Region Of High Electron Density Research Articles

EISCAT observations of plasma patches at sub-auroral cusp latitudes

Abstract. A sequence of 3 patches of high-density (1012 m−3) cold plasma on a horizontal scale-size of 300–700 km was observed near magnetic noon by the EISCAT VHF radar above Svalbard on 17 December 2001. The patches followed a trajectory towards the cusp inflow region. The combination of radar and all-sky observations demonstrates that the patches must have been segmented equatorward of the cusp/cleft auroral display, and hence their properties had not yet been influenced by cusp particle showers and electrodynamics on open flux tubes. The last patch in the sequence was intersected by radio tomography observations, and was found to be located adjacent to a broader region of the same high electron density further south. The patches occurred under moderately active conditions (Kp=3) and the total electron content (TEC) of the high-density plasma was 45 TEC units. The train of patches appeared as a segmentation of the tongue of ionization. The sequence of patches occurred in association with a sequence of flow bursts in the dusk cell return flow. It is proposed that reconnection driven pulsed convection is able to create sub-auroral patches in the region where high density mid-latitude plasma is diverted poleward toward the cusp. It is the downward Birkeland current sheet located at the equatorward boundary of the flow disturbance that represents the actual cutting mechanism.

Fokker-Planck Approach to Laser-Induced Damage in Dielectrics with Subpicosecond Pulses

Extensive numerical simulations are conducted to investigate the non-local characteristics of ultra-short pulse-laser-induced breakdowns of fused silica. The Fokker-Planck (F-P) equation is expanded to space and applied to describe the transient behaviors of electron densities considering the effects of electron avalanche, three-body recombination, and multiphoton ionization (MPI) on generation and recombination of electrons. The present study compares the predicted damage threshold fluences with experimental data for validation. When the electron density exceeds a certain threshold, recombination becomes prominent and contributes to reduce substantially the rate of increase in electron density. It is also found that once high electron density region is formed at intensities above threshold, all further laser energy is deposited within a thin skin depth because the absorbed energy is no longer used for collisional ionization and rather used to increase the average energy per electron, resulting in drastic increase in the absorption coefficient due to the Joule heating process.

Quiescent Radio Emission from Southern Late‐Type M Dwarfs and a Spectacular Radio Flare from the M8 Dwarf DENIS 1048−3956

We report the results of a radio monitoring program conducted at the Australia Telescope Compact Array to search for quiescent and flaring emission from seven nearby Southern late-type M and L dwarfs. Two late-type M dwarfs, the M7 V LHS 3003 and the M8 V DENIS 1048-3956, were detected in quiescent emission at 4.80 GHz. The observed emission is consistent with optically thin gyrosynchrotron emission from mildly relativistic (~1-10 keV) electrons with source densities ne 109 cm-3 in B 10 G magnetic fields. DENIS 1048-3956 was also detected in two spectacular, short-lived flares, one at 4.80 GHz (peak fν = 6.0 ± 0.8 mJy) and one at 8.64 GHz (peak fν = 29.6 ± 1.0 mJy) approximately 10 minutes later. The high brightness temperature (TB 1013 K), short emission period (~4-5 minutes), high circular polarization (~100%), and apparently narrow spectral bandwidth of these events imply a coherent emission process in a region of high electron density (ne ~ 1011-1012 cm-3) and magnetic field strength (B ~ 1 kG). If the two flare events are related, the apparent frequency drift in the emission suggests that the emitting source either moved into regions of higher electron or magnetic flux density or was compressed, e.g., by twisting field lines or gas motions. This emission may be related to a recent optical flare from this source that exhibited indications of chromospheric mass motion. The quiescent fluxes from the radio-emitting M dwarfs are too bright to support the Gudel-Benz empirical radio/X-ray relations, confirming a trend previously noted by Berger et al. The violation of these relations is symptomatic of a divergence in magnetic emission trends at and beyond spectral type M7/M8, where relative X-ray and Hα emission drops precipitously while relative radio emission appears to remain constant or possibly increases. With an apparent decline in chromospheric/coronal heating, the origin of hot coronal plasmas around ultracool dwarfs remains uncertain, although external sources, such as accretion from a residual disk or tidally distorted companions, remain possibilities worth exploring.

Stabilization of macromolecular chromatin complexes in mitotic chromosomes by light irradiation in the presence of ethidium bromide

A method was developed for stabilizing mitotic chromosomes. Light irradiation of permeabilized cells in a low concentration of ethidium bromide made chromatin resistant to high salt concentrations and decondensing buffer. This resistance was abolished by proteinase treatment, but not by DNase or RNase treatment. In photostabilized and extracted chromosomes, chromatin appeared as thick fibers with discrete high electron density regions. These stabilized structures might correspond to the higher-level structures (chromonemata) observed in native chromatin. Moreover, the electron density was higher in the centromeric regions than the chromosome arm material. Thus, the method allows chromatin substructures (chromonemata and centromeric heterochromatin) to be stabilized inside mitotic chromosomes.

Role of Asn-16 and Ser-19 in Anthopleurin B Binding. Implications for the Electrostatic Nature of NaV Site 3,

Anthopleurin B (ApB) is a type 1 sea anemone toxin, which binds to voltage-sensitive sodium channels (Na(V)'s), thereby delaying channel inactivation. Previous work from our laboratories has demonstrated that the structurally unconstrained region involving residues 8-17 of this polypeptide, designated the Arg-14 loop, is important for full toxin affinity (Seibert et al., (2003) Biochemistry 42, 14515). Within this region, important contributions are made by residues Arg-12 and Leu-18 (Gallagher and Blumenthal, (1994) J. Biol. Chem. 269, 254; Dias-Kadambi et al., (1996) J. Biol. Chem. 271, 23828). Moreover, replacement of glycine residues found at positions 10 or 15 of the loop by alanine has been shown to have profound, isoform-selective effects on toxin-binding kinetics (Seibert et al., (2003)Biochemistry 42, 14515). To thoroughly understand the importance of this entire region, the work described here investigates the contribution of ApB residues Asn-16, Thr-17, and Ser-19 to toxin affinity and isoform selectivity. Our results demonstrate that residues within and proximal to the C terminus of the Arg-14 loop are important modulators of ApB affinity for Na(V) channels, indicating that the loop and channel site 3 are likely in close contact. A comparison of the effects of multiple replacements at each position reveals that Asn-16 and Ser-19 are involved in binding, whereas Thr-17 is not. The fact that anionic replacements for Asn-16 or Ser-19 are highly deleterious for toxin binding strongly suggests that site 3 contains either formal anionic residues or regions of high electron density, which could be formed by aromatic clusters. These data represent the first indication of the presence of such residues or regions within Na(V) site 3.

Electronic Structure and Stability of Double Six-Membered Rings of Oxygen-Bridged Silicon and Aluminum Atoms Related to Cation Site Occupancy in FAU Zeolites: a DFT Study

The electronic structure and relative stability of clusters with general composition (Mn+)x/nH12Si12-xAlxO18 with x = 0, 2, 4, M = H+, Li+, Na+, K+, Ca2+ forming double-six-membered rings (D6R), are studied by the B3LYP method. In Ca2H12Si8Al4O18 clusters, maximum separation of the Al atoms is favored, which implies a minimum number of Al−O−Si−O−Al linkages. A large number of isomers with Si,Al distributions strongly related to the type and location of the charge-compensating cations were determined for the ratio Si/Al = 5. All cations favor maximum separation of Al atoms within the T6O6 rings. Concurrent occupation of extraframework cation sites in the center of the D6R and above the T6O6 window is energetically unfavorable for Li+ and Na+ cations, whereas this is achieved with K+, in agreement with experimental data. The Si,Al ordering with one Al atom per T6O6 ring and at the largest distance within the D6R is the most stable one with Li+ and K+ as extraframework cations, whereas Na+ and Ca2+ favor the configuration with two Al atoms in one T6O6 ring. The small and medium size cations Li+, Na+, and Ca2+ approach the regions of high electron density in the D6R. The HOMOs of both the siliceous fragments and the aluminum-containing fragments with the extraframework cations located near the four-membered ring walls consist mainly of O 2p nonbonding AOs. When the extraframework cations take up positions at the D6R center, or near the T6O6 rings, the HOMOs O 2p nonbonding character is reduced: Al 3s and Al 3p AOs are admixed to the O 2p AOs. The maximum electron density is concentrated at the Al atoms and the Al-bonded oxygen atoms. When the Al atoms are in one T6O6 ring of a D6R, the oxygen atoms of this ring bear a higher electron density. Lewis basic sites appear in proximity to the Brønsted acid sites in proton balanced clusters.

Optical Absorption Measurements of Sputtered Ti Ion Density and Discussion of Ionization Mechanisms in Inductively Coupled Plasma-Assisted DC Sputtering

This study discusses the ionization mechanisms of sputtered titanium (Ti) in inductively coupled plasma (ICP)-assisted dc magnetron sputtering based on measurements and model analyses. Ionic and atomic densities of sputtered titanium were measured using an optical absorption method under an Ar pressure of 3.5 Pa against rf(13.56MHz) power applied to the inserted coil. A Langmuir probe provided measurements of electron densities against coil rf power, giving input parameters for model analyses. We adopted a model analysis method presented by J. Hopwood and F. Qian [J. Appl. Phys. 78, 758 (1995)]. Variations of ionic and atomic densities and ionization fractions against electron density from model calculation agreed with those obtained by measurements. The results showed clearly that electron impact ionization dominates ionization of sputtered titanium in high er electron density regions compared to Penning ionization through Ar metastable atoms. Penning ionization played an important role at the lower electron density region because of the longer time for radiative decay of Ar metastable atoms.

New results on GP Com

We present high resolution optical and UV spectra of the 46 min orbital period, helium binary, GP Com. Our data contains simultaneous photometric correction which confirms the flaring behaviour observed in previous optical and UV data. In this system all lines show a triple peaked structure where the outer two peaks are associated with the accretion disc around the compact object. The main aim of this paper is to constrain the origin of the central peak, also called “central spike”. We find that the central spike contributes to the flare spectra indicating that its origin is probably the compact object. We also detect that the central spike moves with orbital phase following an S-wave pattern. The radial velocity semiamplitude of the S-wave is ~10 km s-1 indicating that its origin is near the centre of mass of the system, which in this case lies very close to the white dwarf. Our resolution is higher than that of previous data which allows us to resolve structure in the central peak of the line. The central spike in three of the He i lines shows another peak blueshifted with respect to the main peak. We propose that one of the peaks is a neutral helium forbidden transition excited in a high electron density region. This forbidden transition is associated with the permitted one (the stronger peak in two of the lines). The presence of a high electron density region again favours the white dwarf as their origin. We compute Doppler maps for the emission lines which show three emission regions: an accretion disc, a bright spot and an unidentified low velocity emission region associated with the central spike. We obtain modulation Doppler tomograms for some of the emission lines that map the anisotropic emission from the bright spot region. The HST UV spectra also show a strong flare component and confirm the under abundance of silicon in GP Com.

Near-Field Scanning Optical Microscopy of Quantum Dot Arrays

Near-field scanning optical microscope (NSOM) measurement of n-type GaAs quantum dot arrays is reported. Monochromatic photoluminescence (PL) images clearly reveal periodical PL intensity distribution. The obtained images show that the PL intensity is high in the high electron density region as calculated by a self-consistent calculation. This directly indicates that a localized electron density distribution is formed as defined by the surface gate structure, demonstrating that NSOM-PL measurement is a powerful tool in the study of the electronic states in semiconductor nanostructures.

The application of structure envelopes in structure determination from powder diffraction data

A structure envelope is a special type of periodic nodal surface that separates regions of high electron density from those of low electron density. Once such a surface has been generated, it can be used in combination with direct-space methods to facilitate structure solution from powder data. To generate an informative structure envelope, the phases of the structure factors of a few strong low-order reflections must be determined; an algorithm has been developed for this purpose. The programSayPermcombines (a) the use of error-correcting codes (e.c.c.'s) to sample phase space efficiently, (b) a pseudo-atom approximation of structure fragments to simulate atomic resolution atca2.5 Å, and (c) phase extension and phase set ranking using the Sayre equation. The effect of using a structure envelope in structure solution was first tested in combination with a subroutine for finding zeolite topologies in the programFOCUS. Then extension to molecular structures in combination with a simulated-annealing program was explored. This resulted in the development of the programSafeand the subsequent determination of the structure of a tri-β-peptide (C32N3O6H53) with 17 variable torsion angles.

Cation-pi interaction in a folded polypeptide.

Cationic and aromatic side chains from protein residues interact to stabilize tertiary structure. The stabilization energy originates in part from electrostatic attraction between the cation, and regions of high electron density in pi-orbitals of the aromatic group, leading to the name cation-pi interaction. The lysine and tyrosine containing peptide, N-acetyl-Pro-Pro-Lys-Tyr-Asp-Lys-NH(2), has near uv CD characteristic of tyrosine in a structured environment. Nuclear Overhauser effect (NOE), coupling constant, and ring current chemical shift constraints obtained with (1)H NMR confirm that the peptide (t6p) folds. Simulated annealing consistent with all NMR constraints produces a 40-structure ensemble for t6p with potential energies within one standard deviation of the lowest value observed. Calculated binding energies indicate that cation-pi and cation-phenolic OH interactions exists between the Lys3 and Tyr4 side chains in most of the structures. The t6p peptide in solution is a model for these interactions in a protein. A perturbing electric field from the cationic ground state charge intermingles the excited states of the aromatic group. This intermingling effect may provide a cation-pi signature effect in the tyrosine spectroscopy. The absorption and CD for the lowest energy electronic transitions of the tyrosine phenol were computed for the ensemble. Red-shifted peak energy and hypochromicity in the absorbance band, and decreasing rotational strength, correlates with increasing binding energy of the complex indicating the cation-pi spectroscopic signature. The ensemble average spectroscopic signature effects in t6p are small and in agreement with observation.

Thiazole and thiadiazole analogues as a novel class of adenosine receptor antagonists.

Novel classes of heterocyclic compounds as adenosine antagonists were developed based on a template approach. Structure-affinity relationships revealed insights for extended knowledge of the receptor-ligand interaction. We replaced the bicyclic heterocyclic ring system of earlier described isoquinoline and quinazoline adenosine A(3) receptor ligands by several monocyclic rings and investigated the influence thereof on adenosine receptor affinity. The thiazole or thiadiazole derivatives seemed most promising, so we continued our investigations with these two classes of compounds. The large difference between a pyridine and isoquinoline ring in binding adenosine A(1) and A(3) receptors showed the importance of the second ring of the isoquinoline ligands. We prepared several N-[4-(2-pyridyl)thiazol-2-yl]benzamides, and these compounds showed adenosine affinities in the micromolar range. Most surprising in the series of the N-[4-(2-pyridyl)thiazol-2-yl]amides were the retained adenosine affinities by introduction of a cylopentanamide instead of the benzamide. A second series of compounds, the thiadiazolobenzamide series of compounds, revealed potent and selective adenosine receptor antagonists, especially N-(3-phenyl-1,2,4-thiadiazol-5-yl)-4-hydroxybenzamide (LUF5437, 8h) showing a K(i) value of 7 nM at the adenosine A(1) receptor and N-(3-phenyl-1,2,4-thiadiazol-5-yl)-4-methoxybenzamide (LUF5417, 8e) with a K(i) value of 82 nM at the adenosine A(3) receptor. 4-Hydroxybenzamide 8h is the most potent adenosine A(1) receptor antagonist of this new class of compounds. Structure--affinity relationships showed the existence of a steric restriction at the para-position of the benzamide ring for binding adenosine A(1) and A(3) receptors. The electronic nature of the 4-substituents played an important role in binding the adenosine A(3) receptor. Cis- and trans-4-substituted cyclohexyl derivatives were made next to the 4-substituted benzamide analogues. We used them to study the proposed specific interaction between the adenosine A(1) receptor and the 4-hydroxy group of this class of thiadiazolo compounds, as well as a suggested special role for the 4-methoxy group in binding the A(3) receptor. Both the adenosine A(1) and A(3) receptor slightly preferred the trans-analogues over the cis-analogues, while all compounds showed low affinities at the adenosine A(2A) receptor. Our investigations provided the potent and highly selective adenosine A(1) antagonist N-(3-phenyl-1,2,4-thiadiazol-5-yl)-trans-4-hydroxycyclohexanamide (VUF5472, 8m) showing a K(i) value of 20 nM. A third series of compounds was formed by urea analogues, N-substituted with thiazolo and thiadiazolo heterocycles. The SAR of this class of compounds was not commensurate with the SAR of the previously described quinazoline urea. On the basis of these findings we suggest the existence of a special interaction between adenosine receptors and a region of high electron density positioned between the thia(dia)zole ring and phenyl(pyridyl) ring. Molecular electrostatic potential contour plots showed that for this reason the ligands need either a thiadiazole ring instead of a thiazole or a 2-pyridyl group instead of a phenyl. The derived novel classes of antagonists will be useful for a better understanding of the molecular recognition at the adenosine receptors.

Ionospheric E region remote sensing with ELF radio atmospherics

Radio remote sensing of the ionospheric E region can be difficult, particularly in the nighttime E region valley which lies between two regions of higher electron density. We show that extremely low frequency (ELF) electromagnetic waves launched from below penetrate this region because of their low attenuation and can be reflected from both the D region and the top of the E region valley. This double reflection, also caused by sporadic E layers, produces a measurable effect on the subionospheric propagation of ELF waves, which we demonstrate with numerical Earth‐ionosphere waveguide simulations. This sensitivity opens the possibility of remotely sensing the E region and detecting sporadic E layers with broadband ELF propagation measurements using lightning discharges as the source. From nighttime observations of ELF lightning radiation over the same propagation path on different days, we extract E region electron density profiles that show significant variability not only from day to day but over the course of a single night. This technique is inherently a path‐integrated measurement, enabling tomographic large‐scale ionospheric remote sensing with multiple sources and receivers.

Thermal activation of the trapped proton in diamond crystal: direct molecular dynamics calculation

For simulation of thermal behavior of the proton in the tetrahedral (T) trapping site of a C 26H 32 diamond cluster model, a direct molecular dynamics calculation was accomplished in a temperature range from 100 to 800 K based on the newly developed methodology at the PM3 molecular orbital (MO) level. The proton vibrating around only the T site below 550 K, diffuses to the next T site through the hexagonal (H) site in low electron density region at 600 K. However, at 800 K the proton transfers through the H site to the bond center (BC) site and the middle (M) site designated as a middle point between two neighboring centers of the rhombuses composed of three carbon atoms and the T site on the same level for each. The proton–carbon bond formation (C–H +–C) is occurred at the M site followed by decrease in the potential energy. Finally, the proton is vibrating between the M site and the BC site in high electron density region.

Comparison of edge pedestal parameters for JT-60U and DIII-D H-mode plasmas

Edge pedestal parameters (pedestal temperature and density, pedestal width)for JT-60U and DIII-D are studied and compared. For the discharges used in thestudy,the JT-60U H-mode operation space is in the high edge ion temperature and low edge electron density region, whereas DIII-D discharges have higher edgeelectron density and lower electron temperature. The pedestal width scalinghas been studied separately in each machine. We tested these pedestal scalingsagainst each other using JT-60U ion temperature pedestal width data andDIII-D electron temperature pedestal width data. Three previous scalings forpedestal width (Δ∝ε0.5ρpi,Δ/R∝(ρpi/R)0.66,Δ/R∝(βpPED)0.4) are tested usingtemperature pedestal widths from bothmachines. The relations between pedestal width and dimensionless parametersare examined. We propose a new pedestal width scaling for Te and Ti based onthis study of the two machines. The new scaling includes normalized poloidalgyroradius and Greenwald density: Δ∝aρ*0.4nG*0.3κ-1.5. The result of the comparison ofthese scalings is that the new scaling and Δ/R∝(βpPED)0.4 are well fitted and thefitting errors are almost the same as experimental error. However, furtherstudy is necessary for scaling parameters.

Coronal velocity measurements with Ulysses: multi-link correlation studies during two superior conjunctions

A well-known method for studying the solar wind very close to the Sun (heliocentric distances: 4 to 40 solar radii) is by radio sounding between a spacecraft at superior conjunction and the Earth. The Ulysses Solar Corona Experiment was performed at the spacecraft's two solar conjunctions in summer 1991 and winter 1995, during which dual-frequency ranging and Doppler observations were conducted globally on a nearly continuous basis at the NASA Deep Space Network and other ground stations. The dual-frequency Doppler measurements were used to determine coronal plasma velocities by a cross-correlation analysis during those occasions when tracking data were recorded simultaneously at two well-separated ground stations. A ‘filtering’ technique was developed to suppress noise and enhance the 2-station correlations, a procedure particularly effective at small solar offsets. From the electron content measurements during the two solar conjunctions it was found that regions of higher electron density tend to occur when the two-station correlations yield slower outward flow velocities.

Role of ceramide 1 in the molecular organization of the stratum corneum lipids

The main barrier of the skin is formed by the lipids in the apical skin layer, the stratum corneum (SC). In SC mainly ceramides (CER), free fatty acids (FFA) and cholesterol (CHOL) are present. The CER are composed of at least six different fractions. CER 1 has an exceptional molecular structure as it contains a linoleic acid linked to a long-chain ω-hydroxy acid (C > 30). The SC lipids are organized in two lamellar phases with periodicities of approximately 6 and 13 nm, respectively. Recent studies revealed that ceramides isolated from pig SC mixed with cholesterol in confined ratios mimic stratum corneum lipid phase behavior closely (Bouwstra, J.A., et al. 1996. J. Lipid Res. 37: 999–1011). In this paper the role of CER 1 for the SC lipid lamellar organization was studied. For this purpose lipid phase behavior of mixtures of CHOL and total ceramide fraction was compared with that of mixtures of CHOL and a ceramide mixture lacking CER 1. These studies showed that in the absence of CER 1 almost no long periodicity phase was formed over a wide CHOL/CER molar ratio. A model is proposed for the molecular arrangement of the two lamellar phases. This model is based on the dominant role CER 1 plays in the formation of the long periodicity phase, electron density distribution calculations, and observations, such as i) the bimodal distribution of the fatty acid chain lengths of the ceramides, ii) the phase separation between long-chain ceramides and short-chain ceramides in a monolayer approach, and iii) the absence of swelling of the lamellae upon increasing the water content organization in SC. In this molecular model the short periodicity phase is composed of only two high electron density regions indicating the presence of only one bilayer, similar to that often found in phospholipid membranes. The molecular arrangement in the long periodicity phase is very exceptional. This phase most probably consists of two broad and one narrow low electron density regions. The two broad regions are formed by partly interdigitating ceramides with long-chain fatty acids of approximately 24–26 C atoms, while the narrow low-electron density region is formed by fully interdigitating ceramides with a short free fatty acid chain of approximately 16 to 18 C atoms.—Bouwstra, J. A., G. S. Gooris, F. E. R. Dubbelaar, A. M. Weerheim, A. P. IJzerman, and M. Ponec. Role of ceramide 1 in the molecular organization of the stratum corneum lipids. J. Lipid Res. 1998. 39: 186–196.

Using a structure envelope to facilitate structure solution from powder diffraction data

Given just a few strong low-index reflections, a periodic nodal surface (PNS), which divides the unit cell into regions of high and low electron density, can be generated. Fourteen known zeolite structures were examined to verify the validity of the procedure developed and in all cases the framework atoms were found to lie on just one side of the calculated curved surface. In other words, the surface defines a structure envelope. The same approach was applied to a few ionic and organic structures and was found to be equally valid. Since these reflections, with large d spacings, are precisely the ones that are least likely to be involved in overlap in a powder diffraction pattern, such a PNS can also be calculated using powder data. The resulting restriction in the region of the asymmetric unit in which atoms are likely to be found has immediate implications for any of the direct-space methods of structure determination from powder data. The use of this structure envelope as a mask in a straightforward grid search procedure reduced the computer time required to solve several framework structures by as much as two orders of magnitude.

Quantum electrodynamics of the internal source x-ray holographies: Bremsstrahlung, fluorescence, and multiple-energy x-ray holography

Quantum electrodynamics (qed) is used to derive the differential cross sections measured in the three new experimental internal source ensemble x-ray holographies: bremsstrahlung (BXH), fluorescence (XFH), and multiple-energy (MEXH) x-ray holography. The polarization dependence of the BXH cross section is also obtained. For BXH, we study analytically and numerically the possible effects of the virtual photons and electrons which enter qed calculations in summing over the intermediate states. For the low photon and electron energies used in the current experiments, we show that the virtual intermediate states produce only very small effects. This is because the uncertainty principle limits the distance that the virtual particles can propagate to be much shorter than the separation between the regions of high electron density in the adjacent atoms. We also find that using the asymptotic form of the scattering wave function causes about a 5-10% error for near forward scattering.

Heterocyclic Insecticides Acting at the GABA-Gated Chloride Channel: 5-Alkyl-2-arylpyrimidines and -1,3-thiazines

5-tert-Butyl-2-(4-ethynylphenyl)pyrimidine and the corresponding 2,5-disubstituted-4H-1,3-thiazine block the GABA-gated chloride channel at c.20and c.200 nm, respectively, measured as 50% inhibition of the binding of 1-(4-ethynylphenyl)-4-[3H]propyl-2,6,7-trioxabicyclo[2.2.2]octane (4′-ethynyl-4-n-[3H]propylbicycloorthobenzoate; [3H]EBOB) in house fly and mouse brain membranes, and they are also toxic to topically-treated flies with LD50 values of 6–27 μg g−1 alone and 2–6 μg g−1 with piperonyl butoxide (PB) as synergist. In the pyrimidine series, the general pattern of effectiveness of substituents in the 5-position is tert-butyl>isopropyl≈cyclohexyl≈cyclopropyl>methyl, phenyl and 3- and 4-fluorophenyl, and in the 2-position is 4-ethynylphenyl≪4-bromophenyl. These planar pyrimidines and nearly-planar 4H-1,3-thiazines with 2-ethynylphenyl or 2-bromophenyl and 5-tert-butyl or 5-isopropyl substituents are more effective than the corresponding 6H-1,3-thiazine, 6-oxo-1,3-thiazines and 4,6-dioxo-1,3-thiazine examined, but they are less active than the analogous conformationally flexible trans-1,3-dioxanes and -1,3-dithianes. The heterocyclic moiety confers a region of high electron density and positions the 2- and 5-substituents in a linear or parallel relationship for optimal affinity at the receptor. Two observations indicate that the new pyrimidines and thiazines probably act as chloride channel blockers. First, the poisoning signs are identical to those of EBOB in both mice and house flies. Second, each of the pyrimidines, thiazines and dioxanes falls on the same correlation line for inhibition of [3H]EBOB binding and toxicity to house flies (with PB) as that obtained earlier for EBOB analogs, dithianes and polychlorocycloalkanes, suggesting that they all act at the same or closely coupled binding sites in the GABA-gated chloride channel.