Gas phase conformation in the ibuprofen analogues isobutylbenzene and 2-phenylpropionic acid

Robertson, Evan G.; Morrison, Richard J. S.

doi:10.1080/00268970500085932

Cited by 7 publications

(2 citation statements)

References 25 publications

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“…The same trend of conformational preferences influenced by the stabilising NHÁ Á Áp interactions has been observed with molecules with alternative aromatic rings such as imidazole ring of histamine, 20 and the indole ring of tryptamine 21 and serotonin. 22 The aforementioned link between three dimensional molecular structure and biological function has led us to study species such as enzyme inhibitor 1-phenylimidazole 23 and analogues of ibuprofen 24 and nicotine 25 using R2PI spectroscopy. In the present study, the conformational assignments of APEA are re-examined using an IR-UV ion depletion technique able to measure IR spectra of individual conformers.…”

Section: Introductionmentioning

confidence: 99%

A sting in the tail of flexible molecules: spectroscopic and energetic challenges in the case of p-aminophenethylamine

Lobo

Wilson

Bieske

et al. 2012

Phys. Chem. Chem. Phys.

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The neurotransmitter analogue p-aminophenethylamine (APEA) illustrates many of the pitfalls and challenges associated with spectroscopic and conformational analysis of flexible molecules. The combined experimental-theoretical study presented here resolves a long-standing controversy over its conformational energetic preferences. Jet-cooled resonance enhanced two-photon ionisation (R2PI) and IR-UV ion depletion techniques enabled conformer-specific IR spectra in the NH-CH stretch region to be measured for four distinct conformers of APEA. Comparison of spectra with theoretical calculations (including MP2, M06-2X and B3LYP with aug-cc-pVTZ basis sets) allows the two most populated conformers to be unambiguously identified as those having a gauche arrangement of the side chain, which facilitates an NH···π type hydrogen bond. The other two observed conformers are assigned to structures with an anti-side chain. A fifth gauche conformer, predicted to be least stable, is not observed. Comparison with published conformer specific IR spectra of tyramine (Makara et al., J. Phys. Chem. A, 2008, 112, 13463-13469) and Raman spectra of phenylethylamine (Golan et al., J. Chem. Phys., 2009, 131, 024305) reveals an entirely consistent pattern of spectral signatures associated with the four specific conformations of the ethylamine side chain evident in APEA, and aids assignment of the associated CH and NH stretch fundamentals, some of which have very weak IR intensities. Extensive calculations of the relative energetic trends of the five conformers have been carried out. In comparison to the highest level of theory considered, CCSD(T)-F12b/cc-pVDZ-F12, MP2 overestimate the energy difference, whereas DFT significantly underestimates the energetic preference for NH···π stabilised gauche conformers, although inclusion of dispersion (M06-2X, B3LYP-D3) improves the DFT results.

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Section: Introductionmentioning

confidence: 99%

A sting in the tail of flexible molecules: spectroscopic and energetic challenges in the case of p-aminophenethylamine

Lobo

Wilson

Bieske

et al. 2012

Phys. Chem. Chem. Phys.

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“…Our group has recently been exploring the gas-phase conformers of small, bioactive molecules belonging to the Ph(CH 2 ) 2 X family. − Such molecules model a range of simple biological molecules by substitution of the functional group. Gas-phase experiments are a valuable alternative to as yet unfeasible in vivo experiments for determining the conformational preferences of bioactive molecules.…”

Section: Introductionmentioning

confidence: 99%

A Spectroscopic Study of Nicotine Analogue 2-Phenylpyrrolidine (PPD) Using Resonant Two-Photon Ionization (R2PI), Microwave, and 2D NMR Techniques

et al. 2009

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Conformational preferences of the nicotine analogue 2-phenylpyrrolidine (PPD) have been studied in both gaseous and solution phases. Theoretical calculations at the MP2 and B3LYP levels point to 5-6 stable conformers which differ in three degrees of conformational freedom; torsion between the two rings, inversion at the pyrrolidine (PY) amine, and PY ring puckering, characterized using the Cremer-Pople definition for pseudorotation. Only one conformer has a trans arrangement between the amino hydrogen and the phenyl substituent. It is 6-8 kJ mol(-1) more stable than the cis conformers, has a perpendicular ring arrangement, and puckers at the nitrogen atom--similar to structures reported for nicotine. Resonant two-photon ionization (R2PI) data, including hole burn spectra, indicate only one conformer is present in the free jet expansion, and band contour analysis suggests assignment to the trans conformer. Confirmation was provided by microwave spectroscopy. Fifty-seven lines measured in the 48-72 GHz region were assigned to 206 b-type transitions and fitted to yield rotational constants within 2 MHz of MP2 values predicted for the trans conformer. The solution-phase conformers of PPD were studied using 1D and 2D (1)H NMR spectroscopy and solvent-based theoretical calculations. In marked contrast to the gas phase, NMR data reveals only cis conformers present in solution. Calculations confirm increased stability for these conformers when placed in simulated chloroform or water environments. Solvent molecules are believed to disrupt a crucial N...H(ortho) stabilizing interaction present within the trans conformer.

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Orbital based electronic structural signatures of the guanine keto G-7H/G-9H tautomer pair as studied using dual space analysis

Jones

Wang

Winkler

et al. 2006

Biophysical Chemistry

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Gas phase conformation in the ibuprofen analogues isobutylbenzene and 2-phenylpropionic acid

Cited by 7 publications

References 25 publications

A sting in the tail of flexible molecules: spectroscopic and energetic challenges in the case of p-aminophenethylamine

A sting in the tail of flexible molecules: spectroscopic and energetic challenges in the case of p-aminophenethylamine

A Spectroscopic Study of Nicotine Analogue 2-Phenylpyrrolidine (PPD) Using Resonant Two-Photon Ionization (R2PI), Microwave, and 2D NMR Techniques

Orbital based electronic structural signatures of the guanine keto G-7H/G-9H tautomer pair as studied using dual space analysis

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