Cobalt(III) complexes of some aromatic thiohydrazides – Synthesis, characterization and structure

Co(NH3)(5)Cl]Cl-2 forms neutral 1:3 complex by reaction with aromatic thiohydrazides, i.e. thiobenzhydrazide, o-hydroxythiobenzhydrazide, thiophen-2-thiohydrazide and furan-2-thiohydrazide. All these complexes are diamagnetic and have been characterized by elemental analysis and combination of spectroscopic methods. Cyclic voltammometry of the complexes shows irreversible metal centered and ligand centered electron transfer reactions. One complex, tris-o-hydroxythiobenzhydrazidocobalt(III),has been crystallized from DMSO solution to produce solvated crystals and its structure has been established by X-ray crystallography. Cobalt(III) ion is linked through three hydrazinic nitrogen and three sulfur atoms of three identical deprotonated ligand molecules in a distorted octahedral environment. Involvement of -OH group in intramolecular and intermolecular hydrogen bonding is crucial for crystal formation.

Complex history of a chromosomal paralogy region: insights from amphioxus aromatic amino acid hydroxylase genes and insulin-related genes

Aromatic amino acid hydroxylase (AAAH) genes and insulin-like genes form part of an extensive paralogy region shared by human chromosomes 11 and 12, thought to have arisen by tetraploidy in early vertebrate evolution. Cloning of a complementary DNA (cDNA) for an amphioxus (Branchiostoma floridae) hydroxylase gene (AmphiPAH) allowed us to investigate the ancestry of the human chromosome 11/12 paralogy region. Molecular phylogenetic evidence reveals that AmphiPAH is orthologous to vertebrate phenylalanine (PAH) genes; the implication is that all three vertebrate AAAH genes arose early in metazoan evolution, predating vertebrates. In contrast, our phylogenetic analysis of amphioxus and vertebrate insulin-related gene sequences is consistent with duplication of these genes during early chordate ancestry. The conclusion is that two tightly linked gene families on human chromosomes 11 and 12 were not duplicated coincidentally. We rationalize this paradox by invoking gene loss in the AAAH gene family and conclude that paralogous genes shared by paralogous chromosomes need not have identical evolutionary histories.

Crystallization of random aromatic copolyesters containing flexible spacer chains and side-groups

The crystallization behaviour of a series of random copolymers of varying chemical composition is reported. For polymers containing a high proportion of alternating rigid aromatic units and flexible spacers, conventional liquid crystalline and crystalline phase behaviour is observed. The introduction of a substantial fraction of a second shorter rigid unit containing side-chains leads to a broad endotherm in the d.s.c. scan covering some 150°C. Subsequent isothermal crystallization at any point within the broad endotherm leads to the generation of sharp endotherms at temperatures just above the recrystallization temperature. We attribute this behaviour to the crystallization of clusters of molecules containing similar random sequences. Such crystals are non-periodic along the chain direction.

Janus PEG-based dendrimers for use in combination therapy: controlled multi-drug loading and sequential release

The increasing use of drug combinations to treat disease states, such as cancer, calls for improved delivery systems that are able to deliver multiple agents. Herein, we report a series of novel Janus dendrimers with potential for use in combination therapy. Different generations (first and second) of PEG-based dendrons containing two different “model drugs”, benzyl alcohol (BA) and 3-phenylpropionic acid (PPA), were synthesized. BA and PPA were attached via two different linkers (carbonate and ester, respectively) to promote differential drug release. The four dendrons were coupled together via (3 + 2) cycloaddition chemistries to afford four Janus dendrimers, which contained varying amounts and different ratios of BA and PPA, namely, (BA)2-G1-G1-(PPA)2, (BA)4-G2-G1-(PPA)2, (BA)2-G1-G2-(PPA)4, and (BA)4-G2-G2-(PPA)4. Release studies in plasma showed that the dendrimers provided sequential release of the two model drugs, with BA being released faster than PPA from all of the dendrons. The different dendrimers allowed delivery of increasing amounts (0.15–0.30 mM) and in exact molecular ratios (1:2; 2:1; 1:2; 2:2) of the two model drug compounds. The dendrimers were noncytotoxic (100% viability at 1 mg/mL) toward human umbilical vein endothelial cells (HUVEC) and nontoxic toward red blood cells, as confirmed by hemolysis studies. These studies demonstrate that these Janus PEG-based dendrimers offer great potential for the delivery of drugs via combination therapy.

Determination of orientations of aromatic groups in self-assembled peptide fibrils by polarised Raman spectroscopy

In this paper we describe a novel combination of Raman spectroscopy, isotope editing and X-ray scattering as a powerful approach to give detailed structural information on aromatic side chains in peptide fibrils. The orientation of the tyrosine residues in fibrils of the peptide YTIAALLSPYS with respect to the fibril axis has been determined from a combination of polarised Raman spectroscopy and X-ray diffraction measurements. The Raman intensity of selected tyrosine bands collected at different polarisation geometries is related to the values and orientation of the Raman tensor for those specific vibrations. Using published Raman tensor values we solved the relevant expressions for both of the two tyrosine residues present in this peptide. Ring deuteration in one of the two tyrosine side chains allowed for the calculation to be performed individually for both, by virtue of the isotopic shift that eliminates band overlapping. Sample disorder was taken into account by obtaining the distribution of orientations of the samples from X-ray diffraction experiments. The results provide previously unavailable details about the molecular conformation of this peptide, and demonstrate the value of this approach for the study of amyloid fibrils.

Antioxidant properties of three aromatic herbs (rosemary, thyme and lavender) in oil-in-water emulsions

Lipid oxidation is the major form of deterioration in foods because it decreases food quality and nutritional value, and may have negative health implications. Selected aromatic plant extracts from leaves, flowers and stems of rosemary, thyme and lavender were investigated for their antioxidant activity. The total polyphenol content was determined by the Folin-Ciocalteu assay and the antioxidant capacity was determined by the Trolox equivalent antioxidant capacity, 1,1-diphenyl-2-picrylhydrazyl, oxygen radical absorbance capacity and ferric-reducing antioxidant power assays. For all four antioxidant assays, the extracts from thyme flowers, lavender leaves and thyme leaves had the highest antioxidant activity, followed by rosemary stems, rosemary leaves, and lavender stems, and the lavender flowers and thyme stems had the lowest antioxidant activity. The antioxidant activity was correlated with the polyphenol content, although minor deviations were observed. In oil-in-water emulsion, extracts from rosemary leaves and thyme leaves were most effective at retarding oxidation followed by the rosemary stems and thyme flowers. Extracts from thyme flowers and lavender leaves were less effective in the emulsion than predicted by the homogeneous antioxidant assays. This study demonstrated the potential use of plants extract as substitutes for synthetic antioxidants.

Ring-opening polymerization in molten PEEK: transient reduction of melt-viscosity by macrocyclic aromatic thioetherketones

Blends of PEEK with macrocyclic thioether-ketones show initial melt-viscosities reduced by more than an order of magnitude relative to the polymer itself, enabling more facile processing and fabrication. On raising the temperature of the melt, however, the macrocycle undergoes spontaneous, entropically-driven ring-opening polymerization (ED-ROP), so that the properties of the final polymer should not, in principle, be compromised by the presence of low-MW macrocyclic material.

Bis amide-aromatic-ureasd - highly effective hydro- and organogelator systems

A series of hydro- and organo-supergelators have been synthesised via coupling of simple bis aromaticureas via alkyl amide linkages. These bis amide-aromatic-ureas exhibited reduced critical gelator concentrations, improved gelator stability, mechanical and dye removal properties for potential use in water purification, in comparison to related bis aromatic-ureas. Systematic structure studies via variation of the bis amide-aromatic-urea linker length as well as functionalization of the terminal aromatic moieties have enabled control over the gel properties.

Bis amide-aromatic-ureasd highly effective hydro- and organogelator systems

A series of hydro- and organo-supergelators have been synthesised via coupling of simple bis aromaticureas via alkyl amide linkages. These bis amide-aromatic-ureas exhibited reduced critical gelator concentrations, improved gelator stability, mechanical and dye removal properties for potential use in water purification, in comparison to related bis aromatic-ureas. Systematic structure studies via variation of the bis amide-aromatic-urea linker length as well as functionalization of the terminal aromatic moieties have enabled control over the gel properties.

Controlled variation of monomer sequence-distribution in the synthesis of aromatic poly(ether ketone)s

The effects of varying the alkali metal cation in the high-temperature nucleophilic synthesis of a semi-crystalline, aromatic poly(ether ketone) have been systematically investigated, and striking variations in the sequence-distributions and thermal characteristics of the resulting polymers were found. Polycondensation of 4,4'-dihydroxybenzophenone with 1,3-bis(4-fluorobenzoyl)benzene in diphenylsulfone as solvent, in the presence of an alkali metal carbonate M2CO3 (M= Li, Na, K, or Rb) as base, affords a range of different polymers that vary in the distribution pattern of 2-ring and 3-ring monomer units along the chain. Lithium carbonate gives an essentially alternating and highly crystalline polymer, but the degree of sequence-randomisation increases progressively as the alkali metal series is descended, with rubidium carbonate giving a fully random and non-thermally-crystallisable polymer. Randomisation during polycondensation is shown to result from reversible cleavage of the ether linkages in the polymer by fluoride ions, and an isolated sample of alternating-sequence polymer is thus converted to a fully randomised material on heating with rubidium fluoride.

Synthesis of poly(aspartimide)-based bio-glycoconjugates

The purpose of this programme was to synthesize and analyze new bioconjugates of interest for the potential inhibition of the influenza virus, using poly(aspartimide) as a polymer support. The macromolecular targets were obtained by attaching various sialic acid-linker-amine compounds to poly(aspartimide). 1H and 13C NMR studies were then performed to analyze the degree of incorporation of the sialic acid-linker-amine compounds within the poly(aspartimide). These studies illustrated that the incorporation was dependent on the nature of the spacer between the sugar and the amine functionality. Thus aliphatic spacers favoured the inclusion of sialic acid onto the polymer support whereas compounds having only an aromatic moiety between the sialic acid and the amine could not be easily incorporated.

Remediation of soils contaminated with petrol and diesel with lime

Lime treatment of hydrocarbon-contaminated soils offers the potential to stabilize and solidify these materials, with a consequent reduction in the risks associated with the leachate emanating from them. This can aid the disposal of contaminated soils or enable their on-site treatment. In this study, the addition of hydrated lime and quicklime significantly reduced the leaching of total petroleum hydrocarbons (TPH) from soils polluted with a 50:50 petrol/diesel mixture. Treatment with quicklime was slightly more effective, but hydrated lime may be better in the field because of its ease of handling. It is proposed that this occurs as a consequence of pozzolanic reactions retaining the hydrocarbons within the soil matrix. There was some evidence that this may be a temporary effect, as leaching increased between seven and 21 days after treatment, but the TPH concentrations in the leachate of treated soils were still one order of magnitude below those of the control soil, offering significant protection to groundwater. The reduction in leaching following treatment was observed in both aliphatic and aromatic fractions, but the latter were more affected because of their higher solubilty. The results are discussed in the context of risk assessment, and recommendations for future research are made.

Sequence-selective assembly of tweezer-molecules on linear templates enables frameshift-reading of sequence information

Monomer-sequence information in synthetic copolyimides can be recognised by tweezer-type molecules binding to adjacent triplet-sequences on the polymer chains. In the present paper different tweezer-molecules are found to have different sequence-selectivities, as demonstrated in solution by 1H NMR spectroscopy and in the solid state by single crystal X-ray analyses of tweezer-complexes with linear and macrocyclic oligo-imides. This work provides clear-cut confirmation of polyimide chain-folding and adjacent-tweezer-binding. It also reveals a new and entirely unexpected mechanism for sequence-recognition which, by analogy with a related process in biomolecular information processing, may be termed "frameshift-reading". The ability of one particular tweezer-molecule to detect, with exceptionally high sensitivity, long-range sequence-information in chain-folding aromatic copolyimides, is readily explained by this novel process.

Bis(hydroxy-isoindolinone)s: synthesis, stereochemistry, polymer chemistry, and supramolecular assembly

Pseudoacid chlorides of 2,5-bis(4-fluorobenzoyl) terephthalic acid and 4,6-bis(4-fluorobenzoyl) isophthalic acid condense with primary amines to afford diastereomeric bis(hydroxyindolinone)s in good isolated yields and with diamines to give high molecular weight poly(hydroxyindolinone)s. Bis-N-pyrenemethyl bis(hydroxyindolinone)s assemble, even in dipolar solvents such as DMSO, with macrocyclic diimide-sulfones to give [3]pseudorotaxanes stabilized by electronically complementary aromatic π−π-stacking and shape-complementary van der Waals interactions.