Synthesis of membranes having a saccharide side chain and their optical resolution properties for d-/l- glucose mixtures

The objective of the present investigation is to synthesize new polymeric membranes having a saccharide in the side chain and to clarify the specific affinity of the saccharide chains. During this study chloromethylated polysulfone (CM-PSF), poly(chloromethylated styrene) (P-CM-St), poly(methyl methacrylate) (PMMA), and chlororethylated poly(γ -methyl L-glutamate) (CE-PMLG) as synthetic polymers along with an equal mixture of α-D-2-deoxy-2-aminoglucopyranosyl-(1'→6) -D-sorbitol and mannitol (AGP) as saccharides were used. PMMA+AGP and CE-PMLG+AGP membranes showed the highest permeability of D-glucose in sugars (molecular weight = 180.16), although the CM-PSP+AGP and P-CM-St+AGP membranes showed less permeability. The reason for the high permeability of D-glucose is the high partition coefficient of D-glucose, which may come from an interaction between the AGP terminating D-glucose structure and D-glucose as the solute. The optical resolution could be done by the difference between the D- and L-glucose permeation rates from an equimolar mixture of D-glucose and L-glucose.     

Rational design of fluorescein-based fluorescence probes. Mechanism-based design of a maximum fluorescence probe for singlet oxygen.

Fluorescein is one of the best available fluorophores for biological applications, but the factors that control its fluorescence properties are not fully established. Thus, we initiated a study aimed at providing a strategy for rational design of functional fluorescence probes bearing fluorescein structure. We have synthesized various kinds of fluorescein derivatives and examined the relationship between their fluorescence properties and the highest occupied molecular orbital (HOMO) levels of their benzoic acid moieties obtained by semiempirical PM3 calculations. It was concluded that the fluorescence properties of fluorescein derivatives are controlled by a photoinduced electron transfer (PET) process from the benzoic acid moiety to the xanthene ring and that the threshold of fluorescence OFF/ON switching lies around -8.9 eV for the HOMO level of the benzoic acid moiety. This information provides the basis for a practical strategy for rational design of functional fluorescence probes to detect certain biomolecules. We used this approach to design and synthesize 9-[2-(3-carboxy-9,10-dimethyl)anthryl]-6-hydroxy-3H-xanthen-3-one (DMAX) as a singlet oxygen probe and confirmed that it is the most sensitive probe currently known for (1)O(2). This novel fluorescence probe has a 9,10-dimethylanthracene moiety as an extremely fast chemical trap of (1)O(2). As was expected from PM3 calculations, DMAX scarcely fluoresces, while DMAX endoperoxide (DMAX-EP) is strongly fluorescent. Further, DMAX reacts with (1)O(2) more rapidly, and its sensitivity is 53-fold higher than that of 9-[2-(3-carboxy-9,10-diphenyl)anthryl]-6-hydroxy-3H-xanthen-3-ones (DPAXs), which are a series of fluorescence probes for singlet oxygen that we recently developed. DMAX should be useful as a fluorescence probe for detecting (1)O(2) in a variety of biological systems.     

First synthesis of phenylazomethine dendrimer ligands and structural studies.

Novel dendritic polyphenylazomethines (DPAs), which consist of a pi-conjugated backbone, were synthesized up to the fourth generation by the convergent method via dehydration of aromatic ketones with aromatic amines in the presence of titanium(IV) tetrachloride. The obtained dendrimers, DPA G1-4 (designated as GX, where X is the generation number), show high thermostability (Td(10%) 521 degrees C in DPA G4) and high solubility for the common solvents such as chloroform, THF, and DMSO unlike the conventional linear polyphenylazomethines, which have very low solubilities. The DPA G4 molecule was confirmed to have a spherelike structure by GPC measurement and a molecular model based on the crystal structure of DPA G2. Crystal data for DPA G2: monoclinic space group P2(1)/a, a = 25.352(4) A, b = 8.577(2) A, c = 16.151(2) A, beta = 106.25(1) degrees, V = 3371.6(10) A(3), Z = 2, D(calc) = 1.168 g/cm(3), mu(Cu Kalpha) = 0.536 cm(-1), final R = 0.089, and R(w) = 0.287. The molecular modeling reveals that a DPA G4 molecule has a spherelike structure, in which the height, width, and depth are 2.3, 2.9, and 2.5 nm, respectively. The TEM and AFM pictures show the DPA G4 molecules to have a spherelike structure (the diameter: 2.3 nm) and are regularly assembled on a plate by casting. The occupied area of one DPA G4 molecule in a monolayer on water was estimated by pi-A measurements to be 3.8-4.2 nm(2) (the calculated diameter 2.2-2.3 nm, which agreed with the TEM result). NMR studies (1H NMR at 130 degrees C and T(1) measurements) supported a conformational rigidity of DPA G4 in solution.     

Combinatorial curvature for planar graphs

Regarding an infinite planar graph G as a discrete analogue of a noncompact simply connected Riemannian surface, we introduce the combinatorial curvature of G corresponding to the sectional curvature of a manifold. We show this curvature has the property that its negative values are bounded above by a universal negative constant. We also prove that G is hyperbolic if its curvature is negative. © 2001 John Wiley & Sons, Inc. J Graph Theory 38: 220–229, 2001     

Thermal bleaching of rhodamine 6G in polymethyl methacrylate (PMMA)

Thermal bleaching of rhodamine 6G in PMMA is investigated at temperatures between 65°C and 83°C with a heating time of over 300 hours. The obtained thermal bleaching rate is found to show a sudden change around 70°C.     

Observations of energy metabolism in neuroectodermal tumors using in vivo 31P-NMR

The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor.