Download IJCA 42A(9) 2175-2184

Indian Journal of Chemislry
Vol. 42A, September 2003, pp. 2175-2184
The bioinorganic chemistry of copper
R N Mukheljee
Department of Chem istry, lndian Institute of Technology. Kanpur 208016, India
Reccivcd 2 1mlumy 2003
Man y enzy mes and proteins have copper at their active sites, which plays a key rol e in biology. An important goal of
bioinorganic chemistry is the develop ment of small inorganic coordination complexes that reproduce structural ,
spect roscopic features and functiollal aspects in a manner similar to th ei r natural counterparts. To provide an ove rview of the
activities in this field. some results Oil synthetic modelling of a selected number of copper proteins/enzymes are described in
this article.
Copper is one of the transItIon elements frequently
found at the active site of proteins. The copperconta111mg enzymes and proteins constitute an
important class of biologically active compounds. The
biological function s of copper protei ns/enzymes
include electron transfer. dioxygcn transport,
oxygenation.
oxidation,
reduction
and
disproportionation 1.2 .
In nature, a variety of copper proteins are essential
constituents of aerobic organisms,
including
hemocyanins (arthropodal and molluska n O2 carriers)
and enzymes that "activate" O2 , promoting oxygen
atom incorporation into biological sllbstrates. The
latter include
tyrosinase
(a monooxygenase,
incorporating one oxygen atom to the substrate and
reducing th e other to water) and dopamine ~­
hydroxylase (a mOllooxygenase). "Blue" multicopper
oxidases [e .g., laccase (phenol and diamine
oxidation), ascorbate oxidase (oxidation of [ascorbate) and ceruloplasmin] promote substrate oneelectron oxidation while reducing O2 to water.
Ceruloplasmin may be involved in copper
metabolism. Cytochrome c oxidase transduce energy
from the same 4e-/4H+ reduction of O2 occurring at a
heme-Cu binuclear centre, and couple this to
membrane proton translocation, utilized in ATP
synthesis. Amine oxidases and galactose oxidase
effect amine -7 aldehyde oxidative deaminations and
alcohol -7 aldehyde oxidative dehydrogenations,
respectively. Copper ion reactions with reduced
dioxygen derivatives (e.g., sLlperoxide (02 '), hydrogen
peroxide) are essential in Cu-Zn superoxide
dismutase, and may be involved in copper-mediated
oxidative damage in biological media, including
possibly in Alzheimer's disease.
Correlated with the enzymatic acrivity, the copper
proteins exhibit unique spectroscopic properties and,
accordingly, the proteins are divided in mainly three
types.
Type I copper proteins (also called "blue" copper
proteins) are known to have one copper ion in the
active site. This copper ion shows some remarkable
spectroscopic features: an intense absorption around
600 nm , with an extinction coefficient of about 3000
~I em-I. Another characteristic feature of the Type I
copper proteins is the extremely small hyperfine
splitting in the EPR spectra (A II"" 40-90 x 10- 4 cm- I ).
Type II copper proteins have no distinct unique
prop~rties . The spectroscopic data of these proteins
are comparable to those of "normai" copper
compounds.
Type
III
copper
proteins
contain
antiferromagnetically coupled copper dimers. These
proteins are diamagnetic and therefore are EPR silent.
In some proteins, all three types of copper sites are
present. Such proteins were proposed to classify as
Type IV. In ascorbate oxidase one of the copper ions
is found in a distorted tetrahedral (trigonal pyramidal)
coordination with two histidines, a methionine and a
cysteine. Thi s resembles the active site of the blue
copper protein plastocyanin. Also, a trinuclear copper
site was found consisting of a Type III copper pair
and a "normal" Type II copper ion.
Reactions that copper proteins carry out have long
interested inorganic chemists. Copper is an important
element in oxidation catalysts for laboratory and
industrial use. Interest in the copper-dioxygen
complexes stems from the diverse occurrence of
copper proteins which function as highly efficient
biooxidation catalysts. Copper-dioxygen adducts are
2176
INDIAN J CHEM, SEC A, SEPTEMBER 2003
suggested as key reaction intermediates in these
enzymatic reactions. The differentiation in the
function of these proteins is attributed primarily to the
coordination structure of the copper-dioxygen
intermediate formed in the protein matrices,
depending on the ligand donors, the geometry, and the
coordination mode of the dioxygen. However, the
correlation between these structural factors and the
function/catalysis of the enzymes remains to be
elucidated.
Importance of inorganic model chemistry
Investigations of metallobiomolecules
have
increased markedly during the last two decades. Highresolution X-ray crystallographic results, in particular,
have facilitated detailed considerations of structural,
electronic and reactivity properties at the molecular
level. These metallobiomolecules are highly
elaborated coordination complexes whose metalcontaining sites (coordination units), termed as
"active sites", comprising one or more metal ions and
their ligands, are usually the loci of electron transfer,
binding of exogenous molecules and catalysis. The
demonstrated or potential relation between the
properties of these sites and those of synthetic
coordination complexes has contributed significantly
to~ the emergence of the interdisciplinary field of
bioinorganic chemistry. The complexity of biological
systems renders a detailed study of their mechanism
very difficult. An increasingly popular method of
elucidating structures and mechanisms is the use of a
simple chemical compound or system 3 .
Interest in elucidating or mimicking the physicochemical properties of metalloproteins has led to
spurring activity in the synthesis of numerous
interesting coordination complexes.
However,
recently there has been an increased emphasis upon
functional modelling of proteins. While the structural
and spectroscopic modelling of metalloprotein active
sites is an important and ongoing endeavour, the
realization that coordination chemists can and should
make significant contributions to reactivity studies
and mechanism has become apparent. The value of
models for metalloproteins will always be relative.
One of the difficulties encount~red in simulating a
biosite is that, as time p"sses, the objective may
change with advancing knowledge. If the structure of
the metal ion environment in the metalloprotein is
unknown, the objective may be to reproduce some
property of the system in a similar model coordination
compound. However, when the structure of the biosite
is known, then the complex that it reproduces has, as
far as possible, the known structure. A different
emphasis is obtained when the action of the metal in
the protein is reproduced by a model compound and
the mechanism of a particular reaction is elucidated or
partially explained.
The purpose of models is not necessarily to
duplicate natural properties but to sharpen or focus
certain questions. The goal is to elucidate
fundamental aspects of structure, spectroscopy,
magnetic and electronic structure, reactivity and
chemical mechanism. A synergistic approach to the
study of metalloenzymes can and has yielded crucial
information because synthetic analogues can be used
to investigate the effects of systematic variations in
coordination chemistry, ligation, local environment
and other factors, often providing insights that cannot
be easily attained from protein studies (Fig. 1).
Reproducing complex biological reactivity within a
simple synthetic molecule is a challenging endeavour
with both intellectual and aesthetic goals.
Several researchers 2,4 have endeavoured to
understand the structure and function of copper
proteins involved in copper(l)/02 interactions by
studying inorganic models, i.e., synthetically derived
copper(I) complexes, and their O 2 reactivity. Such
biomimetic approaches can lead to fundamental
insights into the copper-based chemistry. One might
also envision the development of reagents or catalysts
for use in practical oxidation processes 4f•
It is the purpose of this article to highlight recent
advances in bioinorganic model (structurally
characterized) studies on· some selected copper
proteins/enzymes, including some results from
author's laboratory.
Protein(s) and synthetic models
Blue copper proteins: Type I copper
"Blue" copper proteins (azurin, plastocyanin)5,
SynthetiC models
Metalloprotelns
I f'---_ _~I \
Establish relevant
coordination chemistry
Active site
Fig. I-The synergistic relationship between studies involving
metalloprotein biochemistry and inorganic modelling.
MUKHERJEE: THE BIOINORGANIC CHEMISTRY OF COPPER
which function as electron transport agents in a
number of biochemical systems, gain their colour
from an intense electronic absorption band that arises
from a charge transfer transition to the Cu 2+ ion at the
active site from the cysteine thiolate ligand. The
unusually low energy of the transition results from the
coordination geometry about the Cu 2+, which involves
a nearly trigonal arrangement of two imidazole N
atoms and the thiolate S atom, as shown in Fig. 2. The
methionine S atom is found along the trigonal axis at
a long distance, 2.6-3.1 A, reflecting a weak bonding
interaction; sometimes a peptide carbonyl oxygen
atom is located on the other side of the trigonal plane,
at an even longer distance. This bonding arrangement,
together with a high degree of covalency associated
with the short Cu-S (thiolate) bond, leads to reduced
values of the A II Cu hypelfine coupling constant. The
coordination geometry stabilizes the copper(I)
oxidation state and the redox potentials are unusually
high in relation to ordinary copper complexes .
The synthesis and structural characterization of a
thiolate-copper(II) complex which closely mimics the
spectroscopic characteristics of blue copper proteins
have been longtime goals in bioinorganic chemistrl.
The main difficulty in synthesizing an accurate model
for Type I copper comes from the instability of the
copper(II)-thiolate bond [2Cu ll -SR -7 2eu' + RSSR]7.
Kitajima and co-workers 8 were successful in
providing structural proof of a copper(IJ) complex
(trigonal pyramidal) with C6 HsS· coordination
(Fig. 2). The Cu(II)-S(thiolate) distance (2.18 A) is
distinctly shorter than those of the reported
complexes. Spectroscopic features of this complex are
comparable to those of "blue" copper proteins. The xray analysis (poor data set) of a closely similar
complex with Ph 3S· as the thiolate ligand was also
achieved.
Superoxide dismutase: Type II copper
The reduction of dioxygen probably proceeds, in
every instance, by a series of one-electron transfer
reactions . Therefore, unless the intermediate reduction
products are retained within the active site of an
enzyme or coordinated to a metal complex, there is
every likelihood that most oxidation reactions will
generate superoxide as the initial reduction product.
As superoxide ion is toxic to cells, a defense
mechanism must have been initiated by nature. We
now know that essentially all organisms, which use
dioxygen, and many that have to survive an
2177
.
(methionine j ~
•
0
'.3.12A
2.01A~ \
(histidine)N'11'ft~
•. • 1090
o
'0
101\_.'·~cu'f...l.12 A
(histidine)
N~"-..Io
"" S (thiolate)
2.081..-.....-/ 135
(a)
F
[(L)Cu(SC 6F 5)]
(b)
Fig. 2--(a) The active -site of azurin, with the indicated bond
lengths and angles; (b) The model complex
oxygenated environment, contain at least one
superoxide dismutase. The one which is pertinent to
this article is a Cu-Zn protein found in cells that
contain a nucleus (eukaryotic cells). Its function is to
catalyze the disproportionation of superoxide ion
(0 2-), i.e., it is a "superoxide dismutase,,9.
Copper-zinc superoxide dismutase (SOD) contains an
imidazolate-bridged Cu(IJ)-Zn(II) heterodinuclear
metal centre in its active site (Fig. 3). The copper ion
is in a distorted square-pyramidal geometry, while the
zinc ion located at a distance of 6.2 A from the copper
ion is in a distorted tetrahedral structure. The catalytic
cycle (Fig. 4) starts with the replacement of a water
molecule at the axial position by superoxide ion and
reduces the copper to Cu(l). Concomitantly the bond
from Cu to imidazolate is broken and O2 is released.
INDIAN J CHEM, SEC A, SEPTEMBER 2003
2178
second proton from an active-site water,
uncharged hydrogen peroxide is released.
The Cu-facing nitrogen of histidine becomes
protonated and a second O 2- becomes bound. An
electron is transferred from Cu(l), coupled with a
proton transfer from histidine. After addition of a
In the copper ions in the imidazolate-bridged
Cu(Il)-Zn(Il) heterodinuc1ear complex (Fig. 3)
synthesized by Fukuzumi and co-workers 10, the
coordimtion site occupied by a solvent can be
susceptible to ligand substitution, thus providing a
binding site for substrate superoxide. The Cu(H)Zn(II) distance of 6.197(2) A agrees well with that of
native enzyme. The complex catalyzed the
dismutation of superoxide at biological pH.
OH 2
9 (aspartate)
(histidine) N", /N (histidine)
/
(histidine) N
CU ..........
NO
~
~
~z ..-N(histidine)
N-- n
'.
'N (histidine)
(a)
Nitrite reductase: Type 1 alld Type 11 copper
Denitrification, the dissimilatory transformation of
NO,' and N0 2 ' to gaseous N 2 0 or N 2 , is a central
process in the biological nitrogen cycle (Fig. 5)
responsible for depletion of nitrogen, necessary for
plant growth, from soil I I. The copper-containing
nitrite reductases isolated from bacteria and fungi,
comprise an important subclass of the set of
denitrification enzymes. These enzymes catalyze the
reduction of N0 2- to NO, although N 20 generation
has been induced under some conditions. The active
site (Fig. 5) of this enzyme contains a pair of copper
ions, one cf which has been assigned as a "green"
Type I, electron transfer site_ The other site is an
unusual, distorted pseudotetrahedral Type II site.
NCMe
[(L)CuZn(MeCNhl[CI0 41J ·2MeCN
(b)
Fig. 3----(a) The metal-binding region of Cu, Zn-SOD; (b) The
model complex.
/arginine
/arginine
HN
1
HN
1
H-Nt+' N-H
I
H
H-N t+' N--H- -
I
I
H
r.
I
-2
"H~
-"""':cu
O,',H+
I::rginine
1I
1
I I
j-j---N t+' N-H
H
H
H
H
"-..~ ~ /
<Ide" n N-r~
~
/
<I \~N-r~
t
H-N t+' N-H---'Q
H
I "- N~
H
~
/arginlne
H
("'o:'H
H,O,
I
the
N
~hi8lidine
Fig. 4--The catalytic cycle of superoxide dismutase.
MUKHERJEE: THE BIOINORGANIC CHEMISTRY OF COPPER
2179
(a)
OH2
.
du
(histidine) N -/
N (histidine)
. (cysteine)S-\U _ _ N(histidine)
'N.(hlsti~I~)
'}
N (hiItidiDe) ~
I
[(L)Cu(NO)].O;Smcsityione
S (methionine)
[(L)Cu(ONO»
"green" Type I
Typen
12.5
A
•
(b)
m+
NO'
.
H0
'f "}'
+ +
l~' ---.!..- l~'" NO," ~ ""'" NO
2+
="'" "'" • NO
(L)CI(N~]
2
E-Cu2+ ~ B-Cu +. N01·
(c)
Fig. 5-(a) The pathway of denitrification; (b) The active site of
nitrite reductase (the two Cu sites are linked by a dipeptide
fragment); (c) Proposed mechanism for nitrite reduction by nitrite
reductase.
Proposed mechanism for reactions of coppercontaining nitrite reductases is presented in Fig. 5.
Tolman and co-workers i2 provided examples of a
number of substrate-bound copper(I) and copper(U)
complexes (Fig. 6). In an elegant manner they
modelled N20 generation by copper proteins through
reductive disproportionation of Cu-NO species. To
prove the reaction sequence they isolated a nitritebound complex.
Hemocyanins: Type III copper
Hemocyanin2 is a ubiquitous dioxygen carrier for
invertebrates, containing a dinuclear copper site to
which dioxygen is bound as peroxide (Fig. 7); the two
copper ions are divalent in the dioxygen binding state
(so-called oxyhemocyanin, oxy-Hc), Oxy-Hc is EPR
silent and in fact, diamagnetic at room temperature
due to a very strong antiferromagnetic exchange
coupling (-21 > 600 cm- I ) between the two Cu(U)
ions. Furthermore, instead of d-d bands normally
observed at 600-700 nm for Cu(U) complexes, Oxy-
Fig. ~The nitrite reductase model compounds.
Hc exhibits two intense bands at ca. 350 nm (-20
OOO/2Cu) and ca. 580 (-1000), both attributable to
0 22. 7 Cu(U) LMCT transitions.
While studying modelling copper-dioxygen
chemistry Kitajima et al. reported i3 the synthesis of a
JL-peroxo dinuclear complex with 3,5-dimethylsubstituted tris(pyrazolyl)borate ligand, which showed
remarkable physicochemical similarities to oxy-Hc
and oxy-Tyr2. Using 3,5-di-isopropyl-substituted
terminal ligand they provided the first structural proof
(Fig. 7) of the existence of JL-11 2 :11 2 peroxo
dicopper(U) core (copper geometry: distorted square
pyramidal; Cu-Cu: 3.560 A) and reported detailed
characterization properties, which eventually led to
the structural characterization of oxy_HC i4 .
Tolman and co-workers discovered i5 a novel
phenomenon that when copper(I) complex of 1,4,7triisopropyl-triazacyclononane oxygenated at -78°C,
there exists an eqUilibrium between the two
oxygenated species [Cu1I2(JL-112:112-02)]2+ [side-on
peroxodicopper(U)] and [CUIlI2(JL-Oh]2+ [bis(JLoxo)dicopper(ill)] depending on the solvent chosen,
with CH2Clz favouring the former species and THF
favouring the latter.
INDIAN J CHEM, SEC A, SEPTEMBER 2003
2180
N (histidine)
(hisII.dine) N1I11
I
I
"'Gu
(histidine)
/
~
.
N (histidine)
Ii'~
Cu
N (histidine)
(histidine) NIl. 1.
I'N (histidine)
(histidine)
I
'N
n .\\\~O/t.'CIl .,,\\\N (histidine)
'Cit'V U"
1
1 ",.
.
~'O
.
N (histidine)
I
(histidine)
N (hlsUdine)
o
o
Cu... Cu .. j.6A
Cu ... Cu=-4.6A
(a)
(b)
R
R=iPr. LiPr
Fig. 7-{a) The active site of deoxy-Hc; (b) The active site of oxy-Hc; (c) The model complex of oxy-Hc.
Tyrosinase: Type III copper
It is known that when potatoes, apples, bananas,
sweet potatoes or mushrooms are injured they turn
brown. This is due to the conversion of tyrosine to the
pigment melanin, by the sequence of reactions shown
in Fig. 8. The same process cau~es skin tanning,
following exposure to ultraviolet radiation. The
enzymatic reactions are catalyzed by tyrosinase 2 • The
enzyme is present in the interior of the plant material
and since the reaction requires molecular oxygen, the
pigmentation does not occur until the interior is
exposed. Tyrosinase catalyzes (i) the o-hydroxylation
of monophenols to o-diphenols (cresolase activity)
and the further oxidation of these to o-diquinones
(catecholase activity). These qui nones undergo further
enzymatic and nonenzymatic reactions that lead to
polymeric pigmented material. Thus, tyrosinases
possess both monooxygenase and oxidase activity. In
animals, these reactions give skin, eyes and hair their
distinctive pigmentation. In order to deduce the
OH
9-
T~ Jvoo_._.
y
H,
.1
9H,
9H-NH,
9H-NH,
COOH
COOH
:m~ +C(~
melanin pigments
(a)
.g; ~8' ,2+
CtrW/·,/c.m
.
\ /0,/
,"""
#
[(L)CuiOMe)][pP6h
(b)
. Fig. 8--{a) The metabolism of tyrosine; (b) The model complex
of Karlin and co-workers; (c) The model complex from author's
laboratory .
MUKHERJEE: THE BIOlNORGANIC CHEMISTRY OF COPPER
'
CC
HZO
2181
0
. ~
o
(a)
-
Oz
cat
(b)
Fig. 9--{a) Mechanism of cresolase and catecholase activity of tyrosinase and/or catechol oxidase; (b) Catechol oxidase model reaction
structures and mechanism of action of the proteinactive sites, a major focus of research has utilized the
biomimetic approach.
Comparisons of chemical and spectroscopic
properties of tyrosinase and its derivatives with those
of hemocyanin, establish a close similarity of the
active sites structures in these two proteins. The active
site of tyrosinase apparently has greater accessibility
to exogenous ligands, including substrate molecules,
by comparison to the active site in hemocyanin. The
similarity of the oxy-states of hemocyanin and
tyrosinase points to the probable close relationship
between the binding of dioxygen and the ability to
activate it for incorporation into organic substrates.
A considerable number of ligand oxidations has
been reported, where aerobic treatment of a copper(I)
complex, mostly dinuclear, yields a dinuclear
copper(lI) complex with an oxidized ligand, which
can be isolated. Using tailor-made binucleating Ndonor ligands having m-CH2C6~CH2 spacers
between the coordination units, Karlin and co-workers
reported l6 the first model (Fig. 8) consisting of a
ligand that provides two tridentate bis[2-(2pyridylethyl)amine] donor units to each copper ion. A
mechanism was proposed which involves an
electrophilic attack of a bent 1l-11 2 :11 2-peroxide to the
CH bond of the aromatic ring. Interestingly, when 1pyrazolyl or 2-imidazolyl donor groups fully or
INDIAN J CHEM, SEC A, SEPTEMBER 2003
2182
H
HO
H
H
(a)
(tyrosinatc) 0
I
(histidine) N 11,1.
.
"'·"Cu.••• \\\\N (hislldine)
..
'~"0 (tyrosinate)
H2 0
(b)
[Cu(L)]
(c)
Fig. 10-{a) The reaction catalyzed by galactose oxidase; (b) The active site of galactose oxidase at pH 7.0; (c) The model complex.
partially replace the 2-pyridyl ligands hydroxylation
does not occur. However, when Schiff base ligands
providing three or even only two nitrogen donors are
used, hydroxylation takes place. We demonstrated4
the synthesis of the first m-CH2C6~CH2
hydroxylation ligand system, · within the non-Schiff
base family, providing only two nitrogen
coordinations to each copper centre (Fig. 8). While
the Il-peroxo intermediate could not be identified
spectroscopically owing to its instability, on the basis
of the closely related ligand structure to our ligand, it
was demonstrated that the reaction proceeds via a Ilperoxo intermediate.
Catechol oxidase: Type III copper
The ubiquitous plant enzyme catechol oxidases 17,
in contrast to tyrosinases, catalyze exclusively the
oxidation of catechols to the corresponding o-quinone
by molecular oxygen without acting on monophenols.
Thus, catechol oxidase lacks · hydroxylase activity.
The resulting highly reactive quinones autopolymerize to form brown polyphenolic catechol
melanins, a process thought to protect the damage4
plant from pathogens or insects. The enzyme contains
an antiferromagnetically coupled (EPR silent)
dicopper centre. Three-dimensional X-ray crystal
structural analysis of catechol oxidase, from sweet
potato, in the resting Cu(II)-Cu(II) state, the reduced
Cu(l)-Cu(l) form, in complex with the inhibitor have
been achieved. Both copper centres have three
histidine ligands. In the oxidized catechol oxidase
structure the two Cu(II) ions are 2.9 A apart. In
MUKHERJEE: THE BIOINORGANIC CHEMISTRY OF COPPER
addition to the six histidine ligands, a bridging
hydroxide ion completes the four-coordinate trigonal
pyramidal coordination sphere for each Cu(II) ion.
Mechanism of cresolase and catecholase activity of
tyrosinase and/or catechol oxidase is presented in
Fig. 9.
Recently we have shown l8 that the phenoxoIhydroxo-bridged dicopper(II) complex [Fig. 8(c)]
acts as an efficient catalyst for catechol oxidase-like
activity (Fig. 9).
Galactose oxidase: Type II copper
Galactose oxidase l9 is a fungal enzyme that
catalyzes the oxidation of galactose and a number of
other primary alcohols to the corresponding aldehyde,
a reaction in which dioxygen is reduced to hydrogen
peroxide (Fig. 10). The active site structure is
presented schematically in Fig. 10. A unique feature
of this active site embodies the modification of the
tyrosinate residue located in the equatorial plane by a
covalent linkage to the sulphur atom of a nearby
cysteine residue.
Stack et al. were able to synthesize20 nonplanar
copper(II) complexes (Fig. 10) from which they could
obtain the corresponding copper(I) complexes and
relatively
stable
phenoxyl-radical
copper(II)
complexes by reduction and oxidation, respectively.
The complex can act as a catalyst or as a precursor for
a catalyst in the reaction of benzylic and allylic
alcohols with molecular oxygen at room temperature,
yielding the respective aldehyde and hydrogen
peroxide. Turnover numbers as high as 1300 are
reported for the catalytic cycles. Most noteworthy, the
catalytic oxidation seems to proceed by the same
mechanism as the enzyme-catalyzed 'reaction
(Fig. 11).
"Blue" multicopper oxidase - ascorbate oxidase: Type
Ncopper
Ascorbate oxidase2c•d catalyzes the oxidation of lascorbate with concomitant reduction of O2 to water.
The trinuclear Cu site is shown in Fig. 12. Stack and
co-workers reported 21 an unusual 3:1 (copper: O2
stoichiometry) reaction between a mononuclear
copper(I) complex of a N-permethylated (IR, 2R)cyclohexanediamine ligand with dioxygen. The end
product of this reaction, stable at only lowtemperatures (X-ray structure at -40°C) , is a discrete
mixed-valence trinuclear copper cluster (Fig. 12),
with two terminal Cu(II) and a central Cu(III) centre
2183
-
Fig. Il-Postulated reaction mechanism for galactose oxidase.
I~
(hiItidiue) N
N (histidine)
--Cu
3.68
(hiI1idi.ae)
1\3.841
X
~ 13.71 J..\
/ N (histidine)
Cu....-.- Cu
(hiItidiue) N/I
I
",,-,.1.:...._) N
,.............
·a
'0
H / '\' N (hlstldlne)
.
N (histidiDe
(a)
NMez .
. . . .~NMez
C)/\R)i
"I'.
0
0./
01
)
'N
3+
[(LhCul~[CF1S03h·4CH2CI2
(b)
Fig. 12-(a) The trinuclear Cu cluster in the multicopper oxidase.
ascorbate oxidase. The Type I Cu site (not shown) is -12.5 A
from the Type ill Cu atoms. opposite the Type II centre. (b) The
model compound.
(Cu-Cu: 2.641 and 2.704 A). The relevance of this
synthetic complex to the reduction of O2 at the
trinuclear active sites of multicopper oxidases was
discussed (three copper(l) centres produce 4e- to
reduce O2 to H20).
Acknowledgement
Research on copper bioinorganic chemistry carried
out in author's laboratory has been supported by the
Council of Scientific & Industrial Research,
Department of Science & Technology, Government of
2184
INDIAN J CHEM, SEC A, SEPTEMBER 2003
5
India and the Volkswagen Foundation, Germany. The
author thanks the present and past members of his
research group, who have worked in this area. Their
names appear in the appropriate literature citations.
7
References
8
1
2
3
4
Mukherjee R N, in Comprehenive coordination chemistry-II:
From biology to nanotechnology, Vol 5 Copper, edited by
McCleverty J A & Meyer T J (Elsevier) 2003.
(a) Holm R H, Kennepohl P, Solomon E I, Chem Rev, 96
(1996) 2239 and references therein (Thematic issue for
Bioinorganic Enzymology); (b) Bioinorganic chemistry of
copper, edited by Karlin K D & Tyekhir Z (Chapman & Hall,
New York) 1993; (c) Solomon E I & Lowery M D, Science,
259 (1993) 1575 and references therein ; (d) Messerschmidt
A, Adv Inorg Chem, 40 (1994) 121 ; (e) Solomon E I,
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