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Enflurane is a fluorinated volatile anesthetic, whose bioactive conformation is not known. Actually, a few studies have reported on the conformations of enflurane in nonpolar solution and gas phase. The present computational and spectroscopic (infrared and NMR) work shows that three pairs of isoenergetic conformers take place in the gas phase, neat liquid, polar, and nonpolar solutions. According to docking studies, a single conformation is largely preferred over its isoenergetic isomers to complex with the active site of Integrin LFA-1 enzyme (PDB code: 3F78 ), where the widely used anesthetic isoflurane (a constitutional isomer of enflurane) is known to bind. Weak hydrogen bonding from an electrostatic interaction between the CHF2 hydrogen and the central CF2 fluorines was not found to rule the conformational isomerism of enflurane. Moreover, intramolecular interactions based on steric, electrostatic, and hyperconjugative effects usually invoked to describe the anomeric effect are not responsible for the possible bioactive conformation of enflurane, which is rather governed by the enzyme induced fit.

Understanding the molecular recognition process of nucleobases is one of the greatest challenges for both computational chemistry and biophysics fields. In fact, our results point out that it is a hard task to take into account the hydrophobic interactions, such as π-π and T-stacking interactions, by theoretical calculations using conventional force fields due to quantum effects of hyperconjugation and electronic correlation. In this line, our findings put in evidence that simple modifications in the Lennard-Jones potential can improve theoretical predictions in scenarios where hydrophobic interactions can drive the molecular recognition.

The strong gauche preference along with the F-C-C-N(+) fragment in 3-fluoropiperidinium cation and analogues, in the gas phase, is dictated by electrostatic interactions, which can be both hydrogen bond F···H(N(+)) and F/N(+) attraction. In aqueous solution, where most biochemical processes take place, electrostatic effects are strongly attenuated and hyperconjugation is calculated to be at least competitive with Lewis-type interactions.

Some aminofluorobenzoic acids were studied to evaluate the power of the F···HO hydrogen bond and other interactions as driving forces of the conformational isomerism of these compounds. Despite the occurrence of this hydrogen bond in the 2-fluorinated derivatives, as well as attractive O/F nonbonding interactions and NH···O═C hydrogen bond, the O/O repulsion dictates the orientation of the carboxyl group. Unlike 2-fluorophenol, which is reported to not experience a F···HO hydrogen bond, 2-fluorobenzoic acid derivatives were calculated to exhibit such interaction, but it could not be monitored experimentally by means of F/H(O) coupling constant, because of the low solubility of these compounds in nonpolar solvents, the acidity of the carboxyl hydrogen, the small population of some conformers capable of exhibiting hydrogen bond, and the solute self-association in solution, which make their conformational equilibrium different from that in gas phase.

Suitable (3)J(H,H) coupling constants and theoretical calculations were used to define the conformational preferences of trans-2-bromoalkoxycyclohexanes (alkoxy = OMe, OEt, O(i)Pr, and O(t)Bu) for the isolated molecule and as a function of the medium. The diaxial conformer was preponderant, or at least similarly populated to the diequatorial form, for the tert-butoxy derivative only, while the diequatorial conformer was prevalent for the remaining alkoxy derivatives (except for the OMe derivative in CCl(4) solution). The conformational behavior of these compounds was analyzed on the basis of classical steric effects and attractive electron delocalizations, by means of natural bond orbital analysis.

The conformational equilibria for 1,3-difluoro- (DFA), 1,3-dichloro- (DCA), and 1,3-dibromo-acetone (DBA) have been determined through IR spectroscopy, ab initio calculations at the B3LYP/6-311++G(2df,2p) level, and solvation calculations. The CO stretching frequencies of DFA, DCA, and DBA in the vapor phase were calculated theoretically and compared to the experimental CO frequencies in solvents with varying polarities. The theoretical calculations also gave the energy minima and thus the conformational equilibria of these molecules in the vapor phase in terms of the rotamers 1 (cis/cis), 2 (cis/gauche), 3 (cis/trans), 4 (gauche/gauche), 5 (gauche/gauche‘), and 6 (trans/trans). For DFA, the stable conformers in the vapor phase are 1, 3, and 5, conformer 3 being the most stable. The conformer ratio in solution changes from circa 12% for 1, 85% for 3, and 3% for 5 in CCl4 to 34% for 1 and 66% for 3 in CH3CN. For DCA, the most stable forms are the same as those for DFA, but in this case conformer 5 is the m...

The boiling points of a set of 58 aliphatic alcohols have been modeled through an image-based approach, in which descriptors are pixels (binaries) of 2D chemical structures. While some simple descriptors, such as molecular weight, do not account for some structural influences (e.g., in chain and position isomerism) on the studied property, the MIA-QSPR (multivariate image analysis applied to quantitative structure-property relationship) method, coupled to multilinear partial least-squares regression, correlated the chemical structures with the corresponding boiling points satisfactorily well.