The Analysis of the Ortho Effect

Fujita, Toshio; Nishi­oka, Takaaki

doi:10.1002/9780470171912.ch3

Cited by 146 publications

(11 citation statements)

References 25 publications

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“…The observation that σ p – (derived from ionization of phenols) provides an improved correlation relative to σ p (derived from ionization of benzoic acids) indicates that through-resonance effects are significant in the addition of GSH to ortho- and para- N -arylacrylamides; through resonance is generally not considered for meta-substituents . It is also notable that ortho-substituted N -phenylacrylamides are well-modeled by a simple Hammett correlation, and consideration of steric and proximity polar effects unique to ortho-substituents as advanced by the Fujita–Nishioka equations appears to be unnecessary in this case. The reason for this may be that in the case of N -arylacrylamides, the reacting center is separated from the aromatic system by three atoms and is therefore less affected by steric and proximity polar effects.…”

Section: Results and Discussionmentioning

confidence: 99%

Systematic Study of the Glutathione (GSH) Reactivity ofN-Arylacrylamides: 1. Effects of Aryl Substitution

et al. 2015

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Success in the design of targeted covalent inhibitors depends in part on a knowledge of the factors influencing electrophile reactivity. In an effort to further develop an understanding of structure-reactivity relationships among N-arylacrylamides, we determined glutathione (GSH) reaction rates for a family of N-arylacrylamides independently substituted at ortho-, meta-, and para-positions with 11 different groups common to inhibitor design. We find that substituent effects on reaction rates show a linear Hammett correlation for ortho-, meta-, and para-substitution. In addition, we note a correlation between (1)H and (13)C NMR chemical shifts of the acrylamide with GSH reaction rates, suggesting that NMR chemical shifts may be a convenient surrogate measure of relative acrylamide reactivity. Density functional theory calculations reveal a correlation between computed activation parameters and experimentally determined reaction rates, validating the use of such methodology for the screening of synthetic candidates in a prospective fashion.

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Section: Results and Discussionmentioning

confidence: 99%

Systematic Study of the Glutathione (GSH) Reactivity ofN-Arylacrylamides: 1. Effects of Aryl Substitution

et al. 2015

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“…11) compared with p -acetoxybenzoic acid (4.38) has been attributed to the “ ortho effect” that arises from sterically induced non-coplanarity of the carboxylate group with the aromatic ring. 15,9k A close examination of low energy conformation 7 reveals, however, that coplanarity of the carboxylate and the aromatic ring would attenuate the n → π * interaction by increasing the distance between the donor and acceptor groups. Thus, the n → π * interaction could contribute to the anomalously low p K a of aspirin by enforcing non-coplanarity.…”

Section: Resultsmentioning

confidence: 99%

Ann→π* Interaction in Aspirin: Implications for Structure and Reactivity

2011

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Stereoelectronic effects modulate molecular structure, reactivity, and conformation. We find that the interaction between the ester and carboxyl moieties of aspirin has a previously unappreciated quantum mechanical character that arises from the delocalization of an electron pair (n) of a donor group into the antibonding orbital (π*) of an acceptor group. This interaction affects the physicochemical attributes of aspirin, and could have implications for its pharmacology.

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“…As the London dispersion force increases, the lipophilicity interaction increases and as a result, penetration of the compounds into the bacterial membrane is eased [19]. Furthermore, the position of the chlorine atom at the meta-para (2b) position generally correlates well but not for ortho-substituted ones (2c and 2d) due to the ortho steric effect and ortho polar effects which resulted to no antibacterial activity for compounds 2c and 2d that in contrast to 2b [20].…”

Section: Antibacterial Analysismentioning

confidence: 99%

Evaluation of Novel N-(Dibenzylcarbamothioyl)benzamide Derivatives as Antibacterial Agents by Using DFT and Drug-Likeness Assessment

Misral

Sapari

Rahman

et al. 2018

Journal of Chemistry

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Isomers of monothioureas, 2a–2d, derived from the reaction of disubstituted benzoyl isothiocyanate and dibenzylamine were synthesised and characterised by using elementary analysis CHNS and IR, 1H NMR, and 13C NMR spectroscopies. The compounds were screened for their in vitro antibacterial activity by using selected Gram-positive bacteria, and moderate inhibition activity was displayed for compound 2b with the value of inhibition zone 11 ± 0.8 mm at a concentration of 50 mg/ml. The outcomes of Lipinski’s rule of five assessment appeared to be in agreement with all compounds as they adhered to most of the rules, in which they can be preliminarily classified as active drug-like. The frontier molecular orbitals (HOMO and LUMO) for halogen-substituted 3,4-dichloro (2a) and 3,4-difluoro (2b) were also determined by applying the computational method of density functional theory (DFT) to determine their relationship as a molecular descriptor in antibacterial activities. The value of LUMO energy for compound 2b (1.8229 eV) is lower than that of compound 2a (1.8492 eV) which indicates higher antibacterial activities.

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The Analysis of the Ortho Effect

Cited by 146 publications

References 25 publications

Systematic Study of the Glutathione (GSH) Reactivity ofN-Arylacrylamides: 1. Effects of Aryl Substitution

Systematic Study of the Glutathione (GSH) Reactivity ofN-Arylacrylamides: 1. Effects of Aryl Substitution

Ann→π* Interaction in Aspirin: Implications for Structure and Reactivity

Evaluation of Novel N-(Dibenzylcarbamothioyl)benzamide Derivatives as Antibacterial Agents by Using DFT and Drug-Likeness Assessment

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