Institute of Chemistry, Academia Sinica
Over the years, we are endeavoring on the functional studies of metalloproteins towards understanding the underlying fundamental mechanisms of high-valent metal active sites for the applications of the controlled and selective C-H bond oxidation of variable hydrocarbons including methane, natural gas, linear and branched alkanes, simple aromatics including BTX (Benzene, Toluene and Xylene) and poly-aromatics hydrocarbons (PAH) in the production of future fuels/commodity chemicals. Our results have further elucidated how these metalloproteins can perform the sustainable bioremediation processes of polluted chemicals in the prokaryotic bacteria. These outcomes are expected to have long-term impacts in environmental issues, particularly in the areas of alternative green energy, waste water treatments and soil recovery.
The major aim of our research work is to explore various ways to achieve regio-selective and stereo-selective oxidations of hydrocarbons including aliphatics (normal alkanes) and aromatics under ambient conditions with high efficiency and atom economy. When researchers seek to account for differences in the chemical selectivity of metallo-enzymes or monooxygenases, they typically invoke differences in shape selection of substrate pockets as well as differences in specific non-bonding interactions, such as hydrogen bonding, electrostatic forces, and/or van der Waals interactions, in the interactions of the hydrocarbon substrates with the active sites of the metalloenzymes/monooxygenases. (Chem. Eur. J. 2011&2013, Tetrahedron Lett. 2011 and J. Inorg. Biochem. 2014) To explore these effects in depth, we have redesigned the substrate binding pockets of alkane hydroxylase (AlkB) and cytochrome P450 BM3 using a heterogeneous Escherichia coli recombinant system. (Chem. Eur. J. 2017 and Sci. Reports, 2017) These two redesigned proteins are deployed to achieve efficient oxidations of n-butane at its C-1 and C-2 positions, respectively. These studies have enabled us to propose mechanisms used by AlkB and cytochrome P450 BM3 to selectively oxidize inert C-H bonds and oxyfunctionalize a variety of hydrocarbons. The insights gained are expected to contribute to the design of biomimetics or artificial catalysts that selectively oxidize hydrocarbons, including nanomaterial platforms of these biomimetics.
Selective secondary C–H bond oxidation of n-butane mediated by engineered recombinant cytochrome P450 BM3
Selective primary C-H bond oxidation of C3-C12 linear alkanes mediated by the engineered recombinant alkane hydroxylase (AlkB) from Pseudomonas putida GPo1
Superoxide responsive protein (SoxR), a transcriptional factor, is a homodimeric protein with each subunit containing a redox-active [2Fe-2S] center. The iron–sulfur clusters within SoxR regulate transcriptional activity in response to one-electron oxidation, from the paramagnetic mixed-valence [FeII-FeIII] to the diamagnetic [FeIII-FeIII] species; a process that is presumably mediated by oxidative stress. The corresponding oxidation could trigger the expression of the soxS gene and subsequently activate numerous defensive genes, such as superoxide dismutase or catalase in Escherichia coli. In the case of nitrosylated SoxR, the results on about 2-fold spin quantitation relative to the model compounds of low molecular weight-dinitrosyl iron complex (LMW-DNIC) at low temperture EPR spectroscopy, the absence of dichoric spectral features in the responsive area of the nitrosyl iron complexes as well as the lack of Fe-Fe backscattering resolved by EXAFS fitting have strongly supported that the situation appears to be dramatically different that each of the [2Fe-2S] cores in SoxR is dissociated into two individual dinitrosyl iron complexes after nitrosylation. We have recently demonstrated that the formation of DNICs from Fe–S clusters leads to rich chemistry, including the formation of a reduced Roussin's red ester (rRRE) and a diamagnetic species of anionic Roussin's red ester (RRE), which both are redox sensitive. Accordingly, under nitrosative stresses, it is conceivable that the nitrosylated SoxR could also sense oxidative stresses from the cytoplasmic diffusible oxidants, DNA lesion or damage. (Chem. Eur. J. 2012)
X-ray absorption (XAS), circular dichroism (CD) and electron paramagnetic resonance (EPR) spectroscopic studies of SoxR protein from Escherichia coli
Yu laboratory recently discovers a series of Fe/Cu based organic-inorganic hybrid nanoparticle catalysts that can be prepared by their metal salts using H2O2(aq) in CH3CN. (Mol. Catal. 2017 and J. Catal. 2019) These nano-catalysts efficiently conduct the C–H bond activations of benzene to form phenol and/or p-benzoquinone, and of toluene to form benzaldehyde, benzyl alcohol, o-cresol, p-cresol, and/or methyl-p-benzoquinone. These reactions can be facilely tuned and controlled to selectively yield either a single or double oxygenation of benzene as well as a sp3 or sp2 C–H bond oxidation of toluene.
Chain or ring oxidations of toluene by high-valence metal oxygenated species from the active sites of metalloproteins, i.e., cytochrome P450s.
In future, Yu laboratory will direct their research attention towards the research topics of “catalysis” in oxy-functionalization of inert hydrocarbons to develop the metal based monooxygenases/metal oxide nanomaterials catalysts with the metal cluster features that can mimic bacterial monooxygenases for a sustainable oxidation of hydrocarbons by the employment of electrochemical means driven by the renewable energy such as solar and wind power. (Sci. Reports 2017 and Angew. Chem. Int. Ed. 2018) The main research topics will be the controlled partial oxidation of methane, small alkanes and simple aromatics for commodity chemical/fuel production.
Update： 2019-01-07