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New evidence for ancient Greek astronomer Hipparchus’ lost Star Catalogue has come to light thanks to multispectral imaging of a palimpsest manuscript and subsequent decipherment and interpretation. This new evidence is the most authoritative to date and allows major progress in the reconstruction of Hipparchus’ Star Catalogue. In particular, it confirms that the Star Catalogue was originally composed in equatorial coordinates. It also confirms that Ptolemy’s Star Catalogue was not based solely on data from Hipparchus’ Catalogue. Finally, the available numerical evidence is consistent with an accuracy within 1° of the real stellar coordinates, which would make Hipparchus’ Catalogue significantly more accurate than his successor Claudius Ptolemy’s.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) are rare central demyelinating diseases that may affect refractive surgery outcomes. Optic neuritis and brainstem syndromes affecting cranial nerves are particularly relevant to corneal refractive surgery (CRS), such as laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy, or small incision lenticule extraction. There is currently no existing literature concerning the outcomes of CRS in patients with MOGAD or NMOSD. This article reports the clinical outcome of a MOGAD patient who underwent LASIK.

Structural brain changes precede cognitive and clinical symptoms in Alzheimer’s disease (AD). We aimed to examine the gray and white matter tissue changes in individuals with memory decline over a 12-year period, who might be at risk for AD. The participants were selected from the longitudinal Maastricht Aging Study based on their scores on the verbal word learning task. A group with profound memory decline over a 12-year period (n 20) was identified and matched with a group that did not meet this criterion (n 20). All of the participants underwent MRI scanning. Diffusion tensor imaging and cortical thickness analyses were performed to investigate the white and gray matter differences respectively. We found decreased white matter integrity in the memory decline group compared to the control group in frontal and parietal brain regions and in several cortico-cortical and cortico-subcortical tracts. Cortical thinning in the memory decline group was found in frontal, parietal, medial temporal and occipital areas. These results showed similarities with the structural brain changes observed in early AD. Thus, not only may cognitive changes be detected years before the clinical diagnosis, but typical gray and white matter changes appear to be present in older people with memory decline as well. This suggests that a combination of cognitive decline and structural brain changes might be an ideal biomarker for AD pathogenesis.

Organocopper chemistry has long been known to be powerful synthetic methodology leading to the generation of C-C, C-O, C-N, C-S and C-X bonds. Advances in catalytic and stoichiometric organometallic reactions for the formation of C-C bonds from unfunctionalised arenes, e.g. by activation-functionalisation of a C-H bond, provides diverse and applicable reaction conditions for direct functionalisation. This review covers the background, applications and recent advances made in the area of aromatic C-X/C-H-bond couplings promoted by copper and copper/palladium mixed systems. The efficacy and scope of these reactions are discussed and the different methodologies are placed into context. Mechanistic considerations and evidence are highlighted at appropriate junctures in the review.

Computer-assisted structure elucidation (CASE) using a combination of 1D and 2D NMR data has been available for a number of years. These algorithms can be considered as “logic machines” capable of deriving all plausible structures from a set of structural constraints or “axioms”, defined by the spectroscopic data and associated chemical information or prior knowledge. CASE programs allow the spectroscopist not only to determine structures from spectroscopic data but also to study the dependence of the proposed structure on changes to the set of axioms. In this article, we describe the application of the ACD/Structure Elucidator expert system to help resolve the conflict between two different hypothetical hexacyclinol structures derived by different researchers from the NMR spectra of this complex natural product. It has been shown that the combination of algorithms for both structure elucidation and structure validation delivered by the expert system enables the identification of the most probable structure as well as the associated chemical shift assignments.

Unsymmetrical indirect covariance processing methods allow the derivation of hyphenated 2D NMR data from the component 2D spectra, potentially circumventing the acquisition of the much lower sensitivity hyphenated 2D NMR experimental data. Calculation of HSQC-COSY and HSQC-NOESY spectra from GHSQC, COSY, and NOESY spectra, respectively, has been reported. The use of unsymmetrical indirect covariance processing has also been applied to the combination of 1H− 13C GHSQC and 1H− 15N long-range correlation data (GHMBC, IMPEACH, or CIGAR-HMBC). The application of unsymmetrical indirect covariance processing to spectra of vinblastine is now reported, specifically the algorithmic extraction of 13C− 15N correlations via the unsymmetrical indirect covariance processing of the combination of 1H− 13C GHSQC and long-range 1H− 15N GHMBC to produce the equivalent of a 13C− 15N HSQC-HMBC correlation spectrum. The elimination of artifact responses with aromatic solvent-induced shifts (ASIS) is shown in addition to a method of forecasting potential artifact responses through the indirect covariance processing of the GHSQC spectrum used in the unsymmetrical indirect covariance processing.

GHSQC-TOCSY experiments allow sorting of proton–proton connectivity information as a function of 13C chemical shift. GHSQC-TOCSY is a relatively insensitive 2D NMR experiment. Given two coherence transfer experiments, A → B and A → C, it is possible to indirectly determine B ↔ C. Unsymmetrical indirect covariance processing of a 1H– 13C GHSQC and a GCOSY spectrum afforded a GHSQC-COSY spectrum, with an information content analogous to a GHSQC-TOCSY experiment. However, GHSQC-TOCSY is of significantly lower sensitivity and the data require considerably more time to acquire than either of the component experiments. Investigators needing access to GHSQC-TOCSY type data can, in principle, access it from more readily acquired 2D NMR data. Strychnine ( 1) was used as a model compound to illustrate this capability.

An amorphous, catechol-based analogue of PEEK (“o-PEEK”) has been prepared by a classical step-growth polymerization reaction between catechol and 4,4‘-difluorobenzophenone and shown to be readily soluble in a range of organic solvents. Copolymers with p-PEEK have been investigated, including an amorphous 50:50 composition and a semicrystalline though still organic-soluble material comprising 70% p-PEEK. o-PEEK has also been obtained by entropy-driven ring-opening polymerization of the macrocyclic oligomers (MCO's) formed by cyclo-condensation of catechol with 4,4‘-difluorobenzophenone under pseudo-high-dilution conditions. The principal products of this latter reaction were the cyclic dimer 3a(20 wt %), cyclic trimer 3b(16%) cyclic tetramer 3c(14%), cyclic pentamer 3d(13%) and cyclic hexamer 3e(12%). Macrocycles 3a−cwere isolated as pure compounds by gradient column chromatography, and the structures of the cyclic dimer 3a and cyclic tetramer 3c were analyzed by single-crystal X-ray diffraction. A mixture of MCO's, 3, of similar composition, was obtained by cyclodepolymerization of high molar mass o-PEEK in dilute soluion.

A high-throughput method for physical vapor deposition has been applied to the synthesis of libraries of supported gold particles on amorphous substoichiometric TiOxand carbon supports. The TiOxsubstrate stoichiometry can be varied or kept constant across a supporting sample, and subsequent deposition of particle sizes on supports are controlled through the nucleation and growth process. TEM measurements indicate nucleation and growth of Au particles takes place, with the smallest particles initially observed at 1.4 nm with a maximum density of 5.5 × 1012cm-2on titania, and 2.6 nm with concomitantly lower density on carbon. The 1.4-nm particles on titania exhibit a binding energy shift in the Au(4f) core level of 0.3 eV from bulk gold, and the shift is ∼0.1 eV by the time particles grow to a mean size of 2.5 nm. These shifts are associated with final state effects, and the supported gold particles are metallic and appear to be relatively stable in air. When combined with appropriate substrates and screening techniques, this method provides a highly controllable method for the high-throughput synthesis of model supported catalyst.

Expert systems for spectroscopic molecular structure elucidation have been developed since the mid-1960s. Algorithms associated with the structure generation process within these systems are deterministic; that is, they are based on graph theory and combinatorial analysis. A series of expert systems utilizing 2D NMR spectra have been described in the literature and are capable of determining the molecular structures of large organic molecules including complex natural products. Recently, an opinion was expressed in the literature that these systems would fail when elucidating structures containing more than 30 heavy atoms. A suggestion was put forward that stochastic algorithms for structure generation would be necessary to overcome this shortcoming. In this article, we describe a comprehensive investigation of the capabilities of the deterministic expert system Structure Elucidator. The results of performing the structure elucidation of 250 complex natural products with this program were studied and generalized. The conclusion is that 2D NMR deterministic expert systems are certainly capable of elucidating large structures (up to about 100 heavy atoms) and can deal with the complexities associated with both poor and contradictory spectral data.

Protein complexes are dynamic entities; identification and quantitation of their components is critical in elucidating functional roles under specific cellular conditions. We report the first quantitative proteomic analysis of the human cap-binding protein complex. Components and proteins associated with the translation initiation eIF4F complex that may affect complex formation were identified and quantitated under distinct growth conditions. Site-specific phosphorylation of eIF4E and eIF4G and elevated levels of eIF4G:eIF4E complexes in phorbol ester treated HEK293 cells, and in serum-starved tumorigenic human mesenchymal stromal cells, attested to their activated translational states. The WD-repeat, scaffolding-protein Gemin5 was identified as a novel eIF4E binding partner, which interacted directly with eIF4E through a motif (YXXXXL) present in a number of eIF4E-interacting partners. Elevated levels of Gemin5:eIF4E complexes were found in phorbol ester treated HEK293 cells. Gemin5 and eIF4E co-localized to cytoplasmic P-bodies in human osteosarcoma U2OS cells. Interaction between eIF4E and Gemin5 and their co-localization to the P-bodies, may serve to recruit capped mRNAs to these RNP complexes, for functions related to RNP assembly, remodeling and/or transition from active translation to mRNA degradation. Our results demonstrate that our quantitative proteomic strategy can be applied to the identification and quantitation of protein complex components in human cells grown under different conditions.

The aim of this study was to investigate the changes produced in the nanostructures and the photoluminescence spectra of bridged silsesquioxanes containing urea or urethane groups, by varying the relative rates between the self-assembly of organic domains and the inorganic polycondensation. Precursors of the bridged silsesquioxanes were 4,4‘-1,3-phenylenebis(1-methylethylidene)bis(aniline) and 4,4‘-isopropylidenediphenol, end-capped with 3-isocyanatopropyltriethoxysilane. The inorganic polycondensation was produced using either high or low formic acid concentrations, leading to transparent films with different nanostructures as revealed by FTIR, SAXS, and 29Si NMR spectra. For the bridged silsesquioxanes containing urea groups the self-assembly of organic domains was much faster than the inorganic polycondensation for both formic acid concentrations. However, the arrangement was more regular and the short-range order higher when the rate of inorganic polycondensation was lower. The photoluminescence spectra of the most ordered structures revealed the presence of two main processes:  radiative recombinations in inorganic clusters and photoinduced proton-transfer generating NH2and N-defects and their subsequent radiative recombination. In the less-ordered urea-bridged silsesquioxanes a third process was present assigned to a photoinduced proton transfer in H-bonds exhibiting a broad range of strengths. For urethane-bridged silsesquioxanes the driving force for the self-assembly of organic bridges was lower than for urea-bridged silsesquioxanes. When the synthesis was performed with a high formic acid concentration, self-assembled structures were not produced. Instead, large inorganic domains composed of small inorganic clusters were generated. Self-assembly of organic domains took place only when employing low polycondensation rates. For both materials the photoluminescence was mainly due to radiative processes within inorganic clusters and varied significantly with their state of aggregation.

The synthesis, characterization, and ethylene polymerization behavior of a series of iron and cobalt halide complexes LMCl2 (M = Fe, Co) bearing chelating ferrocenyl-modified bis(imino)pyridyl ligands L [Nb= 2,6-(FcArNCMe)2C5H3N] are reported. X-ray diffraction studies show the geometry at the metal centers to be distorted square pyramidal. Electrochemical studies focus on an Fe (7) and a Co (10) complex and in each case show several quasi-reversible oxidation and reduction waves, the ferrocenyl iron atoms being easier to oxidize than the central iron (and cobalt) atoms. Chemical oxidation of these complexes is possible via addition of FcPF6, and good yields of the doubly charged iron and cobalt complexes were isolated. Treatment of the complexes 7 and 10 with methylaluminoxane (MAO) leads to highly active ethylene polymerization catalysts, converting ethylene to highly linear polyethylene (PE), with polymer molecular weights in the region of 900 000. As expected, the Fe catalyst is approximately an order of magnitude more active than the Co species, with activities of 6900 and 440 g mmol-1 bar-1 h-1, respectively. The effect of the polymerization activities by oxidation of the precatalysts to their ferrocenium counterparts was seemingly negated by the reducing properties of the alkyl aluminum activator (MAO).

A one-pot procedure for the conversion of carboxylic acids to N-acyl sulfonamides, via thio acid/azide amidation, is presented. The method is compatible with acid- and base-sensitive amino acid protection. N-Acyl sulfonamide synthesis on solid support, peptide thio acid/sulfonazide coupling, and N-alkyl amide synthesis via selective cleavage of sulfonyl from an N-alkyl-N-acyl sulfonamide are also reported.

Nonconvulsive seizures (NCSs) after traumatic and ischemic brain injury are often refractory to antiepileptic drug therapy and are associated with a decline in patient outcome. We recently characterized an in vivo rat model of focal brain ischemia-induced NCS and here sought to evaluate potential pharmacological treatments. Electroencephalographic activity was recorded continuously for 24 h in freely behaving rats subjected to permanent middle cerebral artery occlusion (MCAo). Rats were treated with an antiepileptic drug from one of seven different drug classes at ED(50) and 2x ED(50) doses (as reported in other rat seizure models), delivered as a single i.v. injection 20 min post-MCAo. Vehicle-treated rats (n = 9) had an 89% incidence of NCS with an average number of NCS of 8.6 +/- 1.9. The latency to onset of NCS was 32.5 +/- 3.4 min post-MCAo with an average duration of 49.1 +/- 8.2 s/event. The high doses of ethosuximide, gabapentin, fos-phenytoin, and valproate significantly reduced the incidence of NCS (11, 14, 14, and 38%, respectively), whereas midazolam, phenobarbital, and dextromethorphan had no significant effect at either dose. Across treatment groups, there was a low but significant correlation between the number of NCS events per animal and volume of brain infarction (r = 0.352). Antiepileptic drug therapy that prevented the occurrence of NCS also reduced mortality from 26 to 7%. Based on combined effects on NCS, infarction, neurological recovery, and mortality, ethosuximide and gabapentin were identified as having the best therapeutic profile.

The elucidation of chemical structures from 2D NMR data commonly utilizes a combination of COSY, HMQC/HSQC, and HMBC data. Generally COSY connectivities are assumed to mostly describe the separation of protons that are separated by 1 skeletal bond (3JHH), while HMBC connectivities represent protons separated from carbon atoms by 1 to 2 skeletal bonds (2JCHand 3JCH). Obviously COSY and HMBC connectivities of lengths greater than those described have been detected. Though experimental techniques have recently been described to aid in the identification of the nature of the couplings the detection of whether a coupling is 2-bond or greater still remains a challenge in most laboratories. In the StrucElucsoftware system the common lengths of the connectivities, 1-bond for COSY and 1- or 2-bond for HMBC, derived from 2D NMR data are set as the default. Therefore, in the presence of any extended connectivities contradictions can appear in the 2D NMR data. In this article, algorithmic methods for the detection and removal of contradictions in 2D NMR data that have been developed in support of StrucElucare described. The methods are based on the analysis of molecular connectivity diagrams, MCDs. These methods have been implemented in the StrucElucsystem and tested by solving 50 structural problems with 2D NMR spectral data containing contradictions. The presence of contradictions was detected by the algorithm in 90% of the cases, and the contradictions were automatically removed in ∼50% of the problems. A method of “fuzzy” structure generation in the presence of contradictions has been suggested and successfully tested in this work. This work will demonstrate examples of the application of developed methods to a number of structural problems.

Ryanodine receptors (RyR) function as Ca(2+) channels that regulate Ca(2+) release from intracellular stores to control a diverse array of cellular processes. The massive cytoplasmic domain of RyR is believed to be responsible for regulating channel function. We investigated interaction between the transmembrane Ca(2+)-releasing pore and a panel of cytoplasmic domains of the human cardiac RyR in living cells. Expression of eGFP-tagged RyR constructs encoding distinct transmembrane topological models profoundly altered intracellular Ca(2+) handling and was refractory to modulation by ryanodine, FKBP12.6 and caffeine. The impact of coexpressing dsRed-tagged cytoplasmic domains of RyR2 on intracellular Ca(2+) phenotype was assessed using confocal microscopy coupled with parallel determination of in situ protein: protein interaction using fluorescence resonance energy transfer (FRET). Dynamic interactions between RyR cytoplasmic and transmembrane domains were mediated by amino acids 3722-4610 (Interacting or "I"-domain) which critically modulated intracellular Ca(2+) handling and restored RyR sensitivity to caffeine activation. These results provide compelling evidence that specific interaction between cytoplasmic and transmembrane domains is an important mechanism in the intrinsic modulation of RyR Ca(2+) release channels.

StrucEluc is an expert system that allows the computer-assisted elucidation of chemical structures based on the inputs of a series of spectral data including 1D and 2D NMR and mass spectra. The system has been enabled to allow a chemist to utilize fragments stored in a fragment database as well as user-defined fragments submitted by the chemist in the structure elucidation process. The association of fragments in this way has been shown to dramatically speed up the process of structure generation from 2D NMR data and has helped to minimize or eliminate the need for user intervention thereby further enabling the vision of automated elucidation. The use of fragments has frequently transformed very difficult 2D NMR elucidation challenges into easily solvable tasks. A strategy to utilize molecular fragments has been developed and optimized based on specific challenging examples. This strategy will be described here using real world examples. Experience gained by solving more than 150 structure elucidation problems from a variety of literature sources is also reviewed in this work.

Subspecies delineations may not reflect actual intraspecific diversity; an issue that becomes important when conservation of populations and/or subspecies that face severe declines is involved. The Grey Duck in New Zealand is considered a separate subspecies Anas superciliosa superciliosa from the Pacific Black Duck A. s. rogersi of Australia, even though poorly differentiated morphologically. Because the New Zealand and Australian populations of A. superciliosa are considered taxonomically distinct, the decline of New Zealand's Grey Duck and its hybridization with the introduced Mallard A. platyrhynchos has led to assignment of "endangered" conservation status. Taxonomic distinction and absence of periodic gene flow between the Australian and New Zealand populations are crucial for acceptance of this status. We used phylogeographic analysis of mitochondrial DNA control region sequences to determine whether haplotypes representing current subspecies are unique or are more consistent with populations in the two countries being considered the same subspecies. Two highly divergent genetic lineages of Grey Duck occur in New Zealand. One lineage (Group I) is found only in New Zealand primarily on North Island, while the other (Group II), occurs in populations throughout New Zealand and Australia. The split between Group I and II lineages is on the order of that found between some avian species. Even though subspecific designations of A. s. superciliosa and A. s. rogersi do not hold up based on molecular data, we identify a need for Grey Duck in New Zealand to be conserved to maintain the historical diversity within the species.

BACKGROUND: Following liver injury, hepatic stellate cells (HSC) transform into myofibroblast-like cells (activation) and are the major source of type I collagen and the potent collagenase inhibitors tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) in the fibrotic liver. The reproductive hormone relaxin has been reported to reduce collagen and TIMP-1 expression by dermal and lung fibroblasts and thus has potential antifibrotic activity in liver fibrosis. AIMS: To determine the effects of relaxin on activated HSC. METHODS: Following isolation, HSC were activated by culture on plastic and exposed to relaxin (1-100 ng/ml). Collagen deposition was determined by Sirius red dye binding and radiolabelled proline incorporation. Matrix metalloproteinase (MMP) and TIMP expression were assessed by zymography and northern analysis. Transforming growth factor beta1 (TGF-beta1) mRNA and protein levels were quantified by northern analysis and ELISA, respectively. RESULTS: Exposure of activated HSC to relaxin resulted in a concentration dependent decrease in both collagen synthesis and deposition. There was a parallel decrease in TIMP-1 and TIMP-2 secretion into the HSC conditioned media but no change in gelatinase expression was observed. Northern analysis demonstrated that primary HSC, continuously exposed to relaxin, had decreased TIMP-1 mRNA expression but unaltered type I collagen, collagenase (MMP-13), alpha smooth muscle actin, and TGF-beta1 mRNA expression. CONCLUSION: These data demonstrate that relaxin modulates effective collagen deposition by HSC, at least in part, due to changes in the pattern of matrix degradation.

We have evaluated the effects of the N-acetylated-alpha-linked acidic dipeptidase (NAALADase) inhibitor, GPI5232 [2-[(pentafluorophenylmethyl)hydroxyphosphinyl]methyl)-pentanedioic acid], to not only decrease brain injury but also to alter the inherent electroencephalographic (EEG) changes observed in a rat model of transient middle cerebral artery occlusion (MCAo). Continuous i.v. infusion of GPI5232 starting 1 h after injury resulted in more than a 50% reduction in brain infarct volume caused by 2 h of MCAo. This effect was dose-dependent and significant even when first treatment was delayed for 2 h post-MCAo. At 24 h post-MCAo, EEG spectral analysis of the injured hemisphere revealed functional improvement in GPI5232-treated rats. Significant recovery in high-frequency EEG power (8-30 Hz) was measured in GPI5232-treated animals in both parietal and temporal brain regions but not in vehicle-treated animals. MCAo-injured rats were also predisposed to developing cortical brain seizures, and GPI5232-treated rats had significantly fewer brain seizures than vehicle-treated animals. In separate experiments, acute high doses of GPI5232 in normal rats did not significantly alter EEG brain activity as evaluated by spectral analysis and did not produce any signs of seizure activity or behavioral abnormalities. These results show GPI5232 to be an effective neuroprotective treatment when given postinjury by reducing brain infarction and ameliorating the pathological EEG associated with focal brain ischemia.

BACKGROUND: Chronic ulcerative conditions in the gastrointestinal tract result in the appearance of the ulcer associated cell lineage (UACL). The glands of this new cell lineage secrete epidermal growth factor, transforming growth factor alpha, and the trefoil factor family (TFF) peptides, which are known to participate in repair processes. Pouchitis is the most frequent complication of ileal pouch-anal anastomosis. AIM: Our aim was to determine whether the mucosal ulceration present in pouchitis can induce the development of UACL glands. METHODS: Biopsies from ileal pouches with pouchitis (n=10), healthy pouches (n=5), and normal terminal ileum (n=5) were studied. Expression of TFF mRNA was assessed by in situ hybridisation. TFF1 and TFF2 proteins were localised by immunochemistry. RESULTS: UACL glands containing TFF1 and TFF2 were observed in six patients with pouchitis. In some glands, there was TFF3 mRNA as has been reported for Crohn's UACL. None of the biopsies from ileal reservoirs without pouchitis showed UACL glands (p<0.05). Neither TFF1 nor TFF2 expression was detected in ileal reservoirs without pouchitis. CONCLUSION: UACL glands arise de novo in ileal pouch mucosa of patients with pouchitis and express all three TFF peptide genes. Chronic inflammation alone, present in healthy pouches, is not enough to stimulate the growth of the UACL, and additional stimuli consequent on ulceration may be needed.

1. Introduction 62 2. Channel structure 63 2.1 Isoforms, primary structure and topology of Ca2+-release channels 63 2.2 Identification of ligand binding sites within the primary sequence of RyR 65 2.2.1 Calcium 66 2.2.2 Calmodulin 66 2.2.3 FK506-binding proteins 66 2.2.4 L-type Ca2+ channel 66 2.2.5 Ryanodine 67 2.3 The three-dimensional structure of the RyR channel 68 3. Channel function 70 3.1 RyR channel gating 70 3.2 Ion translocation and discrimination 71 3.2.1 Monovalent inorganic cations 71 3.2.2 Divalent inorganic cations 74 3.2.3 Organic monovalent cations 75 3.2.4 Permeant ion translocation can be blocked 75 3.3 Summary of ion handling in RyR 76 3.4 Where is the pore and what components of RyR are involved in its formation? 76 3.5 The mechanisms underlying ion translocation and discrimination in RyR 79 3.6 Does RyR employ ion–ion repulsion to attain high unitary conductance? 82 3.6.1 Conductance–activity relationships 83 3.6.2 Concentration dependence of reversal potential 83 3.6.3 The dependence of unitary conductance on mole-fraction 83 3.6.4 Effective valence of channel-blocking cations 84 3.6.5 Modelling ionic conduction 84 3.7 Factors influencing maximum conductance 85 3.8 Factors influencing ion entry 86 3.9 Theoretical design for the pore of RyR 88 4. What do we know about the structure of the conduction pathway in RyR? 88 4.1 The narrowest region of the conduction pathway – the ‘selectivity filter’ of RyR 89 4.2 The voltage drop across RyR – the length of the ‘pore’ 89 4.3 Mechanisms for ion discrimination in RyR 93 4.4 Musings on the structure of the RyR/InsP3R pore 95 5. Summary 98 6. Acknowledgements 98 7. References 98 The purpose of this article is to provide a description of the current state of our understanding of certain aspects of the relationship between the structure and function of the ryanodine receptor (RyR). RyR is an ion channel found in the membranes of the intracellular Ca2+ storage organelles, the endoplasmic reticulum (ER) and its counterpart in muscle cells the sarcoplasmic reticulum (SR), where it provides a regulated pathway for the release of stored Ca2+ during Ca2+ signalling processes such as fertilization and muscle contraction. RyR possesses both high- and low-affinity binding sites for the plant alkaloid ryanodine; however, whilst this ligand gives the channel its name and is of toxicological and pharmacological interest, physiological regulation of channel gating is mediated by the binding of cytosolic ligands (primarily Ca2+, ATP, Mg2+) and in some cases by direct coupling with a surface membrane voltage sensor.

In the solid state, the macrocyclic polyether, tetrabenzo[24]crown-8 (TB24C8), is an interesting molecule. When crystallized from MeCN solution, a bis-MeCN clathrate is formed, in which the TB24C8 macroring—by adopting a conformation with approximate tennis-ball-seam symmetry (D2d)—forms C–H⋯π-linked supramolecular chains. However, when crystallized from CHCl3/Et2O solution, the TB24C8 crystallizes alone—adopting a self-filling ‘flattened-out’ conformation with Cisymmetry—forming C–H⋯π-linked sheets which stack upon one another by virtue of—yet again (!)—C–H⋯π hydrogen bonds. By contrast, the solid-state superstructure of the [2]pseudorotaxane formed between TB24C8 and dibenzylammonium hexafluorophosphate (DBA·PF6), contains no C–H⋯π interactions. However, a multitude of more enthalpically favorable C–H⋯F hydrogen bonds—to a highly-ordered matrix of PF6−anions—stabilizes the formation of the [2]pseudorotaxane array.

Conantokin-G (Con-G), a 17-amino-acid peptide derived from marine snails and a potent N-methyl-D-aspartate (NMDA) antagonist, was evaluated for its neuroprotective properties in vitro and in vivo. In primary cerebellar neurons, Con-G was shown to decrease excitotoxic calcium responses to NMDA and to exhibit differential neuroprotection potencies against hypoxia/hypoglycemia-, NMDA-, glutamate-, or veratridine-induced injury. Using the intraluminal filament method of middle cerebral artery occlusion as an in vivo rat model of transient focal brain ischemia, the neuroprotective dose-response effect of Con-G administration beginning 30 min postocclusion was evaluated after 2 h of ischemia and 22 h of reperfusion. In the core region of injury, an 89% reduction in brain infarction was measured with significant neurological and electroencephalographic recovery at the maximal dose tested (2 nmol), although mild sedation was noted. Lower doses of Con-G (0.001-0.5 nmol) were significantly neuroprotective without causing sedation. Postinjury time course experiments demonstrated a therapeutic window out to at least 4 to 8 h from the start of the injury, providing a 47% reduction in core injury. The neuroprotective effect of Con-G (0. 5 nmol) was also evaluated after 72 h of injury, where a 54% reduction in core brain infarction was measured. Critically, in both recovery models (i.e., 24 and 72 h), the reduction in brain infarction was associated with significant improvements in neurological and electroencephalographic recovery. These data provide evidence for the potent and highly efficacious effect of Con-G as a neuroprotective agent, with an excellent therapeutic window for the potential intervention against ischemic/excitotoxic brain injury.

Tris(N,N-diisopropylmonothiocarbamato)indium(III), In(SOCNiPr2)3, has been prepared by the reaction of indium(III) chloride and lithium N,N-diisopropylmonothiocarbamate. In the solid state, the complex is a distorted trigonal prismatic monomer with a meridional configuration, as characterised by single-crystal X-ray diffraction. In(SOCNiPr2)3 has been used as a single-source precursor for the deposition of tetragonal β-In2S3 thin films by low pressure metal-organic chemical vapour deposition (LP-MOCVD) at temperatures ranging from 300 to 450 °C, on borosilicate glass substrates.

The preparations are reported of a range of complexes formed by 2,3,5,6-tetrafluoro-1,4-bis(4-pyridylsulfenyl)benzene (L) with MnII, CoII, NiII, ZnII and CdII, and single crystal X-ray diffraction studies have been made on four of the compounds. In the complex CoLI2·0.5CH2Cl2, the organic ligand bridges tetrahedrally coordinated CoII centres so as to form chains. The compound Cd2L3(NO3)4 has a more complex structure in which seven-coordinate Cd centres are linked by two different types of L bridges so as to form arrays of 90-membered macrocycles comprising sheets of linked alternating enantiomeric helices. In the complexes MnL2(EtOH)2X2 (X 4;= 4;Br or NCS), the bis(pyridyl) ligand utilises only one of its pyridyl units to coordinate directly to the metal atom. In both cases the Mn coordination environment comprises an all-trans octahedral arrangement of two anions, two ethanol ligands and two pyridyl units derived from two different L ligands. However in both compounds the non-coordinated pyridyl units bridge adjacent Mn centres by forming hydrogen bonds to the ethanol ligands. The resulting, complex networks are, however, dramatically different. The isothiocyanate complex forms sheets of partially interpenetrating helices whereas the bromide forms a system of triply interpenetrating (4,4) nets of ‘over 2-under 2’ type. X- and Q-Band EPR spectra of the manganese complexes are reported as are relevant spectroscopic results for the other complexes.

Reaction of [M(NNPh2)Cl4] with RMgCl followed by addition of pentafluorophenol afforded the tris-alkyl complexes [MoR3(NNPh2)(OC6F5)] [M 4;= 4;Mo, R 4;= 4;CH2CMe2Ph 1; M 4;= 4;W, R 4;= 4;CH2SiMe3 2] in moderate yields. At ca. 80 4;°C in chlorobenzene 1 and 2 are active for the ring-opening metathesis polymerisation of norbornene; intermediate alkylidene complexes are not observed. The crystal structures of 1 and 2 have been determined; the metal centres adopt trigonal bipyramidal geometries in which the isodiazene and pentafluorophenoxide groups are apical. The crystal structure of [WCl2(NNPh2)(OC6F5)2(thf )] 3 is also reported.

A novel phosphorus/sulfur-substituted ferrocenylene ligand, 1-(diphenylphosphino)-1′-(methylsulfanyl)ferrocene has been synthesized by two routes and fully characterised. The co-ordination chemistry of this species and analogous phosphorus/phosphorus- and sulfur/sulfur-substituted ferrocenylene ligands, 1,1′-bis(diphenylphosphino)ferrocene, 1,1′-bis(methylsulfanyl)ferrocene and 1,1′-bis(isopropylthio)ferrocene has been demonstrated by reaction with copper and silver tetrakis(acetonitrile) salts to form a series of metal–ferrocenylene complexes where the metal atom acts as a bridging group of two ring systems. Crystal structure determinations have been carried out on [Ag{(C5H4P(C6H5)2)2Fe}2]BF4 and [Cu{(C5H4SCH3)2Fe}2]PF6 and illustrate that the former shows a distorted tetrahedral geometry around silver and a significant asymmetry in the geometries of the two pseudo six-membered chelate rings and that the latter possesses S4 symmetry with a pronounced exo orientation of the four methyl groups.

Possible routes to [Mo(NNPh2)2R2], where R 4;= 4;alkyl or aryl groups, have been investigated including the interaction of [MoCl2(NNPh2)2(dme)] 1 (dme 4;= 4;1,2-dimethoxyethane) with the standard alkylating agents LiR, RMgX, R2Mg or R2Zn under various conditions of solvent and temperature. There was, however, no evidence to suggest alkylation had taken place. Treatment of 1 with two equivalents of silver trifluoromethanesulfonate, silver triflate (AgOTf ), in the presence of pyridine gave the golden-yellow bis(triflate) complex [Mo(OTf )2(NNPh2)2(py)2] 2 in good yield. In the presence of an excess of bipy (2,2′-bipyridine) the known dicationic species [Mo(NNPh2)2(bipy)2]2+ was isolated as its PF6– salt. Attempts to replace triflate by alkyl groups in 2 were unsuccessful. A similar reaction of 1 with silver triflate in the presence of the bulky tridentate alkoxide 2,6-bis(2-hydroxy-2,2-diphenylethyl)pyridine (H2L) led to loss of an NNPh2 group (presumably as hydrazine) and formation of the green mono-isodiazene complex [MoCl(OTf )(NNPh2)(L)] 3. The compound [Mo(CH2CMe2Ph)2(NBut)2] underwent partial imido ligand exchange with an excess of 1,1-diphenylhydrazine hydrochloride to give the brown bis(isodiazene) chloro-bridged dimer [{MoCl(NNPh2)2(µ-Cl)(NH2But)}2] 4. A chloride substitution reaction of 1 with potassium tris(3,5-dimethylpyrazolyl)hydroborate, (KTp′) afforded the bis(isodiazene) complex [MoTp′Cl(NNPh2)2] 5. The crystal and molecular structures of 2–5 have been determined. The complexes all contain linear isodiazene groups with Mo–N distances in the range 1.755(6) to 1.768(7) Å. In 2 the molybdenum(VI) centre has a pseudo octahedral geometry with axial pyridines and cis-triflate groups. In six-co-ordinate 3 the pyridinediolate ligand has a meridional donor atom arrangement with an equatorial isodiazene ligand. The binuclear compound 4 has slightly asymmetric chloro bridges coplanar with the terminal isodiazene ligands. Complex 5 is octahedral, having a facially co-ordinated Tp′ ligand and linear NNPh2 ligands.

The chromium(VI) imido complex Cr(NAr)2Cl2 (Ar 4;= 4;2,6-iPr2C6H3) reacted with pyridine and PMe3 to form the monoadducts Cr(NAr)2Cl2(py) 1 and Cr(NAr)2Cl2(PMe3) 2 respectively. The reaction between Cr(NAr)2Cl2 and LiNHAr afforded the amide complex Cr(NAr)2(NHAr)Cl 3. Attempts to generate the half-sandwich species CrCp(NAr)2Cl through treatment of the dichloride with LiCp, Mg(Cp)2 or NaCp resulted in the dimeric chromium(V) complex [Cr(NAr)(µ-NAr)Cl]2 4. Reduction of Cr(NAr)2Cl2 with magnesium in the presence of PMe3 or PMe2Ph afforded the chromium(IV) bis-phosphine complexes Cr(NAr)2(PMe3)2 5 and Cr(NAr)2(PMe2Ph)2 6 respectively. The reaction between Cr(NAr)2(PMe3)2 and phenyldiazomethane gave the diazoalkane complex Cr(NAr)2(N2CHPh)(PMe3) 7. Complexes 1, 3, 4 and 7 have been structurally characterised.

The reactions of the homoleptic zirconium alkoxides [Zr2(OPri)8(PriOH)2] and Zr(OBut)4 in n-hexane suspensions or solutions with two equivalents of the aminoalcohols 2-dimethylaminoethanol (Hdmae), 1-dimethylaminopropan-2-ol (Hdmap), or 1,1-bis(dimethylamino)propan-2-ol (Hbdmap) have been studied. Products with the formula [Zr(OR)2(dmae)2] (R 4;= 4;Pri 1 or But 2), [Zr2(OPri)6(L)2] (L 4;= 4;dmap 3 or bdmap 4), and [Zr2(OBut)3(bdmap)4(OH)] 5 have been isolated. Compounds 3 and 4 have been shown by single crystal X-ray crystallography to be asymmetric binuclear complexes in the solid state. The two metal centres are bridged via the two aminoalkoxide oxygen atoms and one isopropoxide ligand. The remaining co-ordination spheres of the binuclear molecules are completed by 3 terminal isopropoxide ligands on one metal centre, and 2 terminal isopropoxide ligands on the other. Compound 5 was found to be binuclear, but instead of a µ-isopropoxide bridge a µ-OH group was observed which intramolecularly hydrogen bonds to one of the free NMe2 groups on a terminal bdmap ligand. The remaining sites in the co-ordination spheres are filled by 3 terminal tert-butoxide ligands on one metal centre and two terminal aminoalkoxide ligands on the other. These are the first binuclear 6/7 co-ordinate zirconium compounds. The structural studies are helpful in understanding the behaviour of these and related complexes as precursors in the MOCVD of ZrO2 films.

OBJECTIVE--To evaluate general practitioner participation in a district health authority's purchasing work. DESIGN--Questionnaire study of 131 Hackney general practitioners and 33 senior health service managers; review of the minutes of 28 meetings of the Hackney General Practitioners' Forum and the contract between City and Hackney Health Authority and the St Bartholomew's NHS Trust. SETTING--Hackney General Practitioners' Forum. MAIN OUTCOME MEASURES--General practitioners' and managers' perceptions of how representative and effective the general practitioners' forum is; proportion of new quality targets and service developments contributed by general practitioners; main issues discussed by the forum and impact on district health authority policy. RESULTS--99 (76%) general practitioners and 27 (82%) managers responded. Both groups perceived the forum as representative. 92% (24/26) of the managers thought the forum was effective but only 74% (70/95) of general practitioners did so, largely because some doubted that the forum was listened to 75% (103/138) of quality targets and 55% (16/29) of service developments planned in the 1993-4 contract were contributed by general practitioners. They also lobbied successfully for more resources for urology and community mental health services. CONCLUSIONS--Input into commissioning via a general practitioners' forum can be both representative and effective. General practitioners need to work closely to achieve a consensus and those involved need administrative support. The relation between general practice and public health medicine needs to be strengthened.

A rotaxane-like complex incorporating a hydroquinone-intercepted acyclic polyether chain terminated by tert-butylaniline rings and encircled by cyclobis(paraquat-p-phenylene) self-assembles spontaneously in acetonitrile solution from which it can be crystallized. Protonation of the nitrogen atoms of the guest is accompanied by the complete dissociation of the supramolecular complex into its free components. Addition of a base restores the original equilibrium affording back the rotaxane-like complex.

The reaction of [Ru(▹CC6H4OMe-4)Cl(CO)(PPh3)2] with [NH4][S2CNC4H8] provides the structurally characterised metallacycle [Ru{κ2-CH(C6H4OMe-4)SC(NC4H8)S}(S2CNC4H8)(CO)(PPh3)], related examples of which arise from the reactions of xanthate or dithiocarbamate salts with the alkylidene compounds [MCl2(&z.dbd;CHR)- (CO)(PPh3)2] (M=Ru or Os; R=Ph or C6H4OMe-4) and [OsCl(&z.dbd;CHR)(OH2)(CO)(PPh3)2]ClO4.

We studied the activation of the human somatostatin5 receptor recombinantly expressed in CHO-K1 cells by using some newly available agonists and antagonists. Somatostatin-28 bound to this receptor with a higher affinity than somatostatin-14 and was more potent in increasing [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding. Somatostatin-14-induced [35S]GTPgammaS binding to membranes from this cell line was decreased in a concentration-related manner by increasing concentrations of GDP and sodium chloride. At 50 mM (low) sodium, agonist EC50 values for stimulating [35S]GTPgammaS binding were lower than those at 150 mM (high) sodium and were closer to their respective affinity estimates (dissociation equilibrium constants) for binding to the receptor in the absence of sodium. Both agonist binding to the high affinity state of the receptor and agonist-induced [35S]GTPgammaS binding were abolished by pertussis toxin pretreatment. The putative somatostatin5 receptor-selective ligand L-362,855, unlike somatostatin-14 and somatostatin-28, showed differential intrinsic activity for stimulation of [35S]GTPgammaS binding, behaving as a partial agonist in high sodium and a full agonist in low sodium. In contrast, BIM-23056 did not behave as an agonist under any conditions studied but was able to antagonize somatostatin-14-induced [35S]GTPgammaS binding. We conclude that measurement of [35S]GTPgammaS binding mediated by somatostatin receptor activation in the presence of different concentrations of sodium chloride provides a useful functional assay for assessing the relative agonist efficacies of novel ligands identified from radioligand binding studies.

The lability of the ligand with a potential hydrogen bond donor–hydrogen bond donor arrangement was found to be the predominant factor in determining the structures of the adducts formed between zinc(II) complexes of thiourea [tu, NH2C(S)NH2] and thiosemicarbazide [tsc, NH2C(S)NHNH2] and the terephthalate anion [tere, C6H4(CO2–)2-1,4]. Reaction of [Zn(tsc)2][NO3]2, containing the bidentate thiosemicarbazide ligand, with sodium terephthalate led to a hydrogen-bonded structure, [Zn(tsc)2(OH2)2][tere]·2H2O, 1, in which the cations and anions are linked into chains through charge-augmented double hydrogen bonds between two NH protons on the tsc ligands and two oxygen lone pairs on the carboxylate. This chain formation is similar to that previously observed for related nickel complexes, although there are major differences in the way in which these chains are linked together into sheets. In contrast to the thiosemicarbazide complex, the reaction of [Zn(tu)4][NO3]2, containing unidentate thiourea ligands, with sodium terephthalate led to the formation of a co-ordinatively-bonded polymer, [Zn2(µ-tu)(tu)2(µ-tere)2]·4H2O, 2, in which the terephthalate anions have displaced some of the thiourea ligands from each zinc co-ordination sphere. The zigzag tapes formed by the terephthalate ligands bridging zinc atoms are linked together into double strands via bridging thiourea ligands.

The reactions between the palladium compounds [Pd4(3-CH)(-Cl)3(PBut 3)4] or [Pd2(-X)2(PBut3)2 ] (X = Br or I) and [Co2(CO)8] have led to the novel palladium–cobalt tetranuclear compounds [CoPd3(3-X)(-CO)3(3 -CO)(CO)(PBut3)3] (X = Cl, Br or I). Structural characterisation of one of them (X = Cl) has shown that the metal cluster geometry is intermediate between a tetrahedron and a butterfly. A second product detected in this reaction {and additionally with [Fe2(CO)9] and [Pd2(-Br)2(PBut3) 2]} is also reported and has been structurally characterised as [Pd6(-Br)4(-CO)4(PBut 3)4] (when X = Br). This hexanuclear cluster has triangular cluster moieties linked by double bromide bridges.

Two new multiply methylthio-substituted ferrocene ligands 1,1′,2-tris- and 1,1′,2,2′-tetrakis-(methylthio)ferrocene have been prepared by a simple, single-step procedure; substitution of the ferrocenyl rings occurs in an adjacent fashion leading to versatile, multidentate ligand behaviour as demonstrated by their reaction with a tungsten carbonyl centre.

The ambient temperature ionic liquid system [bmim]Cl–AlCl3 (where [bmim]+ 4;= 4;1-butyl-3-methylimidazolium cation) has been used to prepare a number of arene(cyclopentadienyl)iron(II) complexes of the type [Fe(C5H5)(arene)]+ from ferrocene. The ionic liquid acts as both solvent and Lewis acid source ([Al2Cl7]–). The products were only formed on addition of a proton source, [bmim][HCl2], confirming mechanistic formulations involving a combination of Lewis and Brønsted acid activity. The X-ray crystal structure analysis of [Fe(η5-C5H5)(η6-C6H5C6H4Br)][PF6] is also reported. The structure clearly shows both π–π stacking interactions between neighbouring cations and hydrogen bonds between the cations and anions.

The new complexes OsO4·nmo (nmo = N-methylmorpholine N-oxide) and OsO4·nmm (nmm = N-methylmorpholine) have been made, their crystal structures determined, and their possible involvement in the catalysed dihydroxylation of alkenes considered. The use of cis-[OsO4(OH)2]2- as a catalyst for the oxidation of alcohols, aldehydes and alkyl halides to carboxylic acids with [Fe(CN)6]3- and other co-oxidants and also for the cleavage and dihydroxylation of alkenes with [Fe(CN)6]3- has been investigated.

The syntheses of the ‘extended reach’ ligand N,N ′-p- phenylenedimethylenebis(4-methylpyridin-2-one) (L) and of a range of its metal complexes with MnII, CoII, NiII, ZnII, CdII, YIII, and lanthanide ions have been accomplished. X-Ray studies showed that in the compound {[MnL3](ClO4)2}+ n octahedrally co-ordinated manganese centres are connected by L bridges so as to form a three-dimensional array of contiguous rhomboidal ‘boxes’. The analogous compounds with CoII, NiII, ZnII and CdII have the same structure. The polymeric compound {[Cu4L5Cl8]·2MeOH} n forms a complex array of cross-linked chains containing both four- (distorted tetrahedral) and five-co-ordinate (distorted square pyramidal) copper centres in equal proportions.

Some silver(I) complexes of acyclic tri- and tetra-dentate nitrogen-containing ligands have been prepared and structurally characterised. In those complexes containing only the silver ion and the ligand a polymeric structure was observed in the solid state. However, the addition of another co-ordinating ligand, e.g. trimethylphosphine, inhibited polymer formation, leading to a dimeric structure.

BACKGROUND: Gall bladder and sphincter of Oddi (SO) function are coordinated by hormonal and neuronal mechanisms. Nerve fibres pass between the gall bladder and the SO via the cystic duct. It is therefore possible that cholecystectomy may alter SO motility. AIM: To investigate the effect of cholecystectomy on SO function. METHODS: SO manometry was performed in five women (median age 52 years), a few days before and six months after laparoscopic cholecystectomy which was undertaken for uncomplicated cholelithiasis. Basal and post-cholecystokinin (CCK) SO motility were measured. RESULTS: All patients were symptom free after laparoscopic cholecystectomy. Prior to surgery common bile duct pressure, and tonic and phasic SO motility were normal and phasic contractions were inhibited by intravenous CCK (1 Ivy Dog Unit/kg). Six months later, common bile duct pressure and baseline tonic and phasic activity were unchanged but CCK failed to suppress phasic activity. CONCLUSION: Cholecystectomy, at least in the short term, suppresses the normal inhibitory effect of pharmacological doses of CCK on the SO. The mechanism of this effect is unknown but it could be due to SO denervation.

A comparison between three different methods commonly used to estimate ring current effects on chemical shifts is presented. Haigh−Mallion, Johnson−Bovey, and classical point-dipole approximations were used to estimate the ring current contribution to chemical shifts for protons in several proteins for which both detailed X-ray crystal structures and chemical shift assignments were available. For the classical point-dipole model, new proportionality constants were calculated by fitting to ring current estimations from both the quantum-mechanical Haigh−Mallion and semiclassical Johnson−Bovey methods and compared with the previously used point-dipole constant of Perkins and Dwek. Statistical analysis of the predictions obtained by all methods indicates that the point-dipole approximation parametrized against quantum-mechanical data is superior to the previously used classical model, comparable to Johnson−Bovey calculations, and slightly poorer than predictions from the Haigh−Mallion theory. The implementation of a pseudoenergy penalty term for use in structure refinement from chemical shift data based on the classical point-dipole model is described, and its usefulness in cases where other NMR information is limited is discussed with a specific example.

A set of force field parameters capable of reproducing the preferred conformations of the biologically important 1,4-benzodiazepines was developed for AMBER and other molecular modeling programs that utilize the Weiner et al. force field. Equilibrium parameters were obtained from representative model compounds found in the Cambridge Structural Database, and bond stretching and torsion potential force constants were estimated using AM1 and PM3 semiempirical Hamiltonians. Parameters obtained with the two semiempirical methods and the existing linear interpolation method are compared. Molecular mechanics and dynamic simulations showed that AM1 derived parameters, together with MNDO ESP fitted atomic charges, predicted the X-ray structure of a number of representative 1,4-benzodiazepines within 0.01 Å, 0.8°, and 5°, from observed bond lengths, bond angles, and bond torsions, respectively.

A simple iterative method for superimposing sets of NMR derived structures and calculation of the root mean square deviation (RMSD) of the sets is described. It was compared to the commonly used algorithm involving pairwise best fitting in the conformational study of the taxoid anticancer drug cephalomannine in lipophobic and lipophilic solvents. Lower RMSD values were obtained, indicating a better superposition of the structures in the sets. The conformations of cephalomannine in the two solvent systems reported are in good agreement with earlier conformational studies on other active taxoids.

Syntheses and structural and luminescence studies of hydrolytic products of diphthalimidodiethylamine (DPDA) and their lanthanide(III) compounds have been undertaken in order to determine the potential for the phthalamate functionality to sensitize intense Eu3+ and Tb3+ emission via the ‘antenna effect’. Acid promoted hydrolysis of the relatively simple DPDA is efficient; hydrolysis is negligible at pH 4;> 4;11. At pH 2–3, hydrolysis to phthalic acid (1) occurs which upon interaction with DPDA yields the phthalic acid–DPDA supramolecular hydrate, DPDAH–HP·1.75H2O. With a potassium carbonate–ethanol–acetonitrile mixture containing a small amount of water, the novel phthalamate–phthalimide H2·H2O is formed while at pH ca. 9–10 the new diphthalamate Na23·3H2O is formed. These transformations have been confirmed by single crystal X-ray analyses of DPDAH–HP·1.75H2O and H2·H2O. The crystal structures of DPDAH–HP· 1.75H2O and H2·H2O reveal that the phthalamates and phthalimides are stabilized by non-covalent (e.g. π–π stacking and hydrogen bonding) interactions which are of interest as potential conduits for energy transfer and are responsible for molecular aggregations seen in FAB mass spectrometry of H2·H2O and Na23·H2O. Europium(III) compounds of 32– and H2 exhibit intense sensitized red emission which is, surprisingly, temperature independent.