pH-Dependent Conformational Switching of Amide Bonds─from Full <i>trans</i> to Full <i>cis</i> and Vice Versa

Thurston, Ryan; Zantop, Viviane; Park, Kristen Sodam; Maid, Harald; Seitz, Anke; Heinrich, Markus R.

doi:10.1021/acs.orglett.2c00938

Cited by 5 publications

(4 citation statements)

References 48 publications

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“…Furthermore, the degrees of freedom left unconstrained by many classes of peptoid residue offer unexplored opportunities for designing flexible, switchable molecules. [74,75] 4.3.2 | How to design a peptoid structure…”

Section: R Groupmentioning

confidence: 99%

Guidelines for designing peptoid structures: Insights from the Peptoid Data Bank

Eastwood

Weisberg²,

Katz

et al. 2023

Peptide Science

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The number of structural studies of peptoids has grown dramatically over the past 20 years. To date, over 100 high-resolution structures have been reported for peptoids, which are typically defined as N-substituted glycine oligomers. We have collected these structures and standardized their sequence representations to facilitate structural analysis as the dataset continues to grow. These structures are presented online as The Peptoid Data Bank (databank.peptoids.org), which also provides persistent links to the published structural data. This review analyzes the present collection of structures and finds extensive support for grouping side chains by their chemistry at the position adjacent to the backbone nitrogen. Groups of side chains with similar chemistry at this position show similar influences on the conformational preferences of the backbone. We also observe a relationship between the side chain and backbone conformations for many monomers that has not previously attracted significant discussion: the values of the χ 1 and ϕ dihedrals are correlated. We outline a general design strategy for attaining a specific backbone conformation based on the patterns seen in the collected structures.

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Section: R Groupmentioning

confidence: 99%

Guidelines for designing peptoid structures: Insights from the Peptoid Data Bank

Eastwood

Weisberg²,

Katz

et al. 2023

Peptide Science

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“…Similarly, the geometries of the tertiary amide bonds in molecules such as peptoids depend on the substituents on the nitrogen atom. , In recent years, the conformational control of tertiary amide bonds of proline and peptoids was actively pursued, and the steric effect, − n O → π* Ar interaction, − carbonyl–carbonyl (CO···CO) n O → π CO * interaction, ,,, cooperative hydrogen bonding, and fluorine inductive effects were explored to stabilize one isomeric form over the other. In a recent study, the pH-dependent conformational switching of tertiary amide bonds was demonstrated by using one bulky and one pH-sensitive substituent on the amide nitrogen atom …”

Section: Introductionmentioning

confidence: 99%

“…In a recent study, the pH-dependent conformational switching of tertiary amide bonds was demonstrated by using one bulky and one pH-sensitive substituent on the amide nitrogen atom. 25 N,N′-diacylhydrazine (Figure 1A) is a small molecule drug scaffold that contains two adjacent amide bonds connected by a N−N single bond. The amide bond isomerization of N,N′diacylhydrazines can produce four different amide bond isomers [trans−trans (t−t), trans−cis (t−c), cis−trans (c−t), and cis−cis (c−c) (Figure 1C),].…”

Section: ■ Introductionmentioning

confidence: 99%

Understanding the Cis–Trans Amide Bond Isomerization of N,N′-Diacylhydrazines to Develop Guidelines for A Priori Prediction of Their Most Stable Solution Conformers

2023

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N,N′-diacylhydrazines (R 1 CO-NR 3 -NR 4 -COR 2 ) are a class of small molecules with a wide range of applications in chemistry and biology. They are structurally unique in the sense that their two amide groups are connected via a N−N single bond, and as a result, these molecules can exist in eight different isomeric forms. Four of these are amide isomers [trans−trans (t−t), trans− cis (t−c), cis−trans (c−t), and cis−cis (c−c)] arising from C−N bond restricted rotation. In addition, each of these amide isomers can exist in two different isomeric forms due to N−N bond restricted rotation, especially when R 3 and R 4 groups are relatively bigger. Herein, we have systematically investigated the conformations of 55 N,N′-diacylhydrazines using a combination of solution NMR spectroscopy, X-ray crystallography, and density functional theory calculations. Our data suggest that when the substituents R 3 and R 4 on the nitrogen atoms are both hydrogens. These molecules prefer twisted trans−trans (t−t) (>90%) geometries (H−N− C�O ∼ 180°), whereas the N-alkylated and N,N′-dialkylated molecules prefer twisted trans−cis (t−c) geometries. Herein, we have analyzed the stabilization of the various isomers of these molecules in light of steric and stereoelectronic effects. We provide a guideline to a priori predict the most stable conformers of the N,N′-diacylhydrazines just by examining their substituents (R 1 -R 4 ).

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“…Recently, an amide-type molecular switch with no appreciable minor peak was reported. 12 As a different approach, we envisioned that if this molecule is protonated in the crystalline state, this will be applicable to an on–off type molecular switch. In addition, the switch in the crystalline state would have its flexible nature reduced.…”

Section: Introductionmentioning

confidence: 99%

Reversible on/off conformational switching of pentafluorobenzoyl amide triggered by acid vapor and sublimation

et al. 2022

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pH-Dependent Conformational Switching of Amide Bonds─from Full trans to Full cis and Vice Versa

Cited by 5 publications

References 48 publications

Guidelines for designing peptoid structures: Insights from the Peptoid Data Bank

Guidelines for designing peptoid structures: Insights from the Peptoid Data Bank

Understanding the Cis–Trans Amide Bond Isomerization of N,N′-Diacylhydrazines to Develop Guidelines for A Priori Prediction of Their Most Stable Solution Conformers

Reversible on/off conformational switching of pentafluorobenzoyl amide triggered by acid vapor and sublimation

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