Switching and Conformational Fixation of Amides Through Proximate Positive Charges

Bartuschat, Amelie L.; Wicht, Karina; Heinrich, Markus R.

doi:10.1002/anie.201502474

Cited by 34 publications

(38 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This move changes dramatically their ability to interact with another molecule or ion, or to pack into lipid bilayers (depending on the nature of R). The moieties of trans ‐3,4‐bis(acyloxy)‐piperidine, trans ‐4‐amino‐3‐piperidinol, 3,7‐diazabicyclo[3.3.1]nonan‐9‐one, arylamide‐substituted diphenylacetylene, trans ‐4,5‐dihydroxyhexahydropyridazine, di(methoxyphenyl)pyridine and substituted amides, and other more complex molecular devices were also suggested recently as new pH sensitive bases for analogous applications.…”

Section: Introductionmentioning

confidence: 99%

Trans‐2‐Aminocyclohexanol derivatives as pH‐triggered conformational switches

Samoshin

Zheng

Liu

2017

J of Physical Organic Chem

View full text Add to dashboard Cite

A series of trans-2-aminocyclohexanol derivatives have been explored as powerful conformational pH triggers. On protonation of the amino group, a conformer with equatorial position of ammonio and hydroxy groups becomes predominant because of an intramolecular hydrogen bond and electrostatic interactions. The energy of these interactions was estimated to be above 10 kJ/mol and in some models exceeded 20 kJ/mol (strong enough to twist a ring in tert-butyl derivatives). As a result of this conformational flip, all other substituents are forced to change their orientation. If the substituents are designed to perform certain geometry-dependent functions, for example, as cation chelators or as lipid tails, such acid-induced transition may be used to control the corresponding molecular properties. The pH sensitivity of conformational equilibria was explored by 1 H nuclear magnetic resonance spectroscopy (NMR), and the titration curves were used for estimation of the pK a values of protonated compounds that varied from 2.6 to 8.5 (in d 4 -methanol) depending on the structure of amino group. Thus, trans-2-aminocyclohexanols can be also used as conformational pH indicators in organic solvents.

show abstract

Section: Introductionmentioning

confidence: 99%

Trans‐2‐Aminocyclohexanol derivatives as pH‐triggered conformational switches

Samoshin

Zheng

Liu

2017

J of Physical Organic Chem

View full text Add to dashboard Cite

show abstract

“…Conformational modulation is usually based on conformational switching. It is reported [24,25] that the conformational preferences can be affected by protonation. Figure 3 (a) displays the potential curves of 2- [6]1N 1 and its conjugate acid, 2- [6] 1NH + 1 a.…”

Section: Conformational Preferences Of O-heteroaromatic Ethers: Effecmentioning

confidence: 99%

Modulation of Conformational Preferences of Heteroaromatic Ethers and Amides through Protonation and Ionization: Charge Effect

Dai

Zhang

2019

ChemistryOpen

View full text Add to dashboard Cite

Multiple approaches reveal the strong effects of a positive charge introduced by protonation or ionization on the conformation of o ‐heteroaromatic ethers and amides. The ethers and amides containing an ortho ‐N heteroatom are syn ‐preferring while those containing an ortho ‐O or ortho ‐S heteroatom are mostly anti ‐preferring. However, for all the monocyclic o ‐heteroaromatic ethers and amides, the protonated ones are all anti ‐preferring while the ionized ones are all syn ‐preferring. Interestingly, although both the protonation and ionization introduce a positive charge, they have such different effects on molecular conformation, very informative for understanding the origin of conformational preferences. Detailed analysis shows that the population of the introduced positive charge dictates the conformational preferences via electrostatic and orbital interactions. Compared to ortho ‐heteroatoms, meta ‐heteroatoms have weaker effect on conformational preference. Achieved by complete inductive method, the regularity of conformational preferences and switching provides easy ways to modulate conformers (by pH or redox), and makes this kind of ether or amide bond a conformational hinge applicable to design of functional molecules (drugs and materials) and modulation of molecular biological processes.

show abstract

“…The variation of amino groups allows a broad tuning of the conformational equilibrium, and the basicity of amino functions could be adjusted for a conformational response within a selected range of pH . Other cyclic and noncyclic scaffolds and more complex molecular devices were also suggested recently as pH‐sensitive conformational switches for similar applications …”

Section: Introductionmentioning

confidence: 99%

Exploration of trans‐2‐(azaarylsulfanyl)‐cyclohexanols as potential pH‐triggered conformational switches

Ruyonga

Mendoza

Browne

et al. 2020

J of Physical Organic Chem

View full text Add to dashboard Cite

A series of trans‐2‐(azaarylsulfanyl)‐cyclohexanols, structurally similar to previously studied trans‐2‐aminocylohexanols, have been synthesized and explored as conformational pH triggers. 1H NMR spectroscopy was used to estimate the position of the chair‐chair conformational equilibrium and its acid‐induced shift towards the conformer with the azaarylsulfanyl and hydroxy groups in equatorial positions due to an intramolecular hydrogen bond and electrostatic interactions. Such acid‐induced transition may be used to control the geometry‐dependent molecular properties. The 1H NMR titration curves were used for estimation of the pKa values of protonated compounds that varied from 2.8 to 4.3 (in d4‐methanol) depending on the structure of the azaarylsulfanyl group.

show abstract

Switching and Conformational Fixation of Amides Through Proximate Positive Charges

Cited by 34 publications

References 70 publications

Trans‐2‐Aminocyclohexanol derivatives as pH‐triggered conformational switches

Trans‐2‐Aminocyclohexanol derivatives as pH‐triggered conformational switches

Modulation of Conformational Preferences of Heteroaromatic Ethers and Amides through Protonation and Ionization: Charge Effect

Exploration of trans‐2‐(azaarylsulfanyl)‐cyclohexanols as potential pH‐triggered conformational switches

Contact Info

Product

Resources

About