Substituent effects on the aromatic edge-to-face interaction

Fischer, Felix R.; Schweizer, W. Bernd; Diederich, François

doi:10.1039/b809058k

Cited by 53 publications

(53 citation statements)

References 22 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The different results between the two studies were initially explained by Cockroft and Hunter by differences in solvation effects in C 6 D 6 and CDCl 3 12. A re‐measurement of both sets of torsion balances in both solvents confirmed all earlier results and showed similar folding behavior in the two solvents 13. A steep linear free enthalpy relationship (LFER) was observed for the torsion balances with an edge‐trifluoromethyl group in both C 6 D 6 and CDCl 3 .…”

Section: Introductionsupporting

confidence: 85%

Structures and Properties of Molecular Torsion Balances to Decipher the Nature of Substituent Effects on the Aromatic Edge‐to‐Face Interaction

Gardarsson

Schweizer

Trapp

et al. 2014

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

Various recent computational studies initiated this systematic re-investigation of substituent effects on aromatic edge-to-face interactions. Five series of Tröger base derived molecular torsion balances (MTBs), initially introduced by Wilcox and co-workers, showing an aromatic edge-to-face interaction in the folded, but not in the unfolded form, were synthesized. A fluorine atom or a trifluoromethyl group was introduced onto the edge ring in ortho-, meta-, and para-positions to the C-H group interacting with the face component. The substituents on the face component were varied from electron-donating to electron-withdrawing. Extensive X-ray crystallographic data allowed for a discussion on the conformational behavior of the torsional balances in the solid state. While most systems adopt the folded conformation, some were found to form supramolecular intercalative dimers, lacking the intramolecular edge-to-face interaction, which is compensated by the gain of aromatic π-stacking interactions between four aryl rings of the two molecular components. This dimerization does not take place in solution. The folding free enthalpy ΔG(fold) of all torsion balances was determined by (1)H NMR measurements by using 10 mM solutions of samples in CDCl3 and C6D6. Only the ΔG(fold) values of balances bearing an edge-ring substituent in ortho-position to the interacting C-H show a steep linear correlation with the Hammett parameter (σ(meta)) of the face-component substituent. Thermodynamic analysis using van't Hoff plots revealed that the interaction is enthalpy-driven. The ΔG(fold) values of the balances, in addition to partial charge calculations, suggest that increasing the polarization of the interacting C-H group makes a favorable contribution to the edge-to-face interaction. The largest contribution, however, seems to originate from local direct interactions between the substituent in ortho-position to the edge-ring C-H and the substituted face ring.

show abstract

Section: Introductionsupporting

confidence: 85%

Structures and Properties of Molecular Torsion Balances to Decipher the Nature of Substituent Effects on the Aromatic Edge‐to‐Face Interaction

Gardarsson

Schweizer

Trapp

et al. 2014

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

show abstract

“…44 However, when the experiments were repeated for both torsion balance molecules in both solvents, the results were still contradictory; the simple equation proposed could not predict at what point electrostatic effects are large enough to overcome solvent-driven energetic effects. 45 Rashkin and Waters used a different architecture, testing substituted N-benzyl-2-(2-fluorophenyl)pyridinium bromide.…”

Section: Experimental Studies Of Aromatic-aromatic Interactionsmentioning

confidence: 99%

Rethinking the term “pi-stacking”

2012

View full text Add to dashboard Cite

“…The NOESY spectrum of Ca 2+ –EWH exhibited connectivity between the aromatic proton resonances of indolyl CH2 (Trp) and Im + CH5 (Im–Ca 2+ ; δ =7.25 ppm; see Figure 4), which is consistent with the indole unit being oriented toward the Im ring through a severely distorted stacking (see MMFF structure below), with a distance between the CH2(indolyl) and CH5(Im + ) being estimated to be about 4.8–5.0 Å by NMR spectroscopy. The evident NOE cross‐peak between the side‐chain rings of His and Trp corroborate an alignment in which the Im + moiety is perpendicular (orthogonal) to the pyrrole ring of the indole moiety, namely, a T‐shaped (edge‐to‐face) alignment (Scheme ), irrespective of the presence of polar solvent (e.g., water) 8a,b,h. This π + –π contact is feasible because the Im + ring is equivalent to a substituted aromatic ring;8i moreover, this interactive mode is generally consistent with a previous finding that a metal‐bound Im + ring cation preferably contacts with the pyrrolo subunit rather than the indole benzene ring 31…”

Section: Resultsmentioning

confidence: 62%

Insights into Intramolecular Trp and His Side‐Chain Orientation and Stereospecific π Interactions Surrounding Metal Centers: An Investigation Using Protein Metal‐Site Mimicry in Solution

Yang

Zhang

2010

Chemistry A European J

View full text Add to dashboard Cite

Metal-binding scaffolds incorporating a Trp/His-paired epitope are instrumental in giving novel insights into the physicochemical basis of functional and mechanistic versatility conferred by the Trp-His interplay at a metal site. Herein, by coupling biometal site mimicry and (1)H and (13)C NMR spectroscopy experiments, modular constructs EDTA-(L-Trp, L-His) (EWH; EDTA=ethylenediamino tetraacetic acid) and DTPA-(L-Trp, L-His) (DWH; DTPA=diethylenetriamino pentaacetic acid) were employed to dissect the static and transient physicochemical properties of hydrophobic/hydrophilic aromatic interactive modes surrounding biometal centers. The binding feature and identities of the stoichiometric metal-bound complexes in solution were investigated by using (1)H and (13)C NMR spectroscopy, which facilitated a cross-validation of the carboxylate, amide oxygen, and tertiary amino groups as the primary ligands and indole as the secondary ligand, with the imidazole (Im) N3 nitrogen being weakly bound to metals such as Ca(2+) owing to a multivalency effect. Surrounding the metal centers, the stereospecific orientation of aromatic rings in the diastereoisomerism is interpreted with the Ca(2+)-EWH complex. With respect to perturbed Trp side-chain rotamer heterogeneity, drastically restricted Trp side-chain flexibility and thus a dynamically constrained rotamer interconversion due to π interactions is evident from the site-selective (13)C NMR spectroscopic signal broadening of the Trp indolyl C3 atom. Furthermore, effects of Trp side-chain fluctuation on indole/Im orientation were the subject of a 2D NMR spectroscopy study by using the Ca(2+)-bound state; a C-H2(indolyl)/C-H5(Im(+)) connectivity observed in the NOESY spectra captured direct evidence that the N-H1 of the Ca(2+)-Im(+) unit interacted with the pyrrole ring of the indole unit in Ca(2+)-bound EWH but not in DWH, which is assignable to a moderately static, anomalous, T-shaped, interplanar π(+)-π stacking alignment. Nevertheless, a comparative (13)C NMR spectroscopy study of the two homologous scaffolds revealed that the overall response of the indole unit arises predominantly from global attractions between the indole ring and the entire positively charged first coordination sphere. The study thus demonstrates the coordination-sphere/geometry dependence of the Trp/His side-chain interplay, and established that π interactions allow (13)C NMR spectroscopy to offer a new window for investigating Trp rotamer heterogeneity near metal-binding centers.

show abstract

Substituent effects on the aromatic edge-to-face interaction

Abstract: Substituent effects on the folding equilibrium of molecular torsion balances are rationalised on the basis of changes in the electrostatic interactions, the exchange repulsion, and the dispersive contributions to the interaction free enthalpy.

Cited by 53 publications

References 22 publications

Structures and Properties of Molecular Torsion Balances to Decipher the Nature of Substituent Effects on the Aromatic Edge‐to‐Face Interaction

Structures and Properties of Molecular Torsion Balances to Decipher the Nature of Substituent Effects on the Aromatic Edge‐to‐Face Interaction

Rethinking the term “pi-stacking”

Insights into Intramolecular Trp and His Side‐Chain Orientation and Stereospecific π Interactions Surrounding Metal Centers: An Investigation Using Protein Metal‐Site Mimicry in Solution

Contact Info

Product

Resources

About