Design and synthesis of Tröger's base ditopic receptors: host–guest interactions, a combined theoretical and experimental study

Reddy, M. B. Madhusudana; Shailaja, M.; Manjula, A.; Premkumar, J. Richard; Sastry, G. Narahari; Sirisha, K.; Sarma, Akella V. S.

doi:10.1039/c4ob02266a

Cited by 12 publications

(5 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our work in this area started by taking advantage of the substantial existing corpus of existing host-guest binding data [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68]. However, many existing data are for systems in organic solvents, whereas aqueous systems are more relevant for biomolecular modelling.…”

Section: Introductionmentioning

confidence: 99%

Toward Expanded Diversity of Host-Guest Interactions via Synthesis and Characterization of Cyclodextrin Derivatives

Kellett¹,

Kantonen²,

Duggan³

et al. 2018

Preprint

View full text Add to dashboard Cite

Researchers developing software to predict the binding constants of small molecules for proteins have, in recent years, turned to host-guest systems as simple, computationally tractable model systems to test and improve these computational methods. However, taking full advantage of this strategy requires aqueous host-guest systems that probe a greater diversity of chemical interactions. Here, we advance the development of an experimental platform to generate such systems by building on the cyclodextrin (CD) class of hosts. The secondary face derivative mono-3-carboxypropionamido-β-cyclodextrin (CP-β-CD) was synthesized in a one-pot strategy with 87% yield, and proved to have much greater aqueous solubility than native β-CD. The complexation of anionic CP-β-CD with the cationic drug rimantadine hydrochloride was explored using one and two-dimensional nuclear magnetic resonance (NMR); NOESY analysis showed secondary face binding of the ammonium moiety of the guest, based on cross-correlations between the amic acid functionality and the side-chain of rimantadine. Isothermal titration calorimetry was furthermore used to determine the standard free energy and enthalpy for this binding reaction, and the results were compared with those of rimantadine with native β-CD.

show abstract

Section: Introductionmentioning

confidence: 99%

Toward Expanded Diversity of Host-Guest Interactions via Synthesis and Characterization of Cyclodextrin Derivatives

Kellett¹,

Kantonen²,

Duggan³

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…In this study, we have constructed a model system consisting of a receptor with an aromatic cavity and a number of ligands bearing different substituents, in order to model the interactions between the side chain of a peptide and an aromatic region of a protein. The receptor is based on Tröger's base, a structure which has previously been employed to study host‐guest chemistry and to quantify intermolecular interactions [24–30] . The model system was studied by a number of NMR methods, affording both quantitative (association constants and binding energies) and qualitative (conformation of the free and bound ligands) data for the binding of the different ligands to the receptor.…”

Section: Introductionmentioning

confidence: 99%

“…The receptor is based on Tröger's base, a structure which has previously been employed to study host‐guest chemistry and to quantify intermolecular interactions. [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ] The model system was studied by a number of NMR methods, affording both quantitative (association constants and binding energies) and qualitative (conformation of the free and bound ligands) data for the binding of the different ligands to the receptor. The experimental data was then used to compare and evaluate a number of molecular mechanics (MM) [31] and dispersion‐corrected density functional theory (DFT) [31] methods.…”

Section: Introductionmentioning

confidence: 99%

Experimental and Computational Models for Side Chain Discrimination in Peptide–Protein Interactions

Lidskog

Dawaigher

Arribas

et al. 2021

Chemistry A European J

View full text Add to dashboard Cite

A bis(18-crown-6) Tröger's base receptor and 4substituted hepta-1,7-diyl bisammonium salt ligands have been used as a model system to study the interactions between non-polar side chains of peptides and an aromatic cavity of a protein. NMR titrations and NOESY/ROESY NMR spectroscopy were used to analyze the discrimination of the ligands by the receptor based on the substituent of the ligand, both quantitatively (free binding energies) and qualitatively (conformations). The analysis showed that an allanti conformation of the heptane chain was preferred for most of the ligands, both free and when bound to the receptor, and that for all of the receptor-ligand complexes, the substituent was located inside or partly inside of the aromatic cavity of the receptor. We estimated the free binding energy of a methyl-and a phenyl group to an aromatic cavity, via CH-π, and combined aromatic CH-π and π-π interactions to be À 1.7 and À 3.3 kJ mol À 1 , respectively. The experimental results were used to assess the accuracy of different computational methods, including molecular mechanics (MM) and density functional theory (DFT) methods, showing that MM was superior. Results and Discussion Description of the model systemReceptor 1 consists of a Tröger's base motif with 18-crown-6 moieties fused to each end of the aromatic cavity, and is synthesized in one step by the condensation of commercially [a] A

show abstract

“…Despite the long history and broad range applications of both TBAs [4] and azo switches [5], no azo carrying TBA was ever fashioned until 2016 [6]. The unique lambda-shape geometry of TBAs can open new possibilities in the design of nanostructures including cyclophanes [7,8], helicates [9,10], molecular cleft receptors [11,12], metal-organic frameworks and mechanically interlocked molecules [1].…”

Section: Introductionmentioning

confidence: 99%

Untitled

Kazem‐Rostami

2020

Asian J. Nanosci. Mater.

View full text Add to dashboard Cite

Hybridization, functionalization, and enantioseparation of ethano-bridged Tröger base analogs have been performed. X-ray crystallographic analysis, chiral HPLC and CD spectroscopy have assigned the absolute configuration of the obtained ethano-bridged Tröger base analogs, confirming their optical purity. These optically active building blocks are readily modifiable and owing to their versatility they offer unique benefits for the growing community of molecular machinists. KEYWORDS Tröger base Enantioseparation Nitrogen stereocenter Chiral discriminator Graphical AbstractEnantiopure asymmetrically functionalized lambda-shape …

show abstract

Design and synthesis of Tröger's base ditopic receptors: host–guest interactions, a combined theoretical and experimental study

Cited by 12 publications

References 78 publications

Toward Expanded Diversity of Host-Guest Interactions via Synthesis and Characterization of Cyclodextrin Derivatives

Toward Expanded Diversity of Host-Guest Interactions via Synthesis and Characterization of Cyclodextrin Derivatives

Experimental and Computational Models for Side Chain Discrimination in Peptide–Protein Interactions

Untitled

Contact Info

Product

Resources

About