To Sandwich Technetium: Highly Functionalized Bis-Arene Complexes [99mTc(η6-arene)2]+ Directly from Water and [99mTcO4]−

The labeling of (bio)molecules with metallic radionuclides such as ^99mTc demands conjugated, multidentate chelators. However, this is not always necessary since phenyl rings can directly serve as integrated, organometallic ligands. Bis-arene sandwich complexes are generally prepared by the Fischer–Hafner reaction. In extension of this, we show that [^99mTc(η⁶-C₆R₆)₂]⁺-type complexes are directly accessible from water and [^99mTcO₄]⁻, even using arenes incompatible with Fischer–Hafner conditions. To unambiguously confirm the nature of these unprecedented ^99mTc complexes, their rhenium homologous have been prepared by substituting naphthalene ligands in [Re(η⁶-C₁₀H₈)₂]⁺ with the corresponding phenyl groups. The ease with which highly stable [^99mTc(η⁶-C₆R₆)₂]⁺ complexes are formed under standard labeling conditions enables a multitude of new potential imaging agents based on commercial pharmaceuticals or lead structures.     

Purification of labelled antibodies by hydrophobic interaction chromatography

In order to improve the sensitivity of immunometric assays, a chromatographic technique was developed that virtually eliminates components causing non-specific background. Labelled antibodies were applied to a phenyl-Sepharose column in physiological buffer. When labelled anitbodies were purified by this technique, the non-specific background of various time-resolved immunofluorometric assays was reduced 3- to 10-fold and was very close to the instrument background. The assay sensitivity was simultaneously increased by a factor of 2 to 16. This purification method might be used to improve the results of immunometric assays in general.     

Synthesis of 1,3-diamino-7,8,9,10-tetrahydropyrido[3,2-f]-quinazolines. Inhibitors of Candida albicans dihydrofolate reductase as potential antifungal agents

A series of novel 1,3-diamino-7,8,9,10-tetrahydropyrido[3,2-f]quinazolines were synthesized starting from 6-amino-5-cyanoquinoline (4). These compounds inhibited Candida albicans dihydrofolate reductase with K_i values of ≤0.60 aM. One analogue exhibited moderate in vivo efficacy in a C. albicans-infected mouse model.     

Liquid-phase microextraction in a microfluidic-chip – High enrichment and sample clean-up from small sample volumes based on three-phase extraction

In this work, a microfluidic-chip based system for liquid-phase microextraction (LPME-chip) was developed. Sample solutions were pumped into the LPME-chip with a micro-syringe pump at a flow rate of 3–4 μL min⁻¹. Inside the LPME chip, the sample was in direct contact with a supported liquid membrane (SLM) composed of 0.2 μL dodecyl acetate immobilized in the pores of a flat membrane of polypropylene (25 μm thickness). On the other side of the SLM, the acceptor phase was present. The acceptor phase was either pumped at 1 μL min⁻¹ during extraction or kept stagnant (stop-flow). Amitriptyline, methadone, haloperidol, loperamide, and pethidine were selected as model analytes, and they were extracted from alkaline sample solution, through the SLM, and into 10 mM HCl or 100 mM HCOOH functioning as acceptor phase. Subsequently, the acceptor phase was either analyzed off-line by capillary electrophoresis for exact quantification, or on-line by UV detection or electrospray ionization mass spectrometry for time profiling of concentrations. The LPME-chip was found to be highly effective, and extraction efficiencies were in the range of 52–91%. When the flow of acceptor phase was turned off during extraction (stop-flow), analyte enrichment increased linearly with the extraction time. After 10 min as an example, amitriptyline was enriched by a factor of 42 from only 30 μL sample solution, and after 120 min amitriptyline was enriched by a factor of 500 from 320 μL sample solution. This suggested that the LPME-chip has great potentials for very efficient analyte enrichments from limited sample volumes in the future.     

Identification and characterization of endonuclein binding proteins: evidence of modulatory effects on signal transduction and chaperone activity

Background  

We have previously identified endonuclein as a cell cycle regulated WD-repeat protein that is up-regulated in adenocarcinoma of the pancreas. Now, we aim to investigate its biomedical functions.     

Raman and Infrared Spectroscopic Investigation of Speciation in BeSO<Subscript>4</Subscript>(aq)

Measurements have been made of the Raman spectra of aqueous solutions of Be(ClO₄)₂, BeCl₂, (NH₄)₂SO₄ and BeSO₄ to 50 cm⁻¹. In some cases low concentrations (0.000770 mol⋅kg⁻¹) have been used and two temperatures (23 and 40 °C) were studied. In BeSO₄(aq), the ν ₁-SO₄^2-\mathrm{SO}_{4}^{2-} mode at 980 cm⁻¹ broadens with increasing concentration and shifts to higher wavenumbers. At the same time, a band at 1014 cm⁻¹ is detectable with this mode being assigned to [BeOSO₃], an inner-sphere complex (ISC). Confirmation of this assignment is provided by the simultaneous appearance of stretching bands for the Be²⁺-OSO₃^2-\mathrm{Be}^{2+}\mbox{-}\mathrm{OSO}_{3}^{2-} bond of the complex at 240 cm⁻¹ and for the BeO₄ skeleton mode of the [(H₂O)₃BeOSO₃] unit at 498 cm⁻¹. The ISC concentration increases with higher temperatures. The similarity of the n₁-SO₄^2-\nu_{1}\mbox{-}\mathrm{SO}_{4}^{2-} Raman bands for BeSO₄ in H₂O and D₂O is further strong evidence for formation of an ISC. After subtraction of the ISC component at 1014 cm⁻¹, the n₁-SO₄^2-\nu_{1}\mbox{-}\mathrm{SO}_{4}^{2-} band in BeSO₄(aq) showed systematic differences from that in (NH₄)₂SO₄(aq). This is consistent with a n₁-SO₄^2-\nu_{1}\mbox{-}\mathrm{SO}_{4}^{2-} mode at 982.7 cm⁻¹ that can be assigned to the occurrence of an outer-sphere complex ion (OSCs). These observations are shown to be in agreement with results derived from previous relaxation measurements. Infrared spectroscopic data show features that are also consistent with a beryllium sulfato complex such as the appearance of a broad and weak n₁-SO₄^2-\nu_{1}\mbox{-}\mathrm{SO}_{4}^{2-} mode at ∼1014 cm⁻¹, normally infrared forbidden, and a broad and asymmetric n₃-SO₄^2-\nu_{3}\mbox{-}\mathrm{SO}_{4}^{2-} band contour which could be fitted with four band components (including n₃-SO₄^2-(aq)\nu_{3}\mbox{-}\mathrm{SO}_{4}^{2-}(\mathrm{aq})). The formation of ISCs in BeSO₄(aq) is much more pronounced than in the similar MgSO₄(aq) system studied recently.     

Cyclization of Propargylic Amides: Mild Access to Oxazole Derivatives

The substrate scope, the mechanistic aspects of the gold‐catalyzed oxazole synthesis, and substrates with different aliphatic, aromatic, and functional groups in the side chain were investigated. Even molecules with several propargyl amide groups could easily be converted, delivering di‐ and trioxazoles with interesting optical properties. Furthermore, the scope of the gold(I)‐catalyzed alkylidene synthesis was investigated. Further functionalizations of these isolable intermediates of the oxazole synthesis were developed and chelate ligands can be obtained. The use of Barluenga’s reagent offers a new and mild access to the synthetically valuable iodoalkylideneoxazoles from propargylic amides, this reagent being superior to other sources of halogens.     

Assembly of π‐Conjugated Phosphole Azahelicene Derivatives into Chiral Coordination Complexes: An Experimental and Theoretical Study

Aza[n]helicene phosphole derivatives have been prepared from aza[n]helicene diynes by the Fagan–Nugent route. Their photophysical properties (UV/Vis absorption and emission behavior) have been evaluated. Their behavior as P,N chelates towards coordination to Pd^II and Cu^I has been investigated: metal–bis(aza[n]helicene phosphole) assemblies are formed by a highly stereoselective coordination process, as demonstrated by X‐ray crystallography. An aza[6]helicene phosphole bearing an enantiopure helicene part has been obtained, which allows the preparation of enantiopure Pd^II and Cu^I complexes with original topologies and high molar rotation (MR) and circular dichroism (CD). The structure–property relationship established from the experimental data has been studied in detail by theoretical studies (TDDFT calculations of UV/Vis, CD, and MR). Aza[n]helicene phosphole derivatives show π conjugation extended over the entire molecule, and its influence on the MR of aza[6]helicene phosphole 5 c has been demonstrated. Finally, it has been shown that the nature of the metal (coordination geometry and electronic interaction) can have a great impact on the amplitude of the chiroptical properties in metal–bis(aza[n]helicene phosphole) assemblies.