2+, Ni2+; X = Cl, Br, I) and ML2X2 (M = Cu2+, X =
11
Cl, Br). Barbiturates were reported to form purple complexes with cobalt(II) ions in
the presence of bases. They were also reported to form stable complexes with silver
and mercury ions. Cobalt and zinc complexes of barbital (with imidazole as base) have
tetrahedral geometry while the copper complex (with pyridine as base) has square
planar geometry. The composition of these complexes was found to the M(barbital)2
(Base)2. Recently, the spectral properties of copper(II) complexes of barbiturates have
been reported.(114)
Metal complexes of cafferine have been reported. Metals studied include
copper,(115,116) ruthenium,(117) rhodium,(118) platinum,(119,120) manganese,(121)
magnesium,(121) and mercury.(122) 1.7. Iron123 and Gold124 Containing Drugs
Iron(II) chelates of monohydroxamic acids and aminohydroxamic acids drew
attention as potential agents to regenerate hemoglobin levels in anemic vertebrates. In
vitro tests using gold complexes with certain sulfa drugs (e.g. sulfadiazine,
sulfamethizole and sulfasomidine) against a wide variety of bacteria showed a higher
antimicrobial activity as compared to the parent sulfur compounds. The gold
sulfamides were found to be bactericides.
Gold complexes of antipyrine derivatives of the type [AuCl4][HL],
thiopolypeptides, 5diazouracil {[AuL2Cl2]Cl.HCl} and auranofin have shown
antitumour properties. Gold(I) salts of thiosulfate, thiomalate, thioglucose and
phosphine thiolates were found to be important agents against rheumatoid arthritis. 1.8 Metal Complexes of Other Drugs
Metal complexes of aminopyrine(125) and antipyrine(126) (known analgesic and
antipyretic drugs) have been reported. Aminopyrine complexes with metal(II)
perchlorate of the types [M(AMP)22H2O](ClO4)2, [M(AMP)2](ClO4)2 and
[M(AMP)2H2O](ClO4)2, where M = Fe(II), Co(II), Ni(II), Cu(II) and
AMP=aminopyrine, have been prepared and characterized by elemental analysis,
12
molar conductivity, magnetic measurements, electronic and infrared spectral
studies.(127)
Copper(II) bis(phenylbutazone) was reported by Sorenson.(128) Complexes of
both diastereoisomers of ephedrine with copper(II) have been known.(129−132) Two new
complexes of copper(II) with (+) pseudoephedrine have been isolated & characterized
as [Cu((+)eph)2]. (+)Heph.2H2O and as [Cu((+)eph)2]3.(133−137)
Bis(theophyllinato)copper(II) dehydrate and its anhydrous form were reported.(138)
Their thermal, spectral and magnetic behaviours have been investigated. Preparation
and thermal behaviour of theophylline complexes of other metals like Co(II), Ag(I),
Zn(II) and Cd(II) have been also reported.(139−142) Theophylline was shown to
coordinate through oxygen and N7 atom. Metal complexes of metformin (used as
antidiabetic and analgesic) with cobalt, nickel, copper and zinc were subjected to
structural investigation and measurement of antimicrobial activity.(143−152) 1.9 Scope of the Present Work
Reports on metal complexes of many drugs of choice in the treatment of
various diseases like rheumatoid arthritis, bronchial asthma, anemia, Wilson’s disease,
cancer, etc., are appearing regularly in the chemical literature. In several instances it
was shown that the metal complexes are more effective and less toxic than the parent
drugs. So it was considered interesting and useful to study the metal complexes of
drugs using various physicochemical methods.
It is proposed to study the metal binding characteristics of some selected
pharmaceuticals mentioned below.
Thiacetazone (pacetamidobenzaldehyde thiosemicarbazone), an antituber
culosis drug is containing acetamido carbonyl oxygen, hydrazine nitrogen,
carbothioamide nitrogen and sulphur as possible key atoms to bind the metal ions.
Sulfanilamide drugs such as sulfamethoxazole and sulfisoxazole are used as
urinary antiseptics. In these heterocyclic derivatives of sulfanilamide, isoxazole ring
nitrogen is also there in addition to aniline nitrogen, sulfonamide nitrogen and sulfonyl
13
oxygen, capable of binding metal ions of interest. Nitrofurantoin, a 5nitrofurfural
derivative of imidazolidine2,4dione, is another urinary antiseptic found interesting
to study its metal coordination behaviour under controlled experimental conditions.
NBis(2hydroxyethyl)glycine, commonly known as bicine, is potential
chelating compound containing hydroxyl oxygen, carboxyl oxygen and tertiary
nitrogen as key atoms.
Dapsone (4,4|diaminodiphenylsulfone) is a popular antileprosy drug
containing two aniline NH2 groups for metal binding.
In addition to biologically important metals like magnesium, iron, cobalt,
copper, zinc, etc., other metals such as manganese, nickel, cadmium, mercury and lead
are also included in the preparation of complexes of the pharmaceuticals mentioned
above. This enables us to characterize the metal complexes prepared effectively, using
various techniques such as UVVisible, infrared and proton magnetic resonance
spectral analyses, magnetic susceptibility measurement and thermal decomposition
study.
The significance of copper complexes of biologically active or inactive
organic compounds in medical pharmacology prompted us to prepare some mixed
ligand copper(II) complexes of salicylamide, acetylsalicyclic acid, isonicotinic
acidhydrazide, pyridoxine, pyrazinamide and theophylline.
The main objective of the present study is to understand the conditions under
which the selected pharmaceuticals form metal complexes and to throw light on the
metal binding nature of these biologically important compounds. Detailed study of any
single complex using methods such as ESR, Xray and polarized spectra is beyond the
scope of this work and no attempt would be made to analyse completely the electronic
and infrared spectra of any complex.
14
CHAPTERI
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