pH-Dependent Hydration Change in a Gd-Based MRI Contrast Agent with a Phosphonated Ligand.

The heptadentate ligand L was shown to form an extremely stable Gd complex at neutral pH with a pGd value of 18.4 at pH 7.4. The X-ray crystal structures of the complexes formed with Gd and Tb displayed two very different coordination behaviors being, respectively, octa- and nonacoordinated. The relaxometric properties of the Gd complex were studied by field-dependent relaxivity measurements at various temperatures and by 17 O NMR spectroscopy. The pH-dependence of the longitudinal relaxivity profile indicated large changes around neutral pH leading to a very large value of 10.1 mm-1 ⋅s-1 (60 MHz, 298 K) at pH 4.7. The changes were attributed to an increase of the hydration number from one water molecule in basic conditions to two at acidic pH. A similar trend was observed for the luminescence of the Eu complex, confirming the change in hydration state. DOSY experiments were performed on the Lu analogue, pointing to the absence of dimers in solution in the considered pH range. A breathing mode of the complex was postulated, which was further supported by 1 H and 31 P NMR spectroscopy of the Yb complex at varying pH and was finally modeled by DFT calculations.

Ultrabright Terbium Nanoparticles for FRET Biosensing and in Situ Imaging of Epidermal Growth Factor Receptors*.

Lanthanide-doped nanoparticles (LnNPs) have become an important class of fluorophores for advanced biosensing and bioimaging. LnNPs that are photosensitized by surface-attached antenna ligands can possess exceptional brightness. However, their functional bioconjugation remains an important challenge for their translation into bioanalytical applications. To solve this problem, we designed a ligand that can be simultaneously applied as efficient light harvesting antenna for Tb surface ions and strong linker of biomolecules to the LnNPs surfaces. To demonstrate generic applicability of the photosensitized TbNP-bioconjugates, we applied them in two prototypical applications for biosensing and bioimaging. First, in-solution biorecognition was shown by time-resolved Förster resonance energy transfer (FRET) between streptavidin-functionalized TbNPs to biotinylated dyes (ATTO 610). Second, in situ detection of ligand-receptor binding on cells was accomplished with TbNP-antibody (Matuzumab) conjugates that could specifically bind to transmembrane epidermal growth factor receptors (EGFR). High specificity and sensitivity were demonstrated by time-gated imaging of EGFR on both strongly (A431) and weakly (HeLa and Cos7) EGFR-expressing cell lines, whereas non-expressing cell lines (NIH3T3) and EGFR-passivated A431 cells did not show any signals. Despite the relatively large size of TbNP-antibody conjugates, they could be internalized by A431 cells upon binding to extracellular EGFR, which showed their potential as bright and stable luminescence markers for intracellular signaling.

Desymmetrizing Hydroformylation of Dihydromuconic Acid Diesters: Application to the Synthesis of (±)-Vindeburnol.

The desymmetrizing hydroformylation of internal alkenes derived from dihydromuconic acid is described. The study of this reaction afforded easy access to polyfunction aldehydes. After the evaluation of the reactivity of the dimethyl ester derivative with various primary amines, this methodology was used to design a rapid synthesis of (±)-vindeburnol from tryptamine in only two steps.