High Concentrations Of Halothane Research Articles

Differential Inhibition of Neuronal Na+–Ca2+Exchange versus Store-operated Ca2+Channels by Volatile Anesthetics in Pheochromocytoma (PC12) Cells

Ca2+ influx is a key component of neuronal intracellular Ca2+ ([Ca2+]i) regulation. The authors hypothesized that volatile anesthetic inhibition of neuronal activity is mediated by inhibition of Ca2+ influx via two major mechanisms: plasma membrane Na+-Ca2+ exchange (NCX) and the novel mechanism of Ca2+ influx triggered by endoplasmic reticulum Ca2+ depletion (store-operated Ca2+ channels [SOCCs]). Differentiated rat pheochromocytoma cells loaded with the Ca2+ indicator fura-2 were Na+-loaded with 0 Ca2+, 145 mm Na+ Tyrode's and 5 microm cyclopiazonic acid plus 10 microm ryanodine (functionally isolating plasma membrane). Influx-mode NCX was rapidly reactivated by 0 Na+ and 2.5 mm Ca2+. The protocol was repeated in the presence of volatile anesthetics (0.5-1.5 minimum alveolar concentration [MAC] halothane, isoflurane, or sevoflurane) or other drugs to characterize NCX. To examine SOCCs, endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in 0 extracellular Ca2+, and Ca2+ influx was triggered by rapid reintroduction of extracellular Ca2+. The protocol was repeated in the presence of anesthetics or other drugs to characterize SOCCs. Influx via NCX was not inhibited by voltage-gated Ca2+ channel blockers but was sensitive to NCX inhibitors. Halothane and isoflurane (0.5-1.5 MAC) significantly inhibited NCX (P < 0.05; paired comparisons), whereas sevoflurane at less than 1.5 MAC did not inhibit NCX. SOCC-mediated Ca2+ influx was insensitive to a variety of Ca2+ channel blockers but was inhibited by Ni2+. Such influx was sensitive only to halothane at greater than 1 MAC but not isoflurane or sevoflurane. These data indicate that volatile anesthetics, especially halothane and isoflurane, interfere with neuronal [Ca2+]i regulation by inhibiting NCX but not SOCC-mediated Ca2+ influx (except high concentrations of halothane).

General anesthetics attenuate gap junction coupling in P19 cell line

Gap junction communication is widespread throughout the mammalian nervous system among neurons as well as glia. We addressed the hypothesis that general anesthetics attenuate gap junction mediated coupling in P19 cell line that can differentiate into neuronal-like cells and astrocytes and oligodendrocytes. We characterized the extent of dye coupling over time in the P19 cell line using colocalization of chlormethylbenzamido-1,1 dioctadecyl-3,3,3',3'-tetramethylindocarbocyamine (CM-DiI) and calcein-AM in donor and recipient cells in cocultures. After seeding, the gap junction permeant dye calcein spreads from donor to recipient cells. CM-DiI and calcein fluorescence identified donor and recipient cells, respectively. The extent of intercellular connections was evaluated using cell counting and flow cytometry up to 2 hr after treatment. Clinically relevant concentrations of the intravenous anesthetics propofol (15 microM) and thiopental (10 microM) attenuated gap junction permeability in P19 cell cultures. In contrast, halothane, a volatile anesthetic in a concentration (0.64 mM) relevant to its free aqueous EC50 had no effect on gap junction coupling; however, very high halothane concentrations (2.8 mM) blocked dye transfer by approximately 90%. The results indicate that halothane concentrations pertinent to clinical anesthesia were unable to attenuate gap junction communication in a cell line that can express neuronal and glial gap junction proteins; however, clinically relevant concentrations of propofol and thiopental depressed gap junction coupling.

This Month in Anesthesiology

This Month in Anesthesiology

The Sensitivity of G Protein-activated K+ Channels toward Halothane Is Essentially Determined by the C Terminus

G protein-activated K(+) channels (GIRKs or Kir3.x) are targets for the volatile anesthetic, halothane. When coexpressed with the m(2) acetylcholine (ACh) receptor in Xenopus oocytes, agonist-activated GIRK1(F137S)- and GIRK2-mediated currents are inhibited by halothane, whereas in the absence of ACh, high concentrations of halothane induce GIRK1(F137S)-mediated currents. To elucidate the molecular mechanism of halothane action on GIRK currents of different subunit compositions, we constructed deletion mutants of GIRK1(F137S) (GIRK1(Delta363*)) and GIRK2 (GIRK2(Delta356)) lacking the C-terminal ends, as well as chimeric GIRK channels. Mutated GIRK channels showed normal currents when activated by ACh but exhibited different pharmacological properties toward halothane. GIRK2(Delta356) showed no sensitivity against the inhibitory action of halothane but was activated by halothane in the absence of an agonist. GIRK1(Delta363*) was activated by halothane more efficiently. Currents mediated by chimeric channels were inhibited by anesthetic concentrations that were at least 30-fold lower than those necessary to decrease GIRK2 wild type currents. Glutathione S-transferase pulldown experiments did not show displacement of bound Gbetagamma by halothane, indicating that halothane does not interfere with Gbetagamma binding. Single channel experiments revealed an influence of halothane on the gating of the channels: The agonist-induced currents of GIRK1 and GIRK2, carried mainly by brief openings, were inhibited, whereas higher concentrations of the anesthetic promoted long openings of GIRK1 channels. Because the C terminus is crucial for these effects, an interaction of halothane with the channel seems to be involved in the mechanism of current modulation.

Effects of halothane and isoflurane on acetylcholine-induced, endothelium-dependent vasodilation in perfused rat mesenteric arterial beds.

The present study was designed to examine the effects of halothane and isoflurane on acetylcholine-induced, endothelium-dependent vasodilation in rat mesenteric arterial beds perfused at a constant flow both in vitro and in situ. In the in-vitro preparation, the mesenteric artery was cannulated and perfused (5 ml x min(-1)). The perfusion pressure was continuously monitored. Under active tone induced by methoxamine, the effects of halothane and isoflurane on the vasodilator response to acetylcholine in either the presence or absence of NG-nitro-L-arginine (L-NA), tetraethylammonium (TEA), or KCl (30 mM)-depolarization were examined. All experiments in these preparations were performed in the presence of indomethacin (10 mM). In the in-situ experimental model, rats were anesthetized with pentobarbital and the lungs were mechanically ventilated via a tracheostomy with a ventilator. The superior mesenteric artery was cannulated and used for the monitoring of the perfusion pressure. Blood shunting with constant flow (2 ml x min(-1)) from the carotid artery to the superior mesenteric artery was introduced with clamping at the immediately distal portion of the mesenteric artery branching. Following 20-min ventilation with halothane or isoflurane at 1 minimum alveolar concentration (MAC) in oxygen, acetylcholine was given from the mesenteric artery, under active tone induced by norepinephrine (100 mg x kg(-1) x hr(-1)). In the in-vitro preparation, the nitric oxide synthase inhibitor, L-NA (100 microM) did not affect vasodilations to acetylcholine (1, 10 nM), while the K+ channel inhibitor TEA (10 mM), as well as KCl (30 mM), significantly reduced these vasodilations. However, only in the presence of L-NA, TEA and KCl completely abolished the vasodilations produced by acetylcholine. The higher concentrations of halothane (2.0%, 3.0%), but neither isoflurane (3.0%) nor the lower concentration of halothane (1.0%), significantly impaired vasodilator responses to acetylcholine in the presence of L-NA, whereas the volatile anesthetics did not affect these vasodilations in the absence of L-NA. Halothane (2.0%) did not alter the vasodilation produced by acetylcholine in the presence of TEA or KCl. In the in-vivo preparation, the vasodilator effects of acetylcholine (1 and 10 nmol) were not affected by the inhalation of halothane (1.0%) or isoflurane (1.3%). These results suggest that, in resistance arteries in conditions of constant flow, halothane and isoflurane do not affect vasodilations in response to an endothelium-dependent agonist. However, in these preparations, once the enzymatic activity of nitric oxide synthase is inhibited, higher concentrations of halothane, but neither isoflurane nor the lower concentration of halothane, appear to impair endothelium-dependent relaxations, probably mediated by TEA-sensitive K+ channels.

An assessment of the cerebroprotective potential of volatile anaesthetics using two independent methods in an in vitro model of cerebral ischaemia

Previous studies using a rat brain slice model of cerebral ‘ischaemia’ (hypoxia and hypoglycaemia) have suggested that volatile anaesthetics may have cerebroprotective potential. In this study, we tested the cerebroprotective profile of four volatile anaesthetics in this model by two independent means: voltammetric measurement of ‘ischaemia’-induced dopamine (DA) release and post-‘ischaemic’ tissue staining with 2,3,5-triphenyltetrazolium chloride (TTC). ‘Ischaemia’ caused a characteristic pattern of DA release. Halothane, isoflurane and enflurane did not affect the time from onset of ‘ischaemia’ to the initiation of DA release. However, all three volatile agents significantly increased ( P<0.01, P<0.05, P<0.001, respectively) the time taken for ‘ischaemia’-induced DA release to reach maximum and reduced the rate of DA release. Enflurane, unlike halothane or isoflurane, reduced the maximal extracellular DA concentration induced by ‘ischaemia’ ( P<0.01). The effects of sevoflurane were inconsistent. At the higher concentrations used, the volatile anaesthetics frequently changed the character of DA release from monophasic to biphasic, an effect only previously seen in this model with Na + channel blockers. ‘Ischaemia’ also diminished the subsequent level of tissue staining with TTC. When the effects of the volatile agents were analysed by TTC staining, only enflurane showed any cerebroprotective effects and these were limited to the striatum ( P<0.01). High concentrations of halothane, isoflurane and enflurane appeared to have some ‘toxic’ effects, reducing TTC staining in control slices. In summary, we do not find any consistent evidence that volatile anaesthetics are cerebroprotective in this model.

G protein-gated inwardly rectifying potassium channels are targets for volatile anesthetics.

G protein-gated inwardly rectifying potassium channels (GIRKs) are a family of homo- and hetero-oligomeric K(+) channels composed of different subunits (GIRK1 to 4 in mammals). GIRK4 and GIRK1 are found mainly in the atrium, whereas neuronal cells predominantly express the GIRK1, GIRK2, and GIRK3 isoforms. When activated, GIRK channels slow the firing rate of atrial myocytes and neuronal cells. Because of their key role in controlling excitability, we investigated the influence of a prototypic anesthetic, halothane, on GIRK channels of different subunit composition expressed in Xenopus laevis oocytes. Halothane enhanced background currents through hetero-oligomeric GIRK1/GIRK4 and homo-oligomeric GIRK1(F137S) channels but not through homo-oligomeric GIRK2 channels. This activation of basal current did not depend on the presence of coexpressed G protein-coupled receptors but instead required the presence of G(beta/gamma). In contrast to basal GIRK currents, the agonist-induced GIRK current (via coexpressed m2 muscarinic receptors) was inhibited by halothane. For GIRK1/GIRK4 and GIRK1(F137S) channels this inhibition was most pronounced at low concentrations of the anesthetic (0.1-0.3 mM) and occurred also when channels had been activated by guanosine-5'-O-(3-thio)triphosphate. This inhibition, however, was overridden by high concentrations of halothane (0.9 mM) and augmentation of the agonist-induced current was observed. This increase in agonist-induced current was never seen with GIRK2 homo-oligomeric channels. Agonist-induced currents mediated by GIRK2 channels were always inhibited by halothane with an IC(50) value of approximately 60 microM. These data suggest a direct interaction of halothane with GIRK channels.

Volatile Anesthetics Give a False-Positive Reading in Chemical Agent Monitors in the “H” Mode

Chemical agent monitors (CAMs) are routinely used by the armed forces and emergency response teams of many countries for the detection of the vesicant sulfur mustard (HD) and the G series of organophosphate nerve agents. Ambient operating room isoflurane levels were found to produce strong positive signals in the "H" mode when the CAM was used to monitor the efficacy of decontamination procedures during routine surgical procedures on HD-poisoned animals requiring up to 8 hours of general anesthesia. Subsequent testing showed that isoflurane, as well as desflurane, sevoflurane, halothane and methoxyflurane, produce two ionization peaks in the CAM response. One of these peaks is interpreted by the CAM processing software as HD, resulting in a CAM "H" mode bar response. No interference was encountered with isoflurane, desflurane, and sevoflurane when the CAM was set to the "G" mode, although extremely high (nonclinical) concentrations of halothane and methoxyflurane yielded a weakly positive bar response. These findings have potentially serious ramifications for the medical management of patients resulting from terrorist, military, or chemical agent decommissioning activity when concomitant chemical injuries are also possible.

Binding of the General Anesthetics Propofol and Halothane to Human Serum Albumin: HIGH RESOLUTION CRYSTAL STRUCTURES

Human serum albumin (HSA) is one of the most abundant proteins in the circulatory system and plays a key role in the transport of fatty acids, metabolites, and drugs. For many drugs, binding to serum albumin is a critical determinant of their distribution and pharmacokinetics; however, there have as yet been no high resolution crystal structures published of drug-albumin complexes. Here we describe high resolution crystal structures of HSA with two of the most widely used general anesthetics, propofol and halothane. In addition, we describe a crystal structure of HSA complexed with both halothane and the fatty acid, myristate. We show that the intravenous anesthetic propofol binds at two discrete sites on HSA in preformed pockets that have been shown to accommodate fatty acids. Similarly we show that the inhalational agent halothane binds (at concentrations in the pharmacologically relevant range) at three sites that are also fatty acid binding loci. At much higher halothane concentrations, we have identified additional sites that are occupied. All of the higher affinity anesthetic binding sites are amphiphilic in nature, with both polar and apolar parts, and anesthetic binding causes only minor changes in local structure.

A comparison of the respiratory effects of high concentrations of halothane and sevoflurane in children

A comparison of the respiratory effects of high concentrations of halothane and sevoflurane in children

A comparison of the respiratory effects of high concentrations of halothane and sevoflurane in children

A comparison of the respiratory effects of high concentrations of halothane and sevoflurane in children

Rapid induction of anesthesia with high concentrations of halothane or sevoflurane in children

Study Objective: To compare the characteristics of the rapid induction of anesthesia in pediatric patients with high concentrations of sevoflurane or halothane, and to determine the ability of anesthesiologists to correctly identify the anesthetic drug when administered in this fashion. Design: Randomized, prospective, open-label study. Setting: Academic university hospital Patients: 78 ASA physical status I and II healthy children scheduled for brief surgical procedures with general anesthesia and medicated with midazolam. Interventions: Assessments were made by 5 pediatric anesthesiologists and 18 anesthesiology residents. Sevoflurane or halothane was randomly selected for anesthetic induction. The anesthetic circuit was primed with the drug (8% sevoflurane or 4% halothane) in 50% nitrous oxide and oxygen. The anesthesiologists were blinded as to the anesthetics being administered. After completion of anesthetic induction, the anesthesiologists were asked to identify the anesthetic and to assess the quality and speed of induction. Measurement and Main Results: The pediatric anesthesiologists correctly identified the anesthetic in 55 of 78 assessments (70.5%). This figure is statistically better than what could be achieved by random guessing ( p < 0.001). The residents correctly identified the anesthetic in only 46 of 78 assessments (60.0%). Statistically, this figure is no better than what could be achieved by random guessing ( p = 0.06). Speed of induction was subjectively felt to be faster with sevoflurane than halothane but there were no differences in actual induction time (sevoflurane group, 3.7 ± 2.7 min; halothane group, 3.7 ± 2.6 min). There were no differences in the quality of induction or the incidence of airway complications. The perceived incidence of tachycardia was significantly higher with sevoflurane than halothane(sevoflurane group, 74%; halothane group 20%). Conclusion: The induction of anesthesia with high concentrations of either halothane or sevoflurane can be safely accomplished. Pediatric anesthesiologists can differentiate between halothane and sevoflurane when either drug is given in high initial concentrations. The presence of tachycardia may have served as the primary clue in determining which drug was being used.

Influence of halothane on phospholipase A2 and enzymatic methylations in the rat retinal membranes.

Phospholipase A2 (PLA2) and phospholipid methylases (PLM) play significant roles in transmitter release and membrane signal transduction, respectively. Previous studies have indicated that PLMs occur in the rat brain synaptosomal and retinal membranes, and they are activated under halothane anesthesia. The influence of halothane on PLA2 is not known. Therefore, we have investigated the effect of halothane on retinal PLA2 activity. Rat retinal sonicates were assayed for PLA2 activity using 1-palmitoyl-2[1-14C]arachidonyl-phosphatidylethanolamine (PE, 2.2 nmol) in Tris buffer (10 mM, pH 7.4) at 37 degrees C with and without halothane (0.25-2.0 mM) in the assay medium. These studies gave the following results: (1) Rat retinal sonicates contained PLA2 activity of 4.2+/-0.8 pmol PE hydrolyzed/100 ng protein/hr; (2) Halothane (0.25-2.0 mM) increased PLA2 activity by 20 to 150% depending upon concentration; (3) The lower concentration of halothane (0.25 mM) exhibited high activation of PLA2 (150%); (4) High concentrations of halothane (1.0-2.0 mM) caused a low degree of activation of PLA2 (20%); and (5) During phospholipid methylation of retinal membranes with S-adenosyl-L-methionine in the presence of halothane, increased amounts of fatty acid methyl esters (FAME) were formed. This increase in FAME (45%) was possibly due to the hydrolysis of phospholipids by activated PLA2, liberating fatty acids which were methylated. This increase in FAME (45%) was inhibited by mepacrine (quinacrine) (10 microM), an inhibitor of PLA2. These observations suggest that the release of retinal transmitters (dopamine, acetylcholine and others) is affected during halothane anesthesia, due to activation of PLA2 and enhanced fusogenic activity of vesicular membranes with plasma membrane and depletion of vesicles.

Halothane, an inhalational anesthetic agent, increases folding stability of serum albumin

Inhalational anesthetic agents are known to alter protein function, but the nature of the interactions underlying these effects remains poorly understood. We have used differential scanning calorimetry to study the effects of the anesthetic agent halothane on the thermally induced unfolding transition of bovine serum albumin. We find that halothane (0.6–10 mM) stabilizes the folded state of this protein, increasing its transition midpoint temperature from 62 to 71°C. Binding of halothane to the native state of serum albumin thus outweighs any non-specific interactions between the thermally unfolded state of serum albumin and halothane in this concentration range. Based on the average enthalpy change Δ H for unfolding of 170 kcal/mol, the increase from 62 to 71°C corresponds to an additional Gibbs energy of stabilization (ΔΔ G) due to halothane of more than 4 kcal/mol. Analysis of the dependence of ΔΔ G on halothane concentration shows that thermal unfolding of a bovine serum albumin molecule is linked to the dissociation of about one halothane molecule at lower halothane concentrations and about six at higher halothane concentrations. Serum albumin is the first protein that has been shown to be stabilized by an inhalational anesthetic.

Effects of halothane on glutamate receptor-mediated excitatory postsynaptic currents. A patch-clamp study in adult mouse hippocampal slices.

The effects of halothane on excitatory synaptic transmission in the central nervous system of mammals have been studied in vivo and in vitro in several investigations with partially contradicting results. Direct measurements of the effects of halothane on isolated glutamate receptor-mediated (glutamatergic) excitatory postsynaptic currents (EPSCs), however, have not been reported to date. The effects of halothane on glutamatergic EPSCs were studied in vitro by using tight-seal, whole-cell recordings from CA1 pyramidal cells in thin slices from the adult mouse hippocampus. The EPSCs were pharmacologically isolated into their non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor-mediated components by using selective antagonists. The effects of halothane on EPSC amplitude and kinetics were analyzed at various membrane potentials and were compared with its effects on currents evoked by exogenously applied glutamatergic agonists. Halothane (0.2-5.1%; 0.37-2.78 mM) reversibly blocked non-NMDA and NMDA EPSCs. This effect was voltage independent; concentrations producing 50% inhibition were 0.87% (0.66 mM) and 0.69% (0.57 mM), respectively. Currents induced by bath-applied glutamatergic agonists were not affected even by the high concentrations of halothane. Halothane depresses glutamatergic EPSCs irrespective of receptor subtype, most likely by inhibition of glutamate release.

Age‐dependent haematological disturbances in anaesthetic personnel chronically exposed to high occupational concentrations of halothane and nitrous oxide

Anaesthetic staff chronically exposed to high occupational concentrations of halothane and nitrous oxide were tested for numerous haematological and cellular function parameters at the peak of the working season and after 3 weeks vacation. The analysis of data was performed to compare differences in subjects younger and older than the age of 40 years, respectively when compared with normal controls. The analysis revealed a higher recovery of erythrocyte count in the blood of older staff, and stronger disturbance of leucocyte formation in younger staff. In contrast, monocytes appeared to be more stable in the younger staff as were the T and B lymphocyte counts. After stimulation with PHA, Con A and PWM mitogens, lymphocytes from the older age group incorporated a significantly higher amount of tritiated thymidine, but stimulation indices did not differ. Natural killer cell numbers appeared equally affected; natural killer cell activity was unaffected, but there was an increase in activity in the younger staff after the vacation. Serum immunoglobulin concentrations tended to be more affected in older individuals at the peak of the working season.

Leakage of mitochondrial and cytosolic GOT in isolated rat hepatocytes exposed to halothane: an immunohistochemical study.

The leakage of mitochondrial (m-) and cytosolic (s-) aspartate aminotransferases (glutamic-oxaloacetic transaminase: GOT) from isolated hepatocytes exposed to halothane was investigated immunohistochemically. In control isolated hepatocytes, a large number of cells were immunopositive (m-GOT, 85%; s-GOT, 98.5%) at various intensities. Reaction products of m-GOT-immunohistochemistry (m-GOT-I) were seen exclusively in mitochondria, while those of s-GOT (s-GOT-I) were seen in the cytoplasm. When treated with low concentrations of halothane (up to 0.75%), the number of strongly m-GOT-I-immunopositive cells was reduced to half, while that of s-GOT-I showed no noticeable change. The number of m-GOT-I-immunonegative cells showed a negligible increase, while that of s-GOT-I increased gradually. At higher concentrations of halothane (1% or more), strongly immunopositive cells in both m- and s-GOT-I almost disappeared, while immunonegative cell numbers predominantly increased. This study showed that the isolated hepatocyte system was not homogeneous with regard to the quantity of GOT isozymes, and that halothane could induce the leakage of these isozymes from hepatocytes, along with inducing ultrastructural abnormalities, even at the lowest concentration used (0.5%). Furthermore, the data appear to indicate that the sensitivity of isolated hepatocytes to halothane is dependent on the nature of the hepatocyte itself and on the nature of both types of GOT isozymes.

Memory facilitation by posttraining exposure to halothane, enflurane, and isoflurane in ddN mice.

The effect of low and high concentrations of halothane, enflurane, and isoflurane on posttraining memory function was studied in male ddN mice. Mice were trained to escape an aversive electric foot shock as an unconditioned stimulus within 3 s after being exposed to light and a buzzer as a conditioned stimulus. Immediately after training (first session: 30 trials), the animals were exposed to halothane, enflurane, or isoflurane for 120 min and then were tested again on the avoidance task (second session: 30 trials) 22 h after cessation of exposure. The performance ratios, [B/A] (i.e., A is the score in the first session, and B the score in the second) were compared between the anesthetized groups and their respective control (nonanesthetized) groups. Mean performance ratios in the control groups ([B/A]c) ranged from 136.8% to 163.9% and those in the anesthetized groups ([B/A]a) ranged from 151.4% to 174.7%. [B/A] in each anesthetized group exceeded [B/A] in its corresponding control group. [B/A]a significantly exceeded [B/A]c by 13.1% in the 1.23 minimum alveolar concentration (MAC) enflurane group (P < 0.05) and by 12.4% in the 0.29 MAC isoflurane group (P < 0.05). These results suggest that posttraining exposure to volatile anesthetics facilitates memory.

Excess molar heat capacities and excess molar volumes of binary mixtures of 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane) with oxygenated and hydrocarbon solvents

Excess molar heat capacities C E p were determined at 298.15 K for the following thirteen mixtures: 2-bromo-2-chloro-1,1,1-trifluorethane (halothane)+acetone (ACT), +dipropyl either (DPE), +diisopropyl ether (DIPE), +methyl fert-butyl ether (MTBE), +tetrahydrofuran (THF), 1,4-dioxane (DIOX), +methyl acetate (MAC), +benzene (BENZ), +cyclohexane (cC6), +n-hexane (nC6), +2,2-dimethylbutane (22DMB), +n-heptane (nC7), and +2,4-dimethylpentane (24DMP). Excess molar volumes V E at 281.15 K were also measured for the following mixtures: halothane + DPE, +DIPE + DIOX, +BENZ, +cC6, +22DMB, +nC7, and +24DMP. V E values for the remaining five mixtures (ACT, MTBE, THF, MAC, and nC6) were previously reported. For all oxygenated solvents, C E p is positive and V E negative, while for the equal-structure hydrocarbon solvents (taken as homomorphs), they are of the opposite sign. This is interpreted in terms of the formation of H-bonded complexes between the oxygen atom in the solvent molecule and the highly acidic hydrogen atom in halothane. For benzene, C E p and V E are positive but small; this is consistent with the weak electron-donor character of benzene and indicates the presence of a weak halothane/BENZ complexation which most probably occurs through a charge transfer mechanism similar to that present in mixtures of fully halogenated frEons, such as Freon 113, with oxygenated solvents. The use of the homomorphs indicated that (i) for halothane + DPE, +DIPE, and +MTBE, the asymmetry of the C E p curves and their opposite-sign curvatures at low and high halothane concentrations are mainly due to the physical contributions to C E p , and (ii) for halothane + ACT, +MAC, and +DIOX, the solutions contain multisolvated species.

Excess molar enthalpies of binary mixtures of 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane) with oxygenated and hydrocarbon solvents

Excess molar enthalpies, H E, were determined at 298.15 K for the following eighteen mixtures: 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane) + acetone, +dipropyl ether, + diisopropyl ether, + methyl tert-butyl ether, + ethylene glycol dimethyl ether or monoglyme, + diethylene glycol dimethyl ether or diglyme, + tetraethylene glycol dimethyl ether or tetraglyme, + methyl phenyl ether, + tetrahydrofuran, + 1,4-dioxane, + methyl acetate, + benzene, + cyclopentane, + cyclohexane, + n-hexane, + n-heptane, + 2,2-dimethylbutane and + 2,4-dimethylpentane. The value of H E for all oxygenated solvents is strongly negative whereas for the equal-structure hydrocarbon solvents (taken as homomorphs) it is positive. This is a clear indication of the formation of a halothaneoxygenated-compound complex. The complexation is through a H-bond between the oxygen atom in the solvent molecules and the hydrogen atom in halothane. As the number of oxygen atoms in the solvent increases, H E becomes more negative and asymmetrical, its minimum being displaced towards higher halothane concentrations. The H E values for halothane mixed with the glymes are amongst the largest ever found for mixtures of non-electrolytes. The increase in asymmetry in going from monoglyme to tetraglyme is indicative of the presence of multisolvated species in the solution. A clear correlation between the solvent Kamlet-Taft β parameter (H-bonding acceptor ability) and H E was found. A comparison between the H E vs. β correlation for the present data and that for chloroform showed that for a given oxygenated solvent H E with halothane is always more negative than with chloroform. This indicates that the acidity of the hydrogen atom in halothane is greater than that in chloroform.