Design and synthesis of site directed maleimide bifunctional chelators for technetium and rhenium

A new family of heterobifunctional linkers (L1-L9) containing a terminus consisting of a tridentate donor set for coordination of the {M(CO)(3)}(+) core (M = Tc, Re), and a thiol reactive maleimide group has been prepared conveniently and in high yield under Mitsunobu reaction conditions by the coupling of an appropriate alcohol derivative with maleimide. The rhenium complexes [Re(CO)(3)(Lx)]Br (x= 1-9) were prepared in good yields from the reactions of the ligands and (NEt(4))(2)[Re(CO)(3)Br(3)] in refluxing methanol. The ligands and their Re complexes were characterized by (1)H and (13)C NMR, IR, and ESI-MS. Ligand L4 and [Re(CO)(3)(L5)]Br have been structurally characterized by X-ray crystallography. Photoexcitation of solutions of the complexes [Re(CO)(3)(Lx)]Br (x= 4-6) gives rise to intense and prolonged luminescence at room temperature (fluorescence lifetimes of ca. 16 micros). The ligands and their Re complexes react smoothly at the maleimide linker with sulfhydryl groups of peptides and proteins at room temperature in phosphate-buffered saline (PBS, pH 7.4) to form stable thioether bioconjugates. The photoluminescence properties of the labeled conjugates are similar to those of the parent complexes, but with even longer lifetimes. The ligands can also be labeled at room temperature with (99m)Tc to give chemically robust complexes. The corresponding hydrazinonicotinamide derivative N-[5-(6'-hydrazinopyridine-3'-carbonyl)aminopentyl]maleimide (L10) was also prepared. While coupling of L10 to cysteine ethylester and synthesis of the rhenium derivative [ReCl(3)(HYNIC-maleimide)(2)] were successfully accomplished, attempts to couple [ReCl(3)(HYNIC-maleimide)(2)] to glutathione or BSA yielded intractable mixtures.     

Design, synthesis and redox properties of two ferrocene-containing iron chelators

Two ferrocene-containing iron(III) chelators were synthesized from desferrioxamine B and kojic acid and their electronic absorption and electrochemical properties were studied in acetonitrile in the absence and presence of ferric ions. The results show a complex behavior arising from the occurrence of competing redox and complexation processes. Such systems are a first step toward the generation of chemosensors for the electrochemical detection of iron(III) in a solution.     

Design and synthesis of a new fluorescent tripod for chemosensor applications

A new yellow-green fluorescent tripod based 1,8-naphthalimide has been synthesized and characterised. Its photophysical properties have been investigated in organic solvents of different polarity. The effect that the metal ions (Cd²⁺, Co²⁺, Zn²⁺, Mn²⁺, Mg²⁺, Ni²⁺, Pb²⁺, Cu²⁺, Ba²⁺, Fe³⁺ and Ag⁺) produce upon the fluorescent intensity of acetonitrile solutions of the tripod has been discussed viewing its potential applications as a detector for metal cations. The influence of protons on the fluorescence intensity of the tripod in DMF and methanol–water (1:4 v/v) solutions has also been investigated.     

Design and synthesis of polyindole - ZnO nano composite for NLO applications

Present paper mainly focuses on the synthesis, characterization polyindole-ZnO nano composites for third order nonlinear optical applications. Polyindole was synthesized through oxidative polymerization technique and its composites were prepared with different ZnO concentration. Structural morphology of the polymer composite was studied using FESEM, XRD and UV Visible spectroscopic technique. Polymer showed broad absorption with absorption maxima of 395 nm. Newly prepared thin films showed excellent nonlinear absorption with very good optical limiting behaviour when it is exposed to He-Ne laser with maximum optical limiting power of 11 mW along with third-order nonlinear susceptibility χ⁽³⁾ of 2.72 × 10^?3 esu. Hence these polymer composites may be potential candidate for optical limiting applications.     

Design, synthesis and applications of hyaluronic acid-paclitaxel bioconjugates

Paclitaxel (1a), a well known antitumor agent adopted mainly for the treatment of breast and ovarian cancer, suffers from significant disadvantages such as low solubility, certain toxicity and specific drug-resistance of some tumor cells. To overcome these problems extensive research has been carried out. Among the various proposed strategies, the conjugation of paclitaxel (1a) to a biocompatible polymer, such as hyaluronic acid (HA, 2), has also been considered. Coupling a bioactive compound to a biocompatible polymer offers, in general, many advantages such as better drug solubilization, better stabilization, specific localization and controlled release. Hereafter the design, synthesis and applications of hyaluronic acid-paclitaxel bioconjugates are reviewed. An overview of HA-paclitaxel combinations is also given.     

Investigation of materials for making a carbon-support zinc-selective electrode

The usefulness of zinc orthophosphate and zinc mercuric thiocyanate to make a carbon-support electrode responsive to zinc was investigated. The best results were obtained with zinc orthophosphate, which produced a Nernstian response to zinc in the concentration range from 10(-5) to 10(-2)M. The electrode response was lowered by the formation of acidic oxides on the surface of the electrode. Different ways of minimizing this problem are discussed. Interference effects from copper(II) (K(pot)(Zn.Cu) = 1.0), cadmium (K(pot)(Zn.Cd) = 8.9) and lead (K(pot)(Zn.Pb) = 10) were observed.     

Recent advances in therapeutical applications of the versatile hydroxypyridinone chelators

Journal of Inclusion Phenomena and Macrocyclic Chemistry - Hydroxypyridinones (HOPOs) are excellent class of chelators that have been gaining attention in the field of pharmaceutical drugs by their...     

Design of iron chelators with therapeutic application

Iron is essential for the proper functioning of all living cells, however it is toxic when present in excess. Thus, using iron chelators as therapeutic agents, namely chelation therapy, has received increasing attention. The objective of this review is to discuss the factors which should be considered when designing clinically useful iron chelators, to present the application of iron chelators in the treatment of iron overload associated with β-thalassaemia major and sickle cell anaemia, and to highlight the potential applications in the treatment of neurodegenerative disorders and microbial infection. This article reviews recent knowledge centred on these themes and indicates the growing importance of the concept of iron chelation in medicine.     

Design and synthesis of monofunctionalized, water-soluble conjugated polymers for biosensing and imaging applications

Water-soluble conjugated polymers with controlled molecular weight characteristics, absence of ionic groups, high emission quantum yields, and end groups capable of selective reactions of wide scope are desirable for improving their performance in various applications and, in particular, fluorescent biosensor schemes. The synthesis of such a structure is described herein. 2-Bromo-7-iodofluorene with octakis(ethylene glycol) monomethyl ether chains at the 9,9'-positions, i.e., compound 4, was prepared as the reactive premonomer. A high-yielding synthesis of the organometallic initiator (dppe)Ni(Ph)Br (dppe = 1,2-bis(diphenylphosphino)ethane) was designed and implemented, and the resulting product was characterized by single-crystal X-ray diffraction techniques. Polymerization of 4 by (dppe)Ni(Ph)Br can be carried out in less than 30 s, affording excellent control over the average molecular weight and polydispersity of the product. Quenching of the polymerization with [2-(trimethylsilyl)ethynyl]magnesium bromide yields silylacetylene-terminated water-soluble poly(fluorene) with a photoluminescence quantum efficiency of 80%. Desilylation, followed by copper-catalyzed azide-alkyne cycloaddition reaction, yields a straightforward route to introduce a wide range of specific end group functionalities. Biotin was used as an example. The resulting biotinylated conjugated polymer binds to streptavidin and acts as a light-harvesting chromophore to optically amplify the emission of Alexa Fluor-488 chromophores bound onto the streptavidin. Furthermore, the biotin end group makes it possible to bind the polymer onto streptavidin-functionalized cross-linked agarose beads and thereby incorporate a large number of optically active segments.     

Design and synthesis of multi-component 18 pi annulenic fluorofullerene ensembles suitable for donor-acceptor applications

A series of trannulene (all-trans annulene) derivatives of [60]fullerene have been prepared by reacting C(60)F(18) with methanetricarboxylate esters that incorporate a range of photoactive functions. All the compounds have the intense emerald-green colour of fullerene trannulenes, characterised by strong bands at ca. 612 and 667 nm. Single crystal X-ray studies show that the packing varies with the nature of the addend, attributable to differing steric effects. UV/vis absorption spectra display transitions of the respective fullerene and addend models, indicating absence of electronic interactions between them in the ground state. These now provide an extensive series for testing photoactive (light-harvesting) properties, with the exceptional properties of having strong visible light absorption. Their exceptional stability is attributed to the 18[small pi] aromatic circuit, inability to undergo nucleophilic substitution without disrupting this circuit, and a curved cage region that is shielded to reagents by the three bulky addends.     

Rapid synthesis of cross-bridged cyclam chelators for copper(II) complex formation

Copper(II) complexes of 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (cross-bridged cyclam) derived chelators show high kinetic stability relative to less rigid non-bridged azamacrocyclic chelators and have applications as radiopharmaceuticals in PET imaging. Rapid synthesis of two novel bis-benzyl cross-bridged cyclam derivatives was achieved in 24 h compared to the typical synthesis times, between 14 and 30 days. The X-ray crystal structures are reported for the copper(II) complexes with 1,3-dibromobenzyl and tolyl derivatives revealing different ligand coordination environments. Both structures show tetradentate coordination of the tetraazamacrocycle with axial elongation along the N–Cu–N axis for the 1,3-dibromobenzyl derivative (Cu–N distances: axial av. 2.48(8) Å, equatorial av. 2.081(7) Å).     

A general synthesis of tris-indole derivatives as potential iron chelators

The development of a novel route for the synthesis of a new class of compounds is described. The first tripodal, tris-indole amines are prepared by straightforward routes.     

Design and synthesis of novel polyglycerol hybrid nanomaterials for potential applications in drug delivery systems

The synthesis of a new drug delivery system based on hybrid nanomaterials containing a β-CD core and hyperbranched PG is described. Conjugating PG branches onto β-CD not only increases its water solubility but also affects its host/guest properties deeply. It can form molecular inclusion complexes with small hydrophobic guest molecules such as ferrocene or FITC with reasonable release. In addition, the achievable payloads are significantly higher as for carriers such as hyperbranched PGs. Short-term in vitro cytotoxicity and hemocompatibility tests on L929 cell lines show that the hybrid nanomaterial is highly biocompatible. Due to their outstanding properties, β-CD-g-PG hybrid nanomaterials are introduced as promising materials for nanomedicine, e.g., for drug delivery issues.     

Design and synthesis of ion‐conductive polyphosphazenes for fuel cell applications: Review

New proton‐conductive fuel cell membranes have been produced by the linkage of acidic functional groups to aryloxy side units attached to a polyphosphazene macromolecular chain. The functional groups include sulfonic acid, phosphonic acid, and sulfonimide units. The different functional groups impart different water retention, proton conduction, and methanol resistance to the membranes. Special advantages are foreseen for uses in direct methanol fuel cells. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2358–2368, 2006     

Chiral ionic liquids,a renewal for the chemistry of chiral solvents? Design,synthesis and applications for chiral recognition and asymmetric synthesis

Chiral ionic solvents were almost unexplored before the last five years. This field which is of increasing importance could constitute a renewal for the chemistry of chiral solvents. So far reported examples are designed either from the chiral pool (aminoacids, hydroxyacids, amines, aminoalcohols, terpenes and alkaloids) or by asymmetric synthesis; they can bear central, axial or planar chirality. Modern applications in asymmetric synthesis, enzymatic chemistry, chiral chromatography and NMR are surveyed. Their use in the field of liquid crystals and for stereoselective polymerisation are also discussed. At the end of the article, a series of tables is compiled including all the CILs described to date and their physical properties.     

Conjugates of methyl 6-aminopenicillanate with biscatechol-hydroxamate chelators: synthesis and siderophoric activity

A synthesis of biscatechol-hydroxamate and triscatechol chelators and of conjugates of the former with methyl 6-aminopenicillanate is described. It is based on the multiple use of the ylide Ph₃PCCO as a C₂ building block in one-pot coupling reactions between aldehydes and alcohols or amines. These conjugates were actively internalized into siderophore-deficient Escherichia coli mutant H5596.     

Design and synthesis of new cationic water‐soluble pyrene containing dendrons for DNA sensory applications

A series of new water‐soluble cationic pyrene‐dendron derivatives, G1 , G2 , and G3, was successfully synthesized and characterized. These new dendrons were designed with the quaternized amino moieties at the periphery of the dendrons for DNA detection and functionalized with pyrene as a fluorescent probe. The electrostatic interactions between the plasmid DNA (pDNA) and cationic charged dendrons in an aqueous solution resulted in a change in the photophysical properties of pyrene, which could be shown in the UV‐vis and fluorescence spectra. Pyrene dendrons showed a high and rapid fluorescence response upon the addition of pDNA, which was strongly dependent on the size and hydrophobicity of the dendrons. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Practical synthesis and applications of benzoboroxoles

A convenient one-pot synthesis of benzoboroxoles has been developed via the reaction of o-bromobenzyl alcohols with NaH, ⁿBuLi, and B(OⁱPr)₃ followed by acidic hydrolysis. Applications of these benzoboroxoles have been demonstrated in Pd-catalyzed cross-coupling reactions and the protocol has been extended for the synthesis of a chiral benzoboroxole. Exceptionally short synthesis of a potent antifungal agent AN2690 and several of its analogs has also been realized.