RADICAL REACTIONS WITH METAL COMPLEXES IN
AQUEOUS SOLUTIONS
1
A. Masarwa1, D. Meyerstein1,2
Department of Chemistry, Ben-Gurion University of the Negev, BeerSheva, Israel
2
Department of Biological Chemistry, The College of Judea and
Samaria, Ariel, Israel
Introduction
Due to their unpaired electrons radicals are highly reactive
species. They play important roles in combustion, atmospheric
chemistry, polymerization, plasma chemistry, biochemistry, and many
other chemical processes, including human physiology.
Transition metal complexes are key participants in biological and
catalytic radical processes due to two major reasons:
а) radicals are usually generated by redox reactions involving
transition metal complexes;
b) the majority of secondary radicals formed in biological and/or
catalytic systems react much faster with transition metal complexes than
with organic substrates. Therefore the participation of the transition
metal complexes determines the nature of the final products.
Keywords: radicals, transition metal complexes, Fenton reactions,
redox, radiation
1. The chemistry of radicals
1.1. Formation of radicals
Radicals can be formed by several different mechanisms:
a) Absorption of ionizing radiation in the medium, e.g. in dilute
aqueous solutions initially forming:
γ ; e.
.
H2O
e-aq (2.65); OH (2.65); H (0.60); H2 (0.45);
H2O2 (0.75); H3O+ (2.65)
(1)
where the values in parentheses are the number of molecules of a given
product formed by the absorption of 100 eV in the medium. The radicals
96
thus formed are powerful redox reagents, i.e. e aq (E° = -2.87 V) is a
.
strong reducing agent; H (E° = ±2.31 V) is an equally strong reducing
.
and oxidizing agent and OH (E° = +2.73 V) is a powerful oxidizing
[1]
agent. Thus a mixture of strong single electron oxidizing- and
reducing- agents is formed.
The primary radicals formed can be transformed into a variety of
secondary inorganic radicals determined by the solution composition
.. .
..(e.g. O2 ; HO2 ; NOx; SOx ; X2 )[2] and mainly via hydrogen
.
abstraction from suitable organic solutes into organic radicals (e.g. CH3;
.
.
.
CH2CH3; CH2OH; CH2CN; etc.)[3] Furthermore radicals can react with
aromatics or unsaturated compounds by addition to double bonds. This
technique, especially pulse radiolysis, is best suited for the study of the
kinetics of reaction of radicals.[4, 5]
b) Homolytic bond breakage of specific molecules induced
by thermolysis or electromagnetic radiation or ultrasound
cavitation.
c) Radical production by photochemistry.
d) Ultrasonic cavitation in aqueous solutions yields hydroxyl
radicals and hydrogen atoms. The major products are .OH radicals.
The yield of radicals depends strongly on the nature of the gases in
equilibrium with the solution and the temperature.[6]
e) Alternatively, radicals can be generated by redox reactions
involving transition metals (e.g. Fenton like reactions, vide infra). A
variety of redox reactions of transition metal complexes with organic
molecules producing radicals exist:
.
Mn + RX  Mn+1 + R + X
(2)
Reaction (2) basically represents the initiation step in ‘Atom
transfer radical polymerization’ (ATRP), an example of living
polymerization, which involves chain initiation by a halogenated organic
species in the presence of a metal halide species, creating a radical that
then starts radical polymerization.
97
Organohalides are severe environmental pollutants. Their toxicity
is due to reaction (2), which produces radicals, which initiate deleterious
biological processes. Also their dehalogenation via reaction (2) is
important in pollution control.
.
Mn+1 + RH  Mn + R + H+
(3)
A classical example for reaction (3) is the catalytic oxidations of
methyl-aryls by O2, which is initiated by Co3+.
.
PhCH3 + Co3+  PhCH2 + Co2+ + H+
(4)
.
.
PhCH2 + O2  PhCH2OO
(5)
H+
.
PhCH2OO + Co2+  PhCH2OOH + Co3+
(6)
.
PhCH2OOH + Co2+  PhCH2O + CoIII(OH)2+
(7)
.
PhCH2O + Co3+  PhCHO + Co2+ + H+
(8)
Under appropriate conditions the aldehydes thus formed can be
.
oxidized to the corresponding acids. The formation of R radicals by
3+
other high valent transition metal ions, e.g. Mn , and Ce4+ is well
documented.
.
A further mechanism, which yields R radicals is:
.
Mn+1 + RCO2  Mn+1-O-C(O)R  Mn + CO2 + R
(9)
i.e. a mechanism analogous to the Kolbe process.
Reaction (10) was studied in efforts to mimic the Cytochrome P450 chemistry.
98
.
Mn+2=O + RH  Mn+1-OH + R
(10)
Though radicals are often implicated in these systems they are
often very short lived as they react in the cage formed via:
.
Mn+1-OH + R  Mn + ROH
(11)
1.2. Redox properties of radicals
Many radicals are highly reactive, owing to the tendency of
electrons to pair. Thus the reactivity of radicals stems mainly from the
fact that they are powerful one electron redox reagents[1].
In theory electron transfer reactions may proceed via two distinct
possible mechanisms:
1) The outer sphere mechanism, where the electron is transferred
between the redox couples, while the inner coordination shells of the
respective reactants remain intact. No chemical bond between the
reactants is formed.
2) The inner sphere mechanism. A chemical bond is formed
between the reactants prior to the electron transfer.
It has to be noted here, that most electron transfer processes of
radicals do not transpire via simple outer sphere electron transfer
processes. Generally electron transfer processes proceed in an outer
sphere mechanism, only when the reaction does not require major bond
rearrangements and therefore the self exchange rates of the couples are
high. Even most of the simple radicals described in table 1 do not adhere
to the requirements for outer sphere electron transfer. Most uncharged
radicals will be converted into charged entities due to the electron
transfer and thus intrinsically have distinctly higher solvation energy
.
.
than the originally uncharged species. Thus for example H or OH
radicals basically only have small hydration energies, while their one
electron redox products H+ or OH- respectively possess high solvation
.
energies. The reduced product of H , H- on the other hand is unstable
99
and requires the follow up reaction with H+ to form H2 for the reaction to
.proceed. CO2 for example is a powerful reducing agent but as it is bent
and its oxidized product CO2 is linear most of its reactions proceed via
.the inner-sphere mechanism. For the reactions of X2 to form X22- the
latter are unstable and therefore the reactions do not proceed via outer
.
sphere mechanisms. N3 on the other hand is a strong outer sphere
oxidizing agent, as N3 does not have high hydration energy.
All the carbon centered organic radicals are relatively strong
single electron oxidizing and reducing agents. The redox properties of
aliphatic carbon-centered radicals depend on the substituents on the
α-carbon.
.
Thus for example radicals of the type CR1R2(OH) are relatively
strong reducing agents; however they do oxidize low-valent transition
metal complexes, e.g. Cr(H2O)62+ and V(H2O)62+. On the other hand
.
.
CCl3 and CH2CO2H and alkyl-peroxyl radicals are relatively strong
./+/.
oxidizing agents. As the self exchange rates for the R and R couples
+
are usually slow, and as the products R and R are highly unstable,
outer sphere reactions are not abundant for these types of molecules.
However outer-sphere reductions of transition metal complexes by
. 1 2
.
CR R OH or CR1R2O radicals were observed. This is reasonable as
these radicals are powerful reducing agents and as the oxidation of these
radicals does not require major bond rearrangements. Thus the self
exchange rate for the couple C(CH3)2OH+/0 has been estimated to be
~103 M-1s-1.[7]
2. The Role of transition metal complexes in radical chemistry
The role of transition metal complexes pertaining to radical
reactions is diverse. On one hand these compounds are capable of
interacting with radicals present in solution in a variety of possible
reactions, on the other hand transition metal complexes can be
100
responsible for the generation of radicals. The reaction with the
.
..
.inorganic radicals OH, X2 , NO2 , CO3 , etc. usually results in the
formation of high valent complexes, e.g. Ni(III) and Cu(III); whereas the
.
.reaction with H , O2 usually results in the reduction of the transition
metal complex yielding a low valent complex, e.g. Cu(I) and Fe(II).
..
However in some systems O2 and especially HO2 act as an oxidizing
agent. Reactions relevant to biological systems can be grouped into two
major classes, which mainly feature: Reactions of transition metal
complexes with radicals (aliphatic radicals or with aliphatic peroxyl
radicals formed in the presence of oxygen), and reactions producing
radicals like reactions (26) and (27) and in particular ‘Fenton like’
.
reactions producing OH radicals or endogenous oxidizing agents. The
.
‘Fenton like’ reactions play an important role in the production of OH
radicals or analogous oxidizing agents in the cell, and they as well as the
first two reactions direct radical initiated processes to the biological sites
where transition metal complexes are located (site specific effect).
Lately metal complexes incorporating stable ligand radicals gain
increased interest, due to their use as model systems for biological
systems, including their role as catalysts, and based on their magnetic
properties.
2.1. Reactions with aliphatic and aliphatic peroxyl radicals
The kinetics and mechanisms of reactions of many carboncentered radicals with a large variety of transition metal complexes were
extensively studied.[3, 7, 8]
.
R + MnLm  products
(12)
The specific rates of these types of reactions are usually
considerably faster than those of the same radicals with organic
constituents present in the biological systems. Therefore carbon-centered
101
radicals are expected to react in biological systems selectively with the
transition metal complexes present in it.
Alternatively, in the presence of dioxygen, aliphatic radicals react
diffusion controlled with dioxygen to yield the corresponding aliphatic
.
peroxyl radicals RO2 , which then further react with the transition metal
complexes in solution (vide infra).[8-11]
RO2. + MnLm  products
(13)
These types of reactions direct the radical-initiated processes to
biological sites where the transition metal complexes are located. They
provide an alternative to the explanation offered by the site-specific
effect. The products of radical reactions with transition metal complexes,
especially those resulting from the decomposition of the transient
complexes (LmMn+1-R and LmMn+1-OOR), are probably the cause of
many biologically deleterious effects initiated by radicals.
2.1.1. Reactions with aliphatic radicals
In principle the reaction of transition metal complexes with
aliphatic radicals might proceed via one of the following mechanisms:
→ Mn±1Lm + R-/+
outer sphere redox process
→ LmMn+1-R or Lm-1Mn+1-R + L formation of M-C bond
(14)
(15)
MnLm + R. → Mn-1Lm-1 + L-R or L± + R-/+ ligand abstraction via
homolytic bond breakage
(16)
ligand abstraction via
transient formation
(17)
→ Lm-1Mn-LR. → Mn±1Lm-1 +
+L-R-/+ or + L± + R-/+
→ Lm-1Mn(L±) + R-/+ →
→ Mn±1Lm + R-/+
metal throughligand
(18)
These equations describe possible reactions of the aliphatic
radicals with metal complexes in outer- (equ. 14) or inner-sphere redox
processes including those incorporating the ligands (equations 16-18)
redox reaction
102
and the formation of a metal-carbon σ-bond between the aliphatic
radical and the central metal cation (equ. 15) in which the metal is
formally oxidized. The choice between inner sphere and outer sphere
mechanism is mainly determined by the nature of the reactants (charge,
steric hindrance, solvation). In outer sphere reactions an electron is
transferred from reductant to oxidant while no chemical bond between
the reaction couple is formed in the transition state. In the inner sphere
mechanism, a bridged complex between oxidant and reductant is formed
before electron transfer occurs. The latter is, as stated above, the
prevailing mechanism due to the low rates of the self exchange reactions
of the R. radicals and as for most of these reactions their exothermicity is
due to the formation of RH or ROH while the formation of R+ and R- are
endothermic.
2.1.1.1. Redox reactions of radicals with transition metal
complexes
Equation (14) describes outer-sphere redox processes. As
discussed above these kinds of reactions are not abundant.
The mechanism of reduction of many cobalt(III) and
ruthenium(III) complexes by different reducing agents has been studied.
It was commonly accepted, that the reduction of [Co(NH3)6]3+ and
[Ru(NH3)6]3+ always proceed via the outer-sphere electron transfer
mechanism, due to the fact that those complexes are relatively
substitution inert and no empty orbital on the amine ligands is available.
Contrary to this it has been reported, that the reaction of [Co(NH3)6]3+
.
with the CH2OH radical does not proceed via the outer-sphere
mechanism. This reaction is pH dependent in slightly acidic solutions
and thus the mechanism suggested involves the coordination of the
radical to the cobalt metal center yielding a seven-coordinated
intermediate or binding of the radical to one of the coordinated amine
groups. Thus the reduction proceeds via an inner sphere or ‘bridged’
mechanism. Therefore the mechanism of reduction of [MIII(NH3)5X]
complexes by aliphatic radicals differs basically from that of the
reduction by low-valent transition metal complexes. Moreover the
mechanisms of reduction of [Co(NH3)6]3+ and [Ru(NH3)6]3+ differ
significantly.[12]
103
.
Radicals of the type CR1R2(OH) and even H. atoms are relatively
strong reducing agents; however they do oxidize low-valent transition
metal complexes, e.g. Cr(H2O)62+ and V(H2O)62+ via the mechanism
outlined in equation (15), vide infra.
Processes following the mechanism described in equation (16) are
mainly observed for halide, and analogous complexes as the oxidizing
species, e.g.:[7, 8]
.
M(NH3)5X2+ + R → RX + M2+aq + 5NH4+
(19)
Processes following the mechanism described in equation (17) are
observed for the addition of alkyl and substituted alkyl radicals to
aromatic ligands followed by the reduction of the central cation and
proton loss from the aromatic ring. In principle the central cation could
also be oxidized by its radical-ligand. However, such reactions are not
known.
Processes following the mechanism described in equation (18),
redox reactions involving the ligand, are abundant, though only
processes in which the ligand is reduced are known. These reactions are
then followed by intramolecular redox reactions (metal-ligand), which
are observed for a variety of complexes with suitable ligands, i.e. when
the ligand is more reactive kinetically.
Comparison between the inter-molecular kinetics of reduction of
[Co(NH3)6]3+ and inter- and intra-molecular kinetics of reduction of
penta-ammine(ligand)cobalt(III) complexes (mono and binuclear) with
several radicals was reported. The reduced ligands included a series of
nitrobenzoate and nitrogen heteroaromatic anions. Rates of
intramolecular electron transfer from the anion radicals to the central
cobalt(III) bound to them via a carboxylate group are reported. [13] These
kinds of systems are of interest in the study of the factors which affect
the rates of intramolecular electron transfer processes and due to their
being model systems for one of the elementary steps in inner sphere
redox reactions. One such system, which was extensively studied, is:
R.+[(NH3)5CoIII(p-O2CC6H4NO2)]2+ 
R++ [(NH3)5CoIII(p-O2CC6H4NO2.-)]+
104
(20)
[(NH3)5CoIII(p-O2CC6H4NO2.-)]+ 
 [(NH3)5CoII(p-O2CC6H4NO2)]+
(21)
2.1.1.2. Formation of transition metal complexes with metalcarbon σ-bonds.
Processes following the mechanism described in equation (15) are
the common mechanism of reaction for “low valent” complexes with
ligand exchange rates, and/or steric structures, which enable a bond
formation between the central metal cation and the attacking radical. The
products of these reactions are transient or stable complexes with metalcarbon σ-bonds.
These reactions are well known for a series of metal complexes in
various oxidation states (e.g. Cr(II), Mn(II), Mn(III), Fe(II), Fe(III),
Co(II), Ni(I), Ni(II), Cu(I), Cu(II)). It should be noted that the rates of
these reactions in general follow the rate of ligand exchange for the
specific metal complex in accord with the above mechanism.
The majority of complexes containing metal carbon σ-bonds are
unstable under physiological conditions and the products of their
decomposition might cause deleterious biological processes. It is of
interest to note that alkyl radicals react also with metal powders
immersed in aqueous solutions forming analogous transients.[7, 8]
Mechanisms of decomposition of the transient complexes
LmMn+1-R.
The mechanisms and kinetics of decomposition of the transient
complexes LmMn+1-R in aqueous solutions depend on the nature of the
central cation, of the ligands, L, of the substituents on the aliphatic
residue, R, on the pH and on the presence and nature of various
substrates, S, in the medium, e.g. O2. In the following paragraphs the
major mechanisms observed are discussed:[7, 8]
Heterolysis of the metal carbon σ-bond
The major decomposition mechanism observed for M-R
σ-bonded complexes is the heterolysis reaction to form RH or ROH/R-H
products.
Mn+1Lm + RH + OH
105
(22)
LmMn+1-R + H2O → Mn-1Lm + ROH/R-H + H3O+
(23)
Thus the oxidized or reduced metal complexes are formed
eventually plus either the source of the radicals (RH) or ROH/R-H.
Reaction (22) is observed mainly for complexes which are not expected
to be reduced (e.g. Mn = Cr(II), Mn(II), Fe(II), Co(II), Ni(I), Cu(I)). If
this reaction occurs in biological system it is usually not expected to
cause damage, except that due to the oxidized metal-complex. Reaction
(23) is mainly observed for complexes which are difficult to oxidize but
can be reduced (e.g. Mn = Fe(III), Cu(II)). This reaction might cause
biological damage, as it changes the nature of the organic substrate. This
is especially true for R= CR1R2(OH) or CR1R2(NH2), which yield
aldehydes and ketones many of which are toxic. Also the reduced form
of the metal complex might cause damage.[7, 8]
Homolysis of the metal carbon σ-bond
In many systems studied the results point out that equation (15) is
an equilibrium process and that the mechanism of decomposition of the
transient complex LmMn+1-R involves radical processes initiated by the
homolytic bond breakage.
Lm-1Mn+1-R + L  MnLm + R.
(24)
As in this case the initial conditions are restored, the homolytic
pathway usually does not contribute to deleterious processes in
biological systems as essentially only the lifetime of the radicals is
prolonged. This mechanism of decomposition has been observed for a
large variety of complexes with Mn+1 = Cr(III), Mn(III), Fe(III), Fe(IV),
Co(III), Ni(III) and Cu(II).[7, 8]
The radicals R. obtained by the homolytic bond breakage can
further react in a variety of possible pathways:
Radical-radical reactions
leading to combination or
disproportionation reactions:
R. +R. → R2 or RH + R -H
106
(25)
Reaction of the radicals with the transient complex with the metalcarbon bond:
L
.
Lm-1Mn+1-R + R → MnLm + R2 or RH + R-H
(26)
i.e. leading to analogous organic products as radical radical reactions.
Reaction of radicals with suitable substrates or scavengers:
R. + S → products
(27)
Reactions with dioxygen:
In the presence of dioxygen, which acts as a scavenger for the
radicals R., homolytic decomposition is followed by:
R. + O2 → RO2. ,
(28)
which is usually followed by:
RO2. + MnLm → Lm-1Mn+1-OOR + L
(29)
Thus the net reaction is a homolytic dioxygen insertion into the
M-C bond. The transient complexes Lm-1Mn+1-OOR thus formed are an
important class of intermediates, vide infra.
It should be noted here that in principle also polymerization
reactions or living polymerizations involving metal complexes as
initiators and/or radical carriers could arise under any conditions where
radicals are present in solutions. However most of these processes are
not carried out in aqueous solutions and are therefore outside the scope
of this report.
β-elimination reactions
Complexes with metal-carbon bonds, containing a good leaving
group X in the β position to the bonded carbon are likely to undergo this
type of decomposition reaction.
LmMn+1-CR1R2CR3R4X → Mn+1Lm + R1R2C=CR3R4 + X
-
(30)
Good leaving groups are OR, NR2, NHC(O)R, and halides. This
reaction results in the formation of an unsaturated carbon compound, the
107
leaving group X , and the oxidized form of the metal complex. Thus
these types of reactions might cause severe transformations in a variety
of important biological compounds (e.g. DNA, RNA, peptides, sugars,
phosphate-esters, etc.) and are therefore presumably responsible for the
majority of radical induced biological deleterious processes.[7, 8]
Other decomposition reactions
Transient complexes with metal-carbon σ -bonds can decompose
in a variety of additional possible decomposition reactions, for a more in
depth overview, the reader is referred to the relevant reviews.
Decomposition reactions include reactions with oxidants or reductants,
β-hydride shift reactions, CO insertion, methyl migration, rearrangement
of the carbon skeleton of R, bimolecular decomposition, methyl transfer
reactions, etc.
2.1.2. Reactions with aliphatic peroxyl radicals
The formation of aliphatic peroxyl radicals via reaction (28) was
established, vide supra. In biological systems and in other radical
induced catalytic processes these radicals are prevalent in the presence
of dioxygen and their reactions with metal complexes in solution via
reaction (29) to form σ-bonded peroxo-metal complexes and their
subsequent decomposition reactions are suggested to contribute foremost
to deleterious biological processes. The transient complexes Lm-1Mn+1OOR are strong oxidizing agents (potentially 3 electrons) and therefore
plausible intermediates in site-specific deleterious processes. Alternative
outer sphere electron transfer reactions of the peroxyl radicals with
metal complexes are not expected to be observed, as the self exchange
.
rates of the couples ROO /ROO are very slow (k~2.10-2 M-1s-1).[8]
Decomposition reactions of transient metal peroxide
complexes Lm-1Mn+1-OOR
Heterolysis of the M-O bond
Peroxometal intermediates mainly decompose via heterolysis of
the M-O bond:
108
Lm-1Mn+1-OOR + H3O+ → Mn+1Lm + HOOR + H2O
(31)
This reaction leads to formation of the corresponding peroxides
HOOR. Alkylhydroperoxides are generally unstable and decompose via
the formation of aldehydes or ketones:
HOOCHR1R2 → R1R2C=O + H2O (Ri = H or alkyl)
(32)
Biological damage may result as a consequence of the toxicity of
the formed aldehydes, the peroxides (if stable) or even the oxidizing
properties of the oxidized metal complex formed.[8]
Heterolysis of the O-O bond
Alternatively a heterolysis of the O-O bond may occur:
Lm-1Mn+1-OOR → LmMn+3=O + ROH
(33)
This mechanism has been proposed as a key step in a variety of
enzymatic and non-enzymatic catalytic processes. However, up to date
this reaction was not observed in homogeneous aqueous solutions.
Homolysis of the M-O bond
In this case, the formation of the peroxo metal complex is an
equilibrium process, accordingly:
.
Lm-1Mn+1-OOR + L  RO2 + MnLm
(34)
This type of decomposition has been reported for (H2O)5FeIIIOOR, (H2NCH2CO2 )2CuIII-OOR and for (cyclam)(H2O)NiIII-OOH. It is
of interest to note, that the equilibrium constants for a variety of
complexes of the type (H2O)5FeIII-OOR are nearly independent of the
nature of R, though electron withdrawing substituents on R increase the
.
redox potential of the radical ROO . This apparent discrepancy was
attributed to the observation that electron withdrawing substituents on R
decrease the pKa of HOOR and therefore the basicity of the ligand ROO,
thus decreasing the stabilizing effect of ROO on the FeIII central
cation.[8]
109
Oxidation of L, R or substrates in solution
The transient complexes Lm-1Mn+1-OOR are strong and potentially
up to three electron oxidizing agents. Thus in principle the
decomposition of peroxo metal complexes can also proceed via
oxidation of the ligands bound to the central metal ion or alternatively
the R group of the peroxyl group or of substrates present in the solution.
If these mechanisms occur in biological systems they will clearly induce
deleterious effects.
Fenton like reactions
The transient complexes Lm-1Mn+1-OOR are peroxides and are
therefore expected to decompose via ‘Fenton like’ (vide infra) reactions:
n+1
n
H3O+/L
Lm-1M -OOR + M Lm
+ Lm-1Mn+2=O + ROH
2Mn+1Lm + RO. or Mn+1Lm +
(35)
Indeed, the complexes (H2O)5FeIII-OOR and the complex
L(H2O)5CoIII-OOCH3 decompose partially via this mechanism. This
.
.
reaction produces RO radicals, which have similar properties to OH
radicals, or higher valent metal complexes, e.g. Fe(IV) and Co(IV).
3. Fenton-like reactions
In 1894 Fenton reported that alcohols are oxidized in the presence
of H2O2 and Fe(H2O)62+.[14] ‘Fenton Reagents’ refer thus to a mixture of
hydrogen peroxide and ferrous salts and ‘Fenton like reactions’ are
analogous reactions of peroxides with metal complexes, MnLm, in their
low valent oxidation states (e.g. Fe(II), Cu(I), Ti(III), Cr(II), Co(II)).
‘Fenton like’ reactions play an important role in a variety of catalytic
and biological processes. In biology these reactions are believed to be
the main source of ROS (Reactive Oxygen Species) in the body. The
detailed mechanism of these kinds of reactions and their active
intermediate are still ambiguous and repeatedly discussed in many
publications and reviews.[15-24] In 1934 Haber and Weiss suggested that
the key step in this process is:[25]
110
H2O2 + Fe(H2O)62+  OH + OH- + Fe(H2O)63+
k = (42-79) M-1s-1 [20]
(36)
The rates of Fenton like reactions depend on the nature of M, L,
ROOR’, and the medium. They might be orders of magnitude faster than
reaction (36) e.g. for Fe2+ with suitable ligands:
ROOH + MnLm  .OR + OH- + Mn+1Lm
(37)
Thus the .OH/RO. radical is suggested to be formed as the active
intermediate via an outer sphere mechanism and radical pathways are
generally assumed throughout the remaining mechanism.
However, detailed kinetic studies and thermodynamic
considerations indicate that not in all these reactions hydroxyl radicals or
RO. radicals are formed.[16, 17, 19, 26-32] The detailed mechanism seems to
involve the formation of a transient low-valent transition-metal-peroxide
complex via a ligand exchange mechanism:[16, 29]
.
H2O2 + MnLm  LmMn.H2O2 or Lm-1Mn H2O2 + L
(38)
Which means that the redox process follows the inner sphere
mechanism. Reaction (38) is followed by one of the ensuing routes:
.
+L
Mn+1Lm + OH + OH
(39a)
.
Lm-1Mn H2O2
+RH
Lm-1Mn+2=O + H2O
(39b)
.
Mn+1Lm + R + H2O + OH
(39c)
.
.
OH + RH  R + H2O
Lm-1Mn+2=O + RH
+L
(40)
.
Mn+1Lm + R + OH-
(41)
(H2O2 is used in these equations for simplicity purposes, but other
peroxides might be involved)
.
Accordingly either the hydroxyl radical (RO radical) or a high
111
valent transition-metal species, e.g. a ferryl species, can be formed, or
the organic substrate can be directly oxidized by the Lm-1Mn.H2O2
transient. Obviously the rates of reaction of those species might well
.
differ from those of the OH radicals with the substrate. In the presence
.
of an organic substrate, RH, often the same radicals R are ultimately
formed.
.
The results point out that the choice of the route to R depends on
the nature of M, of L, of RH and its concentration, and on the medium,
e.g. the pH. [16, 29, 33, 34]
Recent results suggest that for MnLm = Fe(H2O)62+ in strongly
acidic solutions reaction (39b) is the dominant pathway.[27, 31] However it
was recently reported that [(H2O)5FeIV=O]2+, which can be
independently generated by the reaction of [Fe(H2O)6]2+ with ozone (O3)
and characterized by Moessbauer spectroscopy, X-ray absorption and
transfer of the =O atom to DMSO, differs from the Fenton intermediate
in acidic and neutral solutions. This information was derived by
comparing kinetic patterns and products for different substrates in the
Fenton reaction and in the reaction with [(H2O)5FeIV=O]2+.[35] For
Fe(edta) the Fenton product was shown to be undistinguishable from the
.
OH radical under the majority of conditions,[33] whereas for Fe(nta)
oxidations by ferryl species are more favored under most conditions. [34]
Analogously it was shown that also in the aqueous Cu(I) and Cu(I)phen
/H2O2 system the main product is not the hydroxyl radical.[29, 36, 37]
.
In aerated aqueous solutions R radicals produced in Fenton
reactions naturally react diffusion controlled with dioxygen to form the
.
respective peroxyl radicals ROO , and subsequently the transient
complexes Lm-1Mn+1-OOR (vide supra). The decomposition reactions of
these transient peroxo metal complexes determine the products of
reaction.
An important source of H2O2 in biological and catalytic systems is
dioxygen, which can react with low-valent transition metal complexes
via the following sequence:
MnLm + O2  Mn+1Lm + O2 . -
112
(42)
2O2
.-
+ 2H+  H2O2 + O2
.
MnLm + O2 -
H+
(43)
Mn+1Lm + H2O2
(44)
or analogous reactions.
Low-valent transition metal complexes can be formed in systems
containing a reducing agent (e.g. ascorbate) and a higher valent
transition metal complex. This kind of systems are often referred to as
Udenfriend reagents and serve as models for oxygenases.[38, 39] Reactions
.(42-44) are also the main source of O2 and H2O2 in biological systems
and thus the source of biological deleterious processes.
Concluding remarks
The purpose of this manuscript is to point out the role of transition
metal complexes in processes involving radicals. This role is dual:
a) most of the thermal processes leading to the formation of
radicals involve redox reactions of transition metal complexes;
b) secondary radicals formed in biological and/or catalytic
processes often react much faster with transition metal complexes
than with organic substrates. Therefore their reactions with
transition metal complexes usually determine the nature of the
final products.
It should be pointed out that in living organism radicals play dual
roles: on the one hand they play a key role in a large variety of essential
processes. On the other hand they initiate a variety of deleterious
processes. Therefore living organisms require a careful balance of the
different radical constituents. Any external induced change in this
balance might be harmful.
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