A Sr(II)-Zr(IV)-Cd(II) Alkoxide Cluster: Synthesis and X-Ray Structure of [{Cd(OPri)3}Sr{Zr2(OPri)9}]2

New heterotrimetallic alkoxide [{Cd(OPrⁱ)₃}Sr{Zr₂(OPrⁱ)₉}]₂ (1) is obtained quantitatively in an anion-exchange reaction involving well-characterised iodide heterobimetallic alkoxide ICd{Zr₂(OPrⁱ)₉} and the alkali metal reagent KSr(OPrⁱ)₃. The formation of 1 is accompanied with an exchange of metals (Cd(II) and Sr(II)) between the constituting fragments (‘Cd{Zr₂(OPrⁱ)₉}⁺’ and ‘Sr(OPrⁱ)₃ ^?’) and the chelating Zr₂(OPrⁱ)₉ ^? anion, in 1, coordinates to Sr²⁺ in contrast to the precursor ICdZr₂(OPrⁱ)₉ where it is bound to Cd²⁺. The heterotrimetallic nature of 1 is unambiguously established by multinuclear (¹H, ¹³C and ¹¹³Cd) NMR spectral data and a single crystal X-ray diffraction analysis.     

Effect of the Phospholipid Chain Length and Head Group on Beta‐Phase Formation of Poly(9,9‐dioctylfluorene) Enclosed in Liposomes

We have studied the effect of head group and alkyl chain length on β‐phase formation in poly(9,9‐dioctylfluorene) (PFO) solubilized in phospholipid liposomes. Systems studied have three different alkyl chain lengths (1,2‐dimyristoyl‐sn‐glycero‐3‐phosphatidylcholine [DMPC], 1,2‐didodecanoyl‐sn‐glycero‐3‐phosphatidylcholine [DLPC], 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphatidylcholine [DPPC]) and head groups (1,2‐dimyristoyl‐sn‐glycero‐3‐phosphate monosodium salt [DMPA], 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphoethanolamine [DMPE] and 1,2‐dimyristoyl‐sn‐glycero‐3‐phospho‐l ‐serine sodium salt [DMPS]). Changes in liposome size upon addition of PFO are followed by dynamic light scattering. All the phospholipids induce the formation of PFO β‐phase, which is followed by the emission intensity and deconvolution of the absorption spectra. Both the head group and alkyl chain length affect the yield of β‐phase. The photophysics of PFO incorporated in liposomes is characterized by stationary and time‐resolved fluorescence, whereas the polymer‐phospholipid interactions have been studied by the effect of the PFO concentration on the phospholipid phase transitions (differential scanning calorimetry [DSC]).     

Polymorphism and melt crystallisation of racemic betaxolol, a β-adrenergic antagonist drug

We report the polymorphic behaviour, in melt cooling experiments, of racemic betaxolol, a low aqueous solubility selective β₁-adrenergic antagonist drug with a flexible molecular structure. A multidisciplinary approach is employed, using thermal analysis (differential scanning calorimetry, polarised light thermomicroscopy), spectroscopic methods (infrared spectroscopy, magic angle spinning ¹H NMR) and X-ray powder diffraction. A glass phase is obtained, T _g ~ ?10 °C, on cooling the melt, unless the cooling rate is ≤0.5 °C min^?1, while a new metastable form, polymorph II, T _fus = 33 °C, is generated in subsequent heating runs in a two step process. Although either partial crystallisation from the melt in the first step or the formation of an intermediate, metastable, low ordered phase may explain these observations, our results favour the second hypothesis. The stable polymorph I, T _fus = 69 °C, which crystallizes on further heating after form II melting, has also been obtained either from polymorph II or from the molten phase, on standing at 25 °C. The racemic betaxolol crystalline phases are found to exhibit some degree of disorder.     

Photoreduction kinetics of sodium tetrachloroaurate under synchrotron soft X-ray exposure

We report on the time evolution of the sodium tetrachloroaurate (NaAuCl(4)) chemical properties as a function of soft X-ray exposure in a dried sample on a silicon surface using X-ray photoelectron spectroscopy (XPS). Our investigations provide mechanistic insight into the photoreduction kinetics from Au(III) to Au(I) and then Au(I) to Au(0). We unambiguously show that XPS photoreduction occurs in stepwise fashion via the Au(I) state. Both photoreduction steps undergo first-order kinetics.     

Fabrication optimization of a miniaturized array device for cell-free protein synthesis

Cell-free protein synthesis (CFPS) is an attractive alternative to cell-based protein expression systems because of its advantages including speed, simplicity, and adaptability to various formats. However, two major obstacles exist that have been preventing it from being widely used. One is high cost and the other is low protein synthesis yield. We report here a miniaturized CFPS device that addresses these challenges. The cost saving was achieved by miniaturization, which reduced the reagent consumption by two orders of magnitude. The protein synthesis yield was enhanced by prolonging CFPS reactions through continuous supply of reactants (e.g. nutrients and energy components). The reactants were contained in a feeding solution, which was replenished through a nanoporous membrane and microchannel. The design of the miniaturized device was optimized by running continuous-exchange CFPS in devices with a variation in the type of membrane, the size of the exchange interface, and the volume ratio of the reaction solution to the feeding solution. The effects of these design variations on the protein synthesis yield have been studied. Furthermore, the design was expanded into a 96-unit device that can produce a large number of proteins simultaneously, enabling high-throughput proteomics applications.     

Studies of glutathione transferase P1-1 bound to a platinum(IV)-based anticancer compound reveal the molecular basis of its activation

Platinum-based cancer drugs, such as cisplatin, are highly effective chemotherapeutic agents used extensively for the treatment of solid tumors. However, their effectiveness is limited by drug resistance, which, in some cancers, has been associated with an overexpression of pi class glutathione S-transferase (GST P1-1), an important enzyme in the mercapturic acid detoxification pathway. Ethacraplatin (EA-CPT), a trans-Pt(IV) carboxylate complex containing ethacrynate ligands, was designed as a platinum cancer metallodrug that could also target cytosolic GST enzymes. We previously reported that EA-CPT was an excellent inhibitor of GST activity in live mammalian cells compared to either cisplatin or ethacrynic acid. In order to understand the nature of the drug-protein interactions between EA-CPT and GST P1-1, and to obtain mechanistic insights at a molecular level, structural and biochemical investigations were carried out, supported by molecular modeling analysis using quantum mechanical/molecular mechanical methods. The results suggest that EA-CPT preferentially docks at the dimer interface at GST P1-1 and subsequent interaction with the enzyme resulted in docking of the ethacrynate ligands at both active sites (in the H-sites), with the Pt moiety remaining bound at the dimer interface. The activation of the inhibitor by its target enzyme and covalent binding accounts for the strong and irreversible inhibition of enzymatic activity by the platinum complex.     

Test of the Gouy-Chapman theory for a charged lipid membrane against explicit-solvent molecular dynamics simulations

A wealth of experimental data has verified the applicability of the Gouy-Chapman (GC) theory to charged lipid membranes. Surprisingly, a validation of GC by molecular dynamics (MD) simulations has been elusive. Here, we report a test of GC against extensive MD simulations of an anionic lipid bilayer solvated by water at different concentrations of NaCl or KCl. We demonstrate that the ion distributions from the simulations agree remarkably well with GC predictions when information on the adsorption of counterions to the bilayer is incorporated.     

Synthesis and properties of stereoregular fluoro-polymers via ring-opening metathesis polymerization of fluorinated norbornenes and norbornadienes. An overview and progress report

Since the first report of the ring-opening metathesis polymerization of fluorinated monomers in 1979 considerable advances in precision and control of such syntheses have been achieved through the introduction of well defined initiators. It is now possible to carry out well controlled living and stereoregular polymerizations. The products of such syntheses can display unusually high relaxed dielectric constants, an observation which is crucial to the assignment of their tacticities and probably significant with regard to possible applications of this type of material.     

The performance of degradable polymer bags

The use of degradable polymers for the collection and composting of organic wastes is explored within this paper. With reference to one trial where the performance of a ‘degradable’ polyethylene based sack for the kerbside collection of organic wastes was investigated. Areas for consideration were the impacts of the degradable polymer on the composting process and the quality of the finished product. This trial also included a comparative study of two different types of ‘degradable’ polymer sacks currently on the European market (polyethylene and starch). A number of quantitative tests were conducted on the different polymers to assess the mechanisms of degradation and how this affected their suitability for the treatment of organic wastes. Provisional results have indicated that the polyethylene (PE) sacks are not degrading as anticipated within open windrow conditions, adversely affecting both the composting process and the quality of the finished compost product. Whilst the degradable starch based sacks appear to actively degrade within open windrow compost conditions.