RADICAL REACTIONS WITH METAL COMPLEXES IN AQUEOUS SOLUTIONS

A. Masarwa1, D. Meyerstein1,2

1Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel

2Department of Biological Chemistry, The College of Judea and Samaria, Ariel, Israel

IntroductionDue 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 radicalsRadicals 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

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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

agent.[1] 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.

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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)

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

other high valent transition metal ions, e.g. Mn3+, 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 P-450 chemistry.

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H+

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

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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 X2

2- 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)6

2+ 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 .CR1R2OH 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 chemistryThe 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

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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 radicalsThe kinetics and mechanisms of reactions of many carbon-

centered 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

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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 radicalsIn 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 (14)

→ LmMn+1-R or Lm-1Mn+1-R + L formation of M-C bond (15)

MnLm + R. → Mn-1Lm-1 + L-R or L± + R-/+ ligand abstraction via

homolytic bond breakage (16)

→ Lm-1Mn-LR. → Mn±1Lm-1 + +L-R-/+ or + L± + R-/+ ligand abstraction via

transient formation (17)

→ Lm-1Mn(L±) + R-/+ → → Mn±1Lm + R-/+ metal throughligand

redox reaction (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)

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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 complexesEquation (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]

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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)6

2+ 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.-)]+ (20)

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[(NH3)5CoIII(p-O2CC6H4NO2.-)]+

[(NH3)5CoII(p-O2CC6H4NO2)]+ (21)

2.1.1.2. Formation of transition metal complexes with metal-carbon 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 metal-carbon 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.

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Mn+1Lm + RH + OH (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-bondIn 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 (25)

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Reaction of the radicals with the transient complex with the metal-carbon bond:

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 reactionsComplexes 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

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L

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 reactionsTransient 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 radicalsThe 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+1-OOR 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:

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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 bondAlternatively 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 bondIn 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)5FeIII-

OOR, (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,

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thus decreasing the stabilizing effect of ROO- on the FeIII central cation.

[8] 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 reactionsThe transient complexes Lm-1Mn+1-OOR are peroxides and are therefore expected to decompose via ‘Fenton like’ (vide infra) reactions:

Lm-1Mn+1-OOR + MnLm 2Mn+1Lm + RO. or Mn+1Lm +

+ Lm-1Mn+2=O + ROH (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 reactionsIn 1894 Fenton reported that alcohols are oxidized in the presence of H2O2 and Fe(H2O)6

2+.[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

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H3O+/L

the key step in this process is:[25]

H2O2 + Fe(H2O)62+ OH + OH- + Fe(H2O)6

3+

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 Lm-1Mn+2=O + H2O (39b)

+RH Mn+1Lm + R. + H2O + OH

- (39c)

.OH + RH R. + H2O

(40)

Lm-1Mn+2=O + RH +L Mn+1Lm + R. + OH-

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(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

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.

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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 . -

(42)

2O2 . - + 2H+ H2O2 + O2 (43)

MnLm + O2 . - H+ 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 remarksThe 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

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different radical constituents. Any external induced change in this balance might be harmful.

References

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