Substituent effects on aromatic stacking interactions

Cockroft, Scott L.; Perkins, Julie; Zonta, Cristiano; Adams, Harry; Spey, Sharon E.; Low, Caroline M. R.; Vinter, Jeremy G.; Lawson, Kevin R.; Urch, Christopher J.; Hunter, Christopher A.

doi:10.1039/b617576g

Cited by 225 publications

(245 citation statements)

References 83 publications

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“…If, however, the interacting molecules are non-rigid or contain bulky side chains comparable in their dimension with the aromatic chromophore, the disruption of the compact π-stacking structure may occur as was clearly shown in dye-dye hetero-complexes [219]. It is difficult to ascertain whether in this context the principle of 'structural complementarity' must be supplemented by 'electrostatic complementarity' recently introduced for aromatic interactions [36], as differentiation of their influence on hetero-association is not possible with the data available. However, there is direct NMR evidence for the formation of two dimer structures of the antibiotic DAU with either parallel (charges on DAU aminosugar are in close proximity to each other) or antiparallel (charges on DAU aminosugar are well separated) orientations of chromophores [221,222], which suggests that electrostatic factor may not be so significant in aqueous solution.…”

Section: Hetero-association Of Aromatic Drugs With Aromatic Mutagens mentioning

confidence: 99%

“…The hetero-association of specially selected (synthesised) aromatic molecules has been used as a model system to provide insight into various processes of particular importance in chemistry, such as 4 M.P. Evstigneev arrangement of nucleic acid bases derivatives in stacked complexes [23,30], binding of drugs to nucleic acids [31] and aromatic residues of proteins [32,33], protein-DNA and protein-protein interactions [3,34], exciton and charge-transfer interactions [25,34,35], dye chemistry [22], electrostatic complementarity [12,36], and 'energetic composition' of π-stacking [3,8,37]. (2) Biochemical applications.…”

Section: Applications Of Hetero-associationmentioning

confidence: 99%

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Hetero-association of aromatic molecules in aqueous solution

Evstigneev

2014

International Reviews in Physical Chemistry

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Knowledge of the physical chemistry of small molecules complexation (the hetero-association) in aqueous solution is increasingly important in view of the rapidly emerging branch of supramolecular chemistry dealing with the formation of heterogeneous polymeric structures having specific functional roles. In this paper, the 50-year history of scientific studies of hetero-association of heterocyclic aromatic molecules in aqueous solution has been reviewed. Some important correlations of structural and thermodynamic parameters of complexation have been reported based on large data-set of hetero-association parameters accumulated to date. The fundamental problem of 'energetic composition' of π-stacking is extensively discussed. The review has shown that there are some gaps in our understanding of heteroassociation, which provides a challenge for further studies in this area.

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Section: Hetero-association Of Aromatic Drugs With Aromatic Mutagens mentioning

confidence: 99%

Section: Applications Of Hetero-associationmentioning

confidence: 99%

Hetero-association of aromatic molecules in aqueous solution

Evstigneev

2014

International Reviews in Physical Chemistry

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“…3 Some studies have already shown the impact of the electronic properties of the substituents on the stability of these interactions in ligand−receptor binding. 4,5 Therefore, by increasing the electronic density with an electron-donating group, we expected to reinforce the interaction between the distal benzene ring and the Phe 6.52 residue.…”

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confidence: 99%

Enhancing a CH−π Interaction to Increase the Affinity for 5-HT_1A Receptors

Liégeois

Lespagnard

Meneses‐Salas

et al. 2014

ACS Med. Chem. Lett.

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An electrostatic interaction related to a favorable position of the distal phenyl ring and a phenylalanine residue in the binding pocket would explain the higher 5-HT 1A affinity of a 4-phenyl-1,2,3,6-tetrahydropyridine (THP) analogue compared to the corresponding 4-phenylpiperazine analogue. To explore a possible reinforcement of this interaction to increase the affinity for 5-HT 1A receptors, different 4-substituted-phenyl analogues were synthesized and tested. The most important increase of affinity is obtained with two electron-donating methyl groups in positions 3 and 5. KEYWORDS: CH−π interaction, quinoxaline, carboxamide, arylpiperazine, electron-donating, docking R ecently, we reported that a 4-phenyl-1,2,3,6-tetrahydropyridine (THP) analogue was shown to be favorable compared to the corresponding 4-phenyl-piperazine one in terms of affinity for 5-HT 1A receptors in a series of 4-arylpiperazine-ethyl carboxamides. 1 An electrostatic interaction between the distal benzene ring of the molecule and a phenylalanine residue (Phe 6.52) particularly in the 5-HT 1A receptor binding pocket was suggested by molecular modeling approaches. 2 The almost coplanar orientation of both rings displayed in the 4-phenyl-THP compound appeared as an important spatial requirement for an optimal interaction with the 5-HT 1A receptor in the present series. This orientation should stabilize the ligand binding by an edge-to-face CH−π interaction between the phenyl ring of the 4-phenyl-THP compounds and the phenyl ring of the Phe 6.52 residue. 2 This would explain why the chemical modification of the piperazine ring into THP is favorable for receptor affinity.The electron donating/withdrawing properties of an aromatic substituent is an important factor for the electron density of the aromatic ring and consequently for the capacity of these rings to be involved in aromatic stacking interactions. 3 Some studies have already shown the impact of the electronic properties of the substituents on the stability of these interactions in ligand−receptor binding. 4,5 Therefore, by increasing the electronic density with an electron-donating group, we expected to reinforce the interaction between the distal benzene ring and the Phe 6.52 residue. The substituents were positioned either in position 4 or positions 3 and 5 of the distal ring in order to avoid a sterical constraint if present in position 2 or 6. To explore a possible opposite effect linked to the electronic properties of the substituents, electron-withdrawing atoms were also introduced. The THP derivatives were tested, in parallel with the corresponding arylpiperazine derivatives, for their affinity for 5-HT 1A receptors. The intrinsic activity of six selected compounds was also investigated using an electrophysiological approach.The target compounds were prepared by reaction of the appropriate primary amine with the appropriate acyl chloride (2-naphthoyl chloride or 2-quinoxaline chloride) as reported in Scheme 1. The crude amines were synthesized following a Gabriel pro...

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“…A series of Diels-Alder adducts of resin acid with acrylic acid were synthesized, and these showed great antimicrobial activity against different kinds of bacteria by filter paper method (Li et al 2012;Wang et al 2012). It was also reported that aromatic constituents of compounds had broad spectrum anti-fungal activity (Cockroft et al 2007;Pattnaik et al 1997). As an inexpensive natural product, fungicides related to rosin have superiority.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Bioactivity of Rosin Quaternary Ammonium Salt Derivatives

Liang

Zhang

et al. 2012

BioResources

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Two series of rosin quaternary ammonium salts (QAS) were synthesized using the same path. The structure of the target products was characterized by HPLC, MS, IR, and 1 HNMR, and the bioactivity was determined by filter paper method using Trametes versicolor (white-rot fungus) and Gloeophyllum trabeum (brown-rot fungus), which are two kinds of general wood decay fungi in nature. The results showed that all compounds tested had a satisfactory anti-fungal effect at the molarity of 0.025 mmol/mL. Hereinto, acrylpimaric Gemini QAS had better bioactivity than dehydrogenated or tetrahydrogenated rosin QAS against Trametes versicolor. To this fungus, quaternary ammonium groups, which wraps up the membrane of microorganism and disrupts the balance in cell membrane, plays the leading role for its bioactivity. To Gloeophyllum trabeum, the inhibition activity of acrylpimaric QAS and dehydrogenated rosin QAS are almost at the same level and larger than tetrahydrogenated rosin QAS, so we conclude that both quaternary ammonium group and aromatic group play important roles. Compared with dodecyl dimethyl benzyl ammonium chloride (1227), which is a commercially available quaternary ammonium salt type fungicide, acrylpimaric acid quaternary ammonium salts have approximate bioactivity against Gloeophyllum trabeum. In conclusion, rosin derivatives with functional groups would do well in wood preservative applications.

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Substituent effects on aromatic stacking interactions

Cited by 225 publications

References 83 publications

Hetero-association of aromatic molecules in aqueous solution

Hetero-association of aromatic molecules in aqueous solution

Enhancing a CH−π Interaction to Increase the Affinity for 5-HT_1A Receptors

Synthesis, Characterization, and Bioactivity of Rosin Quaternary Ammonium Salt Derivatives

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Substituent effects on aromatic stacking interactions

Cited by 225 publications

References 83 publications

Hetero-association of aromatic molecules in aqueous solution

Hetero-association of aromatic molecules in aqueous solution

Enhancing a CH−π Interaction to Increase the Affinity for 5-HT1A Receptors

Synthesis, Characterization, and Bioactivity of Rosin Quaternary Ammonium Salt Derivatives

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Product

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Enhancing a CH−π Interaction to Increase the Affinity for 5-HT_1A Receptors