Cisplatin cyclodextrin complexes as potential free radical chemoradiosensitizers for enhanced cisplatin treatment of cancers: a quantum mechanical study

It has been shown in this study that {CisPt@[n]CD} complexes formed from the anti-cancer drug cisplatin (CisPt) and cyclodextrins ([n]CD) can be a source of Pt based free radicals such as (H₃N)₂PtCl· and (H₃N)₂Pt·· species in water within a radiation environment which can produce hydrated electrons. Encapsulating CisPt within the [n]CD host takes advantage of the previously described drug delivery and reduced side effect advantages of CDs. Based on quantum mechanical modelling and literature results from other studies, it is predicted that {CisPt@[γ]CD} and the analogous 2-hydroxypropyl[β]cyclodextrin (HPBCD) complex {CisPt@HPBCD} may interact with serum albumin and engage in an enhanced permeation and retention mechanism in solid tumours, offering further synergistic advantages for radiation-{CisPt@[γ]CD} or -{CisPt@HPBCD} regimens over that of the conventional radiation-CisPt regimens in current use in anti-cancer chemoradiotherapies. Comparisons and possible advantages are made with the previously documented chemoradiosensitizing properties of the analogous cucurbit[7]uril based{CisPt@[7]CB} complex with the {CisPt@[γ]CD} and {CisPt@HPBCD} complexes suggest that all three complexes may have different and tailorable anti-tumour uses for a range of different chemotherapeutic environments or protocols.     

A well‐balanced upstream flux‐splitting finite‐volume scheme for shallow‐water flow simulations with irregular bed topography

This study extends the upstream flux‐splitting finite‐volume (UFF) scheme to shallow water equations with source terms. Coupling the hydrostatic reconstruction method (HRM) with the UFF scheme achieves a resultant numerical scheme that adequately balances flux gradients and source terms. The proposed scheme is validated in three benchmark problems and applied to flood flows in the natural/irregular river with bridge pier obstructions. The results of the simulations are in satisfactory agreement with the available analytical solutions, experimental data and field measurements. Comparisons of the present results with those obtained by the surface gradient method (SGM) demonstrate the superior stability and higher accuracy of the HRM. The stability test results also show that the HRM requires less CPU time (up to 60%) than the SGM. The proposed well‐balanced UFF scheme is accurate, stable and efficient to solve flow problems involving irregular bed topography. Copyright © 2009 John Wiley & Sons, Ltd.     

Solvent Effects on Aza‐anionic Cycloaromatization of 2‐(2‐Substituted‐ethynyl)benzonitriles

The methanolysis of 2‐(2‐aryl ethynyl)benzonitriles is accelerated when the polar aprotic solvents are added, which could enhance the 6‐endo pathway and give isoquinolones, though the 5‐exo pathway is occupied mostly. The yields of products would also be in creased.     

Thermal degradation kinetics of biodegradable poly(3‐hydroxybutyrate)/layered double hydroxide nanocomposites

The thermal degradation behaviors of biodegradable poly(3‐hydroxybutyrate) (PHB) and PHB/poly(ethylene glycol) phosphonates (PEOPAs)‐modified layered double hydroxide (PMLDH) nanocomposites have been investigated using thermogravimetric analysis. Effects of PMLDH contents on the isothermal degradation kinetics of PHB were explored. These experimental results show that the degradation kinetics of PHB/PMLDH nanocomposites is the chain‐scission process of cyclic β‐elimination reaction with the following autocatalytic reactions, which is very similar to that of pure PHB matrix. Further calculated data based on the autocatalytic model can fit very well with the experimental data. The E_a value of PHB/PMLDH nanocomposites is increased as the content of PMLDH increases. This can be attributed to the incorporation of more PMLDH loading to PHB induced a decrease in the degradation rate and an increase in the residual weight for PHB/PMLDH nanocomposites. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1207–1213, 2008     

A Note on Exact Moment Computation for Normal Lead Times in the Two-Supplier Case

In the stochastic lead time inventory model with two suppliers and different normal lead times, the mean and variance of the lead-time demand distribution are traditionally computed using numerical integration. Tables are made available to help practitioners determine the minimum size of replenishments when orders to the suppliers are placed at the same time. This paper presents closed-form solutions to evaluate the required quantities of interest and tries to correct some mistakes in the existing tables. The expressions given here may also provide insight into the choice of sole versus dual suppliers.     

Effect of intra- and extra-liposomal distribution of sodium chloride on the stability of large unilamellar vesicles

Three groups of 1,2-dipalmitoyl-rac-glycero-3-phosphocholine (DPPC) large unilamellar vesicle (LUV) dispersions were studied: LUV (A) dispersions with only extraliposomal sodium chloride (NaCl), LUV (B) dispersions with intra- and extraliposomal NaCl, and LUV (C) dispersions with only intraliposomal NaCl. The NaCl concentrations ranged from 0 to 150 mM. An abrupt increase in leakage was observed around -10 degree C for all the three groups of LUV, which coincided with the temperature of extraliposomal ice formation. Within the three groups, leakage of LUV (C) was significantly higher than the other groups. Extraliposomal ice formation and the resulting freeze-concentration of LUV may be the major cause of the leakage. Intraliposomal ice formation observed at -43 degree C seemed to stop leakage of LUV when LUV were frozen below -43 degree C. An exotherm of eutectic crystallization of NaCl was occasionally observed at -37 degree C, with a higher probability of formation at 150 mM extraliposomal NaCl than at 50 mM. The eutectic crystals were thought to cause additional leakage from the LUV (B).     

Rubesanolides A and B: diterpenoids from Isodon rubescens

From the medicinal plant Isodon rubescens, we isolated two novel diterpenes, rubesanolides A (1) and B (2). The compounds contain a unique β-lactone subgroup. This is the first discovery for a natural diterpene having rings A, B, and C in chair, boat, and twist-chair conformations, respectively. The structures were elucidated by analysis of spectroscopic data, and the absolute configuration of 1 was determined by X-ray diffraction.     

Preparation of unsymmetrical distyryl BODIPY derivatives and effects of the styryl substituents on their in vitro photodynamic properties

A series of unsymmetrical distyryl BODIPYs have been prepared which function as highly potent photosensitisers with in vitro IC(50) values as low as 15 nM. Their cellular uptake, subcellular localisation and photocytotoxicity depend greatly on the styryl substituents.     

Synthesis, photophysical properties and in vitro photodynamic activity of axially substituted subphthalocyanines

A new series of subphthalocyanines substituted axially with an oligoethylene glycol chain [SPcB(OCH(2)CH(2))(n)OH, n = 3 (2) or 4 (3)] or a p-phenoxy oligoethylene glycol methyl ether chain [SPcBOC(6)H(4)(OCH(2)CH(2))(n)OCH(3), n = 2 (4) or 3 (5)] have been synthesised by substitution reactions of boron subphthalocyanine chloride SPcBCl (1) with the corresponding oligoethylene glycols, and characterised with various spectroscopic methods and elemental analysis. The molecular structure of one of these compounds (subphthalocyanine 4) has also been determined. As revealed by absorption spectroscopy, these compounds are essentially non-aggregated in DMF. The low aggregation tendency of these compounds results in a strong fluorescence emission and high efficiency to generate singlet oxygen. All these subphthalocyanines, being formulated with Cremophor EL, function as efficient photosensitisers and exhibit a high photocytotoxicity against HepG2 human hepatocarcinoma and HT29 human colon adenocarcinoma cells. The phenoxy analogues 4 and 5 show a relatively high photostability and are particularly potent towards these cell lines, with IC(50) values down to 0.02 microM.