Probing the CH⋅⋅⋅π Weak Hydrogen Bond in Anesthetic Binding: The Sevoflurane–Benzene Cluster

Cooperativity between weak hydrogen bonds can be revealed in molecular clusters isolated in the gas phase. Here we examine the structure, internal dynamics, and origin of the weak intermolecular forces between sevoflurane and a benzene molecule, using multi‐isotopic broadband rotational spectra. This heterodimer is held together by a primary C? H???π hydrogen bond, assisted by multiple weak C? H???F interactions. The multiple nonbonding forces hinder the internal rotation of benzene around the isopropyl C? H bond in sevoflurane, producing detectable quantum tunneling effects in the rotational spectrum.     

Interactions between local anesthetics and lipid dispersions studied with liposome electrokinetic capillary chromatography

In the case of local anesthetic intoxication, intravenous administration of lipid-based Intralipid dispersion (Fresenius Kabi) can be used for the entrapment of hydrophobic drugs. Our long-term aim is to develop a sensitive, efficient, and non-harmful lipid-based formulation to specifically trap harmful substances. In this study liposome electrokinetic capillary chromatography (LEKC) was used to study the interactions between local anesthetics and Intralipid or liposome dispersions. Intralipid dispersion and extruded liposomes with different concentrations of 1-palmitoyl-2-oleyl-sn-glycerophosphatidylcholine (POPC), phosphatidylglycerol, cardiolipin, cholesterol, oleic acid, and linoleic acid were used as a pseudostationary phase in LEKC and their interactions with lidocaine, prilocaine, and bupivacaine were studied. POPC liposomes containing 1 mol% of palmitoyl-2-[12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl]-sn-glycero-3-phosphocholine as a fluorescent marker were used for the first time in LEKC connected with laser-induced fluorescent detection in order to calculate the retention factor for anesthetics.     

Vibrational Analysis and Geometry Optimization of a Local Anesthetic by Means of the Am1 Semiempirical Method

The semiempirical method AM1 was used to optimize the geometric parameters: bond lengths, bond angles and torsional angles in the local anesthetic benzocaine hydrochloride. The frequencies and intensities of the normal modes were computed. These results were compared with the infrared and Raman spectroscopic data. A theoretical spectrum using several scale coefficients was plotted. Electron density maps in two and three dimensions were drawn. Several calculated thermodynamic parameters are discussed.     

Determination of Inhalational Anesthetics in Field and Laboratory by SPME GC/MS

Exposure to inhalational anesthetics in health care workers could lead to several diseases and disorders. This study examined the applicability of solid phase microextraction for sampling and quantification of three inhalational anesthetics including; halothane, isoflurane, and sevoflurane in operating room air. Carboxen-Polydimethylsiloxane in retracted mode was selected and the effects of environmental parameters including temperature, humidity, and air velocity, were studied. There were no significant differences between sampling rates determined at different temperatures and air velocities. On the opposite, relative humidity has a significant effect on sampling rates. Comparison of the results between the developed SPME method and OSHA 103 method on standard test atmosphere and field showed satisfactory agreement.     

麻醉药物发展史略

麻醉药的产生和发展对减轻人类疼痛做出了不可磨灭的贡献。中国是最早使用麻醉药物的国家,从战国时期就有了"毒酒"、东汉末年华佗制成了"麻沸散",宋朝有了"睡圣散",明朝产生了"蒙汗药"。在西方国家,近代最早的麻醉药物是"笑气",以后又发展出了乙醚等麻醉药物。随着现代化学的飞速发展,氙气、丙泊酚和苏干麻德克斯(sugammadex)等麻醉药物已广泛应用,为人类消除疼痛做出了巨大的贡献。     

Low-Flammable Parahydrogen-Polarized MRI Contrast Agents

Many MRI contrast agents formed with the parahydrogen-induced polarization (PHIP) technique exhibit biocompatible profiles. In the context of respiratory imaging with inhalable molecular contrast agents, the development of nonflammable contrast agents would nonetheless be highly beneficial for the biomedical translation of this sensitive, high-throughput and affordable hyperpolarization technique. To this end, we assess the hydrogenation kinetics, the polarization levels and the lifetimes of PHIP hyperpolarized products (acids, ethers and esters) at various degrees of fluorine substitution. The results highlight important trends as a function of molecular structure that are instrumental for the design of new, safe contrast agents for in vivo imaging applications of the PHIP technique, with an emphasis on the highly volatile group of ethers used as inhalable anesthetics.     

1H and 13C NMR Studies of Etidocaine Free Base and Hydrochloride Salt. Solvent and Temperature Dependence

The ¹H and ¹³C NMR spectra of etidocaine free base, 1, and its hydrochloride salt, 2, have been examined at 200 MHz in a variety of solvents. Variable temperature ¹H NMR spectra of 2 were measured between 0° and 90°C at 500 MHz. Both ¹H and ¹³C spectra of the salt were strongly dependent on temperature, solvent and spectrometer frequency. Results are interpreted primarily as a consequence of acid-induced chirality at the amine nitrogen, resulting in solvent-dependent diastereoisomerism. Spectral complexity is explained as the result not only of diastereotopic nuclei due to the fixed “natural” chiral center at carbon, but also, in 2, to the presence of diastereomeric racemates resulting from the second chiral center (at nitrogen).     

Synthesis, spectroscopic, and X-ray structural characterization of pharmacologically active substituted pyrazolyl-acetanilides

Five new pyrazole acetanilides were synthesized by N-alkylation of pyrazole and its derivatives with 4′-propionyl-2-iodoacetanilide. Compounds 1–5 were characterized by ¹H NMR, ¹³C NMR, IR, UV–Vis, MS, and elemental analysis. X-ray structures of representative compounds 1, 3, and 5 established their conformations and solid-state hydrogen bonding preferences. Acute toxicity, local anesthetic, and antiarrhythmic activities were assessed for compounds 1–5 using established protocols. Lower potencies and lower acute toxicities were recorded relative to lidocaine. Enhanced anesthetic activity of compound 3 was attributed to the presence of the propionyl group in the molecule. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Comparison of sonic spray lonization with atmospheric pressure chemical lonization as an interface of liquid chromatography-mass spectrometry for the analysis of some local anesthetics

Summary Sonic spray ionization (SSI) was compared with atmospheric pressure chemical ionization (APCI) as an interface for liquid chromatography (LC)-mass spectrometry (MS) for the analysis of some local anesthetics. Peaks at [M+H]⁺ constituted the base peaks for all compounds by both SSI and APCI, except for prilocaine. The sensitivities by SSI for tetracaine, benzoxinate, dibucaine, bupivacaine and mepivacaine were 4–16 times higher than those by APCI; those by SSI for procaine and lidocaine were equivalent to those by APCI. Only for prilocaine was the sensitivity by SSI two times lower than that by APCI. In view of the higher sensitivities obtained for many local anesthetics by SSI, we established a detailed procedure for the assay of these drugs in human plasma and urine by LC-MS with SSI in combination with a diol-bonded silica gel HPLC column that enabled direct injection of crude biological samples without complicated pretreatment. The recoveries, sensitivities, accuracies and precisions were found satisfactory to quantitate them at their therapeutic levels.