2.1 Oxidations
Nowadays, most of the industrial stoichiometric oxidations of hydrocarbons involve
harsh conditions using strong polluting oxidants, under high pressure and temperature conditions, and occur with low selectivity. There is thus a crucial need to
develop new catalysts that would allow oxidations to take place under mild
eco-compatible conditions, in water as a solvent, and with high selectivity. Nature
has elegantly solved this problem by using the very sophisticated biocatalysts that
are metalloenzymes, including heme and non-heme iron enzymes, that can catalyze
the highly selective oxidation of chemicals at room temperature and under atmospheric pressure [1, 2]. These enzymes can activate molecular dioxygen at their
active site transition metal center, most frequently an iron(III) ion. Mimicking
metalloenzymes thus appears to be a logical strategy for developing new catalysts
that would catalyze oxidation reactions with excellent selectivity and a high turnover number (TON) under mild conditions. Researchers have long been preparing
synthetic models in which a metal ion is inserted into a ligand mimicking the first
coordination sphere of this metal ion in the native enzyme [3]. This strategy was
particularly successful, for example, to prepare metalloporphyrins, including Fe,
Mn, Cr, Co, V … metal ions in their center, that have been used as very efficient
catalysts for the oxidation of organic compounds by various organic and inorganic
oxidants such as PhI = O, H 2 O 2 , KHSO 5 , NaIO 4 … with efficiencies rivaling those
of enzymes themselves [4–7]. However, several problems still remained to be
solved as most of the metal catalysts were only soluble in organic solvents and the
stereoselectivity of the reactions catalyzed was generally low. Taking advantage of
the chiral environment of proteins and their solubility in water, researchers have
prepared ArMs by incorporating metal ions or synthetic metal complexes into
proteins following the strategies detailed in the introduction of this chapter [8, 9].
This allowed them to obtain new water-soluble metal-based hybrid biocatalysts that
catalyzed various oxidation reactions. Among those, ArMs possessing a peroxidase
activity have already been extensively reviewed [10–13]. The present paragraph
will then focus on ArMs designed to catalyze the selective oxidation of substrates of
synthetic interest, starting from the most easily oxidizable ones including alcohols,
amines, and sulfides to the most difficult to oxidize substrates such as aromatics,
alkenes, and alkanes.
2.1.1 Alcohol Oxidation
In 2004, Kaplan and De Grado first reported the de novo design of diiron protein
with four helical bundles displaying phenol oxidase activity [14]. For this, they
started from the Due Ferri (DF) family of de novo-designed diiron proteins in which
the combination of two Fe(II) ions within a single site, allowed to perform
two-electron chemistry with O 2 , thereby avoiding the formation of oxygen radicals.
Indeed, the diiron center reacts quickly with O 2 , with the concomitant formation of
di-Fe(III) species where the two iron(III) ions are bound by an oxo bridge and the
reduction of molecular oxygen. They focused on DFtet, a four-chain heterotetrameric helical bundle whose structure, sequence, and catalytic properties were
366
J.-P. Mahy et al.
Nowadays, most of the industrial stoichiometric oxidations of hydrocarbons involve
harsh conditions using strong polluting oxidants, under high pressure and temperature conditions, and occur with low selectivity. There is thus a crucial need to
develop new catalysts that would allow oxidations to take place under mild
eco-compatible conditions, in water as a solvent, and with high selectivity. Nature
has elegantly solved this problem by using the very sophisticated biocatalysts that
are metalloenzymes, including heme and non-heme iron enzymes, that can catalyze
the highly selective oxidation of chemicals at room temperature and under atmospheric pressure [1, 2]. These enzymes can activate molecular dioxygen at their
active site transition metal center, most frequently an iron(III) ion. Mimicking
metalloenzymes thus appears to be a logical strategy for developing new catalysts
that would catalyze oxidation reactions with excellent selectivity and a high turnover number (TON) under mild conditions. Researchers have long been preparing
synthetic models in which a metal ion is inserted into a ligand mimicking the first
coordination sphere of this metal ion in the native enzyme [3]. This strategy was
particularly successful, for example, to prepare metalloporphyrins, including Fe,
Mn, Cr, Co, V … metal ions in their center, that have been used as very efficient
catalysts for the oxidation of organic compounds by various organic and inorganic
oxidants such as PhI = O, H 2 O 2 , KHSO 5 , NaIO 4 … with efficiencies rivaling those
of enzymes themselves [4–7]. However, several problems still remained to be
solved as most of the metal catalysts were only soluble in organic solvents and the
stereoselectivity of the reactions catalyzed was generally low. Taking advantage of
the chiral environment of proteins and their solubility in water, researchers have
prepared ArMs by incorporating metal ions or synthetic metal complexes into
proteins following the strategies detailed in the introduction of this chapter [8, 9].
This allowed them to obtain new water-soluble metal-based hybrid biocatalysts that
catalyzed various oxidation reactions. Among those, ArMs possessing a peroxidase
activity have already been extensively reviewed [10–13]. The present paragraph
will then focus on ArMs designed to catalyze the selective oxidation of substrates of
synthetic interest, starting from the most easily oxidizable ones including alcohols,
amines, and sulfides to the most difficult to oxidize substrates such as aromatics,
alkenes, and alkanes.
2.1.1 Alcohol Oxidation
In 2004, Kaplan and De Grado first reported the de novo design of diiron protein
with four helical bundles displaying phenol oxidase activity [14]. For this, they
started from the Due Ferri (DF) family of de novo-designed diiron proteins in which
the combination of two Fe(II) ions within a single site, allowed to perform
two-electron chemistry with O 2 , thereby avoiding the formation of oxygen radicals.
Indeed, the diiron center reacts quickly with O 2 , with the concomitant formation of
di-Fe(III) species where the two iron(III) ions are bound by an oxo bridge and the
reduction of molecular oxygen. They focused on DFtet, a four-chain heterotetrameric helical bundle whose structure, sequence, and catalytic properties were
366
J.-P. Mahy et al.