The calcium-mediated addition of diphenylphosphane oxide to organic isocyanates and isothiocyanates yields N-alkyl and N-aryl substituted diphenylphosphorylformamides (E = O, R = iPr, tBu, cHex, Ph, C6H4-4-Br, C6H2-2,4,6-Me3, and Naph) and -thioformamides (E = S, R = iPr, cHex, Ph, and C6H4-4-Me), respectively, of the type Ph2P(O)–C(E)–N(H)R. All derivatives were characterized by IR and NMR spectroscopy as well as X-ray diffraction experiments. The wavenumbers of the N–H stretching modes are smaller for the thio analogues and N-aryl substituents. In the solid state all formamides and thioformamides form dimers by N–H⋯O–P hydrogen bridges. The P–CCE bonds are significantly elongated compared with the P–CPh distances.

In-ovo imaging using ostrich eggs has been described as a potential alternative to common animal testing. The main advantage is its independence from small animal imaging devices as ostrich eggs provide good image quality on regular CT, MRI, or PET used in examinations of humans. However, embryonal motion during dynamic imaging studies produce artifacts. The aims of this study were (1) to explore the feasibility of biomagnetism to detect cardiac signals and embryonal motion and to use these findings (2) to investigate the effect of isoflurane anesthesia on ostrich embryos. A standard magnetoencephalography developed for brain studies was used to detect embryonal signals of ostrich eggs on developmental day 34. Signals were instantly shown on a screen and data were also postprocessed. For assessing the effects of anesthesia, nine ostrich eggs were investigated using isoflurane 6% for 90 min. Biomagnetic signals were recorded simultaneously. A control group consisting of eight different ostrich eggs was also investigated. Cardiac signals similar to electrocardiography were observed in all eggs. Postprocessing revealed frequent motion of embryos without anesthesia. The exposure to isoflurane led to a significant decrease in motion signals in 9/9 ostrich embryos after 8 min. Motion was significantly reduced in the isoflurane group versus control group. There were no isoflurane-related deaths. This study shows that biomagnetism is feasible to detect cardiac signals and motion of ostrich embryos in-ovo. Application of isoflurane is safe and leads to a rapid decrease in embryonal motion, which is an important prerequisite for the implementation of in-ovo imaging using ostrich eggs.

This article reviews the use of metal complexes as contrast agents (CA) and radiopharmaceuticals for the anatomical and functional imaging of the liver. The main focus was on two established imaging modalities: magnetic resonance imaging (MRI) and nuclear medicine, the latter including scintigraphy and positron emission tomography (PET). The review provides an overview on approved pharmaceuticals like Gd-based CA and 99mTc-based radiometal complexes, and also on novel agents such as 68Ga-based PET tracers. Metal complexes are presented by their imaging modality, with subsections focusing on their structure and mode of action. Uptake mechanisms, metabolism, and specificity are presented, in context with advantages and limitations of the diagnostic application and taking into account the respective imaging technique.

We report the isolation of a new type of 1,4-diazepan-6-amine (DAZA)-based ligand. Condensation of aldehydes with DAZA gives a novel class of 1,5-diazabicyclo[3.2.1]octanes in nearly quantitative yields. Subsequent reductive cleavage of these bicyclic aminal species with sodium borohydride selectively leads to N,1,4-tri(4-alkoxy-2-hydroxybenzyl)-1,4-diazepan-6-amines (alkoxy = Me: TMeOHB-DAZA; alkoxy = Et: TEtOHB-DAZA) via a unique reductive alkylation reaction in which a substituent is added to the DAZA moiety without the presence of an alkylating agent. Mass spectrometry studies of the intermediates suggest that the mechanism involves insertion of in situ released carbonyl species into an aminal bond to form hemiaminal intermediates, and subsequent reduction. TMeOHB-DAZA and TEtOHB-DAZA are hexadentate ligands suitable for effectively coordinating Ga(iii) ions. Chelation of the radionuclide 68Ga was achieved within 5 min at 100 °C. In vitro stability studies in PBS and human serum confirmed the kinetic inertness of the tracers as no 68Ga demetallation was observed over a period of 4 h. Positron emission tomography (PET)/computed tomography (CT) imaging after in ovo administration to incubated ostrich eggs showed a high uptake in the liver, namely 27% (60 min post injection), and subsequent biliary excretion. These results suggest that [68Ga]Ga-TMeOHB-DAZA and [68Ga]Ga-TEtOHB-DAZA have excellent potential as hepatobiliary PET/CT imaging agents.

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