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The chromium(0)-carbene complex benzannulation reaction was shown to be applicable to cyclodec-4-yn-1-one. Significant regioselectivity was realized in this reaction with ortho-substituted benzylchromium complexes. Reactions of a novel resultant fused cyclodecenone-naphthoquinone with several bases have been studied. Products apparently arising from either intramolecular Michael addition of a ketone enolate to the quinone or intramolecular aldol condensation of a quinone-stabilized anion with the ketone have been observed. The latter mode constitutes a route to the title substructure and, in principle, a route to reach certain angucycline antibiotics

The first total synthesis of racemic indolizomycin (1) has been achieved. Initial investigations provided the functionalizcd indolizidine, 31, via (i) stereospecific intramolecular vinylsilane/carbinol amide cyclization (15→16), (ii) rhodium(II) acetate mediated diazoacetate insertion into thioamide 17, and (iii) epoxide introduction (25→27→29). Although subsequent attempts to fully elaborate 31 into indolizomycin were unsuccessful, these experiments formed the basis of a revised route which did ultimately produce the natural product

Internal arylation reactions of enol ethers were used to form the 1,5-epoxybenzazocine ring system of FR 900482. An interesting inversion process was observed for Z-enol ethers

A pyranosyl diene appropriately substituted for use in a total synthesis of staurosporine has been synthesized. The mono-epoxides and bis-epoxides obtained from treatment of this diene with dimethyldioxirane are unusually stable.

The chromium(0)-carbene complex benzannulation reaction was shown to be applicable to cyclodec-4-yn-1-one. Significant regioselectivity was realized in this reaction with ortho-substituted benzylchromium complexes. Reactions of a novel resultant fused cyclodecenone-naphthoquinone with several bases have been studied. Products apparently arising from either intramolecular Michael addition of a ketone enolate to the quinone or intramolecular aldol condensation of a quinone-stabilized anion with the ketone have been observed. The latter mode constitutes a route to the title substructure and, in principle, a route to reach certain angucycline antibiotics

Hippocampal CA1 pyramidal cell neurons are sensitized over 30-fold to depolarization by L-2-amino-4-phosphonobutanoic acid (L-AP4) following exposure to L-quisqualic acid. This phenomenon has been termed the QUIS effect. In the present study several novel L-quisqualic acid analogues have been synthesized and tested for their interaction with the different components of the QUIS-effect system. Replacement of the oxadiazolidinedione ring of L-quisqualic acid with several other types of heterocyclic rings yielded the following quisqualic acid analogues: maleimide 2, N-methylmaleimide 3, N-(carboxymethyl)maleimide 4, succinimides 5A and 5B, and imidazolidinedione 6. None of these analogues were able to mimic the effects of L-quisqualic acid and sensitize hippocampal CA1 neurons to depolarization by L-AP4. Also, unlike L-serine O-sulfate, L-homocysteinesulfinic acid, or L-alpha-aminoadipic acid, none of the analogues were able to preblock or reverse the QUIS effect. However, when the IC50 values for inhibition of the CA1 synaptic field potential of analogues 2-6 were determined both before and after hippocampal slices were exposed to L-quisqualic acid, the IC50 values of analogues 3 and 4 were found to decrease more than 7-fold. Thus, these two compounds behave like L-AP4 rather than L-quisqualic acid in this system in that they exhibit increased potencies in slices that have been pretreated with L-quisqualic acid even though they cannot themselves induce this sensitization. Compounds 3 and 4, therefore, represent the first non-phosphorus-containing compounds to which hippocampal neurons become sensitized following exposure to L-quisqualic acid. No change in the IC50 values was observed for 5A or 5B. Analogues 2 and 6, on the other hand, displayed a high potency for inhibition of the evoked field potential even prior to treatment of the slices with L-quisqualic acid.

In 42 type II diabetic patients with nonproliferative diabetic retinopathy the arm-retina time (ART) and arteriovenous passage time (AVP) were measured by means of videofluorescein angiography. Glycosylated hemoglobin (HbAlc) as a parameter of longterm diabetic control and the blood glucose level were determined. The ART in the diabetics was similar to the ART of normals and the AVP was significantly prolonged. HbAlc level ranged between 5.6 and 12.2% (8.6 +/- 1.7%) and the blood glucose level between 4.5 and 22.9 mmol/l (11.4 +/- 4.5 mmol/l). Significant correlations were found between AVP and blood glucose (r = 0.37) and between AVP and HbAlc (r = 0.49). No correlation was found neither between ART and blood glucose nor between ART and HbAlc. A multiple stepwise regression analysis shows that of both investigated parameters HbAlc is the predicting variable for AVP. These results show that in diabetic patients the retinal blood flow is more influenced by the longterm diabetic control than by the blood glucose level at the time of examination.

Hippocampal CA1 pyramidal cell neurons are sensitized to depolarization by l -2-amino-4-phosphonobutanoic acid ( l -AP4) following exposure to l -quisqualic acid (QUIS). We have examined the interaction of 43 structural analogues of l -AP4 with both the ‘induction’ site and the QUIS-sensitive AP4 site in rat hippocampus. The synthesis ofcis- andtrans-4-phosphonoxyl- l -proline, 3-(RS)-amino-5-phosphonopentanoic acid and 2(RS)-amino-5-phenyl-4(RS)-phosphonopentanoic acid (γ-benzyl AP4) are described. None of the test compounds interact with the induction site; thus l -QUIS remains the only compound known to induce this effect. However, one compound ( l -2-amino-3-(5-tetrazolyl) -propanoic acid ( l -aspartate tetrazole) ‘pre-blocked’ and reversed the effects of QUIS. In addition, the potency of 16 analogues increased more than 4-fold following exposure of slices to l -QUIS. Among these, l -AP4, l -AP5, 2-amino-4-(methylphosphino) butanoic acid (AMPB), andE-1(RS)-amino-3(RS)-phosphonocyclopentanecar☐ylic acid (E-cyclopentyl AP4) diplayed IC50 values of less than 0.100mM after QUIS. The results presented here suggest that the QUIS-sensitive AP4 site requires a spatial configuration of functional groups similar to that present inE-cyclopentyl AP4. The presence of a primary amino group and a phosphorus-containing group (either monoanionic or dianionic) appear to be required, however, a car☐yl group is not essential for interaction. The pharmacology of the QUIS-sensitive AP4 site suggest that it is distinct from other known binding sites for l -AP4 in the central nervous system (CNS).

The revised structure of sporol is confirmed by the synthesis of the racemate. Tri-n-butylstannyl radical induced fragmentation of a thionocarbonate and subsequent cyclization is employed to prepare a key component in the synthesis.

Amino amides react as trinucleophiles with vinyl vicinal tricarbonyl esters. Reaction of the primary amino group takes place at the β-position of the α,β-unsaturated ketone along with addition to the central carbonyl group. In a third-stage reaction, the amide residue adds to the iminium ion formed from the intermediate carbinolamine

Rheological parameters (hematocrit, plasma viscosity and red blood cell aggregation index), glycosylated hemoglobin (HbAlc) and retinal arteriovenous passagetime (A vP) were measured in 93 patients with type I diabetes. The stage of diabetic retinopathy was graded by means of ophthalmoscopy and video fluorescein angiography. The mean values of hematocrit (men 46 ± 4%, women 43 ± 3 %), RBC aggregation index (13,8 ± 3,8, normals: 14,6 ± 3,2) were equal to normals. Plasma viscosity (1,33 ± 0,09 mPas, normais:l,24 ± 0,05 mPas) was increased. The groups with increasing stage of diabetic retinopathy showed no difference in hematocrit, RBC aggregation and HbAlc and an increase of plasma viscosity. In patients with bad glycemic control plasma viscosity was increased and RBC aggregation index was similar as compared with patients with good glycemic control. If retinal arteriovenous passagetime was worse plasma viscosity and RBC aggregation were more increased. This indicates, that alterated plasma viscosity and RBC aggregation may be one of the reasons for disturbed microcirculation and fundus changes ill diabetic retinopathy.

Serotonin type 3 receptors (5-HT(3)R) are members of the ligand gated ion channel receptor family. In this study, the interactions of the agonists serotonin (5-HT) and m-chlorophenylbiguanidine (mCPBG) at the binding site of the 5-HT(3A)R were investigated at an atomic level. Site-directed mutagenesis studies in Loop B and E along with our earlier published results from mutations within Loops A, C, and D provide comprehensive data on the interaction of 5-HT and mCPBG with 5-HT(3A)Rs. Using this data we have constructed a refined homology model of the 5-HT(3A)R that considers all of the available experimental data. 5-HT and mCPBG were docked into the newly constructed homology model and the amino acid residues critical in binding of these agonists were compared and analyzed. Our docking results reveal many similar binding interactions for 5-HT and mCPBG. Namely, residues THR181, TRP183, PHE226, ILE228, TYR234 and GLU129 were all found to play key roles in binding of both 5-HT and mCPBG. However, the results also revealed two important differences that exist between the interactions of the two agonists. In our model, a hydrogen bond is formed between the indole hydrogen of 5-HT and the residue TYR153. This interaction is not present in the case of mCPBG. Conversely, a hydrogen bond exists between SER182 and a protonated nitrogen of mCPBG, which does not exist in 5-HT. Our modeling results were found to be in accordance with experimental data.

The reactions of singlet oxygen with 3-methoxy-2-carbalkoxypyrroles lead to 2,5-oxygenation, 2,3-epoxides, or 2,3-oxidative cleavage, depending on substitution patterns and reaction conditions.

Acute anterior ischemic optic neuropathy (AION) is a circulatory disorder of the short posterior ciliary arteries and their branches. 74 patients with AION were examined with video fluorescein angiography for disturbance of the retinal circulation. The armretina time (ART) was slightly (15%, p less than 0.01) increased in patients with AION (12.9 +/- 3.9 s) as compared to healthy persons (11.2 +/- 3.3 s). The prolonged ART was more prominent in the 26 (35.1%) diabetic patients (14.2 +/- 3.9 s). Because of the ART being only moderately prolonged and since the Doppler ultrasonography of the carotid arteries showed in only 3 patients an occlusion or a hemodynamically relevant stenosis of greater than or equal to 50%, prolonged ART may play a considerable role in the course of AION in only few patients. The retinal arteriovenous passage time (AVP) is considerably (77%, p less than 0.01) increased in AION (2.57 +/- 0.89 s) as compared to healthy persons (1.45 +/- 0.40 s). In patients with duration of symptoms less than 10 days (2.78 +/- 0.96 s) the AVP was increased (p less than 0.01) as compared to patients with duration of symptoms between 11 and 30 days (2.11 +/- 0.46 s). The comparison between the eye with AION and the not affected eye showed no difference in ART but an increase of AVP in the eye with AION. The AVP in AION patients without and with diabetes was not different. No differences in ART and in AVP were found between arteriitic and non-arteriitic patients with AION. The results indicate that the retinal microcirculation is disturbed in patients with arteriitic and non-arteriitic AION. This condition may worsen the in AION affected microcirculation of the optic nerve head through the mechanism of decreased blood flow in the retinociliary anastomoses.

The hemodynamic status of 26 patients with retinitis pigmentosa was examined using video fluorescein angiography. The hemorheological parameters hematocrit, plasma viscosity, erythrocyte aggregation and erythrocyte rigidity were determined. The results were compared to a matched pairs-group. Video angiography showed for retinitis pigmentosa patients a normal arm-retina time and a significant increase of the arteriovenous passage time. The rheological parameters for both groups were within the reference range. Interestingly the hemodynamic disturbance of microcirculation could be demonstrated already in early stages with no ophthalmoscopic symptoms and no atrophy of retinal vessels detectable at the time. The results indicate that disturbance of the retinal hemodynamics in early stages of retinitis pigmentosa may play a role in the pathogenesis of the disease.

Enzymatically mediated acetylation of racemic 5 leads to enantiomerically homogeneous precursors of calicheamicinone and ent -calicheamicinone.

Reactions of aryl and hetero vicinal tricarbonyl derivatives with aldehyde Schiff bases of the general structure RCH2CHO lead to pyrrolinone derivatives by benzilic acid-related rearrangements, driven, most probably, by iminium ion intermediates.

A total of 209 diabetic children and adolescents aged 6-17 years (mean, 12.6 +/- 2.3 years) were examined by ophthalmoscopy, video fluorescein angiography and hemoglobin (HbA1c) test. Microaneurysms were found in 26% of the children (ophthalmoscopy, 11%; angiography, 23%). The prevalence of retinopathy was 16% in patients aged 6-10 years, 27% in those aged 11-13 years and 36% in those aged 14-17 years. Only five diabetics aged 11-17 years showed lesions other than microaneurysms (hard exudates, intraretinal hemorrhages or retinal capillar leakage). Retinal blood flow was quantified using video fluorescein angiography. The arm-retina time (ART) and the arteriovenous passage time (AVP) as parameters of the retinal microcirculation were obtained using an image analysing system. The mean value for ART was 9.7 +/- 2.5 s and that for AVP was 1.43 +/- 0.52 s. AVP was significantly shorter in diabetic children and adolescents with good glycemic control (HbA1c, less than 7%; AVP, 1.35 +/- 0.44 s) than in those with bad glycemic control (HbA1c, greater than or equal to 9%; AVP, 1.65 +/- 0.51 s).

The self-assembly of organic molecules on surfaces is a promising approach for the development of nanoelectronic devices. Although a variety of strategies have been used to establish stable links between molecules, little is known about the electrical conductance of these links. Extended electronic states, a prerequisite for good conductance, have been observed for molecules adsorbed on metal surfaces. However, direct conductance measurements through a single layer of molecules are only possible if the molecules are adsorbed on a poorly conducting substrate. Here we use a nanoscale four-point probe to measure the conductivity of a self-assembled layer of cobalt phthalocyanine on a silver-terminated silicon surface as a function of thickness. For low thicknesses, the cobalt phthalocyanine molecules lie flat on the substrate, and their main effect is to reduce the conductivity of the substrate. At higher thicknesses, the cobalt phthalocyanine molecules stand up to form stacks and begin to conduct. These results connect the electronic structure and orientation of molecular monolayer and few-layer systems to their transport properties, and should aid in the rational design of future devices.

Microcantilevers (MCLs) hold a position as a cost-effective and highly sensitive sensor platform for medical diagnostics, environmental analysis and fast throughput analysis. MCLs are unique in that adsorption of analytes on the microcantilever (MCL) surface changes the surface characteristics of the MCL and results in bending of the MCL. Surface stress due to conformation change of proteins and other polymers has been a recent focus of MCL research. Since conformational changes in proteins can be produced through binding of anylates at specific receptor sites, MCLs that respond to conformational change induced surface stress are promising as transducers of chemical information and are ideal for developing microcantilever-based biosensors. The MCL can also potentially be used to investigate conformational change of proteins induced by non-binding events such as post-translational modification and changes in temperature or pH. This review will provide an overview of MCL biosensors based on conformational change of proteins bound to the MCL surface. The models include conformational change of proteins, proteins on membranes, enzymes, DNA and other polymers.

Reaction of ReH 3 (CO)(PMe 2 Ph) 3 with Ph 3 SiH and Ph 3 SnH in refluxing THF leads to the formation of ReH 2 (EPh 3 )(CO)(PMe 2 Ph) 3 (E=Si (2), Sn (3)). The solution spectroscopic data are consistent with the formulation of 2 and 3 as seven-coordinate with no H...H or Si...H interactions, but they are stereochemically rigid on the NMR time scale even at elevated temperatures, which is unusual for seven-coordinate complexes containing only monodentate ligands. Compound 2 has been structurally characterized by single-crystal X-ray crystallography in solvated and unsolvated forms. Crystal data for 2: monoclinic, space group P2 1

A new polyhydroxylated lactone, discodermolide (1), was isolated from a Caribbean marine sponge, Discodermia dissoluta, and its structure was elucidated through a combination of spectroscopic techniques, in particular NMR spectroscopy, and verified by X-ray crystallographic analysis. The carbon skeleton displayed by discodermolide is new; discodermolide is immunosuppressive and cytotoxic

The synthesis of a racemic, which contains the relative stereochemistry appropriate to a synthesis of (9S)-dihydro-6-deoxyerythronolide B, is described. The synthesis features three Lewis acid catalyzed diene aldehyde cyclocondensation reactions, using, in each instance, (E,E)-1-methoxy-2-methyl-3-(trimethylsilyloxy) penta-1,3-diene

The lanthanide-iodide compounds Cp{double prime}{sub 2}Ln(I)(NCMe){sub 2} (Ln = La, Ce; Cp{double prime} = 1,3-C{sub 5}H{sub 3}(SiMe{sub 3}){sub 2}) serve as useful precursors for complexes containing the early-lanthanide fragments (Cp{double prime}{sub 2}Ln{sup III}){sup +}. This moiety has been incorporated into compounds in which it binds either neutral or anionic ligands. Among these is the heterobimetallic compound (Cp{double prime}{sub 2}Ce({mu}-{eta}{sup 2}-OC)W(CO)(Cp) ({mu}-{eta}{sup 2}-CO)){sub 2} (3), which is unusual in that the cerium(III) center is wholly nonemissive. This observation is explained on the basis of cerium-to-tungsten excited-state energy transfer, since dissolution in polar solvent (acetonitrile) leads to symmetrically solvated ions, loss of close Ce-W contact, and cerium(III) luminescence. Finally, the ionic compounds (Cp{double prime}{sub 2}Ln(NCMe)(DME))(BPh{sub 4}){center dot}0.5DME (5) have been prepared and the lanthanum analogue (5b) has been structurally characterized.

General protocols for the transformation of substituted dihydroisoquinolines into functionalized benzazepine products are described. An important element involves initial hydrolytic succinoylation of a dihydroisoquinoline to afford a ring-opened intermediate. Subsequent closure to the homologous benzazepine ring is accomplished by condensation of several carbenoid-type equivalents with monothioimide and thioamide carbonyl groups. Application of this methodology to a formal synthesis of cephalotaxine is described

We have investigated the sensing performance of protein-based microcantilever biosensors prepared from multiple surface conjugation chemistries. The 11-mercaptoundecanoic acid monolayers were prepared according to both traditional and modified processes. In three protein-based biosensors, the modified process improved microcantilever sensing performance by increasing the bending amplitude, a critical step toward developing a cost-effective microcantilever-based sensor platform for medical diagnostics and environmental and drug screening applications. Scanning electron microscopy (SEM) images demonstrated that proteins immobilized on the microcantilever surface using the modified chemistry approach formed a compact layer.

OBJECTIVES: Arctic and northern peoples are spread across Alaska, Canada, Russia and the Scandinavian countries. Inhabiting a variety of ecosystems, these 4 million residents include Indigenous populations who total about 10% of the population. Although Arctic peoples have very diverse cultural and social systems, they have health issues related to environmental impacts and knowledge/treatment disparities that are common to other minority and Indigenous peoples around the world. Research that explores the neuroscience and behavioural aspects of these health disparities offers challenges and significant opportunities. As the next generation of neuroscientists enter the field, it is imperative that they view their contributions in terms of translational medicine to address health disparities. STUDY DESIGN: A workshop was designed to bring neuroscientists together to report on the current directions of neuroscience research and how it could impact health disparities in the North. This workshop produced research recommendations for the growth of neuroscience in the North. METHODS: On May 31, 2006 the National Institute of Neurological Disorders and Stroke, the Burroughs Wellcome Foundation, the Arctic Division of AAAS and the University of Alaska co-sponsored a workshop entitled "Arctic Peoples and Beyond: Decreasing Health Disparities through Basic and Clinical Research." Also, the role and goals of the International Union for Circumpolar Health (IUCH) were presented at the meeting. RESULTS: A set of recommendations related to research opportunities in neuroscience and behaviour research and ways to facilitate national and international partnerships were developed. CONCLUSIONS: These recommendations should help guide the development of future health research in circumpolar neuroscience and behaviour. They provide ideas about research support and informational exchange that will address health challenges. Keywords: behaviour; brain disease; health disparity research; international collaboration; SIDS; stroke (Int J Circumpolar Health 2007; 66(3):264-275)

We have determined the on-site molecular Coulomb interaction energy U of a (C59N)2 bulk film and find values ranging from 1.10+/-0.10 eV for the highest occupied molecular orbital to 1.35+/-0.10 eV for the deeper lying orbitals, comparable to values found in C60. The on-site Coulomb interaction between a carbon core hole and valence electrons, Uc, is, however, substantially lower than in C60 at 1.35+/-0.07 eV. Resonant photoemission (RESPES) results show a weakened participator decay channel, especially around the N 1s threshold, where resonance of the highest occupied molecular orbital shoulder is absent. Near-edge x-ray absorption fine structure and constant initial state measurements, taken in parallel with the RESPES data, indicate, however, that matrix element effects cannot be ruled out.

Organic molecules are rapidly finding their way into electronic architectures and photovoltaic devices. In recent years a pronounced increase in efficiency has been achieved, which is largely due to the virtually unlimited tunability of the building blocks. Indeed, by selecting specific molecular structures and chemically optimizing their interaction with substrates and each other we can dramatically affect the macroscopic properties of novel assemblies. Metallo-organic molecules, like the phthalocyanines, are of particular interest as they can also carry localized magnetic moments. Phthalocyanines are a class of stable, blue-green synthetic pigments which can be synthesized with a variety of metal ions at their center. They are related to the biologically important porphyrin family, which includes molecules like heme and chlorophyll. Within molecular nanotechnology their strong optical absorption is already being exploited in photovoltaic devices containing phthalo-fullerene mixed phases. However, they also display other useful bulk optical properties including dichroism and luminescence, and are used in gas-detection. We have focused our experiments on cobalt phthalocyanine (CoPc) which consists of a planar carbon and nitrogen macrocycle with a single cobalt ion (see Fig. 1, inset). The cobalt ion has a partially filled 3d-orbital and is magnetically active. With this in mind, restricting phthalocyanine assemblies to one or two dimensions raises a variety of exciting issues as to what will happen to the electronic structure and hence to their optical, magnetic and transport properties. A particularly powerful method of forming one-dimensional molecular arrays is the encapsulation in a carbon nanotube. The selection of carbon nanotubes as the container structures is motivated in part by the fact that nanotubes can act as a confining, as well as a shielding, environment. Since we are dealing with planar molecules the precise internal stacking order will be important in assessing the physical properties of this assembly. Previously, planar molecules with a large aspect ratio, such as rectangular perylene-3,4,9,10-tetracarboxylic-3,4,9,10dianhydride (PTCDA) have been shown to align virtually parallel to the nanotube axis, whereas the elliptical fullerene C70 will align their long axis with the nanotube axis in narrow nanotubes (diameter 13.6 A), but stand up in wider nanotubes (≥ 14.9 A). Magnetic effects have been observed recently in the encapsulation of azafullerene (C59N). [11]