Ultrasound attenuation computed tomography assessment of PAGAT gel dose

Ultrasound has been previously investigated as an alternative readout method for irradiated polymer gel dosimeters, with authors reporting varying dose responses. We extend previous work utilizing a new computed tomography ultrasound scanner comprising of two identical 5 MHz, 128-element linear-array ultrasound transducers, co-axially aligned and submerged in water as a coupling agent, with rotational of the gel dosimeter between the transducers facilitated by a robotic arm. We have investigated the dose-dependence of both ultrasound bulk attenuation and broadband ultrasound attenuation (BUA) for the PAGAT gel dosimeter. The ultrasound bulk attenuation dose sensitivity was found to be 1.46  ±  0.04 dB m −1 Gy −1, being in agreement with previously published results for PAG and MAGIC gels. BUA was also found to be dose dependent and was measured to be 0.024  ±  0.003 dB MHz −1 Gy −1; the advantage of BUA being its insensitivity to frequency-independent attenuation mechanisms including reflection and refraction, thereby minimizing image reconstruction artefacts.

Unimolecular reaction chemistry of a charge-tagged beta-hydroxyperoxyl radical

β-Hydroxyperoxyl radicals are formed during atmospheric oxidation of unsaturated volatile organic compounds such as isoprene. They are intermediates in the combustion of alcohols. In these environments the unimolecular isomerization and decomposition of β-hydroxyperoxyl radicals may be of importance, either through chemical or thermal activation. We have used ion-trap mass spectrometry to generate the distonic charge-tagged β-hydroxyalkyl radical anion, ˙CH2C(OH)(CH3)CH2C(O)O−, and investigated its subsequent reaction with O2 in the gas phase under conditions that are devoid of complicating radical–radical reactions. Quantum chemical calculations and master equation/RRKM theory modeling are used to rationalize the results and discern a reaction mechanism. Reaction is found to proceed via initial hydrogen abstraction from the γ-methylene group and from the β-hydroxyl group, with both reaction channels eventually forming isobaric product ions due to loss of either ˙OH + HCHO or ˙OH + CO2. Isotope labeling studies confirm that a 1,5-hydrogen shift from the β-hydroxyl functionality results in a hydroperoxyalkoxyl radical intermediate that can undergo further unimolecular dissociations. Furthermore, this study confirms that the facile decomposition of β-hydroxyperoxyl radicals can yield ˙OH in the gas phase.

Hydrogen-bonded supramolecular polymers as self-healing hydrogels: Effect of a bulky adamantyl substituent in the ureido-pyrimidinone monomer

In an attempt to generate supramolecular assemblies able to function as self-healing hydrogels, a novel ureido-pyrimidinone (UPy) monomer, 2-(N ′-methacryloyloxyethylureido)-6-(1-adamantyl)-4[1H]-pyrimidinone, was synthesized and then copolymerized with N,N-dimethylacrylamide at four different feed compositions, using a solution of lithium chloride in N,N-dimethylacetamide as the polymerization medium. The assembling process in the resulting copolymers is based on crosslinking through the reversible quadruple hydrogen bonding between side-chain UPy modules. The adamantyl substituent was introduced in order to create a “hydrophobic pocket” that may protect the hydrogen bonds against the disruptive effect of water molecules. Upon hydration to equilibrium, all copolymers generated typical hydrogels when their concentration in the hydrated system was at least 15%. The small-deformation rheometry showed that all hydrated copolymers were hydrogels that maintained a solid-like behavior, and that their extrusion through a syringe needle did not affect significantly this behavior, suggesting a self-healing capacity in these materials. An application as injectable substitutes for the eye's vitreous humor was proposed

Two-dimensional coordination polymeric structures in caesium complexes with ring-substituted phenoxyacetic acids

The two-dimensional polymeric structures of the caesium complexes with the phenoxyacetic acid analogues (4-fluorophenoxy)acetic acid, (3-chloro-2-methylphenoxy)acetic acid and the herbicidally active (2,4-dichlorophen­oxy)acetic acid (2,4-D), namely poly[[5-(4-fluorophenoxy)acetato][4-(4-fluorophenoxy)acetato]dicaesium], [Cs2(C8H6FO3)2]n, (I), poly[aqua[5-(3-chloro-2-methylphenoxy)acetato]caesium], [Cs(C9H8ClO3)(H2O)]n, (II), and poly[[7-(2,4-di­chlorophenoxy)acetato][(2,4-dichlorphenoxy)acetic acid]caesium], [Cs(C8H5Cl2O3)(C8H6Cl2O3)]n, (III), are described. In (I), the Cs+ cations of the two individual irregular coordination polyhedra in the asymmetric unit (one CsO7 and the other CsO8) are linked by bridging carboxylate O-atom donors from the two ligand molecules, both of which are involved in bidentate chelate Ocarboxy,Ophenoxy interactions, while only one has a bidentate carboxylate O,O'-chelate inter­action. Polymeric extension is achieved through a number of carboxylate O-atom bridges, with a minimum CsCs separation of 4.3231 (9) Å, giving layers which lie parallel to (001). In hydrated complex (II), the irregular nine-coordination about the Cs+ cation comprises a single monodentate water molecule, a bidentate Ocarboxy,Ophenoxy chelate interaction and six bridging carboxylate O-atom bonding interactions, giving a CsCs separation of 4.2473 (3) Å. The water mol­ecule forms intralayer hydrogen bonds within the two-dimensional layers, which lie parallel to (100). In complex (III), the irregular centrosymmetric CsO6Cl2 coordination environment comprises two O-atom donors and two ring-substituted Cl-atom donors from two hydrogen bis[(2,4-dichlorophenoxy)acetate] ligand species in a bidentate chelate mode, and four O-atom donors from bridging carboxyl groups. The duplex ligand species lie across crystallographic inversion centres, linked through a short O-HO hydrogen bond involving the single acid H atom. Structure extension gives layers which lie parallel to (001). The present set of structures of Cs salts of phenoxyacetic acids show previously demonstrated trends among the alkali metal salts of simple benzoic acids with no stereochemically favourable interactive substituent groups for formation of two-dimensional coordination polymers.

SERS-barcoded colloidal gold NP assemblies as imaging agents for use in biodiagnostics

There is a growing need for new biodiagnostics that combine high throughput with enhanced spatial resolution and sensitivity. Gold nanoparticle (NP) assemblies with sub-10 nm particle spacing have the benefits of improving detection sensitivity via Surface enhanced Raman scattering (SERS) and being of potential use in biomedicine due to their colloidal stability. A promising and versatile approach to form solution-stable NP assemblies involves the use of multi-branched molecular linkers which allows tailoring of the assembly size, hot-spot density and interparticle distance. We have shown that linkers with multiple anchoring end-groups can be successfully employed as a linker to assemble gold NPs into dimers, linear NP chains and clustered NP assemblies. These NP assemblies with diameters of 30-120 nm are stable in solution and perform better as SERS substrates compared with single gold NPs, due to an increased hot-spot density. Thus, tailored gold NP assemblies are potential candidates for use as biomedical imaging agents. We observed that the hot-spot density and in-turn the SERS enhancement is a function of the linker polymer concentration and polymer architecture. New deep Raman techniques like Spatially Offset Raman Spectroscopy (SORS) have emerged that allow detection from beneath diffusely scattering opaque materials, including biological media such as animal tissue. We have been able to demonstrate that the gold NP assemblies could be detected from within both proteinaceous and high lipid containing animal tissue by employing a SORS technique with a backscattered geometry.

Numerical analysis for the interlayer toughening of piezoelectric smart composite plate

The piezoelectric composite material could engender stress concentration resulting from small cracks during layers easily, as the cracks growth will lead to the failure of the whole structure. In this paper, a finite element model for piezoelectric composite materials by ABAQUS including interlayer crack was established, and the J integral and crack tip stress of different types PZT patches were calculated by using the equivalent integral method. Then, the J integral for adhesive layers with different thickness, elastic modulus considering and not considering piezoelectricity was investigated. The results show that the J integral of mode I, II reduces with thicker adhesive layer and lower elastic modules, and the J integral of mode II decreases more sharply than that of mode I.

In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs

The biodistribution of micelles with and without folic acid targeting ligands were studied using a block copolymer consisting of acrylic acid (AA) and polyethylene glycol methyl ether acrylate (PEGMEA) blocks. The polymers were prepared using RAFT polymerization in the presence of a folic acid functionalized RAFT agent. Oxoplatin was conjugated onto the acrylic acid block to form amphiphilic polymers which, when diluted in water, formed stable micelles. In order to probe the in vivo stability, a selection of micelles were cross-linked using 1,8-diamino octane. The sizes of the micelles used in this study range between 75 and 200 nm, with both spherical and worm-like conformation. The effects of cross-linking, folate conjugation and different conformation on the biodistribution were studied in female nude mice (BALB/c) following intravenous injection into the tail vein. Using optical imaging to monitor the fluorophore-labeled polymer, the in vivo biodistribution of the micelles was monitored over a 48 h time-course after which the organs were removed and evaluated ex vivo. These experiments showed that both cross-linking and conjugation with folic acid led to increased fluorescence intensities in the organs, especially in the liver and kidneys, while micelles that are not conjugated with folate and not cross-linked are cleared rapidly from the body. Higher accumulation in the spleen, liver, and kidneys was also observed for micelles with worm-like shapes compared to the spherical micelles. While the various factors of cross-linking, micelle shape, and conjugation with folic acid all contribute separately to prolong the circulation time of the micelle, optimization of these parameters for drug delivery devices could potentially overcome adverse effects such as liver and kidney toxicity.

Imaging tumour distribution of a polymeric drug delivery platformin vivoby PET-MRI

Background Over the past decade, molecular imaging has played a key role in the progression of drug delivery platforms from concept to commercialisation. Of the molecular imaging techniques commonly utilised, positron emission tomography (PET) can yield a breadth of information not easily accessible by other methodologies and when combined with other complementary imaging modalities, is a powerful tool for pre- and clinical development of therapeutics. However, very little research has focussed on the information available from complimentary imaging modalities. This paper reports on the data-rich methodologies of contrast enhanced PET/CT and PET/MRI for probing efficacy of polymer drug delivery platforms. Results The information available from an ExiTron nano 6000 contrast enhanced PET/CT and a gadolinium (Gd) enhanced PET/MRI image of a 64Cu labeled HBP in the same mouse was qualitatively compared. Conclusions Gd contrast enhanced PET/MRI offers a powerful methodology for investigating the distribution of polymer drug delivery platforms in vivo and throughout a tumour volume. Furthermore, information about depth of penetration away from primary blood vessels can be gleaned, potentially leading to development of more efficacious delivery vehicles for clinical use.

Aptamer-targeted hyperbranched polymers: Towards greater specificity for tumours in vivo

Hyperbranched polymers conjugated to a peptide-aptamer were prepared using a combination of RAFT polymerisation and click chemistry for targeting tumour cells in vivo. The polymers showed enhanced cell-uptake in vitro (compared to unconjugated polymer)while excellent specificity for solid tumours was observed in vivo using a mouse model of melanoma.