A new bis(3-hydroxy-4-pyridinone)-IDA derivative as a potential therapeutic chelating agent. Synthesis, metal-complexation and biological assays

A new bis(3-hydroxy-4-pyridinone) derivative of iminodiacetic acid, imino-bis(acetyl(1-(3'-aminopropyl)-3-hydroxy-2-methyl-4-pyridinone)), IDAPr(3,4-HP)(2), has been prepared and studied in its interaction with a set of hard metal ions. This tetradentate ligand presents a much higher chelating efficiency for trivalent hard metal ions (Fe, Ga, Al) than the monodentate derivative Deferriprone, namely at the diluted conditions prevailing in physiological conditions and at low clinical doses. A similar behaviour was also observed for the complexation with Zn(II) but at a significantly lower extent. This compound presents a moderate hydrophilic character at physiological pH (logD=-1.72). In vivo assays showed much more rapid clearance of (67)Ga from most tissues of metal-loaded mice than the drug Deferriprone and the radioactivity excretion occurs mostly through the kidneys. Therefore, results from in vitro and in vivo studies indicated good perspectives for this compound to be a potential decorporating agent for hard metal ions in overload situations without depletion of essential metal ions such as zinc.     

New Insight on Carbon Dioxide-Mediated Hydrogen Production**

A new approach to hydrogen production from water is described. This simple method is based on carbon dioxide-mediated water decomposition under UV radiation. The water contained dissolved sodium hydroxide, and the solution was saturated with gaseous carbon dioxide. During saturation, the pH decreased from about 11.5 to 7–8. The formed bicarbonate and carbonate ions acted as scavengers for hydroxyl radicals, preventing the recombination of hydroxyl and hydrogen radicals and prioritizing hydrogen gas formation. In the presented method, not yet reported in the literature, hydrogen production is combined with carbon dioxide. For the best system with alkaline water (0.2 m NaOH) saturated with CO₂ under UV-C, the hydrogen production amounted to 0.6 μmol h⁻¹ during 24 h of radiation.     

Synthesis of twist-twist pi-conjugated di-sec-alkylstilbenes and stilbene polymers

Twist-twist pi-conjugated (TTPC) pi systems promise unique properties with their 90 degrees twist angles. Di-sec-alkyl substituted stilbenes, 5, were prepared by low-valent titanium coupling of phenyl ketones, 4. Long alkyl chains stopped the coupling reaction. Stilbenes 5 were shown to be approximately 90% TTPC. Inserting TTPC units into poly(p-phenylene) polymers created highly fluorescent, soluble, TTPC pi systems with weak electronic segmentation for organic light emitting diode (OLED) studies.     

Die Destillation von Ammoniak bei der Stickstoffbestimmung

Ohne Zusammenfassung     

99mTc(CO)3-labeled pamidronate and alendronate for bone imaging

Bone scintigraphy with (99m)Technetium-methylenediphosphonate ((99m)Tc-MDP) or (99m)Technetium-hydroxymethylenediphosphonate ((99m)Tc-HMDP) presents several limitations, namely low specificity, uncertainty in the radiopharmaceutical's molecular structure and long acquisition time after injection. Aiming to find bone-seeking radiotracers based on the core fac-[(99m)Tc(CO)(3)](+) with improved chemical and biological properties, we synthesized new conjugates (pz-PAM and pz-ALN), comprising a pyrazolyl-diamine chelating unit (pz: N,N,N donor atom set) for metal stabilization and a pendant pamidronate (PAM) or alendronate (ALN) moiety for bone targeting. The reaction of the conjugates with fac-[(99m)Tc(CO)(3)](+) yielded (> 95%) the stable complexes fac-[(99m)Tc(CO)(3)(pz-PAM)](-) (2a) and fac-[(99m)Tc(CO)(3)(pz-ALN)](-) (3a), which have been characterized by comparing their HPLC gamma-traces with the UV-vis traces of the Re surrogates 2 and 3, respectively. 2a and 3a bind strongly onto hydroxyapatite. The biodistribution studies in Balb-c mice have shown that 2a and 3a presented an high bone uptake (2a 18.3 ± 0.6% I.D./g, 3a 17.3 ± 6.1% I.D./g, at 1 h post injection), similar to (99m)Tc-MDP (17.1 ± 2.4% I.D./g, at 1 h post injection), with comparable clearance from most tissues and increased total excretion (2a 66% I.D., 3a 67% I.D. and (99m)Tc-MDP 49% I.D., at 1 h post injection). The bone-to-blood (2a 86.2, 3a 74.7) and the bone-to-muscle ratios (2a 77.7, 3a 79.0) are higher than the ones found for (99m)Tc-MDP (70.9, 47.9), at 4 h post injection. Planar whole-body gamma camera images of the rats injected with the (99m)Tc(CO)(3)-labeled pamidronate (2a) and alendronate (3a) confirmed the overall adequate biological profile of the new radiotracers for bone imaging.     

Radiopharmaceuticals for renal studies: Evaluation of protein binding

Determination of total in vitro protein binding was evaluated for the following radiopharmaceuticals:^99mTc-diethylenetriaminepentaacetic acid (DTPA),^99mTc-dimercaptosuccinic acid (DMSA),^99mTc-glucoheptonate (GH) and^99mTc-fosfomycin (PHO). For that they were incubated wtih human serum at 37°C. After three and sixty minutes of incubation, the bound fraction was evaluated by two different methods: gel filtration and precipitation with trichloroacetic acid (TCA). The percentage of the^99mTc-kidney agents bound by human serum proteins is different for each one. Determination by TCA precipitation always leads to higher results. For renal imaging agents (DMSA, GH and PHO) the percentage of binding by each serum proteic constituent was also evaluated by electrophoretic analysis. All proteic constituents of human serum bind with those radiopharmaceuticals but the percentage of binding is different in accordance with both the radiopharmaceutical and the proteic constituent.