Gated Proton Release during Radical Transfer at the Subunit Interface of Ribonucleotide Reductase.

The class Ia ribonucleotide reductase of Escherichia coli requires strict regulation of long-range radical transfer between two subunits, α and ß, through a series of redox-active amino acids (Y122•[ß] ↔ W48?[ß] ↔ Y356[ß] ↔ Y731[α] ↔ Y730[α] ↔ C439[α]). Nowhere is this more precarious than at the subunit interface. Here, we show that the oxidation of Y356 is regulated by proton release involving a specific residue, E52[ß], which is part of a water channel at the subunit interface for rapid proton transfer to the bulk solvent. An E52Q variant is incapable of Y356 oxidation via the native radical transfer pathway or non-native photochemical oxidation, following photosensitization by covalent attachment of a photo-oxidant at position 355[ß]. Substitution of Y356 for various FnY analogues in an E52Q-photoß2, where the side chain remains deprotonated, recovered photochemical enzymatic turnover. Transient absorption and emission data support the conclusion that Y356 oxidation requires E52 for proton management, suggesting its essential role in gating radical transport across the protein-protein interface.

Experimental and theoretical study of rhenium radioisotopes production for manufacturing of new compositional radiopharmaceuticals.

Rhenium therapeutic radioisotopes, namely rhenium-186 and 188, are radionuclides that have been used in combination with various ligands to provide different radiopharmaceuticals for the treatment of different diseases for many years. Each of these radioisotopes has its own special attributes, which make it appropriate to destroy special-sized tumors. High energy, long range beta particles in 188Re can give this certainty that large tumors can be eradicated with high efficiency. On the other hand, 186Re with low energy, short range beta particles is adequate item to ruin small tumors with minimum side effects and high yield. Thus, each of these radioisotopes has features that can cover just part of the treatment individually. So we thought accompanying 186Re and 188Re must have the best outcome to treat tumors with various sizes. Irradiating natural rhenium with neutrons has this potential to produce parallel 186Re and 188R together. We are looking for investigating whether the natural rhenium irradiation, in addition the concurrent production of these radioisotopes, gives us the appropriate radioactivity values to produce compositional radiopharmaceuticals? In this research, the experimental and theoretical assessments of 186Re and 188R simultaneous production to reach compositional radiopharmaceutical by natural rhenium irradiation in the Tehran research reactor, as well as the type and amount of produced impurities have been investigated. The results showed that experimental data are in good agreement with theoretical calculations. The maximum relative error in data has been calculated 8%. The results showed that, in the simultaneous production 186Re and 188R via the natural rhenium irradiation method, the amounts of impurities are trivial compared to the main products, and the activities of main products are properly enough to produce compositional radiopharmaceuticals.

Defect complexes in Re3+-doped magnesium sulphate phosphors.

A series of magnesium sulphate phosphors MgSO4:RE3+,X ( RE = Dy, Tm, Eu and X = P, Mn) have been prepared and studied. Based on the experimental results of thermoluminescence (TL) emission spectra and dose responses studies, it is proposed that in these phosphors large defect complexes are formed, which include intrinsic imperfections and dopants. These defect complexes were formed in the course of preparation of phosphors and could be regarded as basic elements in the TL multi-stage processes. This defect model might be applicable to the most of TL materials.

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.

pH-dependent photophysical behavior of rhenium complexes containing hydroxypyridine ligands.

Data related to the pH-dependent photophysics of a class of rhenium complexes containing the hydroxypyridine ligand are presented. Data include ground-state pK(a) values, emission energies, and lifetimes. The complexes all have ground-state pK(a) values near 7.0 and exhibit a dramatic change in emission intensity near this pH. The lifetimes of these complexes, however, are constant over this pH range. A model is presented to account for the observed photophysical behavior. The pH-dependent emission properties of these species make them good candidates for luminescence-based pH probes, especially in the environmental and biomedical fields.

Radionuclide production for therapeutic radiopharmaceuticals.

A fundamental task within the framework of a project searching for new radiopharmaceuticals for systemic therapy was the evaluation of the capabilities of the Portuguese Research Reactor (RPI) for the production of several important radionuclides. The feasibility of producing 64Cu, 77As, 153Sm, 165Dy, 166Ho, 170Tm, 177Lu, 186Re, 199Au and 111Ag in useful quantities was evaluated for the present RPI operation schedule (12 h cycles) and for continuous operation. The main evaluation criteria are expressed in terms of specific activity for continuous irradiation and/or 12 h cycle and the use of natural or enriched targets if necessary. Selected samples were irradiated and a comparison between measured activities and values calculated according to the irradiation schedule and using the same software was performed.

Investigation of activation cross-section data of proton induced nuclear reactions on rhenium.

In the frame of systematic investigations of activation cross-section data for different applications the excitation functions of (nat)Re(p,x)(185)Os, (183m)Os, (183g)Os, (182)Os, (181m)Os, (186g)Re, (184m)Re, (184g)Re, (183)Re, (182m)Re, (182g)Re and (181g)Re reactions were measured up to 70MeV. The data for the (nat)Re(p,x) (183m)Os, (183g)Os, (182)Os, (181g)Os,(186g)Re, (184m)Re,(182m)Re, (182g)Re, and (181)Re reactions are reported for the first time. The activation method, the stacked foil irradiation technique and γ-spectroscopy for activity detection were used. The experimental data were compared with predictions of three theoretical codes. From the measured cross-section thick target integral yields were also calculated and presented.

Reduction of ß-radiation exposure during preparation of 188Re-labelled Lipiodol for hepatocellular carcinoma treatment.

Rhenium-188 (188Re) is of widespread interest for treating various diseases because of its attractive physical and chemical properties. The routine preparation of therapeutic doses of 188Re-labelled tracers can result in significant radiation exposure to the operator. We studied the impact of automating the preparation of 188Re-Lipiodol on the radiochemist's exposure, as well as the importance of the model of syringe shielding. To monitor radiation exposure continuously readable electronic personal dosimeters were used. Thermoluminescence dosimeters were fixed to the probable most exposed fingers of the radiochemist during preparation of the radiotracer and during the syringing. Dose rates were measured using a Babyline. Automation of the synthesis reduced personal dose equivalents from 2.60±4.35 to 1.61±1.20 µSv/GBq [Hp(10)] and from 38.37±55.28 to 21.84±16.14 µSv/GBq [Hp(0.07)]. Dose to the extremities was also reduced (-80% for the right hand; -58% for the left one). The Lemer-Pax PSWG syringe shield led to a slightly lower dose to the hands compared with the Medisystem (1.1±0.27 vs. 1.34±0.6 mSv/GBq for the right finger). Automation of the synthesis leads to a significant decrease in radiation exposure to the operator. The Lemer-Pax PSWG syringe shield provides better hand protection than the smaller Medisystem Mediclic.

Production study of high specific activity NCA Re-186g by proton and deuteron cyclotron irradiation.

Very high specific activity (A(S)) (186g)Re could be produced by either proton or deuteron cyclotron irradiation on highly enriched (186)W target in no-carrier-added (NCA) form, leading to a A(S) very close to the theoretical carrier free (CF) value of 6.88GBqmicrog(-1). Thick target yields (TTYs), obtained irradiating both thick metal W targets of natural isotopic composition and highly enriched pressed powdered (186)W targets, were measured at different particles energies taking into account high accuracy and precision on both yield and beam energy. The measurement of radionuclidic purity of (186g)Re obtained activating highly enriched (186)W by both p and d beams were also carried out and accurately compared. The excitation function as thin-target yields (tty, i.e. proportional to the reaction cross-sections) and the integrated TTYs for all Re (A=181, 182, 183, 184, 186 and their metastable levels), W and Ta co-produced radionuclides will be presented elsewhere in deep details.

Extraction separation of no-carrier-added 103Pd from irradiated Rh target, Cu and Zn using alpha-furyldioxime, dimethylglyoxime and alpha-benzildioxime.

Solvent extraction of no-carrier-added (103)Pd from irradiated rhodium target hydrochloric solution was investigated using alpha-furyldioxime, dimethylglyoxime and alpha-benzildioxime as extracts in chloroform. The best extractant yield for a single run was 96.9% with dimethylglyoxime from 0.93M HCl and (103)Pd purity was better than 99.99%.

Picosecond time-resolved infrared spectroscopic investigation into electron localisation in the excited states of Re(i) polypyridyl complexes with bridging ligands.

Mono- and binuclear complexes of (Re(CO)3Cl) with dipyrido[2,3-a:3',2'-c]-6,7-dimethylphenazine (ppbMe2) were synthesised and their photophysical properties probed using picosecond time-resolved infrared spectroscopy (TRIR). Excitation of these complexes in solution at 400 nm produces short-lived excited states. The IR spectrum of the excited state of the mononuclear [Re(CO)3Cl(ppbMe2)] have nu(CO) bands shifted to higher wavenumber relative to those of the ground state. This is consistent with formation of a (3)MLCT excited state. The IR spectrum of the excited state of the bimetallic [(Re(CO)3Cl)2(micro-ppbMe2)] shows the formation of two distinct groups of nu(CO) bands. This is interpreted as the formation of two distinct Re sites arising from a localised MLCT state with formally oxidised Re centre and a formally reduced bridging ligand. The nu(CO) bands of the adjacent Re centre are affected by the reduction of the bridging ligand. On the IR timescale the excited state structure is best formulated as [Cl(CO)3Re(II)(micro-ppbMe2 *-)Re(I)(CO)3Cl].