Effect of particle size of drug on conversion of crystals to an amorphous state in a solid dispersion with crospovidone

The effect of particle size on amorphization of drugs in a solid dispersion (SD) was investigated for two drugs, indomethacin (IM) and nifedipine (NP). The SD of drugs were prepared in a mixture with crospovidone by a variety of mechanical methods, and their properties investigated by particle sizing, thermal analysis, and powder X-ray diffraction. IM, which had an initial particle size of 1 μm and tends to aggregate, was forced through a sieve to break up the particles. NP, which had a large initial particle size, was jet-milled. In both cases, reduction of the particle size of the drugs enabled transition to an amorphous state below the melting point of the drug. The reduction in particle size is considered to enable increased contact between the crospovidone and drug particles, increasing interactions between the two compounds.     

Reduction‐Induced Highly Selective Uptake of Cesium Ions by an Ionic Crystal Based on Silicododecamolybdate

Cation adsorption and exchange has been an important topic in both basic and applied chemistry relevant to materials synthesis and chemical conversion, as well as purification and separation. Selective Cs⁺ uptake from aqueous solutions is especially important because Cs⁺ is expensive and is contained in radioactive wastes. However, the reported adsorbents incorporate Rb⁺ as well as Cs⁺, and an adsorbent with high selectivity toward Cs⁺ has not yet been reported. Highly selective uptake of Cs⁺ by an ionic crystal (etpyH)₂[Cr₃O(OOCH)₆(etpy)₃]₂[α‐SiMo₁₂O₄₀]?3 H₂O (etpy =4‐ethylpyridine) is described. The compound incorporated up to 3.8 mol(Cs⁺) mol(s)^?1 (where s=solid) by cation‐exchange with etpyH⁺ and reduction of silicododecamolybdate with ascorbic acid. The amount of Cs⁺ uptake was comparable to that of Prussian blue, which is widely recognized as a good Cs⁺ adsorbent. Moreover, other alkali‐metal and alkaline‐earth‐metal cations were almost completely excluded (<0.2 mol mol(s)^?1).     

Synthesis of a dialuminum-substituted silicotungstate and the diastereoselective cyclization of citronellal derivatives

A novel dialuminum-substituted silicotungstate TBA(3)H[gamma-SiW(10)O(36){Al(OH(2))}(2)(mu-OH)(2)] x 4 H(2)O (1, TBA = tetra-n-butylammonium) was synthesized by the reaction of the potassium salt of [gamma-SiW(10)O(36)](8-) (SiW10) with 2 equiv of Al(NO(3))(3) in an acidic aqueous medium. It was confirmed by the X-ray crystallographic analysis that compound 1 was a monomer of the gamma-Keggin dialuminum-substituted silicotungstate with the {Al(2)(mu-OH)(2)} diamond core. The cluster framework of 1 maintained the gamma-Keggin structure in the solution states. The reaction of 1 with pyridine yielded TBA(3)[(C(5)H(5)N)H][gamma-SiW(10)O(36){Al(C(5)H(5)N)}(2)(mu-OH)(2)] x 2 H(2)O (2), and the molecular structure was successfully determined by the X-ray crystallographic analysis. In compound 2, two of three pyridine molecules coordinated to the axial positions of aluminum centers and one of them existed as a pyridinium cation, showing that compound 1 has two Lewis acid sites and one Br?nsted acid site. Compound 1 showed high catalytic activity for the intramolecular cyclization of citronellal derivatives such as (+)-citronellal (3) and 3-methylcitronellal (4) without formation of byproduct resulting from etherification and dehydration. For the 1-catalyzed cyclization of 3, the diastereoselectivity toward (-)-isopulegol (3a) reached ca. 90% and the value was the highest level among those with reported systems so far. The reaction rate for the 1-catalyzed cyclization of 3 decreased by the addition of pyridine, and the cyclization hardly proceeded in the presence of 2 equiv of pyridine with respect to 1. On the other hand, the reaction rate and diastereoselectivity to 3a in the presence of 2,6-lutidine were almost the same as those in the absence. Therefore, the present cyclization is mainly promoted by the Lewis acid sites (aluminum centers) in 1. DFT calculations showed that the formation of the transition state to produce 3a is sterically and electronically more favorable than the other three transition states for the present 1-catalyzed cyclization of 3.     

Disilane- and siloxane-bridged biphenyl and bithiophene derivatives as electron-transporting materials in OLEDs

Optical, electrochemical, and electron-transporting properties of disilane- and siloxane-bridged biphenyl and bithiophene derivatives were investigated, in comparison with those of the monosilane-bridged analogues (siloles). The UV spectra and cyclic voltammograms indicated that elongation of the silicon bridge suppresses the π-conjugation, in accordance with the results of DFT calculations. The DFT calculations indicated also that the disilane-bridged biphenyl and siloxane-bridged bithiophene should have the low-lying HOMOs and LUMOs. The electron-transporting properties were evaluated by the performance of triple-layered OLEDs having vapor-deposited films of the Si-bridged compound, Alq₃, and TPD, as the electron-transport, emitter, and hole-transport, respectively. Of these, the device with a disilane-bridged biphenyl exhibited the high performance with the maximum current density of 590 mA/cm² at the applied electric field of 12 × 10⁷ V/m (applied bias voltage = 13 V) and the maximum luminance of 22 000 cd/m² at 13 × 10⁷ V/m.     

Systemically Injectable Enzyme‐Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors

The design and construction of nanoreactors are important for biomedical applications of enzymes, but lipid‐ and polymeric‐vesicle‐based nanoreactors have some practical limitations. We have succeeded in preparing enzyme‐loaded polyion complex vesicles (PICsomes) through a facile protein‐loading method. The preservation of enzyme activity was confirmed even after cross‐linking of the PICsomes. The cross‐linked β‐galactosidase‐loaded PICsomes (β‐gal@PICsomes) selectively accumulated in the tumor tissue of mice. Moreover, a model prodrug, HMDER‐βGal, was successfully converted into a highly fluorescent product, HMDER, at the tumor site, even 4 days after administration of the β‐gal@PICsomes. Intravital confocal microscopy showed continuous production of HMDER and its distribution throughout the tumor tissues. Thus, enzyme‐loaded PICsomes are useful for prodrug activation at the tumor site and could be a versatile platform for enzyme delivery in enzyme prodrug therapy.     

Dissociation of DNA from histone by reaction of anti-cancer drug cis-diamminedichloroplatinum(II) with DNA-histone complexes used as cellular model

Although both cis-diamminedichloroplatinum(II) (cisplatin or cis-DDP) and trans-diamminedichloroplatinum(II) bind to DNA, only cis-DDP is widely used as a chemotherapeutic agent; the stereoisomer trans-DDP is inactive. DNA, generally, is wound around the histone core in the nucleus of living cells and forms the nucleosome structure. To understand the essentially different anticancer activities of cis-DDP and trans-DDP, it is necessary to investigate the interaction of cis-DDP (or trans-DDP) with DNA around the histone in the nucleosome. Here, we used psiX174DNA-histone(LNCaP) complexes prepared by the reaction of psiX174DNA with histone(LNCaP) extracted from LNCaP cells. We first show that the ability of cis-DDP to dissociate the DNA from psiX174DNA-histone(LNCaP), as a nucleosome model, is much stronger than that of trans-DDP. As a result of the action of cis-DDP, the DNA in the nucleosome is rendered naked, and the naked DNA is vulnerable to cis-DDP (or other drugs). This study describes a new model showing that the difference in the activities of cis-DDP and trans-DDP is related to the difference in their abilities to dissociate the DNA from the nucleosome.