Byu Ri Sim,Jie Gu,Yvette Ley,Shenggan Luo,Yihan Liu,Qin Chen,Yao Nie,Yi-Lei Zhao
Candida parapsilosiscarbonyl reductases (CpRCR) have been widely used for the reductive conversion of ketone precursors and chiral alcohol products in pharmaceutical industries. The enzymatic enantioselectivity is believed to be related to the shape complementation between the cavities in the enzymes and the substitutions of the ketone substrates. In this work, we reported an unexpected enantioselectivity in the enzyme reductions of dihydrofuran-3(2H)-one (DHF) to (S)-tetrahydrofuran-3-ol (DHF-ol, enantiomeric excess: 96.4%), while dihydrothiophen-3(2H)-one substrate (DHT) was unproductive under the same experimental conditions. To rationalize the exclusiveS-configuration and the specific reactivity ofDHF, we carried out molecular dynamics simulations for the reacting complexations ofDHFwithCpRCR, andDHTwithCpRCR. Our calculations indicate thatDHFpreferentially binds to the small cavity near L119, F285, and W286, while the large cavity near theα1helix was mainly occupied by solvent water molecules. Moreover, the pre-reaction state analysis suggests that thepro-Sconformations were more abundant than thepro-R, in particular forDHF. This suggests that the non-polar interaction of substrate C4-C5 methylene contacting the hydrophobic side-chains of L119-F285-W286, and the polar interaction of funanyl oxygen exposing the solvent environment play important roles in the enantioselectivity and reactivity. The phylogenetic tree ofCpRCR homologues implies that a variety of amino acid combinations at positions 285 and 286 were available and thereby potentially useful for redesigning enantioselective reductions of 5-membered-ring heterocyclic ketones.Keywords:carbonyl reductases;enantioselectivity;heterocyclic ketone;molecular modelling
Yilin Zhang,Sen Li,Xianliang Qiao,Qingxin Guan,Wei Li
Cu-based catalysts are a promising alternative to toxic mercury catalysts for acetylene hydrochlorination, but their effectiveness is limited due to the poor dispersion and deactivation caused by reduction, agglomeration, and carbon deposition. In this study, the activity and stability of carbon-supported CuCl2 catalysts were largely improved by introducing N-heterocyclic ketones. Remarkably, N-methyl-2-pyridone (NM2P) coordinated Cu-based catalysts exhibited over 95% acetylene conversion with better stability under the reaction conditions of T = 180 °C, GHSV (C2H2) of 80 h−1, and VHCl/VC2H2 = 1.2. The combined results of characterization and exhaustive density functional theory (DFT) calculations revealed that the O–Cu coordination between the NM2P ligand and Cu cation strengthened the combination of reactants and Cu active sites, lowering the key reaction energy barrier, thereby leading to high activity. Meanwhile, the addition of the NM2P ligand significantly inhibited the reduction of Cu2+ to Cu+/Cu0, avoiding the formation of CuCl aggregates and the coking caused by Cu0, enhancing the catalytic stability. Overall, our study provides important insights into the design and optimization of Cu-based catalysts for acetylene hydrochlorination.
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