Chelator-facilitated removal of iron from transferrin: Relevance to combined chelation therapy

Current iron chelation therapy consists primarily of DFO (desferrioxamine), which has to be administered via intravenous infusion, together with deferiprone and deferasirox, which are orally-active chelators. These chelators, although effective at decreasing the iron load, are associated with a number of side effects. Grady suggested that the combined administration of a smaller bidentate chelator and a larger hexadentate chelator, such as DFO, would result in greater iron removal than either chelator alone [Grady, Bardoukas and Giardina (1998) Blood 92, 16b]. This in turn could lead to a decrease in the chelator dose required. To test this hypothesis, the rate of iron transfer from a range of bidentate HPO (hydroxypyridin-4-one) chelators to DFO was monitored. Spectroscopic methods were utilized to monitor the decrease in the concentration of the Fe–HPO complex. Having established that the shuttling of iron from the bidentate chelator to DFO does occur under clinically relevant concentrations of chelator, studies were undertaken to evaluate whether this mechanism of transfer would apply to iron removal from transferrin. Again, the simultaneous presence of both a bidentate chelator and DFO was found to enhance the rate of iron chelation from transferrin at clinically relevant chelator levels. Deferiprone was found to be particularly effective at ‘shuttling’ iron from transferrin to DFO, probably as a result of its small size and relative low affinity for iron compared with other analogous HPO chelators

The iron binding-sites of chicken ovotransferrin

We have shown previously that the EXAFS spectrum of diferric chicken ovotransferrin (Fe2COT) can only be adequately simulated assuming a split first shell co-ordination [1]. EXAFS and XANES spectra of Fe2COT measured in solution and as a freeze-dried powder provide evidence for perturbation of the iron-binding sites on freeze-drying which involves the loss of one of the long (~2.04 Å) first shell ligands (presumably water). Measurement of the XANES of the C-terminal monoferric COT and a C-terminal domain fragment suggests that the metal binding site remains largely unperturbed by the fragmentation process. The possibility of site interaction is briefly discussed.We gratefully acknowledge the SERC for financial support and provision of facilities

Targeted β-Phase Formation in Poly(fluorene)-Ureasil Grafted Organic-Inorganic Hybrids

© 2017 American Chemical Society. The development of synthetic strategies to control the molecular organization (and inherently linked optoelectronic properties) of conjugated polymers is critical for the development of efficient light-emitting devices. Here, we report a facile route using sol-gel chemistry to promote the formation of the β-phase through the covalent-grafting of poly[(9,9-dioctylfluorene)-co-(9,9-bis(8-hydroxyoctyl)fluorene)] (PFO-OH) to poly(oxyalkylene)/siloxane hybrids known as ureasils, due to the urea linkages binding the organic and inorganic components. Although grafting occurs within the siliceous domains, the degree of branching of the organic backbone determines the packing of the PFO-OH chains within the ureasil framework. Moreover, photoluminescence studies indicate that physical confinement also plays a key role in promoting the evolution of the β-phase of PFO-OH as the sol-gel transition proceeds. Spectroscopic and structural analyses reveal that dibranched ureasils promote linear packing of the PFO-OH chains, while tribranched ureasils exhibit a more open, distorted structure that restricts the packing efficacy and reduces the number of covalent anchorages. These results indicate that the organic-inorganic hybrid structure induces distinct levels of β-phase formation and that covalent grafting is a versatile approach to design novel poly(fluorene) hybrid materials with tailored optical properties

The orientation-preserving diffeomorphism group of S^2 deforms to SO(3) smoothly

Smale proved that the orientation-preserving diffeomorphism group of S^2 has a continuous strong deformation retraction to SO(3). In this paper, we construct such a strong deformation retraction which is diffeologically smooth.Comment: 16 page

Photoactive organic-inorganic hybrid polymer waveguides for optical device technologies

© 2020 SPIE. Organic-inorganic hybrid polymers based on ureasils have found application as waveguides in luminescent solar concentrators and visible light communications. The mechanical properties, and thus processability of ureasils, has previously been qualitatively linked to the chemical structure, but has not yet been studied in detail. In this study, a series of low molecular weight ureasil polymers has been synthesised, and the correlation between the chemical structure and the optical and mechanical properties investigated. A wide-range of techniques are employed to investigate this relationship, including steady-state photoluminescence and Fourier-transform infrared spectroscopy, 4-point flexural testing, and uniaxial tensile testing.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 818762 - SPECTRACON). T. J. F. S. thanks the EPSRC (EP/N509620/1) for financial support

From Molecular Cores to Planet-forming Disks with SIRTF

The SIRTF mission and the Legacy programs will provide coherent data bases for extra-galactic and Galactic science that will rapidly become available to researchers through a public archive. The capabilities of SIRTF and the six legacy programs are described briefly. Then the cores to disks (c2d) program is described in more detail. The c2d program will use all three SIRTF instruments (IRAC, MIPS, and IRS) to observe sources from molecular cores to protoplanetary disks, with a wide range of cloud masses, stellar masses, and star-forming environments. The SIRTF data will stimulate many follow-up studies, both with SIRTF and with other instruments.Comment: 6 pages, from Fourth Cologne-Bonn-Zermatt-Symposium, The Dense Interstellar Matter in Galaxie

Flexible Blue-Light Fiber Amplifiers to Improve Signal Coverage in Advanced Lighting Communication Systems

Visible-light communication (VLC) based on white light-emitting diodes has recently attracted much attention to provide high-bitrate data communication in indoor environments. One of the remaining challenges to be resolved to enable the proliferation of VLC systems is related to channel attenuation and multiple path fading. Here, we introduce an advanced VLC system integrating an optical amplifier as a promising solution to overcome channel impairments, providing high bitrate coverage. The optical amplifier is a flexible fiber based on a poly(fluorene)-based lumophore doped within a di-ureasil organic-inor- ganic hybrid. Optical amplification is demonstrated for pre-amplifier and relay node scenarios, yielding a maximum gain of 5.9 G 0.2 dB and 3.7 G 0.2 dB, respectively, establishing the proposed approach as a promising cost-effective solution for VLCs. Additionally, numerical simulations show, for a realistic envi- ronment, a 207% improvement in the coverage area, using existing lighting infrastructure without extra cost.R.C.E. acknowledges funding from the European Research Council (ERC) under the European Union’s Ho- rizon 2020 research and innovation programme (grant agreement no. 818762 - SPECTRACON)