Partial Character Research Articles

First model of spontaneous vagal hyperreactivity and its mode of genetic transmission.

The main purpose of our study was to define an animal model of vagal hyperreactivity and its genetic transmission. We first investigated the vagal reactivity with phenylephrine in conscious rabbits. Barosensitivity and the maximal bradycardic response were measured at the upper mean blood pressure plateau. Hyperreactive (H) animals were selected and crossbred with normal (N) ones. Results showed no significant difference between calculated barosensitivity values after the different doses of phenylephrine. In contrast, an increase of the values and a great dispersion appeared 1 to 5 beats after the end of the ramp. Marked pauses (6000 to 20 000 ms) were obtained with some rabbits, which were blocked by atropine. A significant excess of hyperreactive offspring was observed in HxH crossings compared with NxN ones (39.4% male and 42.3% female offspring versus 14.4% and 4.4%, respectively). Few female offspring were hyperreactive compared with males in NxH and NxN crossings (4.1% versus 23.4% and 4.4% versus 14.4%, respectively). This study describes the first model of spontaneous vagal pauses. The inheritance could be polygenic with a partial sex-limited character.

Reactivity of carbanions of Fischer-type carbene complexes with pyrylium salts. Synthesis and characterization of new γ-methylenepyran carbene complexes via an addition–oxidation–deprotonation process

The condensation reaction between γ-unsubstituted pyrylium salts and carbanions of Fischer-type carbene complexes allowed the synthesis of new γ-methylenepyran carbene complexes. NMR data, single crystal X-ray analysis, and DFT calculations suggest that these complexes have a partial pyrylium character due to the π electron-accepting ability of the carbenic fragment and to the electron-releasing properties of the methylenepyran part.

Chemostratigraphy of the Neoproterozoic Alona Bay lavas, Ontario

A basal sequence of flood basalt lavas associated with the Neoproterozoic Midcontinent rift system crops out in Alona Bay along the southeastern shore of Lake Superior in Ontario. The Alona Bay lava succession is about 1200 m thick and lies just north of the well-studied, contemporaneous Mamainse Point Formation. Detailed chemostratigraphy of the Alona Bay lavas suggests they are grossly correlative with the basal portion of the Mamainse Point Formation. For instance, like the basal part of Mamainse Point Formation, the Alona Bay section contains numerous high-MgO lavas and can be subdivided into 4–5 groups with distinct chemical characteristics. Chemical variations within the Alona Bay groups are largely the result of fractional crystallization, likely at moderate pressures. One small group of Alona Bay lavas also carries the compositional imprint of crustal contamination. The remaining inter-group chemical distinctions at Alona Bay are the consequence of temporal changes in partial melting and source character. With time and development of the Midcontinent rift, degrees of melting increased; mean pressures of melting decreased, reducing garnet control; and lithospheric source contributions waned. Similar temporal variations during flood basalt evolution have been documented elsewhere.

Sensitization of singlet oxygen via encounter complexes and via exciplexes of ππ* triplet excited sensitizers and oxygen

Both excited singlet states, 1sigma(g)+ and 1delta(g), and the triplet ground state, 3sigma(g)-, of molecular oxygen are competitively formed during the quenching by O2 of triplet (T1) excited sensitizers of sufficient energy. The corresponding overall rate constants kT(1sigma), kT(1delta), and kT(3sigma) as well as the T1 state energies E(T) and the oxidation potentials E(ox), have been determined for a series of six fluorene derivatives. Graduated and in part strong charge transfer (CT) effects on kT(1sigma), kT(1delta), and kT(3sigma) are observed. These and literature data strongly indicate that quenching occurs in two different channels each capable of producing O2(1sigma(g)-), O2(1delta(g)), and O2(3sigma(g)-). One proceeds via internal conversion (IC) of excited 1,3(T1 x 3sigma) complexes with no CT character (nCT), which cannot be distinguished from encounter complexes, the other via IC of 1,3(T1 x 3sigma) exciplexes with partial CT character (pCT). The contributions of nCT and pCT deactivation channels to the overall formation of O2(1sigma(g)+), O2(1delta(g)). and O2(3sigma(g)-) depend on E(T) and E(ox). The rate constants of the nCT channel are controlled by the excess energies of the respective IC processes by an energy gap law. The rate constants of the pCT channel depend on the change of free energy deltaG(CET) for complete electron transfer from T1 excited sensitizer to O2. Equations are presented which show the functional form of the dependence of the oxygen quenching rate constants on E(T) and E(ox). Particular emphasis is laid on the question of whether these relations could generally be valid for pipi* triplet sensitizers.

Atomic-scale models of interactions between inversion domain boundaries and intrinsic basal stacking faults in GaN

Interactions between inversion domain boundaries (IDBs) and intrinsic basal stacking faults (SFs) in wurtzite-structured GaN grown on (0001) sapphire were studied using high-resolution electron microscopy (HREM) observations and empirical potential calculations. In one type of interaction, an SF terminates on an IDB, thereby inducing a transformation from a low-energy and electrically non-active IDB structure to a high-energy, electrically active one. In a second interaction, the SF crosses the IDB without changing its structure. These configurations were topologically established a priori, and were confirmed by experimental observations. It was found that the first junction line exhibits partial dislocation character, while the second is defect-free. Atomic-scale periodic supercells of the interactions have been produced and the relative energy values are discussed.

A reinvestigation of the molecular structures, vibrations and rotation of methyl group in o-methylaniline in S 0 and S 1 states studied by laser induced fluorescence spectroscopy and ab initio calculations

The UV fluorescence excitation and dispersed fluorescence spectra of a jet-cooled o-methylaniline have been obtained for the S 1←S 0 transition, in which some of the bands have been observed and assigned for the first time. The origin of the electronic transition appears at 34,328.4 cm −1. It was found that the spectra exhibit an important feature corresponding to the internal rotation of the methyl group in the electronic ground and excited states. Ab initio calculations at MP2/6-31+G* and CIS/6-31+G* show that the optimised structure of o-methylaniline in the ground state is not planar with the amino group having sp 3 hybridation-like character due to the existence of lone paired electrons on the N atom. Upon electronic excitation, the CN bond exhibits a partial double character, as in the case of other aniline derivatives.

SN2 reactions at amide nitrogen – theoretical models for reactions of mutagenic N-acyloxy-N-alkoxyamides with bionucleophiles

The reactions of N-formyloxy-N-methoxyformamide 4 with ammonia 2 and methanethiol 3 have been modeled at theAM1, HF/6-31G* and Density Functional computational levels. The reaction process is similar geometrically and electronically to classical SN2 reactions at carbon. Near- linear transition states reveal extensive charge separation and partial nitrenium ion character at the formamide nitrogen indicative of a non-synchronous process involving early stretching of the formate-formamide nitrogen bond. Activation energies, computed from pBP/DN* energies of HF/6-31G* ground state and transition state geometries, are in the range of experimental values and a strong solvation effect is predicted. Evidence for anomeric weakening of the N-formate bond by the geminal alkoxyl oxygen was obtained from a comparison of the reactions of ammonia with 4 and N-formyloxy-N-methylformamide 5. An N-alkyl group leads to a much larger activation energy in accordance with the experimental findings for N-acyloxy-N- alkylamides, which are resistant to attack by nucleophiles and are non-mutagenic.

Association Complexes between Cationic Metallophthalocyanines and Anionic Metalloporphyrins I: Spectrometric Studies of Electronic Interactions

The formation and spectroscopic properties of several metalloporphyrin−metallophthalocyanine complexes have been investigated. The complexes consist of negatively charged tetrasulfonatophenyl or tetracarboxyphenyl porphyrins in ion pairs with positively charged crown ether substituted metallophthalocyanines. The positive charge was delivered to the modified phthalocyanine molecules by inserting potassium ions into the crown ether cavities. The complexes were formed by mixing the constituent tetrapyrrole compounds in DMSO or ethanol. UV−vis spectrophotometric studies of the ground-state complexes showed loss of the metallophthalocyanine spectrum and the appearance of new spectral bands at longer wavelengths, indicating strong electronic coupling between the components. Analysis of the porphyrin−phthalocyanine complex by the method of continuous variations revealed formation of dimeric and trimeric species. Cyclic voltammetric and spectroelectrochemistry experiments indicated a degree of partial charge transfer character for the ground-state complexes. The free-base/free-base complex showed emission only from the charge transfer state, regardless of the excitation wavelength. The lifetime of the charge transfer state was 3.65 ns. Ultrafast transient absorption studies of the free-base/free-base complex showed that the charge transfer state was fully formed in less than 5 ps after excitation at either 400 or 720 nm. The observed transients were independent of the excitation wavelength and showed little decay on the 500 ps time scale, consistent with the observed fluorescence lifetime.

Electronic to vibrational energy conversion and charge transfer contributions during quenching by molecular oxygen of electronically excited triplet statesDedicated to Professor Frank Wilkinson on the occasion of his retirement.

The bimolecular rate constants kqT for quenching of some substituted naphthalene triplet states by molecular oxygen (O2(3Σg−)) in acetonitrile and cyclohexane and the efficiencies, fΔT, with which singlet oxygen (O2*(1Δg)) is thereby produced are reported for naphthalene derivatives with a wider range of oxidation potentials than those previously measured. The magnitude of kqT and fΔT are inversely correlated, and both parameters exhibit pronounced sensitivity to the oxidation potential (EMOX) of the naphthalene derivative and to the solvent polarity. The modified charge transfer mediated mechanism of quenching based on singlet and triplet channels for oxygen quenching is invoked to discuss these results. In cyclohexane the maximum value for fΔT of one is observed for compounds with high oxidation potentials indicating no contribution from the triplet channel whilst in acetonitrile the limit for fΔT of 0.25 expected when singlet and triplet channels give equal contributions, when spin statistics is taken into account, is observed for 2,6-dimethoxynaphthalene, which is the derivative with the lowest oxidation potential. These results are combined with those previously reported by ourselves in cyclohexane in order to examine the dependence of the quenching rate constants due to energy transfer on the energy gap (ET–E1Σ). This allows the quenching rate constants due to energy transfer in cyclohexane to be separated into contributions with and without charge transfer assistance. The latter contribution shows a smooth dependence on (ET–E1Σ) and the same dependence on the electronic energy, which has to be converted into vibrational energy, probably applies when the solvent is acetonitrile since making this assumption results in similar dependences of the charge transfer contributions in both singlet and triplet channels in acetonitrile. The free energy of activation for charge transfer assisted quenching is shown to have a linear dependence on the free energy change for full charge transfer but the indications are that quenching is via singlet and triplet charge transfer complexes with only partial charge transfer character being 12.5% and 17% in acetonitrile and cyclohexane respectively.

Domain IV of mouse laminin beta1 and beta2 chains.

Domain IV, consisting of about 230 residues, represents a particular protein module so far found only in laminin beta1 and beta2 chains. Both domains were obtained by recombinant production in mammalian cells. They showed a globular structure, as expected from electron microscopic examination of laminins. Fragment beta1IV was obtained as a monomer and a disulfide-bonded dimer, and both were modified to approximately 50% by a single chondroitin sulfate chain attached to Ser721 of an SGD consensus sequence. Dimerization is caused by an odd number of cysteines, with three of them having a partial thiol character. Whether both modifications also occur in tissue forms of laminin remains to be established. Fragment beta2IV was only obtained as a monomer, as it lacked one crucial cysteine and the SGD sequence. It required, however, the presence of two adjacent LE modules for proper folding. Polyclonal antibodies raised against both fragments showed no cross-reaction with each other and allowed establishment of beta chain-specific radioimmunoassays and light and electron microscopic immunostaining of tissues. This demonstrated a 5-25-fold lower content of beta2 compared with beta1 chains in various tissue extracts of adult mice. Tissues derived from beta2-deficient mice failed to react with the beta2-specific antibodies but showed a twofold higher content of beta1 than heterozygotes. The antibodies to beta2 showed broader tissue staining than reported previously, including in particular a distinct reaction with the extrasynaptic endomysium of skeletal muscle. Immunogold staining localized both beta chains primarily to basement membranes of kidney, muscle and various other tissues.

Formation of O2(1Σg+), O2(1Δg), and O2(3Σg-) during Oxygen Quenching of nπ* Triplet Phenyl Ketones: The Role of Charge Transfer and Sensitizer-Oxygen Complex Structure

Rate constants of formation of O2(1Σg+), O2(1Δg), and O2(3Σg-) in the quenching of triplet states T1 by O2 have been determined for a series of nine benzophenones (BPs) of strongly varying oxidation potential, Eox, but almost constant triplet-state energy ET. These data are analyzed considering data determined previously for T1(ππ*) sensitizers of very different ET and Eox. Much weaker charge transfer (CT) effects are observed for the T1(nπ*) BPs compared with those obtained with a series of structurally related T1(ππ*) biphenyls. The quenching proceeds for T1(nπ*) and T1(ππ*) sensitizers via two different channels, each capable of producing O2(1Σg+), O2(1Δg), and O2(3Σg-). One channel originates from excited 1,3(T1·3Σ) complexes with no CT character and the other from 1,3(T1·3Σ) exciplexes with partial CT character. Different energy gap relations determine the formation of O2(1Σg+), O2(1Δg), and O2(3Σg-) of T1(ππ*) and T1(nπ*) sensitizers in the nCT channel, whereby the excess energy (ΔE) dependence of t...

Structural transition of inversion domain boundaries through interactions with stacking faults in epitaxial GaN

In epitaxial wurtzite GaN, structural transformations of inversion domain boundaries on prismatic planes are observed at their intersections with stacking faults on the basal plane. High resolution electron microscopy observations show that, following the growth direction, the inversion domain boundaries are transformed from the low-energy and electrically nonactive IDB* type to the high-energy, electrically active, Holt-type structure. By using the topological theory of interfacial defects, it is proved that these transitions are due to the interaction of two distinct planar defects, and can be attributed to the different growth rates of adjacent domains of inverse polarity. The junction lines of the planar defects are characterized by employing the circuit mapping technique as formulated mathematically for multicomponent crystal systems. It is found that these lines exhibit partial dislocation character and an analytical account of such lines is presented.

Solvent effect on the quenching of singlet oxygen by 3-methylindole

Detection of O2(1Δg) emission, λmax = 1270 nm, following laser excitation and steady-state methods were employed to measure total, kT , and chemical, kR , reaction rate constants for the reaction between 3-methylindole and singlet oxygen in several solvents. Values of kT range from 0.12 ± 0.008 × 107 M−1 s−1 in n-heptane to 32.0 ± 1.12 × 107 M−1 s−1 in D2O at pD = 7.4. Analysis of the solvent effect on kT by using the semiempirical and theoretical linear solvent free-energy relationship (LSER and TLSER) solvatochromic equations indicates that singlet oxygen deactivation by 3-methylindole is accelerated by solvents with large π* values. This result supports the participation of an exciplex intermediate with partial charge transfer character, leading to either chemical reaction or physical quenching. The contribution of chemical reaction to total quenching depends significantly on the solvent. Chemical reaction can be neglected in non-polar solvents, whereas in hydrogen-bond donor solvents, such as methanol or D2O, chemical reaction is near to 30–40%. Solvents with larger π* and α values increase the contribution of chemical reaction relative to that of physical quenching.

Resonance Raman spectroscopy and density functional theoretical calculations of manganese corroles.: A parallelism between high-valent metallocorroles and metalloporphyrins, relevant to horseradish peroxidase and chloroperoxidase compound I and II intermediates

Soret-excited resonance Raman (RR) spectra are reported for the Mn(III) and Mn(IV)Cl derivatives of meso-tris( p-(trifluoromethyl)phenyl)corrole, H 3T( p-CF 3-P)Cor, and the Mn(III) derivative of β-octabromo- meso-tris( p-(trifluoromethyl)phenyl)corrole, H 3Br 8T( p-CF 3-P)Cor. Three high-frequency bands in the RR spectrum of Mn III[T( p-CF 3-P)Cor] at 1465, 1524 and 1615 cm −1 appear to upshift to 1486, 1528 and 1620 cm −1 for Mn IV[T( p-CF 3-P)Cor]Cl. This suggests that the electronic character of the corrole ligand is significantly different for these two compounds, which is consistent with electrochemical evidence for partial radical character of the corrole ligand for Mn IV[T( p-CF 3-P)Cor]Cl but not for Mn III[T( p-CF 3-P)Cor]. The observed upshifts are also consistent with DFT calculations showing a shortening of some of the relevant bonds in the Mn(IV)Cl derivative relative to the Mn(III) derivative. The results raise the possibility of an extensive parallelism between the electronic structures of high-valent metallocorroles and metalloporphyrins. Three high-frequency bands in the RR spectrum of Mn III[T( p-CF 3-P)Cor] at 1331, 1465 and 1545 cm −1 appear to downshift to 1320, 1457 and 1537 cm −1 for Mn III[Br 8T( p-CF 3-P)Cor]. This is consistent with the suspected longer carbon–carbon bond lengths in the brominated corrole macrocycle.

Electronic Effects on the Stability of Isomeric Alkyl Transition Metal Compounds

Density functional calculations on a variety of alkyl−transition metal complexes R−M are reported. Specifically, the following compounds have been studied: zirconocene complexes [Cp2Zr(H)R], [Cp2Zr(Cl)R], [Cp2ZrR]+, and [Cp*2Zr(Cl)R]; iron compounds [CpFe(CO)2R] and [CpFe(CO) {P(CH3)3}]; dimethylamino−dithiocyanato−palladium complexes [{(CH3)2NCS2}Pd{P(CH3)3}R]; and cationic diimino palladium complexes [{NN}Pd(L)R]+ (with {NN} = HNCH−CHNH or N,N‘-(o,o‘-bis-diisopropylphenyl)diiminoacenaphthalene, and L = nothing, Cl-, (CH3)2O, (CH3)2S, C2H4, or CH3CN). The R groups considered are methyl, n-propyl, isobutyl, isopropyl, and tert-butyl, thus covering the whole range from primary groups to tertiary ones. It is shown that primary alkyl complexes are usually more stable than secondary and tertiary ones and that this is an electronic effect, due to the partial carbanionic character of the alkyl group. Steric effects, which are usually invoked in the literature whenever this issue is considered, are shown to play only a minor role in many cases. Notable exceptions occur in the case of extremely bulky compounds or for systems in which the metal−carbon bond is less polar.

Influence of Charge Transfer Interactions on the Sensitization of Singlet Oxygen: Formation of O2(1Σg+), O2(1Δg), and O2(3Σg-) during Oxygen Quenching of Triplet Excited Biphenyl Derivatives

Both excited singlet states 1Σg+ and 1Δg and the triplet ground state 3Σg- of molecular oxygen are formed with varying rate constants kT1Σ, kT1Δ, and kT3Σ, respectively during the quenching by O2 of triplet states T1 of sufficient energy ET. The present paper reports these rate constants for a series of 10 biphenyl sensitizers of very different oxidation potential, Eox, but almost constant and rather large ET. Strong and graduated charge transfer (CT) effects on kT1Σ, kT1Δ, and kT3Σ are observed. These data are analyzed considering data of kT1Σ, kT1Δ, and kT3Σ determined previously for sensitizers of very different ET and Eox. The results clearly demonstrate that the quenching of triplet states by O2 proceeds via two different channels, each capable of producing O2(1Σg+), O2(1Δg), and O2(3Σg-). One quenching channel originates from excited 1,3(T1·3Σ) complexes with no CT character (nCT); the other originates from 1,3(T1·3Σ) exciplexes with partial charge transfer character (pCT). A common energy gap law d...

Probing opioid receptor-ligand interactions by employment of indolizidin-9-one amino acid as a constrained Gly(2)-Gly(3) surrogate in a leucine-enkephalin mimic.

The relationship between the conformation and biological activity of Leu-enkephalin was studied using (2S,6R,8S)-9-oxo-8-N-(Boc)amino-1-azabicyclo[4.3.0]nonane-2-carboxylic acid [(2S,6R,8S)-1, I(9)AA] as a constrained Gly(2)-Gly(3) dipeptide surrogate. [I(9)AA](2,3)-Leu-enkephalin 12 was assembled using solid-phase peptide synthesis on Merrifield resin with TBTU as the coupling reagent. The in vitro assays indicated that [I(9)AA](2,3)-Leu-enkephalin 12 exhibited affinities for the mu- and delta-opioid receptors that were three orders of magnitude lower than that of Leu-enkephalin, as well as partial agonist character for both receptors. In in vivo assays for spinal analgesia, the indolizidinone analog 12 showed significantly enhanced duration of action, indicating an increased metabolic stability. Conformational analysis was performed using NMR and CD spectroscopy. The amide temperature coefficients and 3J(NH-CalphaH) coupling constants for 12 could not support a hydrogen-bonded beta-turn structure; however, its CD spectrum indicated a turn conformation. Incorporation of indolizidinone amino acid 1 into Leu-enkephalin thus provided additional support for the importance of a turn conformation for the biological activity of the native peptide.

Crystal Structure of a Mutant hERα Ligand-binding Domain Reveals Key Structural Features for the Mechanism of Partial Agonism

The crystal structure of a triple cysteine to serine mutant ERalpha ligand-binding domain (LBD), complexed with estradiol, shows that despite the presence of a tightly bound agonist ligand, the protein exhibits an antagonist-like conformation, similar to that observed in raloxifen and 4-hydroxytamoxifen-bound structures. This mutated receptor binds estradiol with wild type affinity and displays transcriptional activity upon estradiol stimulation, but with limited potency (about 50%). This partial activity is efficiently repressed in antagonist competition assays. The comparison with available LBD structures reveals key features governing the positioning of helix H12 and highlights the importance of cysteine residues in promoting an active conformation. Furthermore the present study reveals a hydrogen bond network connecting ligand binding to protein trans conformation. These observations support a dynamic view of H12 positioning, where the control of the equilibrium between two stable locations determines the partial agonist character of a given ligand.

A Note on the Convolution of the Uniform and Related Distributions and Their Use in Quality Control

Consider a product with quality characteristic X. Assume that the product is composed of n parts each with quality characteristic Xi ,a nd and let X = X1 + ··· + Xn Assume that there is a lower specification L and an upper specification U for X. Then the problem arises how to select suitable specifications for the quality characteristics Xi of the parts. If the type of distributions of the partial quality characteristics Xi are known, then for solving the specification problem, the distribution of X = X1 + ··· + Xn is needed. In case of measurable quality features, usually the normal model is assumed for the Xi and the problem of deriving the distribution of X is solved in the well-known way. However, generally the only feature of Xi which is known with certainty is its bounded support, which follows from technical conditions. In such a case the normal approximation which is based on an unbounded support of each Xi may lead to a distribution of X which does not reflect reality sufficiently well. In this paper, the uniform or a related distribution is assumed for the partial quality character- istics and an explicit expression for the distribution of the sum X is derived. The usefulness of the result is illustrated by an example taken from industrial practice.

The first noncoordinated phosphonium diylide, [Me2P(C13H8)2]-, and its ylidic and cationic counterparts: synthesis, structural characterization, and interaction with the heavy group 2 metals.

Treatment of potassium or lithium fluorenide with MePCl2 generates the organophosphine MeP(C13H9)2, which on reaction with methyl iodide produces the phosphonium species [Me2P(C13H9)2]I in 74% yield. In the solid state, H...I contacts of < 3.3 A help generate a layered structure in which the fluorenyl rings are nearly parallel. On subsequent reaction of [Me2P(C13H9)2]I with either KH or K[N(SiMe3)2], the corresponding neutral phosphoylide, Me2P(C13H9)(C13H8), forms in 67% yield and was structurally characterized. The phosphonium iodide [Me2P(C13H9)2]I was allowed to react with Ae[N(SiMe3)2]2 (Ae = Ca, Ba), and the product from the reaction with the calcium complex was structurally identified as the salt [CaI(thf)5][Me2P(C13H8)2]. The anion, which is outside the coordination sphere of the calcium, represents the first structurally authenticated example of a free phosphonium diylide. The P-C(ylidic) bond length of 1.748(4) A reflects some partial multiple bond character. 1H and 31P NMR spectra suggest that the barium analogue is similar. Density functional theory calculations were performed on representative phosphonium diylides as an aid to interpreting the bonding in this class of compounds. Despite the strong electrostatic attraction that usually drives metal-ligand binding in highly ionic systems, calcium and barium prefer to coordinate to a single iodide ion and several neutral oxygen donors rather than to the charged diylide.