Application of Palladium-Mediated 18F-Fluorination to PET Radiotracer Development: Overcoming Hurdles to Translation

New chemistry methods for the synthesis of radiolabeled small molecules have the potential to impact clinical positron emission tomography (PET) imaging, if they can be successfully translated. However, progression of modern reactions from the stage of synthetic chemistry development to the preparation of radiotracer doses ready for use in human PET imaging is challenging and rare. Here we describe the process of and the successful translation of a modern palladium-mediated fluorination reaction to non-human primate (NHP) baboon PET imaging–an important milestone on the path to human PET imaging. The method, which transforms [18F]fluoride into an electrophilic fluorination reagent, provides access to aryl–18F bonds that would be challenging to synthesize via conventional radiochemistry methods.Chemistry and Chemical Biolog

Solvent effects on Grubbs’ pre-catalyst initiation rates

Initiation rates for Grubbs and Grubbs-Hoveyda second generation pre-catalysts have been measured accurately in a range of solvents. Solvatochromic fitting reveals different dependencies on key solvent parameters for the two pre-catalysts, consistent with different mechanisms by which the Grubbs and Grubbs-Hoveyda pre-catalysts initiate

Solvatochromic probes for detecting hydrogen-bond-donating solvents

Hydrogen bonding heavily influences conformations, rate of reactions, and chemical equilibria. The development of a method to monitor hydrogen bonding interactions independent of polarity is challenging as both are linked. We have developed two solvatochromic dyes that detect hydrogen-bond-donating solvents. The unique solvatochromism of the triazine architecture has allowed the development of probes that monitor hydrogen-bond-donating species including water

A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging

The unnatural isotope fluorine-18 $(^{18}F)$ is used as a positron emitter in molecular imaging. Currently, many potentially useful $^{18}F$-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of $^{18}F$ requires rapid syntheses for which $[^{18}F]$fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment. However, conventional $[^{18}F]$fluoride chemistry has been limited to nucleophilic fluorination reactions. We report the development of a palladium-based electrophilic fluorination reagent derived from fluoride and its application to the synthesis of aromatic $^{18}F$-labeled molecules via late-stage fluorination. Late-stage fluorination enables the synthesis of conventionally unavailable positron emission tomography (PET) tracers for anticipated applications in pharmaceutical development as well as preclinical and clinical PET imaging.Chemistry and Chemical Biolog

Ein neues, unkompliziertes Verfahren zur Bestimmung der Zusammensetzung binärer Flüssigkeitsgemische

Ein neues Verfahren zur Bestimmung der Zusammensetzung binärer Flüssigkeitsgemische mit Hilfe solvatochromer Farbstoffe wird beschrieben. Die Analyse erfolgt durch einfache UV/VIS-Absorptionsmessung und ist unter Verwendung einer Zwei-Parameter-Gleichung ein exakter Schnelltest

Synthesis of new fluorescent 2-(2’, 2’’-bithienyl)-1,3-benzothiazoles

Bithienyl-1,3-benzothiazole derivatives were synthesised by reacting various 5-formyl-5’-alkoxy- or 5-formyl-5’-N,N-dialkylamino-2,2’-bithiophenes with ortho-aminobenzenethiol in good to excellent yields. Evaluation of the fluorescence properties of these compounds was carried out. They show strong fluorescence in the 450-600 nm region, as well as high quantum yields and large Stokes’ shifts.Fundação para a Ciência e Tecnologia

Physicochemical characterization of the PEG8000-Na2SO4 aqueous two-phase system

The polyethylene glycol-sodium sulfate aqueous two-phase system has been characterized at 23 °C. Tielines for the phase diagram were obtained experimentally. Phases in equilibrium were characterized by means of the solvatochromic parameters π*, α, and β, which provide a measurement of the polarity/polarizability and the H-bond donor and acceptor abilities, respectively. The ability of the phases to participate in hydrophobic interactions was characterized by means of the free energy of transfer of a methylene group between the conjugated phases, using the partition of a homologous series of dinitrophenylated amino acids. The results show the effect of the presence of polymer and salt in the aqueous phase, and a comparison of both phases with pure water is made.LSRE-PortoUniversidade Católica PortuguesaEscola Superior de Biotecnologia do PortoFundação para a Ciência e a Tecnologia (FCT