Hydrogen-bonding in cyclic imides and amide carboxylic acid derivatives from the facile reaction of cis-cyclohexane-1,2-carboxylic anhydride with o- and p-anisidine and m- and p-aminobenzoic acids

The structures of the open chain amide carboxylic acid rac-cis-[2-(2-methoxyphenyl)carbamoyl]cyclohexane-1-carboxylic acid, C15H19NO4, (I) and the cyclic imides rac-cis-2-(4-methoxyphenyl)-3a,4,5,6,7,7-hexahydroisoindole-1,3-dione,C15H17NO3, (II), chiral cis-2-(3-carboxyphenyl)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione, C15H15NO4,(III) and rac-cis-2-(4-carboxyphenyl)- 3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione monohydrate, C15H15NO4. H2O) (IV), are reported. In the amide acid (I), the phenylcarbamoyl group is essentially planar [maximum deviation from the least-squares plane = 0.060(1)Ang. for the amide O atom], the molecules form discrete centrosymmetric dimers through intermolecular cyclic carboxy-carboxy O-H...O hydrogen-bonding interactions [graph set notation R2/2(8)]. The cyclic imides (II)--(IV) are conformationally similar, with comparable phenyl ring rotations about the imide N-C(aromatic) bond [dihedral angles between the benzene and isoindole rings = 51.55(7)deg. in (II), 59.22(12)deg. in (III) and 51.99(14)deg. in (IV). Unlike (II) in which only weak intermolecular C-H...O(imide) hydrogen bonding is present, the crystal packing of imides (III) and (IV) shows strong intermolecular carboxylic acid O-H...O hydrogen-bonding associations. With (III), these involve imide O-atom acceptors, giving one-dimensional zigzag chains [graph set C(9)], while with the monohydrate (IV), the hydrogen bond involves the partially disordered water molecule which also bridges molecules through both imide and carboxyl O-atom acceptors in a cyclic R4/4(12) association, giving a two-dimensional sheet structure. The structures reported here expand the structural data base for compounds of this series formed from the facile reaction of cis-cyclohexane-1,2-dicarboxylic anhydride with substituted anilines, in which there is a much larger incidence of cyclic imides compared to amide carboxylic acids.

Cyclic Imide and Open-Chain Amide Carboxylic Acid Derivatives from the Facile Reaction of cis-Cyclohexane-1,2-dicarboxylic Anhydride with Three Substituted Anilines

The structures of the compounds from the reaction of cis-cyclohexane-1,2-dicarboxylic anhydride with 4-chloroaniline [rac-N-(4-chlorophenyl)-2-carboxycycloclohexane-1-carboxamide] (1), 4-bromoaniline [2-(4-bromophenyl)-perhydroisoindolyl-1,3-dione] (2) and 3-hydroxy-4-carboxyaniline (5-aminosalicylic acid) [2-(3-hydroxy-4-carboxyphenyl)-perhydroisoindolyl-1,3-dione] (3) have been determined at 200 K. Crystals of the open-chain amide carboxylic acid 1 are orthorhombic, space group Pbcn, with unit cell dimensions a = 20.1753(10), b = 8.6267(4), c = 15.9940(9) Å, and Z = 8. Compounds 2 and 3 are cyclic imides, with 1 monoclinic having space group P21 and cell dimensions a = 11.5321(3), b = 6.7095(2), c = 17.2040(5) Å, β = 102.527(3)o. Compound 3 is orthorhombic with cell dimensions a = 6.4642(3), b = 12.8196(5), c = 16.4197(7) Å. Molecules of 1 form hydrogen-bonded cyclic dimers which are extended into a two-dimensional layered structure through amide-group associations: 3 forms into one-dimensional zigzag chains through carboxylic acid…imide O-atom hydrogen bonds, while compound 2 is essentially unassociated. With both cyclic imides 2 and 3, disorder is found which involves the presence of partial enantiomeric replacement of the cis-cyclohexane-1,2-substituted ring systems.

Vibrational spectroscopy of the borate mineral henmilite Ca2Cu[B(OH)4]2(OH)4

Henmilite is a triclinic mineral with the crystal structure consisting of isolated B(OH)4 tetrahedra, planar Cu(OH)4 groups and Ca(OH)3 polyhedra. The structure can also be viewed as having dimers of Ca polyhedra connected to each other through 2B(OH) tetrahedra to form chains parallel to the C axis. The structure of the mineral has been assessed by the combination of Raman and infrared spectra. Raman bands at 902, 922, 951, and 984 cm−1 and infrared bands at 912, 955 and 998 cm−1 are assigned to stretching vibrations of tetragonal boron. The Raman band at 758 cm−1 is assigned to the symmetric stretching mode of tetrahedral boron. The series of bands in the 400–600 cm−1 region are due to the out-of-plane bending modes of tetrahedral boron. Two very sharp Raman bands are observed at 3559 and 3609 cm−1. Two infrared bands are found at 3558 and 3607 cm−1. These bands are assigned to the OH stretching vibrations of the OH units in henmilite. A series of Raman bands are observed at 3195, 3269, 3328, 3396, 3424 and 3501 cm−1 are assigned to water stretching modes. Infrared spectroscopy also identified water and OH units in the henmilite structure. It is proposed that water is involved in the structure of henmilite. Hydrogen bond distances based upon the OH stretching vibrations using a Libowitzky equation were calculated. The number and variation of water hydrogen bond distances are important for the stability off the mineral.

Growth of C36-films on diamond surface through molecular dynamics simulation

In this paper, the initial stage of films assembled by energetic C36 fullerenes on diamond (001)–(2 × 1) surface at low-temperature was investigated by molecular dynamics simulation using the Brenner potential. The incident energy was first uniformly distributed within an energy interval 20–50 eV, which was known to be the optimum energy range for chemisorption of single C36 on diamond (001) surface. More than one hundred C36 cages were impacted one after the other onto the diamond surface by randomly selecting their orientation as well as the impact position relative to the surface. The growth of films was found to be in three-dimensional island mode, where the deposited C36 acted as building blocks. The study of film morphology shows that it retains the structure of a free C36 cage, which is consistent with Low Energy Cluster Beam Deposition (LECBD) experiments. The adlayer is composed of many C36-monomers as well as the covalently bonded C36 dimers and trimers which is quite different from that of C20 fullerene-assembled film, where a big polymerlike chain was observed due to the stronger interaction between C20 cages. In addition, the chemisorption probability of C36 fullerenes is decreased with increasing coverage because the interaction between these clusters is weaker than that between the cluster and the surface. When the incident energy is increased to 40–65 eV, the chemisorption probability is found to increased and more dimers and trimers as well as polymerlike-C36 were observed on the deposited films. Furthermore, C36 film also showed high thermal stability even when the temperature was raised to 1500 K.

Energy window effect in chemisorption of C36 on diamond (001)-(/2×1) surface

In this paper, the collision of a C36, with D6h symmetry, on diamond (001)-(/2×1) surface was investigated using molecular dynamics (MD) simulation based on the semi-empirical Brenner potential. The incident kinetic energy of the C36 ranges from 20 to 150 eV per cluster. The collision dynamics was investigated as a function of impact energy Ein. The C36 cluster was first impacted towards the center of two dimers with a fixed orientation. It was found that when Ein was lower than 30 eV, C36 bounces off the surface without breaking up. Increasing Ein to 30-45 eV, bonds were formed between C36 and surface dimer atoms, and the adsorbed C36 retained its original free-cluster structure. Around 50-60 eV, the C36 rebounded from the surface with cage defects. Above 70 eV, fragmentation both in the cluster and on the surface was observed. Our simulation supported the experimental findings that during low-energy cluster beam deposition small fullerenes could keep their original structure after adsorption (i.e. the memory effect), if Ein is within a certain range. Furthermore, we found that the energy threshold for chemisorption is sensitive to the orientation of the incident C36 and its impact position on the asymmetric surface.

Characterisation of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline both in Australia and globally. Hence, the cellular and molecular pathways associated with UVR-induced photocarcinogenesis urgently need to be elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular the highly-mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which to some extent have limited their relevance to the in vivo situation. To address this, we characterised a 3-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically-relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB-irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53 and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration following photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage.

A satellite RNA of barley yellow dwarf virus contains a novel hammerhead structure in the self-cleavage domain

An RNA molecule with properties of a satellite RNA was found in an isolate of barley yellow dwarf virus (BYDV), RPV serotype. It is 322 nucleotides long, single-stranded, and does not hybridize to the viral genome. Dimers of the RNA, which presumably represent replicative intermediates, were able to self-cleave into monomers. In vitro transcripts from cDNA clones were capable of self-cleavage in both the plus (encapsidated) and minus orientations. The sequence flanking the minus strand cleavage site contained a consensus " hammerhead" structure, similar to those found in other self-cleaving satellite RNAs. Although related to the hammerhead structure, sequences flanking the plus strand termini showed differences from the consensus and may be folded into a different structure containing a pseudoknot. © 1991.

Diporphyrins linked by two-atom bridges synthestic, structural and theoretical studies

The syntheses, properties and electronic structures of a series of porphyrin dimers connected by two-atom bridges were compared. The study found that an azo linker results in the most efficient electronic communication between the two porphyrin rings, and is the superior connector for dimers, trimers and oligomers in the design of nonlinear optical materials. This has implications for the design of molecular probes and sensors, photodynamic therapy, microfabrication, and three-dimensional optical data storage. The research led to the synthesis of a number of new porphyrin monomers and dimers, which were characterised using structural, spectroscopic and spectrometric techniques.

A comparison of the gas phase acidities of phospholipid headgroups: Experimental and computational studies

Proton-bound dimers consisting of two glycerophospholipids with different headgroups were prepared using negative ion electrospray ionization and dissociated in a triple quadrupole mass spectrometer. Analysis of the tandem mass spectra of the dimers using the kinetic method provides, for the first time, an order of acidity for the phospholipid classes in the gas phase of PE < PA << PG < PS < PI. Hybrid density functional calculations on model phospholipids were used to predict the absolute deprotonation enthalpies of the phospholipid classes from isodesmic proton transfer reactions with phosphoric acid. The computational data largely support the experimental acidity trend, with the exception of the relative acidity ranking of the two most acidic phospholipid species. Possible causes of the discrepancy between experiment and theory are discussed and the experimental trend is recommended. The sequence of gas phase acidities for the phospholipid headgroups is found to (1) have little correlation with the relative ionization efficiencies of the phospholipid classes observed in the negative ion electrospray process, and (2) correlate well with fragmentation trends observed upon collisional activation of phospholipid \[M - H](-) anions. (c) 2005 American Society for Mass Spectrometry.

Xanthones from fungi, lichens, and bacteria : the natural products and their synthesis

Many fungi, lichens, and bacteria produce xanthones (derivatives of 9H-xanthen-9-one, “xanthone” from the Greek “xanthos”, for “yellow”) as secondary metabolites. Xanthones are typically polysubstituted and occur as either fully aromatized, dihydro-, tetrahydro-, or, more rarely, hexahydro-derivatives. This family of compounds appeals to medicinal chemists because of their pronounced biological activity within a notably broad spectrum of disease states, a result of their interaction with a correspondingly diverse range of target biomolecules. This has led to the description of xanthones as “privileged structures”.(1) Historically, the total synthesis of the natural products has mostly been limited to fully aromatized targets. Syntheses of the more challenging partially saturated xanthones have less frequently been reported, although the development in recent times of novel and reliable methods for the construction of the (polysubstituted) unsaturated xanthone core holds promise for future endeavors. In particular, the fascinating structural and biological properties of xanthone dimers and heterodimers may excite the synthetic or natural product chemist.

Hybrid polymer/metal nanoparticles with surface enhanced raman tracking for potential use in nanomedicine

This project was a preliminary step towards the development of novel methods for early stage cancer diagnosis and treatment. Diagnostic imaging agents with high Raman signal enhancement were developed based on tailored assemblies of gold nanoparticles, which demonstrated potential for non-invasive detection from deep under the skin surface. Specifically designed polymers were employed to assemble gold nanoparticles into controlled morphologies including dimers, nanochains, nanoplates, globular and core-satellite nanostructures. Our findings suggest that the Raman enhancement is strongly dependent on assembly morphology and can be tuned to adapt to the requirements of the diagnostic agent.

Genotoxicity of inorganic lead salts and disturbance of microtubule function

Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 μM lead chloride and 0.05 μM lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20-60 μM lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 μM. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 μM and reached half-maximal inhibition of motility at about 50 μM. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels.

In vitro investigations on the effect of dermal fibroblasts on keratinocyte responses to ultraviolet B radiation

Exposure to ultraviolet radiation is closely linked to the development of skin cancers in humans. The ultraviolet B (UVB) radiation wavelength (280-320 nm), in particular, causes DNA damage in epidermal keratinocytes, which are linked to the generation of signature premalignant mutations. Interactions between dermal fibroblasts and keratinocytes play a role in epidermal repair and regeneration after UVB-induced damage. To investigate these processes, established two and three-dimensional culture models were utilized to study the impact of fibroblast-keratinocyte crosstalk during the acute UVB response. Using a coculture system it was observed that fibroblasts enhanced keratinocyte survival and the repair of cyclobutane pyrimidine dimers (CPDs) after UVB radiation exposure. These findings were also mirrored in irradiated human skin coculture models employed in this study. Fibroblast coculture was shown to play a role in the expression and activation of members of the apoptotic cascade, including caspase-3 and Bad. Interestingly, the expression and phosphorylation of p53, a key player in the regulation of keratinocyte cell fate postirradiation, was also shown to be influenced by fibroblast-produced factors. This study highlights the importance of synergistic interactions between fibroblasts and keratinocytes in maintaining a functional epidermis while promoting repair and regeneration following UVB radiation-induced damage.

Small gold nanoparticles as crystallization "catalysts": Effect of seed size and concentration on Au-ZnO hetero nanoparticles

This work reports the effect of seed nanoparticle size and concentration effects on heterogeneous crystal nucleation and growth in colloidal suspensions. We examined these effects in the Au nanoparticle-seeded growth of Au-ZnO hetero-nanocrystals under synthesis conditions that generate hexagonal, cone-shaped ZnO nanocrystals. It was observed that small (~ 4 nm) Au seed nanoparticles form one-to-one Au-ZnO hetero dimers and that Au nanoparticle seeds of this size can also act as crystallization ‘catalysts’ that readily promote the nucleation and growth of ZnO nanocrystals. Larger seed nanoparticles (~9 nm, ~ 11 nm) provided multiple, stable ZnO-nucleation sites, generating multi-crystalline hetero trimers, tetramers and oligomers.