Synthesis of dendritic bisphosphonates as bone targeting ligands

A dendritic bisphosphonate carrying three bisphosphonate (BP) units in close proximity was designed as a ligand to conjugate large therapeutic molecules for their bone selective delivery. The Bu₃P-catalyzed conjugate addition of nitromethane to vinylidene bisphosphonate was effective to construct a quaternary carbon center carrying BP units. Owing to multivalent interactions, the dendritic bisphosphonate showed considerable affinity for the bone mineral hydroxyapatite even in the presence of a competitor, demonstrating potential as a bone targeting ligand.     

Alternative preparation and characterization of platinum(II) organometallic dinuclear complexes and oligomers with 3,8-diethynylphenanthroline derivatives

Novel platinum(II) organometallic dinuclear complexes and oligomers with two types of phenanthroline ligands, namely 3,8-diethynylphenanthroline (L1) and 3,8-bis-(4-ethynyl-phenylethynyl)-1,10-phenanthroline (L2), were synthesized from trans-Pt(PBu₃)₂(1-ethynyl-4-methyl-benzene)Cl and trans-Pt(PBu₃)₂Cl₂ by transmetalation of copper ion. The alternative procedure targeted platinum oligomer termination selection of either chloride or respective phenanthrolines and was successfully performed with different purifications by extraction and column chromatography. The structural formulae of these platinum complexes and oligomers were revealed with by analysis of both ³¹P{¹H}-NMR and ¹H-NMR spectral data. Alternative preparations of platinum oligomers with two types between chloride and respective phenanthroline termination are very useful for the selective synthesis for hybrid polymers with the coupling reaction with two different platinum oligomers with different diethynylaryl ligands. The platinum organometallic compounds showed similar absorption bands in the UV–Vis region. Those prepared with L1 had a strong absorption band at around 400 nm, assignable to the lowest energy metal-perturbed ¹[π–π*] transitions, while in compounds prepared with L2, the strong band appeared around 410 nm, because L2 has an extended π conjugation relative to L1. No distinct differences were observed in the absorption spectra of these platinum oligomers between the different terminal structures, chloride or various phenanthrolines. The luminescence spectra of the platinum compounds prepared with either L1 or L2, however, showed a distinct difference. Those with L1 showed only a phosphorescence assignable to a typical metal-perturbed ³[π–π*] transition with vibronic progressions centered at around 530 nm in deoxygenated CH₂Cl₂ at room temperature, while those with L2 showed weak dual emissions assignable to a mixture of typical metal-perturbed ¹[π–π*] and ³[π–π*] transitions in the visible region.     

Concise synthesis of indole-fused 1,4-diazepines through copper(I)-catalyzed domino three-component coupling-cyclization-N-arylation under microwave irradiation

Indole-fused benzo-1,4-diazepines were synthesized by copper-catalyzed domino three-component coupling-indole formation- N-arylation under microwave irradiation from a simple N-mesyl-2-ethynylaniline. This method was also applicable to the formation of heterocycle-fused 1,4-diazepines.     

Palladium-catalysed biscyclisation of allenic bromoalkenes through a zipper-mode cascade

Treatment of allenic bromoalkenes bearing a nucleophilic moiety with a catalytic amount of palladium(0) in the presence of TBAF or Cs(2)CO(3) in MeCN affords bicyclic heterocycles in good to high yields, through zipper-mode cascade cyclisation.     

Total synthesis of mycestericin A

The first total synthesis of mycestericin A (1) starting from tartrates is described. The Overman rearrangement of an allylic trichloroacetimidate generated a tetra-substituted carbon with nitrogen, and subsequent stereoselective transformations afforded the highly functionalized vinyl iodide. The cross-coupling of the vinyl iodide with a chiral organozinc species under Negishi conditions, followed by deprotection, completed the total synthesis of 1.     

Linear dichroism of Zn(II)-tetrapyridylporphine aggregates formed at the toluene/water interface

The apparent circular dichroism (CD) and the linear dichroism (LD) spectra of the aggregates of achiral zinc(II)-5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine (ZnTPyP), formed at the toluene/water interface in a centrifugal liquid membrane (CLM) cell, were investigated by comparison with the microscopic CD and LD spectra of a single interfacial aggregate of ZnTPyP about 100 mum in length, measured by a microscope-spectropolarimeter. The interfacial ZnTPyP aggregate showed two types of flat trapezoidal shapes, one had a seedlike core at an edge (type I) and another a needlelike core at an edge (type II). The microscopic CD and LD spectra were observed by varying the angle between the parallel axis of the trapezoidal aggregate and the perpendicular axis of a polarized light for LD. The plot of the CD intensity against the LD intensity for a single aggregate, observed at a given wavelength, showed a rotated elliptical shape with a long axis through the origin, when the orientation angle was changed. From these results, it was concluded that the apparent CD spectra observed by the CLM-CD method were mainly due to the large linear dichroism of the aggregate. Both type I and type II structures showed two transition dipole moments, parallel and perpendicular to the long axis of the structure, but suggesting a more developed J-aggregate in type II structure. AFM measurements showed that the interfacial ZnTPyP aggregate had a multilayer structure, in which the unit monolayer thickness was 1.58 +/- 0.23 nm. Finally, the orientation angle of the interfacial aggregate in the CLM cell was estimated as 41 degrees -44 degrees to the rotating axis of the cell.     

Nanomosaic: formation of nanodomains confined in a two-dimensional molecular plane

Atomic force microscopy observations of a (hydrocarbon guanidinium/fluorocarbon carboxylic acid) mixed monolayer revealed that a nanoscopic phase-separated structure was formed by a combination of attractive interaction between the oppositely charged head groups and repulsive phase separation of the hydrocarbon and fluorocarbon chains.     

Design of polymeric carriers for cancer-specific gene targeting: utilization of abnormal protein kinase Calpha activation in cancer cells

We succeeded in cancer cell specific gene expression by using a polyplex responsive to protein kinase Calpha, which is activated in various types of cancer cells.