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Related Concept Videos

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution00:52

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

1.2K
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
1.2K
Conformations of Cyclohexane02:11

Conformations of Cyclohexane

15.0K
Cyclohexane does not exist in a planar form due to the high angle and torsional strain it would experience in the planar structure. Instead, it adopts non-planar chair and boat conformations.
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
15.0K
Conformations of Cycloalkanes02:29

Conformations of Cycloalkanes

13.9K
Adolf von Baeyer attempted to explain the instabilities of small and large cycloalkane rings using the concept of angle strain — the strain caused by the deviation of bond angles from the ideal 109.5° tetrahedral value for sp3  hybridized carbons. However, while cyclopropane and cyclobutane are strained, as expected from their highly compressed bond angles, cyclopentane is more strained than predicted, and cyclohexane is virtually strain-free. Hence, Baeyer’s theory that...
13.9K
Chair Conformation of Cyclohexane02:02

Chair Conformation of Cyclohexane

17.7K
The chair conformation is the most stable form of cyclohexane due to the absence of angle and torsional strain. The absence of angle strain is a result of cyclohexane’s bond angle being very close to the ideal tetrahedral bond angle of 109.5° in its chair conformer. Similarly, the torsional strain is also absent owing to the perfectly staggered arrangement of bonds.
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this...
17.7K
¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR01:15

¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR

1.6K
The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
1.6K
Stereoisomerism of Cyclic Compounds02:33

Stereoisomerism of Cyclic Compounds

10.8K
In this lesson, we delve into the role of ring conformation and its stability, which determines the spatial arrangement and, consequently, the molecular symmetry and stereoisomerism of cyclic compounds. 1,2-Dimethylcyclohexane is used as a case study to evaluate the possible number of stereoisomers. Here, given the multiple (n = 2) chiral centers, there are 2n = 4 possible configurations that lack a plane of symmetry, as the ring skeleton exists in a non-planar chair conformation. In addition,...
10.8K

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Related Experiment Video

Updated: Dec 30, 2025

Spatial Separation of Molecular Conformers and Clusters
10:37

Spatial Separation of Molecular Conformers and Clusters

Published on: January 9, 2014

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Conformational analysis of macrocycles: comparing general and specialized methods.

Gustav Olanders1, Hiba Alogheli1, Peter Brandt2

  • 1Department of Medicinal Chemistry, Uppsala University, BMC, Box 574, 751 23, Uppsala, Sweden.

Journal of Computer-Aided Molecular Design
|January 23, 2020
PubMed
Summary

Optimized general methods like Monte Carlo Multiple Minimum (MCMM) and Mixed Torsional/Low-Mode sampling (MTLMOD) accurately predict macrocycle conformations. These enhanced general methods offer a competitive alternative to specialized techniques for drug design.

Keywords:
Conformational samplingDrug designMacrocycles

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Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
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Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR

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Interactive Molecular Model Assembly with 3D Printing
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Interactive Molecular Model Assembly with 3D Printing

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Interactive Molecular Model Assembly with 3D Printing
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Interactive Molecular Model Assembly with 3D Printing

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Area of Science:

  • Computational chemistry
  • Medicinal chemistry
  • Drug discovery

Background:

  • Macrocycles are crucial in drug discovery due to their unique biological properties.
  • Understanding macrocycle conformational preferences is vital for effective drug design.
  • Accurate macrocycle-protein modeling aids in identifying potent drug candidates.

Purpose of the Study:

  • To systematically compare established and specialized conformational analysis methods for macrocycles.
  • To evaluate method performance in generating unique conformers and identifying bioactive conformations.
  • To guide practitioners in selecting optimal computational tools for macrocycle modeling.

Main Methods:

  • Comparison of Monte Carlo Multiple Minimum (MCMM) and Mixed Torsional/Low-Mode sampling (MTLMOD) against specialized MacroModel (MD/LLMOD) and Prime (PRIME-MCS) methods.
  • Evaluation based on conformer generation, global energy minimum identification, and similarity to X-ray crystallography data (X-rayppw).
  • Analysis of computational speed and conformational coverage for each method.

Main Results:

  • Optimized general methods (MCMM, MTLMOD) performed comparably to specialized techniques for macrocycle conformational sampling.
  • Enhanced settings for MCMM and MTLMOD demonstrated superior accuracy in regenerating X-rayppw conformations.
  • MD/LLMOD proved most efficient for identifying global energy minima.

Conclusions:

  • General conformational search methods can be effectively optimized for macrocycle modeling by adjusting ring closure bond settings.
  • Optimized MCMM and MTLMOD offer a robust and accurate approach for macrocycle conformational analysis in drug discovery.
  • The study provides valuable insights for selecting appropriate computational strategies in macrocycle-based drug design.