An assessment of mucosal damage in vivo: effect of oral pretreatment with 5-fluorouracil on the intestinal first-pass metabolism of salicylamide in rabbits.

An assessment of 5-fluorouracil (5-FU)-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The mucosal damage in the intestine 48 h after oral administration of 5-FU (30 mg/kg) was examined using a scanning electron microscope. By the oral pretreatment with 5-FU, the morphological changes of jejunal and ileal mucosa were recognized compared with the control. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with 5-FU, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with 5-FU orally. However, the blood concentration of SAMG after intravenous administration of SAM was not increased compared with the control. These findings suggest that the change in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage by oral pretreatment with 5-FU. The alteration of intestinal first-pass metabolism of a marker compound may be utilized for the assessment of intestinal mucosal damage in vivo.     

2-Oxo-1,2-ethylenedioxy group as a linker for solution-, liquid-, and solid-phase syntheses to discover drug-like small molecules

2-Oxo-1,2-ethylenedioxy (2-OED) functionality has been prepared on a soluble MPEG polymer and solid (HM resin and Lanterns) supports as platforms for discovery of drug-like small molecules. The functionality is cleaved either by Yb(OTf)₃ or TMSCHN₂ in MeOH, or by various amines to release small molecules synthesized on the platform in good yield. Application of these platforms aiming for discovery of potent agonists for growth hormone secretagogue is reported by using the Ugi four-component coupling reaction.     

Light-harvesting heptadecameric porphyrin assemblies

New porphyrin assemblies containing 17 porphyrin molecules are constructed by using free base TPP-type porphyrins having eight pyrazine moieties 1. Spectroscopic titration of dimeric [meso-tetrakis(2-carboxy-4-nonylphenyl)porphyrinato]zinc(II) 2 with these porphyrins shows that the processes of the formation of the heptadecameric porphyrin assemblies may be analyzed as eight independent equilibrium processes with an identical binding constant. All binding constants are larger than 5 x 107 M-1 which is the determinable upper limit of the present titration method. In all cases, the fluorescence spectrum of the 1:8 mixture of 1 and 2 consists of the major fluorescence of 1 and the minor one of 2.pyrazine complex even in the presence of the large excess of the antenna pigments. The observed spectra are well reconstructed by the form of faF1 + fbF2, where F1 and F2 are the fluorescence of 1 and the 2.pyrazine complex measured separately at the corresponding concentrations. Interestingly, the general trend that values of fa are nearly equal to those of r564 x (1 - fb) in all cases is found, where r564 is the absorption ratios of the 2.pyrazine moiety and the central free base porphyrin in the assemblies at 564 nm. The observation indicates the excitation of the central porphyrin is directly enhanced by the absorption of the antenna pigments even in such large scale assemblies. Thus, the antenna effect for 1 having largest r564 results in 77 times fluorescence enhancement of the central free base porphyrin. The systems also show interesting dependency of energy-transfer efficiencies on the topological arrangement of the antenna elements.     

The indium subnitrides Ae6In4(InxLiy)N(3-z)(Ae = Sr and Ba)

The indium nitrides Sr6In4(In(0.32)Li(0.92))N(2.49) and Ba6In(4.78)N(2.72) have been synthesized from an excess of molten sodium. They crystallize in a stuffed variant of the eta-carbide structure type in the cubic space group Fdm with Z = 8. The lattice parameters are a = 14.3752(4) and 15.216(1) A, with cell volumes 2970.6(2) and 3523.3(6) A3, respectively. In both compounds there are vacancies on some of the indium and nitrogen sites and, in the case of Sr6In4(In(0.32)Li(0.92))N(2.49), mixed lithium-indium occupancy of one metal site. It is demonstrated that the partial and mixed occupancies act to carefully tune to electron count to almost fulfill the bonding requirements of the stellar quadrangular subnets of both compounds. Four probe resistivity measurements performed upon a pellet of Sr6In4(In(0.32)Li(0.92))N(2.49) show it to have a room-temperature resistivity of 6.3 mOmega.cm with a weak temperature dependence.     

The first synthesis and absolute configuration of glaucescenolide

The first synthesis of glaucescenolide (1), a cytotoxic sesquiterpene isolated from the liverwort, Schistochila glaucescens, was achieved by starting from 2,2,6-trimethylcyclohexanone (2). The absolute configuration of the naturally occurring 1 was confirmed as 5S,7S,10R.     

Photoinitiated cationic polymerization of oxetane formulated with oxirane

Photoinitiated cationic polymerization of oxetane, oxirane (epoxide), and a formulation of both was carried out and their reactivity compared. To investigate a formulated system of oxetane and oxirane in photoinitiated cationic polymerization, computational and experimental methods were used. In the computational study, we employed a semiempirical molecular orbital method (AM1). On the other hand, the reactivities of each system were evaluated and compared experimentally by a real-time FT-IR method. The computational study reveals that oxetane seems to polymerize in S_N2 mechanism, but two possibilities, of S_N1 mechanism through the α-cleavage and of S_N2 mechanism through β-cleavage, are implied for oxirane. Using the real-time FT-IR method, the formulation of oxetane and oxirane was proved to possess rather high reactivities of oxetane toward photoinitiated cationic polymerization. The formulated system exhibited slightly lower number-average molecular weight than oxetane but higher than oxirane. These experimental observations are well explained in terms of the calculated reaction paths. © 1995 John Wiley & Sons, Inc.     

High pressure-temperature Brillouin study of liquid water: evidence of the structural transition from low-density water to high-density water

The structural transformations occurring to water from low-density (LDW) to high-density (HDW) regimes have been studied by Brillouin scattering for the first time at temperatures up to 453 K and at pressures up to the solidification point. At ambient temperature (293 K) a discontinuity in pressure response of the sound velocity is observed. Furthermore, there are evident breaks in the linear behavior of log10 C11 versus log10(rho/rho0) when pressure increases up to 0.29, 0.21, and 0.19 GPa at the temperature of 293, 316, and 353 K, respectively. It is supposed to indicate the structural transition from LDW to HDW, and the possible transition boundary between LDW and HDW is in good agreement with the molecular-dynamics simulation.     

Isolation and structure of trichotomine and trichotomine G1

The new pigments, trichotomine (1) and trichotomine G₁ (12), which have a novel carbon skelton, have been isolated from the fruits of the plant Clerodendron trichotomum Thunb. On the basis of physical and chemical evidence, the structure of trichotomine (1)^1,2 was elucidated as an oxidative dimeric compound of 3 - oxo - 2,3 - 5,6 - tetrahydro - 11 H indolizino[8,7-b]indole 5-carboxylic acid and its stereostructure containing the absolute configuration was further determined by means of an x-ray crystallographic analysis.³ The structure of trichotomine G₁ (12), a N-β-D-glucopyranosyl trichotomine, is also based on spectral and chemical evidence. A N-β-D-glucopyranosyl indole derivative such as (12) is the first naturally occurring example.⁴     

Design of a novel artificial nucleobase for the selective formation of a triple-complex with a cytosine-guanine base pair

A new artificial nucleobase (1) was designed for the selective formation of a triple-complex with a cytosine-guanine base pair at the major groove site. It has been proved based on the 1D- and 2D ¹H-NMR spectra that the protected 2′-oxy-1 (7) forms a triplex complex with the GC pair selectively.     

Nanotubes of lepidocrocite titanates

Titanate nanotubes were synthesized in hydrothermal treatment of anatase titania powders and concentrated NaOH solution and their structure was investigated. It was suggested that the nanotubes might be constructed from lepidocrocite H_xTi_{2− x/4}□_x/4O₄ (x0.7, □: vacancy) sheets. The newly proposed lepidocrocite titanate nanotube model was supported by X-ray diffraction, electron diffraction, and thermogravimetry studies.