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Mechanistic insights into artificial metalloenzymes towards imine reduction.
Phys Chem Chem Phys. 2019 Nov 14; 21(42):23408-23417.PC

Abstract

In the field of artificial metalloenzyme (ArM) catalysis, how to identify the critical factors affecting the catalytic activity and enantioselectivity remains a challenge. In this work, the mechanism of enantioselective reduction of imine catalyzed by using [Rh(Me4Cpbiot)Cl2]·S112H Sav (denoted as S112H) and [Rh(Me4Cpbiot)Cl2]·K121H Sav (denoted as K121H) was studied by using molecular dynamics (MD) simulations combined with density functional theory (DFT) calculations. Four binding modes of imine, two proton sources (hydronium ion and lysine) and eight proposed reaction pathways were systematically discussed. The results showed that due to the anchoring effect of the mutation site of ArMs, the rhodium complex which oscillated like a pendulum was bound to a specific conformation, which further determined the chirality of the reduced product. C-Hπ, cation-π and ππ weak interactions played an important role in imine binding, and the favorable binding mode of imine was catalyzed by S112H in landscape orientation and catalyzed by K121H in portrait orientation, respectively. LYS121 is the most possible proton source in the S112H catalytic process while the proton source in the K121H catalytic process is the hydronium ion of the active sites. Furthermore, based on the reaction mechanism, modification of Rh(Me4Cpbiot)Cl2 was carried out in S112H and K121H, and the results suggested that the reaction barrier could be effectively reduced by replacing the methyl groups on Cp* with an amino group. This work gives a fundamental understanding of the mechanism of ArMs toward the imine reduction reaction, in the hope of providing a strategy for reasonable designs of ArMs with high enantioselectivity.

Authors+Show Affiliations

State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China. zhangxin@mail.buct.edu.cn.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31625550

Citation

Feng, Haisong, et al. "Mechanistic Insights Into Artificial Metalloenzymes Towards Imine Reduction." Physical Chemistry Chemical Physics : PCCP, vol. 21, no. 42, 2019, pp. 23408-23417.
Feng H, Guo X, Zhang H, et al. Mechanistic insights into artificial metalloenzymes towards imine reduction. Phys Chem Chem Phys. 2019;21(42):23408-23417.
Feng, H., Guo, X., Zhang, H., Chen, L., Yin, P., Chen, C., Duan, X., Zhang, X., & Wei, M. (2019). Mechanistic insights into artificial metalloenzymes towards imine reduction. Physical Chemistry Chemical Physics : PCCP, 21(42), 23408-23417. https://doi.org/10.1039/c9cp04473f
Feng H, et al. Mechanistic Insights Into Artificial Metalloenzymes Towards Imine Reduction. Phys Chem Chem Phys. 2019 Nov 14;21(42):23408-23417. PubMed PMID: 31625550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanistic insights into artificial metalloenzymes towards imine reduction. AU - Feng,Haisong, AU - Guo,Xuan, AU - Zhang,Hui, AU - Chen,Lifang, AU - Yin,Pan, AU - Chen,Chunyuan, AU - Duan,Xinli, AU - Zhang,Xin, AU - Wei,Min, Y1 - 2019/10/18/ PY - 2019/10/19/pubmed PY - 2019/11/28/medline PY - 2019/10/19/entrez SP - 23408 EP - 23417 JF - Physical chemistry chemical physics : PCCP JO - Phys Chem Chem Phys VL - 21 IS - 42 N2 - In the field of artificial metalloenzyme (ArM) catalysis, how to identify the critical factors affecting the catalytic activity and enantioselectivity remains a challenge. In this work, the mechanism of enantioselective reduction of imine catalyzed by using [Rh(Me4Cpbiot)Cl2]·S112H Sav (denoted as S112H) and [Rh(Me4Cpbiot)Cl2]·K121H Sav (denoted as K121H) was studied by using molecular dynamics (MD) simulations combined with density functional theory (DFT) calculations. Four binding modes of imine, two proton sources (hydronium ion and lysine) and eight proposed reaction pathways were systematically discussed. The results showed that due to the anchoring effect of the mutation site of ArMs, the rhodium complex which oscillated like a pendulum was bound to a specific conformation, which further determined the chirality of the reduced product. C-Hπ, cation-π and ππ weak interactions played an important role in imine binding, and the favorable binding mode of imine was catalyzed by S112H in landscape orientation and catalyzed by K121H in portrait orientation, respectively. LYS121 is the most possible proton source in the S112H catalytic process while the proton source in the K121H catalytic process is the hydronium ion of the active sites. Furthermore, based on the reaction mechanism, modification of Rh(Me4Cpbiot)Cl2 was carried out in S112H and K121H, and the results suggested that the reaction barrier could be effectively reduced by replacing the methyl groups on Cp* with an amino group. This work gives a fundamental understanding of the mechanism of ArMs toward the imine reduction reaction, in the hope of providing a strategy for reasonable designs of ArMs with high enantioselectivity. SN - 1463-9084 UR - https://www.unboundmedicine.com/medline/citation/31625550/Mechanistic_insights_into_artificial_metalloenzymes_towards_imine_reduction L2 - https://doi.org/10.1039/c9cp04473f DB - PRIME DP - Unbound Medicine ER -