Low-Mode Conformational Search Method with Semiempirical Quantum Mechanical Calculations

Application to Enantioselective Organocatalysis

Takashi Kamachi, Kazunari Yoshizawa

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

A conformational search program for finding low-energy conformations of large noncovalent complexes has been developed. A quantitatively reliable semiempirical quantum mechanical PM6-DH+ method, which is able to accurately describe noncovalent interactions at a low computational cost, was employed in contrast to conventional conformational search programs in which molecular mechanical methods are usually adopted. Our approach is based on the low-mode method whereby an initial structure is perturbed along one of its low-mode eigenvectors to generate new conformations. This method was applied to determine the most stable conformation of transition state for enantioselective alkylation by the Maruoka and cinchona alkaloid catalysts and Hantzsch ester hydrogenation of imines by chiral phosphoric acid. Besides successfully reproducing the previously reported most stable DFT conformations, the conformational search with the semiempirical quantum mechanical calculations newly discovered a more stable conformation at a low computational cost.

Original languageEnglish
Pages (from-to)347-353
Number of pages7
JournalJournal of Chemical Information and Modeling
Volume56
Issue number2
DOIs
Publication statusPublished - Feb 22 2016

Fingerprint

Conformations
Cinchona Alkaloids
costs
Imines
Alkylation
Phosphoric acid
Discrete Fourier transforms
Eigenvalues and eigenfunctions
Hydrogenation
Costs
Esters
energy
interaction
Catalysts

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

Cite this

@article{73438728aca543538d9e088c1a0da4f3,
title = "Low-Mode Conformational Search Method with Semiempirical Quantum Mechanical Calculations: Application to Enantioselective Organocatalysis",
abstract = "A conformational search program for finding low-energy conformations of large noncovalent complexes has been developed. A quantitatively reliable semiempirical quantum mechanical PM6-DH+ method, which is able to accurately describe noncovalent interactions at a low computational cost, was employed in contrast to conventional conformational search programs in which molecular mechanical methods are usually adopted. Our approach is based on the low-mode method whereby an initial structure is perturbed along one of its low-mode eigenvectors to generate new conformations. This method was applied to determine the most stable conformation of transition state for enantioselective alkylation by the Maruoka and cinchona alkaloid catalysts and Hantzsch ester hydrogenation of imines by chiral phosphoric acid. Besides successfully reproducing the previously reported most stable DFT conformations, the conformational search with the semiempirical quantum mechanical calculations newly discovered a more stable conformation at a low computational cost.",
author = "Takashi Kamachi and Kazunari Yoshizawa",
year = "2016",
month = "2",
day = "22",
doi = "10.1021/acs.jcim.5b00671",
language = "English",
volume = "56",
pages = "347--353",
journal = "Journal of Chemical Information and Modeling",
issn = "1549-9596",
publisher = "American Chemical Society",
number = "2",

}

TY - JOUR

T1 - Low-Mode Conformational Search Method with Semiempirical Quantum Mechanical Calculations

T2 - Application to Enantioselective Organocatalysis

AU - Kamachi, Takashi

AU - Yoshizawa, Kazunari

PY - 2016/2/22

Y1 - 2016/2/22

N2 - A conformational search program for finding low-energy conformations of large noncovalent complexes has been developed. A quantitatively reliable semiempirical quantum mechanical PM6-DH+ method, which is able to accurately describe noncovalent interactions at a low computational cost, was employed in contrast to conventional conformational search programs in which molecular mechanical methods are usually adopted. Our approach is based on the low-mode method whereby an initial structure is perturbed along one of its low-mode eigenvectors to generate new conformations. This method was applied to determine the most stable conformation of transition state for enantioselective alkylation by the Maruoka and cinchona alkaloid catalysts and Hantzsch ester hydrogenation of imines by chiral phosphoric acid. Besides successfully reproducing the previously reported most stable DFT conformations, the conformational search with the semiempirical quantum mechanical calculations newly discovered a more stable conformation at a low computational cost.

AB - A conformational search program for finding low-energy conformations of large noncovalent complexes has been developed. A quantitatively reliable semiempirical quantum mechanical PM6-DH+ method, which is able to accurately describe noncovalent interactions at a low computational cost, was employed in contrast to conventional conformational search programs in which molecular mechanical methods are usually adopted. Our approach is based on the low-mode method whereby an initial structure is perturbed along one of its low-mode eigenvectors to generate new conformations. This method was applied to determine the most stable conformation of transition state for enantioselective alkylation by the Maruoka and cinchona alkaloid catalysts and Hantzsch ester hydrogenation of imines by chiral phosphoric acid. Besides successfully reproducing the previously reported most stable DFT conformations, the conformational search with the semiempirical quantum mechanical calculations newly discovered a more stable conformation at a low computational cost.

UR - http://www.scopus.com/inward/record.url?scp=84961137745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961137745&partnerID=8YFLogxK

U2 - 10.1021/acs.jcim.5b00671

DO - 10.1021/acs.jcim.5b00671

M3 - Article

VL - 56

SP - 347

EP - 353

JO - Journal of Chemical Information and Modeling

JF - Journal of Chemical Information and Modeling

SN - 1549-9596

IS - 2

ER -