Strong amide–halothane hydrogen-bonding observed by nuclear magnetic resonance

Abstract

The widely-used halothane anaesthetic CF3CHBrCl exhibits a proton magnetic resonance signal in CCl4 solution which is strongly deshielded by addition of N-methylpyrrolidone. This is interpreted as a hydrogen-bonding interaction with halothane C—H as donor and carbonyl as acceptor. From the temperature dependence of the halothane C—H proton chemical shift in the presence of varying concentrations of N-methylpyrrolidone, thermodynamic parameters ΔH0 = −4.7 kcal mol−1 and ΔS0 = −14 cal mol−1deg−1 were obtained. The carbon magnetic resonance spectrum of the two components in CCl4 shows desheilding of the carbonyl carbon at higher concentrations of CF3CHBrCl the halocarbons (1-H) undecafluorobicycloheptane and (1-H,4-H)decafluorobicycloheptane show similar H-bonding behaviour which is comparable with that exhibited by CHCl3.These results are discussed in relation to their possible relevance to the mechanism of action of halocarbon anaesthetics.

Quantum chemical and statistical thermodynamic investigations of anesthetic activity. 3. The interaction between CH4, CH3Cl, CH2Cl2, CHCl3, CCl4, and an O—H … O hydrogen bond

“…All these conditions conform to empirical knowledge and the spectroscopic evidence related to anesthetics (5)(6)(7)(8)(17)(18)(19)(20).…”

Halogenated Benzenes Bound within a Non-polar Cavity in T4 Lysozyme Provide Examples of I⋯S and I⋯Se Halogen-bonding

“…The hydrogen atom of C 6 HF 5 , for example, shows much higher acidity (pK a = 24.2) than that of C 6 H 6 (pK a =43). 20 Thus, the iodine atom in C 6 F 5 I will tend to make a stronger halogen bond than is the case for C 6 H 5 I. This is consistent with the observed differences in binding behavior.…”

Infrared and Nuclear Magnetic Resonance Spectroscopic Study of Secondary Amide Hydrogen Bonding in Benzoyl PABA Derivatives (Retinoids)

“…There have been extensive spectroscopic studies on the subject of hydrogen bonding of small molecules containing the secondary amide group using infrared (IR) spectroscopy [1][2][3][4][5][6][7][8][9][10] and nuclear magnetic resonance (NMR). [11][12][13][14][15][16][17][18] Hydrogen bonding characteristics of drug molecules have important implications for physical properties such as solubility and bioavailability and for predicting interactions with other molecules that can affect biological activity. Using solution infrared data and varying concentration, intramolecular Hbonds involving the secondary amide N-H group can be differentiated from intermolecular H-bonds because the former are not dependent on concentration.…”

“…Also, intramolecular hydrogen-bonded N-H can have a stretching frequency that falls in a different range than that of intermolecular H-bonded N-H, depending on the acceptor atom in the H-bonds. 2 NMR spectra provide N-H resonances that are shifted downfield with H-bond formation [9][10][11][12][13] and coupling constants J X-H between the amide proton and the Hbond acceptor atom. [14][15][16] In the present study, the N-H bond of the secondary amide in a series of eight structurally related benzoyl derivatives of paminobenzoic acid esters (retinoids) was examined using infrared and NMR spectroscopies.…”