Conformational Flexibility of Mephenesin

Écija, Patricia; Evangelisti, Luca; Vallejo‐López, Montserrat; Basterretxea, Francisco J.; Lesarri, Alberto; Castaño, Fernando; Camináti, Walther; Cocinero, Emilio J.

doi:10.1021/jp5014785

Cited by 4 publications

(4 citation statements)

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“…For o-cresol (2), Welzel et al also reported on both the syn-and the anti-conformers [143]. Due to steric hindrance arising from the bulkier methoxy group, only the anti-conformer of o-methylanisole (9) [127] was observed; the syn-conformer was too high in energy, similar to the situation found for mephenesin (12) [152].…”

Section: Cresol and Methylanisole Derivativesmentioning

confidence: 65%

“…Although some chemical properties such as vapor pressure, color, smell, and acidity are similar, the effects of methyl internal rotation, which often depend on the steric and electronic surroundings, are completely different for these isomers, as shown in Figure 5. 1) The prototype toluene [137][138][139][140][141][142], (2) o-cresol [143], (3) m-cresol [144], (4) p-cresol [145], (5) p-thiocresol [146], (6) anti-carvacrol (two conformers, A and B) [147], (7) syn-thymol [147], (8) creosol [148], (9) o-methyl anisole [127], (10) m-methyl anisole [149,150], (11) p-methylanisole [151], ( 12) mephenesin (two conformers, A and B) [152], (13) 3-methylphenylacetylene [153].…”

Section: Cresol and Methylanisole Derivativesmentioning

confidence: 99%

“…Barriers to methyl internal rotation in toluene and cresol derivatives (in cm −1 ). (1) The prototype toluene[137][138][139][140][141][142], (2) o-cresol[143], (3) m-cresol[144], (4) p-cresol[145], (5) p-thiocresol[146], (6) anti-carvacrol (two conformers, A and B)[147], (7) syn-thymol[147], (8) creosol[148], (9) o-methyl anisole[127], (10) m-methyl anisole[149,150],(11) p-methylanisole[151], (12) mephenesin (two conformers, A and B)[152], (13) 3-methylphenylacetylene[153].…”

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confidence: 99%

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The LAM of the Rings: Large Amplitude Motions in Aromatic Molecules Studied by Microwave Spectroscopy

2022

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Large amplitude motions (LAMs) form a fundamental phenomenon that demands the development of specific theoretical and Hamiltonian models. In recent years, along with the strong progress in instrumental techniques on high-resolution microwave spectroscopy and computational capacity in quantum chemistry, studies on LAMs have become very diverse. Larger and more complex molecular systems have been taken under investigation, ranging from series of heteroaromatic molecules from five- and six-membered rings to polycyclic-aromatic-hydrocarbon derivatives. Such systems are ideally suited to create families of molecules in which the positions and the number of LAMs can be varied, while the heteroatoms often provide a sufficient dipole moment to the systems to warrant the observation of their rotational spectra. This review will summarize three types of LAMs: internal rotation, inversion tunneling, and ring puckering, which are frequently observed in aromatic five-membered rings such as furan, thiophene, pyrrole, thiazole, and oxazole derivatives, in aromatic six-membered rings such as benzene, pyridine, and pyrimidine derivatives, and larger combined rings such as naphthalene, indole, and indan derivatives. For each molecular class, we will present the representatives and summarize the recent insights on the molecular structure and internal dynamics and how they help to advance the field of quantum mechanics.

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Section: Cresol and Methylanisole Derivativesmentioning

confidence: 65%

Section: Cresol and Methylanisole Derivativesmentioning

confidence: 99%

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confidence: 99%

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The LAM of the Rings: Large Amplitude Motions in Aromatic Molecules Studied by Microwave Spectroscopy

2022

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“…Commonly used protocols such as Catalyst [24], MOE [25] and MacroModel [26] implement both approaches [15, 27]. Significance of the conformational sampling and challenges in finding the bioactive pose among an ensemble of generated conformers were previously discussed in several studies [14, 28–32]. …”

Section: Introductionmentioning

confidence: 99%

Searching for bioactive conformations of drug-like ligands with current force fields: how good are we?

Gürsoy

Smieško

2017

J Cheminform

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Drug-like ligands obtained from protein–ligand complexes deposited in the Protein Databank were subjected to conformational searching using various force fields and solvation settings. For each ligand, the resulting conformer pool was examined for the presence of the bioactive (crystal pose-like) conformation. Similarity of conformers toward the crystal-pose was quantified as the best achievable root mean squared deviation (RMSD, heavy atoms only). Analyzing the conformer pools generated by various force fields revealed only small differences in the likelihood of finding a crystal pose-like conformation. However, employing different solvents in the conformational search was found to be very important for achieving RMSDs below 1.0 Å. The best statistical values of likelihood were observed with a recently released force field covering a large portion of dihedral angles occurring in drug-like compounds in combination with the water as solvent. In order to enable computational chemists and modelers to efficiently use available software tools, we have additionally performed several focused analyses on ligands, grouped according to descriptors most relevant for the rational drug design.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-017-0216-0) contains supplementary material, which is available to authorized users.

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Quantum Tunneling: History and Mystery of Large Amplitude Motions over a Century

Nguyen

2024

J. Phys. Chem. Lett.

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Large amplitude motions (LAMs), most notably represented by proton tunneling, mark a significant departure from small amplitude vibrations where protons merely oscillate around their equilibrium positions. These substantial displacements require tunneling through potential energy barriers, leading to splittings in, e.g., rotational spectra. Since Hund's pioneering work in 1927, proton tunneling has offered a unique glimpse into the internal dynamics of gas-phase molecules, with microwave spectroscopy being the key technique for such investigations. The ubiquous LAM type is methyl internal rotation, characterized by 3-fold potentials arising from the interaction between methyl rotors and their molecular frame, with the barrier hindering methyl torsion and the orientation of the torsional axis being defining features. Investigating methyl internal rotations plays a key role in fields ranging from molecular physics, where the methyl rotor serves as a sensitive probe for molecular structures, to atmospheric chemistry and astrophysics, where methyl-containing species have been detected in the Earth's atmosphere and interstellar environments and even discussed as potential probes for effects beyond the standard model of physics. Despite nearly a century of study, modeling methyl internal rotations with appropriate model Hamiltonians and fully understanding the origins of these motions, particularly the factors that influence torsional barriers, remain partially unresolved, reflecting the enduring mystery of quantum tunneling. This Perspective reviews the history of LAMs, highlights advances in decoding their complex spectra, and explores future research directions aimed at uncovering the remaining mysteries of these fascinating motions.

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Conformational Flexibility of Mephenesin

Cited by 4 publications

References 57 publications

The LAM of the Rings: Large Amplitude Motions in Aromatic Molecules Studied by Microwave Spectroscopy

The LAM of the Rings: Large Amplitude Motions in Aromatic Molecules Studied by Microwave Spectroscopy

Searching for bioactive conformations of drug-like ligands with current force fields: how good are we?

Quantum Tunneling: History and Mystery of Large Amplitude Motions over a Century

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