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

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

847
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...
847
Conformations of Ethane and Propane02:18

Conformations of Ethane and Propane

14.0K
In an organic molecule, free rotation about the carbon-carbon single bond results in energetically different conformers of the molecule. Due to this rotation, called the internal rotation, ethane has two major conformations — staggered and eclipsed.
Staggered conformation is a low energy and more stable conformation with the C-H bonds on the front carbon placed at 60°dihedral angles relative to the C-H bonds on the back carbon, leading to a reduced torsional strain. In staggered...
14.0K
¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR01:15

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

1.1K
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.
1.1K
Conformations of Butane02:20

Conformations of Butane

14.3K
Unlike ethane and propane that have only two major conformations, butane has more than two conformers. The staggered form of butane in which the bulky methyl groups on the two carbons are placed on opposite sides, that is, at a dihedral angle of 180°, is the lowest energy, most stable form — called the anti conformer. This conformation is stabilized due to the absence of steric repulsion between the largely spaced out methyl groups. The other two staggered conformations are...
14.3K
Kinetic Molecular Theory and Gas Laws Explain Properties of Gas Molecules02:34

Kinetic Molecular Theory and Gas Laws Explain Properties of Gas Molecules

32.7K
The test of the kinetic molecular theory (KMT) and its postulates is its ability to explain and describe the behavior of a gas. The various gas laws (Boyle’s, Charles’s, Gay-Lussac’s, Avogadro’s, and Dalton’s laws) can be derived from the assumptions of the KMT, which have led chemists to believe that the assumptions of the theory accurately represent the properties of gas molecules.
32.7K
Molecular Comparison of Gases, Liquids, and Solids02:26

Molecular Comparison of Gases, Liquids, and Solids

41.2K
Particles in a solid are tightly packed together (fixed shape) and often arranged in a regular pattern; in a liquid, they are close together with no regular arrangement (no fixed shape); in a gas, they are far apart with no regular arrangement (no fixed shape). Particles in a solid vibrate about fixed positions (cannot flow) and do not generally move in relation to one another; in a liquid, they move past each other (can flow) but remain in essentially constant contact; in a gas, they move...
41.2K

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Related Experiment Video

Updated: Jul 5, 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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Molecular Gas-Phase Conformational Ensembles.

Susanta Das1, Kenneth M Merz1

  • 1Department of Chemistry, Michigan State University, 578 S. Shaw Lane, East Lansing, Michigan 48824, United States.

Journal of Chemical Information and Modeling
|January 11, 2024
PubMed
Summary

This study compares four conformational search engines (Auto3D, CREST, Balloon, ETKDG) for finding molecular global minima. Experimental collisional cross-section (CCS) data from ion mobility-mass spectrometry validates their effectiveness, aiding in accurate molecular structure determination.

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Last Updated: Jul 5, 2025

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Area of Science:

  • Computational Chemistry
  • Molecular Modeling
  • Analytical Chemistry

Background:

  • Accurate determination of global molecular minima is crucial for drug design, materials science, and chemical synthesis.
  • Conformational search engines explore molecular conformational space to identify stable structures.

Purpose of the Study:

  • To compare the effectiveness of four freely available conformational search engines: Auto3D, CREST, Balloon, and ETKDG (RDKit).
  • To introduce experimental gas-phase collisional cross-section (CCS) values as a validation metric for conformational search accuracy.
  • To establish a gas-phase conformation library (GPCL) for validating conformational search engines.

Main Methods:

  • Comparison of Auto3D, CREST, Balloon, and ETKDG conformational search engines.
  • Utilizing machine learning (ML) potential-based, semiempirical, and force field-based approaches.
  • Validation using experimental gas-phase collisional cross-section (CCS) values from ion mobility-mass spectrometry.

Main Results:

  • Evaluation of the performance of different conformational search engines in locating global minima.
  • Demonstration of CCS values as a reliable experimental validation tool for conformational searches.
  • Establishment of the gas-phase conformation library (GPCL) with 20 small molecules for community use.

Conclusions:

  • The study provides insights into the strengths and limitations of various conformational search engines.
  • Experimental CCS data offers a robust method for validating computationally predicted global minima.
  • The GPCL and proposed validation workflow enhance the accuracy of molecular structure determination, particularly for metabolite identification and unknown compound prediction.