Diimine ligand as a novel chemiluminescence enhancer of luminol-containing compounds.

A series of diimine ligands (DLs) have been synthesized and evaluated for their non-enzymatic chemiluminescence (CL) enhancement of isoluminol or luminol-containing compounds. Of the DLs, N,N'-bis(m-hydroxylbenzylidene)propylenediamine (DL 10) was found to greatly enhance their CLs approximately 40 folds for isoluminol, 10 folds for luminol and 6 folds for a luminol-containing polymer. The CL enhancement of the compounds was observed in the presence of CH(3)CN, H(2)O(2), tetra-n-propylammonium hydroxide (TPA), and Fe (III) ion. The possible mechanism of this CL enhancement was discussed on the basis of the chelate formation of the ligand and the metal ions.

Synthesis of poly(vinyl alcohol)-doxorubicin conjugates containing cis-aconityl acid-cleavable bond and its isomer dependent doxorubicin release.

Aconityl-doxorubicin (ADOX) was synthesized by the modified method of Shen and Ryser. Two isomers of cis-ADOX (cis-configuration) and trans-ADOX (trans-configuration) were generated in the reaction of DOX and cis-aconitic anhydride. These products were separated completely by using HPLC and analyzed by TOF-MS spectroscopy and (1)H- and (13)C-NMR experiments. The yields of cis-ADOX and trans-ADOX were 36.3 and 44.8%, respectively. The free gamma-carboxylic group of ADOX molecule was coupled to poly(vinyl alcohol) (PVA) via ethylenediamine spacer, resulting the macromolecular conjugates of PVA-cis-ADOX and PVA-trans-ADOX, respectively. The DOX content of the conjugates estimated by the hydrolysis method detected the aglycone of DOX which can be estimated as the PVA-bound DOX selectively was 4.4 w/w% which was similar to 4.6 w/w% by the ordinary UV method. Both PVA-cis-ADOX and PVA-trans-ADOX were very stable at neutral pH, but the release of DOX was increased markedly under acidic conditions. Half-life of the release of DOX from PVA-cis-ADOX at pH 5.0 was 3 h which was 4.7-fold shorter than that from PVA-trans-ADOX (14 h). The cytotoxicities of PVA-cis-ADOX and PVA-trans-ADOX were evaluated by using J774.1 cells employing a [(3)H]uridine incorporation assay as a measure of RNA synthesis. A significant difference in antitumor activity between PVA-cis-ADOX and PVA-trans-ADOX was observed where the former was much active than the later. It was suggested that the conjugate enters the cells and reaches the lysosomal/endosomal compartment, and that the aconityl spacer releases DOX from the conjugate in the acidic compartment of lysosomes/endosomes due to the participation of a free carboxylic group.

A vector-selective reaction enables efficient construction of specific topology upon the primary side of beta-cyclodextrin.

N-dansylcysteines attached on the primary side of beta-cyclodextrin reacted with the saccharide hydroxyl groups in a vector-selective manner, affording the corresponding lactones. The desired topology of the lactones can be efficiently constructed simply by the selection of the proper enantiomer of D/L-cysteines. In comparison with the exo-lactone, the endo-lactone displayed 4 times stronger fluorescence intensity, stronger binding affinity to sodium adamantanecarboxylate, and 15 times larger signal changes in fluorescence intensity upon binding.

Cerium complexes of cyclodextrin dimers as efficient catalysts for luminol chemiluminescence reactions.

The chemiluminescence of a luminol-H(2)O(2) system is found to be remarkably enhanced by the Ce(IV) complexes of EDTA-bridged cyclodextrin dimers. The dimers were proved to work much more efficiently than the corresponding monomer. The cavity shape of cyclodextrin moieties and their cooperation displayed an important role in amplifying the chemiluminescence. Further modification of either the cyclodextrin rims or the EDTA linker altered significantly the catalytic abilities of the cyclodextrin dimers, and the examination of the effect of substituents on the chemiluminescence outputs suggested that the proximity between the cyclodextrin cavity and the metallic center might account for the amelioration of the chemiluminescence output.

Selective modification of beta-cyclodextrin: an unexpected tandem reaction enables the cross-linking of C2(A) and C2(B) via a sulfur atom.

2(A),3(A)-Alloepithio-2(B)-sulfonyl-beta-cyclodextrin undergoes a tandem reaction to generate an unprecedented C2(A)-S-C2(B)-bridged glucosyl-3(A),6(A)-anhydroglucoside segment.

The first topologically controlled synthesis of doubly bridged beta-cyclodextrin dimers.

Reaction 6(A),6(B)-di(O-tosyl)-beta-cyclodextrin with Na(2)S in DMF gave the cis-dimer of beta-cyclodextrin in 21% isolated yield while the trans-dimer was not detected.

Clockwise-counterclockwise differentiation on the upper rim of a monofunctional gamma-cyclodextrin: efficient topological control in the syntheses of capped cyclodextrins.

Intramolecular condensation of 6(A)-(N-dansyl-l-cysteine)-gamma-cyclodextrin occurred only at 6(B)-OH of the many OH groups to afford the corresponding lactone with an exo-topology.

Shortcut synthesis of beta-cyclomannin from beta-cyclodextrin.

Beta-cyclomannin, a cyclic oligosaccharide consisting of seven alpha-D-mannosides connected together by the (1-->4) glycoside linkage, has been efficiently synthesized by the OsO4 oxidation of heptakis(2,3-didehydroxy)-beta-cyclodextrin which was prepared from beta-cyclodextrin by a five-step transformation. The novel cyclooligosaccharide not only showed water solubility high enough to meet the requirement for drug formulation but also demonstrated strong binding ability toward guest molecules. [reaction: see text]

The first hetero-bifunctionalization of the secondary face of beta-cyclodextrin: selective and efficient conversion of the A-ring of a 2A,2B-disulfonate to 2A,3A-epoxymannoside.

The A-ring of 2(A),2(B)-O,O-di(mesitylenesulfonyl)-beta-cyclodextrin was converted to 2(A),3(A)-epoxymannoside without affecting the other sulfonylated residue, which affords the first approach to hetero-bifunctionalization at the secondary hydroxyl side of cyclodextrins.

1H NMR studies on the hydrogen-bonding network in mono-altro-beta-cyclodextrin and its complex with adamantane-1-carboxylic acid.

The hydrogen-bond network in mono-altro-beta-cyclodextrin and in its inclusion complex with adamantane-1-carboxylic acid were investigated by (1)H NMR spectroscopy using the chemical shifts, temperature coefficients and vicinal coupling constants of the exchangeable hydroxy protons. The chemical shifts of the 3-OH signals indicated that the hydrogen-bond network between the 2-OH and 3-OH groups was disturbed not only on each side of the altrose residue, but also along the whole dextrin chain. Upon addition of adamantane-1-carboxylic acid, altrose underwent a conformational change from the (1)C(4) to the (O)S(2) form, allowing a more continuous belt of hydrogen bonding, as evidenced by the downfield shift experienced by the 3-OH proton signals of the glucose residues.

Functionalization of cyclodextrins via reactions of 2,3-anhydrocyclodextrins.

Three types of reactions of 2,3-anhydro-beta-cyclodextrins, namely nucleophilic ring-opening, reduction to 2-enopyranose, and reduction to 3-deoxypyranose, have been investigated to regio- and stereoselectively functionalize the secondary face of beta-cyclodextrin. Upon treatment with various nucleophiles, both 2,3-mannoepoxy and 2,3-alloepoxy-beta-cyclodextrins are found to undergo nucleophilic ring-opening reaction generating 3- and 2-modified cyclodextrin derivatives. In each case, the 3-position is more easily accessible than the 2-position. By using these ring-opening reactions, imidazolyl, iodo, azido, and benzylmercapto groups are selectively introduced to the secondary face of beta-cyclodextrin in place of the 2- or 3-hydroxyl groups. The functionalized cyclodextrins have either modified glucosidic subunits or modified altrosidic subunits that make the hydrophobic cavity slightly distorted from that of native beta-cyclodextrin. Thiourea also reacts with the cyclodextrin epoxides. In this case, thiirane and olefin species are generated instead of any ring-opening products. By ameliorating the reaction condition, cyclodextrin olefin, diene, and triene derivatives are prepared in moderate to good yields. Reduction of per[6-(tert-butyldimethyl)silyl]-beta-cyclodextrin permannoepoxide with lithium aluminum hydride produces the per(3-deoxy)-beta-cyclomannin. All these chemically modified cyclodextrins are structurally well characterized and most of them are expected to serve as versatile scaffolds for diverse purposes such as the construction of catalysts and development of synthetic receptors and molecular containers.

The first successful crystallographic characterization of a cyclodextrin dimer: efficient synthesis and molecular geometry of a doubly sulfur-bridged beta-cyclodextrin.

Beta-cyclodextrin is transannularly disulfonylated at the 6(A)- and 6(B)-positions, and then converted to the corresponding 6(A),6(B)-diiodide and 6(A),6(B)-dithiol. Cross-coupling of the latter two species yields a single head-to-head-coupled beta-cyclodextrin dimer 5 with two sulfur linkers at adjacent 6-methylene carbons. NMR and X-ray analysis revealed the trans-type ("aversive") linkage of both beta-cyclodextrin units. In the solid-state structure of 5.5 MeOH.23 H(2)O, the undistorted cyclodextrin macrocycles feature almost parallel ring planes pointing away from each other, leaving 5 with a "handcuff-like" appearance of approximate C(2) symmetry. This work represents the first successful crystallographic study on a cyclodextrin dimer.

Crystal structure of mono[3-(2-imidazolylthio)]-altro-beta-cyclodextrin: elliptical distortion of the cavity and unique 'Yin-Yang' stacking.

The title compound is elliptically distorted due to the unusual 1C4 geometry of the altrose portion. In packing, a unique fourfold helical structure is elaborated with head-to-head dimers as the repeating motif. The imidazolyl moieties mutually reside on each other's cavities thereby resembling the Yin-Yang type balancing of antagonisms.

Fluorophore-capped cyclodextrins as efficient chemical-to-light energy converters.

Bisbenzimidazole-capped cyclodextrins, capable of forming supramolecules, harvest chemical energy from the oxidation reaction of a bis(aryl)oxalate and emit light two orders of magnitude more efficiently than fluorescein does.

The first successful investigation into a cyclodextrin-based enzyme model as an efficient catalyst for luminol chemiluminescent reaction.

The chemiluminescence of the luminol-H2O2 system is found for the first time to be remarkably enhanced by the Ce(IV) complexes of cyclodextrin dimers.