Diamine Precursor Research Articles

Interdiffusion of thermoplastics and epoxy resin precursors: investigations using experimental and molecular dynamics methods

AbstractToughening of epoxy thermosets with thermoplastics is an important avenue towards improved properties of high‐performance systems. The main focus of the work reported was to study the complex issue of interdiffusion between thermoplastics and epoxy resin precursors, using a combination of experimental and numerical simulation methods, in order to understand the key parameters driving the process. Diameter changes of thermoplastic filaments in contact with epoxide and diamine precursors have been followed and an original approach using carbon nanotubes as tracers of the filament swelling front has been developed. This method shows that the improved mobility of low‐molecular‐weight resin monomers as well as the greater mobility of phenoxy of lower glass transition temperature as compared to poly(ether sulfone) control dissolution by favouring the penetration of precursors into the thermoplastic and lead to both swelling of the outer part of the filaments and reduction of the inner unaffected core. Simulation by molecular dynamics supports the idea that diffusion of polymer macromolecules remains limited compared to the dominant effect of precursor diffusion. Indeed, low diffusion coefficients have been predicted for thermoplastic oligomers compared to resin monomers. For the latter, the calculated values correlate well with the experimental data measured during interdiffusion. Copyright © 2012 Society of Chemical Industry

Impact of precursor size on the chain structure and mechanical properties of solvent-swollen epoxy gels

The thermal and mechanical properties of solvent-swollen epoxy gels were investigated as a function of pre-cursor size in a model end-linked network. The epoxy networks were formed by cross-linking diepoxide and diamine precursors in the presence of a low volatility solvent, dibutylphthalate (DBP). Both precursors were end functionalized and contained a poly(propylene glycol) (PPG) spacer between the epoxy and amine functionality, respectively. The lengths of both precursors were controlled by varying the molecular weight of the PPG spacer between functional groups. The glass transition temperature for the gels as a function of solvent loading was well predicted by the Fox equation. The scaling factors of shear storage modulus versus solvent loading increased with increasing diamine precursor molecular weight to values much larger (3.91) than the theoretical value of 2.3, for entanglement dominated network formation in a theta solvent. In contrast, the scaling factor increased with decreasing epoxy precursor molecular weight to values near 4.5. The large, molecular weight dependent scaling factors are attributed to loop defect formation as the result of the amine cross-linker architecture, which consists of two difunctional reactive end groups separated by a spacer. Rather than equal spacing of all four reactive sites, the amine end groups contain two reactive hydrogens that increase the local concentration of reactive species, and facilitates loop formation. We anticipate that this work will aid in the development of non-aqueous gels and provide enhanced tailoring of the gel properties over a broad range of stiffness.

Polyamine catabolism: target for antiproliferative therapies in animals and stress tolerance strategies in plants

Metabolism of polyamines spermidine and spermine, and their diamine precursor, putrescine, has been a target for antineoplastic therapy since these naturally occurring alkyl amines were found essential for normal mammalian cell growth. Intracellular polyamine concentrations are maintained at a cell type-specific set point through the coordinated and highly regulated interplay between biosynthesis, transport, and catabolism. A correlation between regulation of cell proliferation and polyamine metabolism is described. In particular, polyamine catabolism involves copper-containing amine oxidases and FAD-dependent polyamine oxidases. Several studies showed an important role of these enzymes in several developmental and disease-related processes in both animals and plants through a control on polyamine homeostasis in response to normal cellular signals, drug treatment, environmental and/or cellular stressors. The production of toxic aldehydes and reactive oxygen species, H(2)O(2) in particular, by these oxidases using extracellular and intracellular polyamines as substrates, suggests a mechanism by which the oxidases can be exploited as antineoplastic drug targets. This minireview summarizes recent advances on the physiological roles of polyamine catabolism in animals and plants in an attempt to highlight differences and similarities that may contribute to determine in detail the underlined mechanisms involved. This information could be useful in evaluating the possibility of this metabolic pathway as a target for new antiproliferative therapies in animals and stress tolerance strategies in plants.

Synthesis, Structural Characterization and Metal Inclusion Properties of 18‐, 20‐ and 22‐Membered Oxaazacyclophanes and Oxaazacalix[4]arene Analogues: Macrocyclic Amine and Schiff Base Receptors with Variable NxOy Donor Sets

AbstractA series of oxaazacyclophanes and oxaazacalix[4]arene analogues with 18‐, 20‐ and 22‐membered rings have been synthesized from diamine and dialdehyde building blocks and structurally characterized by spectroscopic methods. One diamine precursor and four macrocycles have additionally been analysed by single‐crystal X‐ray diffraction. Two of the oxaazacalix[4]arene analogues were employed for metal ion complexation studies based on UV/Vis absorption spectroscopy, showing both compounds to be able to form complexes with Cu2+ and Zn2+.

ChemInform Abstract: Direct Asymmetric Aldol Reaction with Recyclable Fluorous Organocatalyst.

AbstractThe new fluorous sulfonamide PFSA promotes effectively the aldol reaction at room temperature and in a shorter time compared to the diamine precursor.

Deposition of chemically reactive and repellent sites on biosensor chips for reduced non-specific binding

The performances of new polymeric materials with excellent optical properties and good machinability have led the biomedical diagnostics industry to develop cheap disposable biosensor platforms appropriate for point of care applications. Zeonor, a type of cycloolefin polymer (COP), is one such polymer that presents an excellent platform for biosensor chips. These polymer substrates have to be modified to have suitable physico-chemical properties for immobilizing proteins. In this work, we have demonstrated the amine functionalization of COP substrates, by plasma enhanced chemical vapour deposition (PECVD), through codeposition of ethylene diamine and 3-aminopropyltriethoxysilane precursors, for building chemistries on the plastic chip. The elemental composition, adhesion, ageing and reactivity of the plasma polymerized film were examined. The Si–O functionality present in amino silane contributed for a good interfacial adhesion of the coating to COP substrates and also acted as a network building layer for plasma polymerization. Wet chemical modification was then carried out on the amine functionalized chips to create chemically reactive isothiocyanate sites and protein repellent fluorinated sites on the same chip. The density of the reactive and repellent sites was altered by choosing appropriate mixtures of homofunctional phenyldiisothiocyanate (PDITC), pentafluoroisothiocyanate (5FITC) and phenylisothiocyanate (PITC) compounds. By tailoring the density of reactive binding sites and protein repellent sites, the non-specific binding of ssDNA has been decreased to a significant extent.

A chiral diamine bis-phenolate complex of dioxomolybdenum(VI)

A new chiral tetradentate ligand reacts with [MoO 2 (acac) 2 ] to form a monomeric complex. The syntheses and X-ray crystal structures of the ligand and the complex are reported. A new dioxomolybdenum(VI) complex with a chiral tetradentate ligand is reported. The tripodal ligand containing two nitrogen atoms and two phenolic oxygen atoms was synthesized starting from a chiral diamine precursor. Further reaction with [MoO 2 (acac) 2 ] yielded a monomeric molybdenum complex as a bright yellow solid. The structures of the molybdenum complex and the free diamine bis-phenol ligand were determined by X-ray diffraction.

Synthesis and characterization of some novel thermally stable poly(amide–imide)s

Two new diamines with built-in amide linkage were synthesized from p-nitrobenzoyl chloride in two steps and characterized by their melting points, elemental analyses, FT-IR and 1H–NMR spectral studies. One of the diamine precursors was also characterized by single crystal X-ray analysis indicating the trans orientation of amide bonds. The planes of the aromatic rings formed dihedral angles in the range of 11.7°–56.2° and the crystal packing was stabilized by N–H···O hydrogen bonds. The synthesized diamines were then polymerized with three commercially available dianhydrides either by one-step solution technique or by two-step procedure involving ring-opening poly-addition to give polyamic acid followed by cyclic dehydration. The resulting poly(amide–imide)s were characterized by their elemental analyses and FTIR spectroscopy. The polymers possessed excellent chemical resistance and were found insoluble in almost all the common solvents tested except conc. H2SO4, in which these showed inherent viscosities in the range 0.47–0.73 dL g−1 at 28 °C. The thermal behavior of the polymers, investigated by the DSC and TG analyses, revealed that the products were stable up to 300 °C in nitrogen. The activation energies of pyrolysis, entropy, and enthalpy values for each of the synthesized polymers were also estimated by Horowitz and Metzger method using thermal degradation data. These values were high exhibiting the remarkable thermal stability of the poly(amide–imide)s. Wide-angle X-ray studies of the polymers were also carried out which provided information about their morphology.

Rac- andR-(+)-[4,4′,5,5′-2H4]-2-(1′-[2′′,6′′-dichlorophenoxy]-ethyl)-Δ2-imidazoline (lofexidine)

The synthesis of the d4-forms of rac- and R-lofexidine was accomplished. Two methods are described; one method is a two-step synthesis of rac-d4-lofexidine from 2-chloropropionitrile, the second method is a three-step preparation of R-d4-lofexidine in absolute enantiomeric purity from S-methyl lactate. The commercial availability of R-methyl lactate makes this latter enantioselective synthesis applicable also to the synthesis of S-d4- lofexidine. These procedures also conserve the utilization of the relatively expensive [1,1′,2,2′-2H4]ethylene diamine precursor. The availability of S- and R-d4-lofexidines will enable pharmacokinetic studies to be carried out to determine if differential in vivo metabolism of the two enantiomers of lofexidine occurs. Copyright © 2009 John Wiley & Sons, Ltd.

Synthesis of 11C-Labeled Uracil Derivative for a PET Tracer Targeting Thymidine Phosphorylase

The expression of thymidine phosphorylase (TP) is closely associated with angiogenesis in tumors. For developing a TP-expression-based positron emission tomography (PET) radiotracer for diagnosis and prognosis of cancer chemotherapy, we synthesized a novel 11 C-labeled oxoimidazolidinylmethyluracil ([C]-2a), which was designed on the basis of one of the most potent inhibitors, 5-bromo-6-[(2-iminoimidazolidinyl)-methyl]uracil hydrobromide (5BIMU), through a ring closure reaction of [ 11 C]phosgene with a developed diamine precursor (la). After purification by HPLC, the total synthesis was accomplished in just 23 min after bombardment, and the yield was 1653 MBq at the end of synthesis (EOS).

Imidazolidines as new anti- Trypanosoma cruzi agents: Biological evaluation and structure–activity relationships

Imidazolidine derivatives were studied as anti- Trypanosoma cruzi agents. Imidazolines can be considered as ethylenediamine/carbonyl precursors and therefore interfere with the biosynthesis of polyamines into the parasite. Some of the derivatives were found to have high and selective activity against the proliferative stages of the parasite, with IC 50 values against the epimastigote form in the low micromolar range as the reference drug Nifurtimox. The imidazolidines demonstrated to be stable after five days of incubation in buffer glucose, pH 7, indicating that diamines were not obtained in these conditions. But it was found that two of the studied diamine precursors were as active as the parent compounds. Probably, the imidazolidines affect the mitochondrial integrity according to the excreted end-products found in the NMR studies. The QSAR studies indicated that the bioactivities are correlated with the lipophilicities. In conclusion, we have described a new and relevant bioactivity for imidazolidines. The results support further in vivo studies of some of these imidazolidine derivatives.

Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases

The polyamines spermidine and spermine and their diamine precursor putrescine are naturally occurring, polycationic alkylamines that are essential for eukaryotic cell growth. The requirement for and the metabolism of polyamines are frequently dysregulated in cancer and other hyperproliferative diseases, thus making polyamine function and metabolism attractive targets for therapeutic intervention. Recent advances in our understanding of polyamine function, metabolic regulation, and differences between normal cells and tumour cells with respect to polyamine biology, have reinforced the interest in this target-rich pathway for drug development.

Metathesis-Mediated Route to 6,6-Bicyclic Malonamides

A synthetic approach involving classical Grignard and modern metathesis chemistry affording 6,6-bicyclic malonamides (BMA) is presented. Starting with a double allyl Grignard addition to ethyl formate followed by base-mediated malonate alkylation affords the requisite meta­thesis precursor which, under Grubbs I catalytic conditions, leads to the expected cyclopentene. Pedagogically well-accepted strategy for the construction of acyclic functionalized derivatives by ozonolysis of cyclic olefins is then followed and leads to a diamine precursor which, upon reductive amination and hydrogenolysis, affords the BMA derivatives. The synthesis of 10 BMAs is ­described.

Thermal behavior of zinc γ-zirconium phosphate intercalation compounds

The layered ion-exchangers γ-zirconium phosphate and γ-zirconium phosphate containing intercalated diamines, obtained by exchanging zinc ions, have been synthesized and characterized. Zinc ions are able to form coordination compounds between the layers of the host matrix and consequently form zinc complexes formed in situ. The zinc ions uptake, the thermal behavior and the structural characterization of the compounds obtained have also been examined. The thermal stability and X-ray spectra of these compounds depend on the type of isomeric diamine precursor. The zinc fully exchanged γ-zirconium phosphate is able to form ZnS particles in the host matrix. The X-ray spectra of this obtained material matched those of the initial γ-zirconium phosphate precursor.

Combination of 5-Fluorouracil and N1,N11-Diethylnorspermine Markedly Activates Spermidine/Spermine N1-Acetyltransferase Expression, Depletes Polyamines, and Synergistically Induces Apoptosis in Colon Carcinoma Cells

The thymidylate synthase inhibitor 5-fluorouracil (5-FU) is used widely for chemotherapy of colorectal carcinoma. Recent studies showed that 5-FU affects polyamine metabolism in colon carcinoma cells. We therefore examined whether combinations of 5-FU with drugs that specifically target polyamine metabolism, i.e. N1,N11-diethylnorspermine (DENSPM) or alpha-difluoromethylornithine (DFMO), have synergistic effects in killing HCT116 colon carcinoma cells with wild-type or absent p53. Our results showed that simultaneous 5-FU and DENSPM, a spermine analogue, synergistically increased transcript levels of the polyamine catabolism enzyme spermidine/spermine N1-acetyltransferase, depleted spermine and spermidine, increased acetylated spermidine, and produced synergistic tumor cell apoptosis in both p53 wild-type and p53-null variants. By contrast, simultaneous combination of 5-FU with DFMO, an inhibitor of the polyamine biosynthetic enzyme ornithine decarboxylase, depleted putrescine but did not produce synergistic cell killing. Some pre-treatment and post-treatment regimens of DENSPM and DFMO were antagonistic to 5-FU depending on cellular p53 status. Protein and transcriptome expression analysis showed that combined 5-FU and DENSPM treatment activated caspase 9, but not caspase 3, and significantly suppressed NADH dehydrogenases and cytochrome c oxidases, consistent with the observed increase in hydrogen peroxide, loss of mitochondrial membrane potential, and release of cytochrome c. Our findings demonstrate the importance of the polyamine pathway in 5-FU effects and suggest that the combination of 5-FU with DENSPM has potential for development as therapy for colorectal carcinoma.

Manganese(II), Cobalt(II), and Nickel(II) Perchlorate Complexes Containing N, O Donor Macrocyclic Ligands

AbstractMononuclear macrocyclic complexes of manganese(II), cobalt(II) and nickel(II) perchlorate using 10 different oxaazamacrocyclic ligands (L1 — L10) have been prepared and characterized. The complexation reactions with the diiminic ligands were obtained by template condensation of the appropriate dialdehyde and diamine precursors; the reduced macrocycle complexes were synthesized using a direct route. The complexes have been characterized by elemental analyses, molar conductivity, mass spectrometry, IR, UV‐vis spectroscopy, diffuse reflectance and magnetic susceptibility measurements.

Lanthanide(III) Complexes of Two Novel N3O4-donor Macrocycles Derived from 3,6-Dioxa-1,8-Octanediamine

Two novel N3O4 macrocycles, L1 and L2, have been synthesised, and their complexation potential towards Ln(III) ions has been investigated. Direct cyclocondensation between 2,6-bis(2-formylphenoxymethyl)pyridine and 3,6-dioxa-1,8-octanediamine yields the macrocycle L1 as the main product. The diamine macrocycle L2 is formed by reaction of the diamine and dicarbonyl precursors followed by an in situ reduction with NaBH4. Series of Ln(III) complexes have been obtained for both ligands, by direct synthesis between L1 or L2 and different Ln(III) hydrated nitrates or perchlorates; however, attempts to synthesise the corresponding Ln(III) complexes with L1 following a template method have been unsuccessful. All complexes obtained with L1 give a [2 : 1, Ln : L1] stoichiometry. The reduction of the diiminic bonds increases the flexibility of the macrocycle and leads to a change in the stoichiometry; all complexes obtained with L2 show a [3 : 1, Ln : L2] relation.

Coordination chemistry of copper(II) with oxaaza macrocyclic ligands. Crystal structure of a dinuclear tetramer copper(II) complex

A new series of copper(II) nitrate and perchlorate complexes with eight different oxaaza macrocyclic ligands (L 1–L 8) have been prepared and characterised. Complexes with the diiminic ligands L 1–L 6 have been obtained by template condensation of the appropriate dialdehyde and diamine precursors; the reduced L 7 and L 8 macrocycles have been synthesised using a direct route. The overall geometry and bonding mode have been deduced on the basis of elemental analysis data, IR, FAB, UV–Vis spectroscopy, cyclic voltammetry, and conductivity and magnetic susceptibility measurements. After treatment of an acetonitrile solution of the complex [L 6Cu](ClO 4) 2·5H 2O with acetic acid 15%, dark blue single crystals, the result of a secondary reaction, were isolated and characterised as a new binuclear tetramer copper(II) complex, with formula C 13H 28ClCu 2N 3O 10.

Epoxy Networks Containing Large Mass Fractions of a Monofunctional Polyhedral Oligomeric Silsesquioxane (POSS)

A polyhedral oligomeric silsesquioxane (POSS) containing one epoxy group and seven isobutyl groups per molecule was incorporated into an epoxy network following a two-stage process. In the first stage, POSS was reacted with an aromatic diamine, employing a 1:1 molar ratio of both reactants. The distribution of species at the end of reaction, determined by size exclusion chromatography (SEC), was close to the ideal one. In a second step, this precursor was reacted with the stoichiometric amount of an aromatic diepoxide to generate an organic−inorganic hybrid material containing 51.8 wt % POSS. A primary liquid−liquid phase separation process occurred at the time of adding the diepoxide to the POSS−diamine precursor. This led to a macrophase separation into epoxy-rich and POSS-rich regions, possibly derived from the incompatibility of the isobutyl groups attached to the POSS with the aromatic epoxy−amine network. A secondary phase separation occurred in the epoxy-rich phase in the course of polymerization, producing a dispersion of small POSS domains. Both modulated local thermal analysis (LTA) and differential scanning calorimetry (DSC) showed that most POSS-rich domains were amorphous. A small fraction of POSS crystals was also detected. A postcure cycle led to an increase in the glass transition temperature and the disappearance of crystallinity. A reference network was synthesized by replacing POSS by phenyl glycidyl ether (PGE) in equimolar amounts. The resulting network was homogeneous but exhibited a lower glass transition temperature than the POSS-modified network. As both networks had the same topology, the higher Tg observed for the POSS-modified epoxy may be associated with the hindering of polymer chain motions by their covalent bonding to POSS clusters. The most important concept arising from these results is that a phase separation process may take place when employing a POSS bearing organic groups that are not compatible with the epoxy network.

Antizyme induction by polyamine analogues as a factor of cell growth inhibition.

The polyamines spermidine and spermine and their diamine precursor putrescine are essential for mammalian cell growth and viability, and strategies are sought for reducing polyamine levels in order to inhibit cancer growth. Several structural analogues of the polyamines have been found to decrease natural polyamine levels and inhibit cell growth, probably by stimulating normal feedback mechanisms. In the present study, a large selection of spermine analogues has been tested for their effectiveness in inducing the production of antizyme, a key protein in feedback inhibition of putrescine synthesis and cellular polyamine uptake. Bisethylnorspermine, bisethylhomospermine, 1,19-bis-(ethylamino)-5,10,15-triazanonadecane, longer oligoamine constructs and many conformationally constrained analogues of these compounds were found to stimulate antizyme synthesis to different levels in rat liver HTC cells, with some producing far more antizyme than the natural polyamine spermine. Uptake of the tested compounds was found to be dependent on, and limited by, the polyamine transport system, for which all these have approximately equal affinity. These analogues differed in their ability to inhibit HTC cell growth during 3 days of exposure, and this ability correlated with their antizyme-inducing potential. This is the first direct evidence that antizyme is induced by several polyamine analogues. Selection of analogues with this potential may be an effective strategy for maximizing polyamine deprivation and growth inhibition.