Related Experiment Video
Updated: Aug 6, 2026
10:02
Submillisecond Conformational Changes in Proteins Resolved by Photothermal Beam Deflection
Published on: February 18, 2014
Temperature-controlled conformational switching of squaramides enabled by side-chain hydrogen bonding
Kazusa Kuyama1, Kimiko Tanaka1, Fumi Takeda1
1Department of Chemistry, Faculty of Science, Ochanomizu University Tokyo Japan tanatani.aya@ocha.ac.jp.
RSC Advances
|August 5, 2026
Summary
Researchers developed a method to control molecular shapes using temperature. A specific side chain on squaramide molecules allows for reversible shape changes, enabling new stimulus-responsive materials.
Area of Science:
- Organic Chemistry
- Materials Science
- Supramolecular Chemistry
Background:
- Precise control over molecular conformation is key for designing stimulus-responsive aromatic architectures.
- Amide-derived scaffolds, like squaramides, offer tunable rotational barriers for thermodynamic control without permanent locking.
Purpose of the Study:
- To demonstrate how a hydrogen-bond-accepting side chain can enable thermodynamic programming of squaramide conformations.
- To investigate the structural requirements for temperature-dependent conformational switching in squaramides.
Main Methods:
- Synthesis of squaramide analogues with varying side chains (TEG-substituted, n-propyl, diphenyl).
- Variable-temperature Nuclear Magnetic Resonance (NMR) spectroscopy to monitor conformational changes.
- Van't Hoff analysis to quantify thermodynamic parameters (ΔH°, ΔS°).
Main Results:
- Squaramide 1c with a triethylene glycol (TEG) side chain exhibited reversible temperature-dependent switching between (trans, trans) and (cis, trans) conformations.
- The N-n-propyl analogue (1b) without a hydrogen-bonding side chain remained exclusively in the (cis, trans) form.
- A diphenyl analogue (1d) without extended π-surfaces also showed reversible thermal behavior, indicating π-extension is not essential but influences conformational bias.
Conclusions:
- Introduction of a hydrogen-bond-accepting side chain is a viable strategy for thermodynamically programming squaramide conformations.
- This side-chain-enabled approach allows for reversible, temperature-dependent molecular switching.
- The findings establish a design principle for creating tunable, stimulus-responsive aromatic architectures.
Related Concept Videos
01:22Protein Folding
Overview
01:25Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
01:15¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR
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.
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
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...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...