(+)‐Gibberellin C: hydrogen‐bonding pattern of the monohydrate of a non‐racemic pentacyclic diterpenoid

In the monohydrate of the title compound, (+)‐2β,4aα‐di­hydroxy‐1,7‐di­methyl‐8‐oxo‐4bβ,7α‐gibbane‐1α,10β‐di­carb­ox­yl­ic acid‐1,4a‐lactone, C₁₉H₂₄O₆·H₂O, intermolecular hydrogen bonding progresses helically along b from carboxyl to ketone [O?O = 2.694 (5) Å]. The carboxyl and lactone carbonyl groups in translationally related mol­ecules within a helix both accept hydrogen bonds from the same water of hydration. The oxy­gen of this water in turn accepts a hydrogen bond from the hydroxyl group of a third screw‐related mol­ecule in an adjacent counterdirectionally oriented helix, yielding a complex three‐dimensional hydrogen‐bonding array. Intermolecular O?H—C close contacts were found to the carboxyl and lactone carbonyls, the hydroxyl, and the water.     

A substrate-free activity-based protein profiling screen for the discovery of selective PREPL inhibitors

Peptidases play vital roles in physiology through the biosynthesis, degradation, and regulation of peptides. Prolyl endopeptidase-like (PREPL) is a newly described member of the prolyl peptidase family, with significant homology to mammalian prolyl endopeptidase and the bacterial peptidase oligopeptidase B. The biochemistry and biology of PREPL are of fundamental interest due to this enzyme's homology to the biomedically important prolyl peptidases and its localization in the central nervous system. Furthermore, genetic studies of patients suffering from hypotonia-cystinuria syndrome (HCS) have revealed a deletion of a portion of the genome that includes the PREPL gene. HCS symptoms thought to be caused by lack of PREPL include neuromuscular and mild cognitive deficits. A number of complementary approaches, ranging from biochemistry to genetics, will be required to understand the biochemical, cellular, physiological, and pathological mechanisms regulated by PREPL. We are particularly interested in investigating physiological substrates and pathways controlled by PREPL. Here, we use a fluorescence polarization activity-based protein profiling (fluopol-ABPP) assay to discover selective small-molecule inhibitors of PREPL. Fluopol-ABPP is a substrate-free approach that is ideally suited for studying serine hydrolases for which no substrates are known, such as PREPL. After screening over 300,000 compounds using fluopol-ABPP, we employed a number of secondary assays to confirm assay hits and characterize a group of 3-oxo-1-phenyl-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitrile and 1-alkyl-3-oxo-3,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-4-carbonitrile PREPL inhibitors that are able to block PREPL activity in cells. Moreover, when administered to mice, 1-isobutyl-3-oxo-3,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-4-carbonitrile distributes to the brain, indicating that it may be useful for in vivo studies. The application of fluopol-ABPP has led to the first reported PREPL inhibitors, and these inhibitors will be of great value in studying the biochemistry of PREPL and in eventually understanding the link between PREPL and HCS.     

A pyrene-based fluorescent sensor for Zn2+ ions: a molecular 'butterfly'

A simple pyrene-based triazole receptor has been synthesised and shown to self-assemble in the presence of ZnCl(2) in an exclusively 2:1 ratio, whereas a mixture of 2:1 and 1:1 ratios are observed for other Zn(2+) salts. The pyrene units are syn in orientation; this is supported by a strong excimer signal observed at 410 nm in the presence of ZnCl(2) in acetonitrile. DFT calculations and 2D NMR support the proposed structure.     

Integration of a macro/micro architectured compartmentalised neuronal culture device using a rapid prototyping moulding process

The rapid prototyping of a reversible and one step moulded compartmentalised neuron glass/PDMS device with a thin wall barrier directly adjacent to the reservoirs is presented. A simple moulding technique to produce these devices results in a barrier of 560 μm where the 3 μm deep by 8 μm wide channels can be reversibly fabricated in either the glass base or PDMS compartmentalised mould depending on the type of application required. Using glass substrates with commercially laser engraved microchannels, both the PDMS planar and PDMS channelled device can be easily fabricated in a standard laboratory. The compartmentalised device has several advantages including good experimental accessibility and versatility with a variety of end user applications.     

Novel Strategy for Non-Aqueous Bioconjugation of Substituted Phenyl-1,2,4-triazole-3,5-dione Analogues

A novel 4-[4-(pentafluoro-λ⁶-sulfanyl)phenyl]-1,2,4-triazole-3,5-dione (5a) was synthesised as a potential [¹⁸F]radio-prosthetic group for radiolabelling peptides and proteins via selective bioconjugation with the phenolic side chains of tyrosine residues. Preliminary conjugation tests revealed the rapid hydrolysis of 5a under semi-aqueous conditions; these results led to further investigation into the electronic substituent effects of PTAD derivatives and corresponding hydrolytic stabilities. Five derivatives of 5a with para substituents of varying electron donating and withdrawing effects were synthesised for the investigation. The bioconjugation of these derivatives with model tyrosine was monitored in both aqueous and organic media in the presence of a variety of catalysts. From these investigations, we have found HFIP to be an effective catalyst when used in tandem with DCM as a solvent to give PTAD-tyrosine conjugate products (6a–f) in satisfactory to good yields (54–79%), whereas analogous reactions performed in acetonitrile were unsuccessful. The discovery of this system has allowed for the successful conjugation of electron-deficient PTAD derivatives to tyrosine, which would otherwise be unachievable under aqueous reaction conditions. The inclusion of these electron-deficient, fluorinated PTAD derivatives for use in the PTAD-tyrosine conjugation will hopefully broaden their applicability within fields such as ¹⁹F-MRI and PET imaging.     

Characterization of the triplet state of tris(8-hydroxyquinoline)aluminium(III) in benzene solution

The lowest triplet state of tris(8-hydroxyquinoline)aluminium(III) (Alq3) has been prepared by pulse radiolysis/energy transfer from appropriate donors in benzene solutions and has an absorption maximum around 510 nm with a lifetime of about 50 mus. It is quenched by molecular oxygen, leading to singlet oxygen formation. From flash photolysis and singlet oxygen formation measurements, a quantum yield of triplet formation of 0.24 was determined for direct photolysis of the complex. A value of 2.10 +/- 0.10 eV was determined for the energy of the lowest triplet state by energy transfer studies and was confirmed by phosphorescence measurements on Alq3, either in the heavy atom solvent ethyl iodide or photosensitized by benzophenone in benzene. Dexter (exchange) energy transfer was observed from triplet Alq3 to platinum(II) octaethylporphyrin.     

The Necessary Maximality Principle for c. c. c. forcing is equiconsistent with a weakly compact cardinal

The Necessary Maximality Principle for c. c. c. forcing with real parameters is equiconsistent with the existence of a weakly compact cardinal. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

COMBINING METHODS OF PEST CONTROL: COMPLEMENTARITY OF METHODS AND A GUIDING PRINCIPLE

Four sets of models are examined which represent various pairwise combinations of several methods of pest control. These methods involve the release of sterile male pests, the inundative release of parasitoids, insecticide application, pheromone trapping and food-baited trapping with either insecticides or sterilants. It was observed that two pest control methods will combine synergistically, and thus be complimentary, if their optimal action is at different pest densities and varies differently with pest density. The synergism thus generated by differing dependence on density, can however, be obscured if the two control methods interfere with each other in some other way, as occurs for example with the use of both insecticides and inundative release of parasitoids.     

Substitution reactions of dicyclooctatetraeneiron. A simple route to zerovalent iron—organophosphorus compounds

Fe(cot)₂ (cot = cyclooctatetraene) reacts with certain phosphines and phosphites to give Fe(cot)L₃ compounds in good yield. Reaction of Fe(cot)₂ with Ph₂PCH₂CH₂PPh₂ under N₂ gives a complex containing coordinated dinitrogen, which is converted into Fe(cot)(Ph₂PCH₂CH₂PPh₂)(CO) on reaction with CO or formate esters.