Metal complexes of a tetraazacyclophane: solution and molecular modelling studies

An alternative synthetic approach to yield the compound 2,3,5,6,8,9,11,14-octahydrobenzo[1][ 1,4,7,10]tetraazacyclotetradecine (bz[14]N-4) is presented. The protonation constants of bz[14]N-4 and the stability constants of its complexes with Ni2+, Cu2+, Zn2+, Cd2+, Pb2+ were determined in H2O at 25degreesC with ionic strength 0.10 mol dm(-3) in KNO3 and they were compared with structurally related macrocycles cyclam (1,4,8,11-tetraazacyclotetradecane) and cyclen (1,4,7,10-tetraazacyclododecane). These studies indicate that only 1 : 1 ( M : L) species are formed in solution, and the ligand exhibits a high affinity for larger ions such as Cd2+ and Pb2+. The X-ray study of [bz[14]N4H3](3+) shows that an inclusion compound with a chloride counter-anion is formed through NH...Cl hydrogen bonds. Spectroscopic data in solution ( electronic and NMR spectra) showed that the macrocycle adopts a planar arrangement upon metal complexation. Molecular mechanics calculations reveal that in spite of the presence of the benzene ring in the macrocyclic framework this ligand can encapsulate metal ions with different stereo-electronic sizes in square planar arrangements. Our results indicate that the presence of the benzene ring in the backbone of the bz[14]N-4 confers a coordination behaviour intermediate between that of cyclam and cyclen.

Stille reactions of 2,3-bis(stannyl)butenoates: an unexpected regioselectivity

The palladium-catalyzed cross-coupling reaction of methyl (Z)-2,3-bis(tributylstannyl)butenoate with aryl iodides is regioselective, leading to 2-aryl-3-stannylated products; this selectivity is the opposite to that observed in the reaction between halides and 3,4-bis(stannyl)furan-2(5H)-one. Since the resulting butenoates can be converted into the corresponding furanones, the method provides useful flexibility in the preparation of functionalized butenoates and furanones.

First efficient and general copper-catalyzed [2,3]-rearrangement of tetrahydropyridinium ylids

The factors affecting the copper-catalyzed rearrangement of ammonium ylids derived from tetrahydropyriclines and diazoesters; have been examined,and the first examples of high-yielding metal-catalyzed [2,3]-sigmatropic rearrangements of a wide range of such ylids are reported. The nature of the alpha-substituent in the diazo component of the reaction has a dramatic effect upon the yields of the reaction, with electron-withdrawing substituents enhancing the yield of the reaction.

Asymmetric [2,3]-rearrangement of glycine-derived allyl ammonium ylids

The first examples of highly enantioselective [2,3]-sigmatropic rearrangements of acyclic allylic ammonium ylids are reported. Thus, a range of N-{2‘-[(N‘-allyl-N‘,N‘-dialkyl)ammonium]}acetyl camphor sultams undergo rearrangement at 0 °C in DME solution with high diastereofacial control (up to 99:1 dr) to give allylglycines in generally high yield. The power of the method has been demonstrated in a rapid and efficient synthesis of (R)-allyl glycine.

The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.

Aldol reaction of butane-2,3-diacetal protected methyl glycerate

The addition of aldehydes to butane-2,3-diacetal has been investigated. The reaction was shown to be both regioselective and diastereoselective by 1H NMR spectroscopy. The configuration of the newly formed stereocenter was determined by Mosher’s ester analysis.

Changes in race-specific virulence in pseudomonas syringae pv. phaseolicola are Associated with a chimeric transposable element and rare deletion events in a plasmid-borne pathogenicity island

Virulence for bean and soybean is determined by effector genes in a plasmid-borne pathogenicity island (PAI) in race 7 strain 1449B of Pseudomonas syringae pv. phaseolicola. One of the effector genes, avrPphF, confers either pathogenicity, virulence, or avirulence depending on the plant host and is absent from races 2, 3, 4, 6, and 8 of this pathogen. Analysis of cosmid clones and comparison of DNA sequences showed that the absence of avrPphF from strain 1448A is due to deletion of a continuous 9.5-kb fragment. The remainder of the PAI is well conserved in strains 1448A and 1449B. The left junction of the deleted region consists of a chimeric transposable element generated from the fusion of homologs of IS1492 from Pseudomonas putida and IS1090 from Ralstonia eutropha. The borders of the deletion were conserved in 66 P. syringae pv. phaseolicola strains isolated in different countries and representing the five races lacking avrPphF. However, six strains isolated in Spain had a 10.5-kb deletion that extended 1 kb further from the right junction. The perfect conservation of the 28-nucleotide right repeat of the IS1090 homolog in the two deletion types and in the other 47 insertions of the IS1090 homolog in the 1448A genome strongly suggests that the avrPphF deletions were mediated by the activity of the chimeric mobile element. Our data strongly support a clonal origin for the races of P. syringae pv. phaseolicola lacking avrPphF.

A genetic linkage map of an apple rootstock progeny anchored to the Malus genome sequence

An apple rootstock progeny raised from the cross between the very dwarfing ‘M.27’ and the more vigorous ‘M.116’ (‘M.M.106’ × ‘M.27’) was used for the construction of a linkage map comprising a total of 324 loci: 252 previously mapped SSRs, 71 newly characterised or previously unmapped SSR loci (including 36 amplified by 33 out of the 35 novel markers reported here), and the self-incompatibility locus. The map spanned the 17 linkage groups (LG) expected for apple covering a genetic distance of 1,229.5 cM, an estimated 91% of the Malus genome. Linkage groups were well populated and, although marker density ranged from 2.3 to 6.2 cM/SSR, just 15 gaps of more than 15 cM were observed. Moreover, only 17.5% of markers displayed segregation distortion and, unsurprisingly in a semi-compatible backcross, distortion was particularly pronounced surrounding the self-incompatibility locus (S) at the bottom of LG17. DNA sequences of 273 SSR markers and the S locus, representing a total of 314 loci in this investigation, were used to anchor to the ‘Golden Delicious’ genome sequence. More than 260 of these loci were located on the expected pseudo-chromosome on the ‘Golden Delicious’ genome or on its homeologous pseudo-chromosome. In total, 282.4 Mbp of sequence from 142 genome sequence scaffolds of the Malus genome were anchored to the ‘M.27’ × ‘M.116’ map, providing an interface between the marker data and the underlying genome sequence. This will be exploited for the identification of genes responsible for traits of agronomic importance such as dwarfing and water use efficiency.

Structural variations in self-assembled coordination complexes of Zn(II) with hexamethylenetetramine and isomeric 2-, 3- and 4-nitrobenzoates

Three new zinc(II)-hexamethylenetetramine (hmt) complexes [Zn-2(4-nbz)(4)(mu(2)-hmt)(OH2)(hmt)] (1). [Zn-2(2-nbz)(4)(mu(2)-hmt)(2)](n) (2) and [Zn-3(3-nbz)(4)(mu(2)-hmt)(mu(2)-OH)(mu(3)-OH)](n) (3) with three isomeric nitrobenzoate, [4-nbz = 4-nitrobenzoate, 2-nbz = 2-nitrobenzoate and 3-nbz = 3-nitrobenzoate] have been synthesized and structurally characterized by X-ray crystallography. Their identities have also been established by elemental analysis: IR, NMR, UV-Vis and mass spectral studies. 1 is a dinuclear complex formed by bridging hmt with mu(2) coordinating mode. The geometry around the Zn centers in 1 is distorted tetrahedral. Paddle-wheel centrosymmetric Zn-2(2-nbz)(4) units of complex 2 are interconnected by mu(2)-hmt forming a one-dimensional chain with square-pyramidal geometries around the Zn centers. Compound 3 contains a mu(2)/mu(3)-hydroxido and mu(2)-hmt bridged 1D chain. In this complex, varied geometries around the Zn centers are observed viz, tetrahedral, square pyramidal and trigonal bipyramidal. Various weak forces, i.e. lone pair-pi, pi-pi and CH-pi interactions, play a key role in stabilizing the observed structures for complexes 1,2 and 3. This series of complexes demonstrates that although the nitro group does not coordinate to the metal center, its presence at the 2-, 3- or 4-position of the phenyl ring has a striking effect on the dimensionality as well as the structure of the resulted coordination polymers, probably due to the participation of the nitro group in 1.p.center dot center dot center dot pi and/or C-H center dot center dot center dot pi interactions.

The neurochemically diverse intermedius nucleus of the medulla as a source of excitatory and inhibitory synaptic input to the nucleus tractus solitarii

Sensory afferent signals from neck muscles have been postulated to influence central cardiorespiratory control as components of postural reflexes, but neuronal pathways for this action have not been identified. The intermedius nucleus of the medulla (InM) is a target of neck muscle spindle afferents and is ideally located to influence such reflexes but is poorly investigated. To aid identification of the nucleus, we initially produced three-dimensional reconstructions of the InM in both mouse and rat. Neurochemical analysis including transgenic reporter mice expressing green fluorescent protein in GABA-synthesizing neurons, immunohistochemistry, and in situ hybridization revealed that the InM is neurochemically diverse, containing GABAegric and glutamatergic neurons with some degree of colocalization with parvalbumin, neuronal nitric oxide synthase, and calretinin. Projections from the InM to the nucleus tractus solitarius (NTS) were studied electrophysiologically in rat brainstem slices. Electrical stimulation of the NTS resulted in antidromically activated action potentials within InM neurons. In addition, electrical stimulation of the InM resulted in EPSPs that were mediated by excitatory amino acids and IPSPs mediated solely by GABA(A) receptors or by GABA(A) and glycine receptors. Chemical stimulation of the InM resulted in (1) a depolarization of NTS neurons that were blocked by NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonoamide) or kynurenic acid and (2) a hyperpolarization of NTS neurons that were blocked by bicuculline. Thus, the InM contains neurochemically diverse neurons and sends both excitatory and inhibitory projections to the NTS. These data provide a novel pathway that may underlie possible reflex changes in autonomic variables after neck muscle spindle afferent activation.

Synthesis, chemical, electrochemical characterization of oxomolybdenum(V) complexes of 2-(3,5-dimethyl pyrazol-1-yl) benzothiazole ligand: crystal structure of ligand and oxomolybdenum(VI) complex and density functional theory (DFT) calculation

This work reports the ligational behavior of the neutral bidentate chelating molecule 2-(3,5-dimethyl pyrazol-1-yl) benzothiazole towards the oxomolybdenum(V) center. Both mononuclear complexes of the type (MoOX3L)-O-V and binuclear complexes of the formula (Mo2O4X2L2)-O-V (where X = Cl, Br) are isolated in the solid state. The complexes are characterized by elemental analyses, various spectroscopic techniques (UV-Vis IR), magnetic susceptibility measurement at room temperature, and cyclic voltammetry for their redox behavior at a platinum electrode in CH3CN. The mononuclear complexes (MoOX3L)-O-V are found to be paramagnetic while the binuclear complexes Mo2O4X2L2 are diamagnetic. Crystal and molecular structure of the ligand and the dioxomolybdenum complex (MoO2Br2L)-O-VI (obtained from the complex MoOBr3L during crystallization) have been solved by single crystal X-ray diffraction technique. Relevant DFT calculations of the ligand and the complex (MoO2Br2L)-O-VI are also carried out.

Intramolecular Diels-Alder furan-mediated synthesis of 8-aryl-3, 4-di-hydroisoquinolin-1(2H)-ones, convenient precursors of indeno[1,2,3-ij]isoquinolines

We describe herein preliminary studies on the Intramolecular Diels-Alder Furan-Mediated Synthesis of 8-Aryl-3, 4-di-hydroisoquinolin-1(2H)-ones that constitutes a new, formal synthesis of Indeno[1,2,3-ij]isoquinolines.

Zinc mediated azide-alkyne ligation to 1,5- and 1,4,5-substituted 1,2,3-triazoles

A mild method for regioselective formation of 1,5-substituted 1,2,3-triazoles is described. The zinc-mediated reaction works at room temperature and is successful across a wide range of azido/alkynyl substrates. Additionally, the triazole 4-position can be further functionalized through the intermediate aryl-zinc to accommodate a diverse three-component coupling strategy.