2.1.7 Dihydroxylation
Dihydroxylation of double bonds is another oxidation reaction of synthetic interest,
that is generally carried out in organic solvents using most often a
high-oxidation-state transition metal such as osmium tetroxide as an oxidant [58].
In a biological medium, this reaction either requires a two-step process involving
the first epoxidation by a monooxygenase followed by hydrolysis of the epoxide by
an epoxide hydrolase or a one-step dihydroxylation, like for example Rieske
dioxygenases that use O 2 as an oxidant in a complex process that also involves
electron transfer from a biological reductant (generally NADH) mediated by a
reductase, a ferredoxin containing [2Fe–2S] Rieske cluster [59]. There is thus a
double interest to find artificial metalloenzymes that would perform such a reaction
in one step under eco-compatible conditions.
The first team that tackled this challenge in 1983, was that of Okano et al., who
used serum albumins derived ArMs for this purpose. They inserted osmium
tetroxide into BSA and the formed ArM catalyzed the stereoselective cisbis-hydroxylation of up to 40 equivalents of a-methylstyrene by
t
BuOOH with 68%
ee in favor of the (S)-diol [60]. Later, Ward and coll. also prepared an osmium
tetroxide-loaded SAV that catalyzed enantioselective olefin cis-dihydroxylation
with up to 97% ee in favor of the (R)-product at $ 20 TON in the presence of
potassium ferricyanide [61].
Finally, Ménage et al. also took advantage of their NikAFeN 2 Py 2 artificial
metalloenzyme, and, by combining model chemistry and protein X-ray crystallography, they were able to study the intramolecular dihydroxylation of one of the
N-benzyl substituents of the [N-benzyl-N′-(2-hydroxybenzyl)-N,N′-ethylenediaminediacetic acid] ligand. Indeed, the bound complex was able to activate dioxygen in
the presence of a reductant (Dithiothreitol, DTT), leading to the formation of catechol as the sole product. The X-ray diffraction structure determination of four of
the catalytic cycle intermediates and the end product showed that the hydroxylation
reaction implicated an iron peroxo, which was also observed in natural iron
monooxygenases (Fig. 8) [62].
2.2 Reductions
2.2.1 Hydrogen Production
With the inevitable future shortage of fossil fuels, it becomes crucial to develop
alternative energy sources and hydrogen appears to possess almost ideal features to
fulfill this challenge. Moreover, hydrogen is a clean and renewable energy source.
Hydrogen is still essentially produced by steam reforming of methane but other
fossil fuel independent processes are actively investigated such as water splitting.
In nature hydrogen metabolism is ensured by enzymes called hydrogenases that
catalyze the interconversion between protons and dihydrogen. Hydrogenases are
metalloenzymes containing iron and/or nickel in their active site. One of the
best-studied hydrogenases is the [FeFe]-hydrogenase. Its active site (the H-cluster)
contains a diiron cluster connected to a [4Fe4S] cluster via a cysteine bridge
376
J.-P. Mahy et al.
Dihydroxylation of double bonds is another oxidation reaction of synthetic interest,
that is generally carried out in organic solvents using most often a
high-oxidation-state transition metal such as osmium tetroxide as an oxidant [58].
In a biological medium, this reaction either requires a two-step process involving
the first epoxidation by a monooxygenase followed by hydrolysis of the epoxide by
an epoxide hydrolase or a one-step dihydroxylation, like for example Rieske
dioxygenases that use O 2 as an oxidant in a complex process that also involves
electron transfer from a biological reductant (generally NADH) mediated by a
reductase, a ferredoxin containing [2Fe–2S] Rieske cluster [59]. There is thus a
double interest to find artificial metalloenzymes that would perform such a reaction
in one step under eco-compatible conditions.
The first team that tackled this challenge in 1983, was that of Okano et al., who
used serum albumins derived ArMs for this purpose. They inserted osmium
tetroxide into BSA and the formed ArM catalyzed the stereoselective cisbis-hydroxylation of up to 40 equivalents of a-methylstyrene by
t
BuOOH with 68%
ee in favor of the (S)-diol [60]. Later, Ward and coll. also prepared an osmium
tetroxide-loaded SAV that catalyzed enantioselective olefin cis-dihydroxylation
with up to 97% ee in favor of the (R)-product at $ 20 TON in the presence of
potassium ferricyanide [61].
Finally, Ménage et al. also took advantage of their NikAFeN 2 Py 2 artificial
metalloenzyme, and, by combining model chemistry and protein X-ray crystallography, they were able to study the intramolecular dihydroxylation of one of the
N-benzyl substituents of the [N-benzyl-N′-(2-hydroxybenzyl)-N,N′-ethylenediaminediacetic acid] ligand. Indeed, the bound complex was able to activate dioxygen in
the presence of a reductant (Dithiothreitol, DTT), leading to the formation of catechol as the sole product. The X-ray diffraction structure determination of four of
the catalytic cycle intermediates and the end product showed that the hydroxylation
reaction implicated an iron peroxo, which was also observed in natural iron
monooxygenases (Fig. 8) [62].
2.2 Reductions
2.2.1 Hydrogen Production
With the inevitable future shortage of fossil fuels, it becomes crucial to develop
alternative energy sources and hydrogen appears to possess almost ideal features to
fulfill this challenge. Moreover, hydrogen is a clean and renewable energy source.
Hydrogen is still essentially produced by steam reforming of methane but other
fossil fuel independent processes are actively investigated such as water splitting.
In nature hydrogen metabolism is ensured by enzymes called hydrogenases that
catalyze the interconversion between protons and dihydrogen. Hydrogenases are
metalloenzymes containing iron and/or nickel in their active site. One of the
best-studied hydrogenases is the [FeFe]-hydrogenase. Its active site (the H-cluster)
contains a diiron cluster connected to a [4Fe4S] cluster via a cysteine bridge
376
J.-P. Mahy et al.