New ionic liquids containing an appended hydroxyl functionality from the atom-efficient, one-pot reaction of 1-methylimidazole and acid with propylene oxide

New ionic liquids containing ( 2- hydroxypropyl)- functionalized imidazolium cations have been synthesized by the atom- efficient, room temperature reaction of 1- methylimidazole with acid and propylene oxide; the acid providing the anionic component of the resultant ionic liquids. The incorporation of the secondary hydroxyl- functionality in the cation causes some interesting modifications to the behavior of these ionic liquids, increasing hydrophilicity and resulting in the unprecedented formation of liquid - liquid biphases with acetone. The single crystal structure of 1-( 2- hydroxypropyl)- 3- methylimidazolium tetraphenylborate, prepared by metathesis of the corresponding chloride- containing ionic liquid, has also been determined.

A retrievable and highly selective fluorescent probe for monitoring dihydrogen phosphate ions based on a naphthalimide framework

A novel selective fluorescent chemosensor based on naphthalimide derivatives (AN-SB) was synthesized and characterized. Once combined with Cu2+, compound AN-SB could give rise to a visible yellow to orange color change and fluorescence quenching, while other metal ions showed subtle disturbance. The complex (AN-SB-Cu2+) formed by Cu2+ and AN-SB displayed high specificity for H2PO4-. Among the various anions, only H2PO4- induced the revival of color and fluorescence of AN-SB, resulting in "off-on" type sensing of H2PO4- anion. The signal transduction occured via reversible formation-separation of complex AN-SB-Cu2+, however, slight changes were observed in the presence of other anions. (C) 2013 Elsevier B.V. All rights reserved.

4-Amino-1,8-naphthalimide-based Tröger's bases as high affinity DNA targeting fluorescent supramolecular scaffolds

The synthesis and photophysical and biological investigation of fluorescent 1,8-naphthalimide conjugated Troger's bases 1-3 are described. These structures bind strongly to DNA in competitive media at pH 7.4, with concomitant modulation in their fluorescence emission. These structures also undergo rapid cellular uptake, being localized within the nucleus within a few hours, and are cytotoxic against HL60 and (chronic myeloid leukemia) K562 cell lines.

Polyploid measles virus with hexameric genome length

Particles of most virus species accurately package a single genome, but there are indications that the pleomorphic particles of parainfluenza viruses incorporate multiple genomes. We characterized a stable measles virus mutant that efficiently packages at least two genomes. The first genome is recombinant and codes for a defective attachment protein with an appended domain interfering with fusion-support function. The second has one adenosine insertion in a purine run that interrupts translation of the appended domain and restores function. In that genome, a one base deletion in a different purine run abolishes polymerase synthesis, but restores hexameric genome length, thus ensuring accurate RNA encapsidation, which is necessary for efficient replication. Thus, the two genomes are complementary. The infection kinetics of this mutant indicate that packaging of multiple genomes does not negatively affect growth. We also show that polyploid particles are produced in standard infections at no expense to infectivity. Our results illustrate how the particles of parainfluenza viruses efficiently accommodate cargoes of different volume, and suggest a mechanism by which segmented genomes may have evolved.

A novel structural class of photoswitchable oligonucleotide

Directed Michaelis–Arbuzov reactions of support-bound internucleotide O-benzyl- or O-methyl-phosphite triesters with meta-phenylazobenzylamine or alkane-/glycol-linked a,x-diamines were effected in the presence of iodine. The corresponding tritylated phosphoramidate-linked 11-mers were fully deprotected and released from the support under standard conditions and the fast- and slow-diastereoisomers of both the E- and the Z-meta-phenylazobenzyl-appended oligomers were readily resolved by RP-HPLC. The primary amine-functionalised oligonucleotides were either purified, detritylated and then finally treated with Nhydroxysuccinimidyl carboxylic acid ester derivatives of photoswitchable moieties (Route A) or first derivatised and then subsequently purified and detritylated (Route B). This latter route enabled resolution of fast- and slow-isomers of the trityl-on oligomers bearing novel photoswitchable azopyridine or 9-alkoxyanthracene moieties using RP-HPLC, following which the pure diastereoisomers were detritylated and characterised by MALDI-MS.

Strategies toward the design of energetic ionic liquids: nitro- and nitrile-substituted N,N '-dialkylimidazolium salts

Twelve novel 1,3-dialkylimidazolium salts containing strongly electron-withdrawing nitro-and cyano-functionalities directly appended to the cationic heterocyclic rings have been synthesized; the influences of the substituents on both formation and thermal properties of the resultant ionic liquids have been determined by DSC, TGA, and single crystal X-ray diffraction, showing that an electron-withdrawing nitro-substituent can be successfully appended and has a similar influence on the melting behaviour as that of corresponding methyl group substitution. Synthesis of di-, or trinitro-substituted 1,3-dialkylimidazolium cations was unsuccessful due to the resistance of dinitro-substituted imidazoles to undergo either N-alkylation or protonation, while 1-alkyl- 4,5-dicyanoimidazoles were successfully alkylated to obtain 1,3-dialkyl-4,5-dicyanoimidazolium salts. Five crystal structures ( one of each cation type) show that, in the solid state, the NO2-group has little significant effect, beyond the steric contribution, on the crystal packing.

Uranyl Complexes of Carboxyl-Functionalized Ionic Liquids

Uranium(VI) oxide has been dissolved in three different ionic liquids functionalized with a carboxyl group: betainium bis[trifluoromethyl)sulfonyl]imide, 1-(carboxymethyl)-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, and N-(carboxymethyl)-N-methylpyrrolidinium bis[(trifluoromethyl)sulfonyl]imide. The dissolution process results in the formation of uranyl complexes with zwitterionic carboxylate ligands and bis[trifluoromethyl)sulfonyl]imide (bistriflimide) counterions. An X-ray diffraction study on single crystals of the uranyl complexes revealed that the crystal structure strongly depends on the cationic core appended to the carboxylate groups. The betainium ionic liquid gives a dimeric uranyl complex, the imidazolium ionic liquid a monomeric complex, and the pyrrolidinium ionic liquid a one-dimensional polymeric uranyl complex, Extended X-ray absorption fine structure measurements have been performed on the betainium uranyl complex. The absorption and luminescence spectra of the uranyl betainium complex have been studied in the solid state and dissolved in water, in acetonitrile, and in the ionic liquid betainium bistriflimide. The carboxylate groups remain coordinated to uranyl in acetonitrile and in betainium bistriflimide but not in water.

Solid and liquid charge-transfer complex formation between 1-methylnaphthalene and 1-alkyl-cyanopyridinium bis{(trifluoromethyl)sulfonyl}imide ionic liquids

Liquid charge-transfer (CT) complexes were observed to form on contacting electron-rich aromatics with electron withdrawing group appended 1-alkyl-4-cyanopyridinium ionic liquids (ILs). Cooling below the melting point of the ionic liquid resulted in crystallisation of ionic liquid from the complex for 2-cyano and 3-cyano pyridinium isomers and in the formation of a 1 : 1 IL : aromatic crystalline CT-complex with the 4-cyanopyridinium isomer. The liquid structure of a 1 : 1 mixture of 1-methyl-4-cyanopyridinium bis{(trifluoromethyl)sulfonyl} imide with 1-methylnaphthalene has been probed by neutron diffraction experiments and molecular dynamics simulations. A high degree of correlation between the experimental data and the simulations was found with a significant displacement of the anions from around the cation by the aromatic species and the resulting structure having pi-pi stacks between the cations and the aromatic.

ISOLATION AND PRIMARY STRUCTURE OF A NOVEL AVIAN PANCREATIC-POLYPEPTIDE FROM 5 SPECIES OF EURASIAN CROW

Chicken pancreatic polypeptide is the prototype of the neuropeptide Y (NPY)/PP superfamily of regulatory peptides. This polypeptide was appended the descriptive term avian, despite the presence of some 8600 extant species of bird. Additional primary structures from other avian species, including turkey, goose and ostrich, would suggest that the primary structure of this polypeptide has been highly-conserved during avian evolution. Avian pancreatic polypeptides structurally-characterised to date have distinctive primary structural features unique to this vertebrate group including an N-terminal glycyl residue and a histidyl residue at position 34. The crow family, Corvidae, is representative of the order Passeriformes, generally regarded as the most evolutionarily recent and diverse avian taxon. Pancreatic polypeptide has been isolated from pancreatic tissues from five representative Eurasian species (the magpie, Pica pica; the jay, Garrulus glandarius; the hooded crow, Corvus corone; the rook, Corvus frugilegus; the jackdaw, Corvus monedula) and subjected to structural analyses. Mass spectroscopy estimated the molecular mass of each peptide as 4166 +/- 2 Da. The entire primary structures of 36 amino acid residue peptides were established in single gas-phase sequencing runs. The primary structures of pancreatic polypeptides from all species investigated were identical: APAQPAYPGDDAPVEDLLR-FYNDLQQYLNVVTRPRY. The peptides were deemed to be amidated due to their full molar cross-reactivity with the amide-requiring PP antiserum employed. The molecular mass (4165.6 Da), calculated from the sequences, was in close agreement with mass spectroscopy estimates. The presence of an N-terminal alanyl residue and a prolyl residue at position 34 differentiates crow PP from counterparts in other avian species. These residues are analogous to those found in most mammalian analogues. These data suggest that the term avian, appended to the chicken peptide, is no longer tenable due to the presence of an Ala1, Pro34 peptide in five species from the largest avian order. These data might also suggest that, in keeping with the known structure/activity requirements of this peptide family, crow PP should interact identically to mammalian analogues on mammalian receptors.

Photocontrolled Binding and Binding-Controlled Photochromism within Anthracene-Modified DNA

Modified DNA strands undergo a reversible light-induced reaction involving the intramolecular photodimerization of two appended anthracene tags. The photodimers exhibit markedly different binding behavior toward a complementary strand that depends on the number of bases between the modified positions. By preforming the duplex, photochromism can be suppressed, illustrating dual-mode gated behavior.

The Use of Electrospray Mass Spectrometry to Determine Speciation in a Dynamic Combinatorial Library for Anion Recognition

The composition of a dynamic mixture of similar 2,2'-bipyridine complexes of iron(II) bearing either an amide (5-benzylamido-2,2'-bipyridine and 5-(2-methoxyethane)amido-2,2'-bipyridine) or an ester (2,2'-bipyridine-5-carboxylic acid benzylester and 2,2'-bipyridine-5-carboxylic acid 2-methoxyethane ester) side chain have been evaluated by electrospray mass spectroscopy in acetonitrile. The time taken for the complexes to come to equilibrium appears to be dependent on the counteranion, with chloride causing a rapid redistribution of two preformed heteroleptic complexes (of the order of 1 hour), whereas the time it takes in the presence of tetrafluoroborate salts is in excess of 24^^h. Similarly the final distribution of products is dependent on the anion present, with the presence of chloride, and to a lesser extent bromide, preferring three amide-functionalized ligands, and a slight preference for an appended benzyl over a methoxyethyl group. Furthermore, for the first time, this study shows that the distribution of a dynamic library of metal complexes monitored by ESI-MS can adapt following the introduction of a different anion, in this case tetrabutylammonium chloride to give the most favoured heteroleptic complex despite the increasing ionic strength of the solution. 

Controlled fragrance delivery in functionalised ionic liquid-enzyme systems

It is often believed that both ionic liquids and surfactants generally behave as non-specific denaturants of proteins. In this paper, it is shown that amphiphilic ionic liquids bearing a long alkyl chain and a target molecule, where the target molecule is appended via a carboxylic ester functionality, can represent super-substrates that enable the catalytic activity of an enzyme, even at high concentrations in solution. Menthol has been chosen as the target molecule for slow and controlled fragrance delivery, and it was found that the rate of the menthol release can be controlled by the chemical structure of the ionic liquid. At a more fundamental level, this study offers an insight into the complex hydrophobic, electrostatic, and hydrogen bond interactions between the enzyme and substrate.

Pro-fragrant ionic liquids with stable hemiacetal motifs: water-triggered release of fragrances

Stable liquid and solid salts in the form of elusive hemiacetals, appended with fragrant alcohols, have been synthesised as pro-fragrances, and the controlled release of these fragrances, triggered by water, is demonstrated

The structure of an unconventional HD-GYP protein from Bdellovibrio reveals the roles of conserved residues in this class of cyclic-di-GMP phosphodiesterases

UNLABELLED: Cyclic-di-GMP is a near-ubiquitous bacterial second messenger that is important in localized signal transmission during the control of various processes, including virulence and switching between planktonic and biofilm-based lifestyles. Cyclic-di-GMP is synthesized by GGDEF diguanylate cyclases and hydrolyzed by EAL or HD-GYP phosphodiesterases, with each functional domain often appended to distinct sensory modules. HD-GYP domain proteins have resisted structural analysis, but here we present the first structural representative of this family (1.28 Å), obtained using the unusual Bd1817 HD-GYP protein from the predatory bacterium Bdellovibrio bacteriovorus. Bd1817 lacks the active-site tyrosine present in most HD-GYP family members yet remains an excellent model of their features, sharing 48% sequence similarity with the archetype RpfG. The protein structure is highly modular and thus provides a basis for delineating domain boundaries in other stimulus-dependent homologues. Conserved residues in the HD-GYP family cluster around a binuclear metal center, which is observed complexed to a molecule of phosphate, providing information on the mode of hydroxide ion attack on substrate. The fold and active site of the HD-GYP domain are different from those of EAL proteins, and restricted access to the active-site cleft is indicative of a different mode of activity regulation. The region encompassing the GYP motif has a novel conformation and is surface exposed and available for complexation with binding partners, including GGDEF proteins.

IMPORTANCE: It is becoming apparent that many bacteria use the signaling molecule cyclic-di-GMP to regulate a variety of processes, most notably, transitions between motility and sessility. Importantly, this regulation is central to several traits implicated in chronic disease (adhesion, biofilm formation, and virulence gene expression). The mechanisms of cyclic-di-GMP synthesis via GGDEF enzymes and hydrolysis via EAL enzymes have been suggested by the analysis of several crystal structures, but no information has been available to date for the unrelated HD-GYP class of hydrolases. Here we present the multidomain structure of an unusual member of the HD-GYP family from the predatory bacterium Bdellovibrio bacteriovorus and detail the features that distinguish it from the wider structural family of general HD fold hydrolases. The structure reveals how a binuclear iron center is formed from several conserved residues and provides a basis for understanding HD-GYP family sequence requirements for c-di-GMP hydrolysis.