“Double gating” – a concept for enzyme-responsive imaging probes aiming at high tissue specificity

International audienceA new archetype of activatable imaging probe is described that responds in an off–on mode with a fluorescent signal only after being consecutively converted by two different enzymes. Pre-pro-proteins are a well-established concept employed by Nature, but “pre-pro-fluorescent” molecular probes have been unknown until now, even though they promise to furnish precious extra information and added specificity over habitual probe technologies. Our prototype probe discriminates cells that express both active β-D-galactosidase and leucine amino-peptidase from those which lack one of these enzymes thanks to the release of a precipitating fluorescent tag

Multigram Four-Step Synthesis of 1,4,7-Triazacyclononanes with 2Ra/Rb N-Functionalization Pattern by Starting from Diethylenetriamine

International audiencePolyazamacrocycles and their derivatives are appreciated for the strength of their corresponding metal complexes. 1,4,7-Triazacyclononane (TACN) derivatives have been employed in an ever increasing number of applications. To this day, all synthetic routes to TACN derivatives that have identical or differing substituents require the initial preparation of unprotected TACN. Herein, we report the four-step synthesis of TACN derivatives that have a 2Ra/Rb N-functionalization pattern by starting from diethylenetriamine and employing an organic template strategy

A pair of highly biotolerated diamagnetic and paramagnetic iron(II) complexes displaying electroneutrality

International audienceA pair of structurally analogous macrocyclic iron(II) complexes witha magnetic off-on relationship is reported that exhibit electroneutrality at neutral pH and high stability in physiological media. This has been achieved by external charge compensation using nicotinate pendent arms. No contact toxicity was observed for cells up to 4 mM for the low-spin and 2 mM for the high-spin complex. These results are a necessary precursor to the future design of turn-on probes with elevated biotolerance

Bispidine Platform Grants Full Control over Magnetic State of Ferrous Chelates in Water

International audienceA bicyclic ligand platform for iron(II), which allows total control over the complex’s magnetic properties in aqueous solution simply by varying one of the six coordination sites of the bispidine ligand, is reported. To achieve this, an efficient synthetic route to an N5 bispidine framework (ligand L4) that features an unsubstituted N-7 site is established. Then, by choosing appropriate N-7-coordinating substituents, the spin state of choice can be imposed on the corresponding ferrous complexes under environmentally relevant conditions in water and near-room temperature. Importantly, the first low-spin and diamagnetic iron(II) chelates in the bispidine series, both in the solid state and in aqueous solution, are reported. The eradication of head-on steric clashes between pendent coordinating arms is at the origin of this success. A new pair of constitutionally similar ferrous coordination compounds of a multidentate ligand system is obtained, which exhibits a distinctly binary (off–on) magnetic relationship. The new synthetic intermediate L4 may be substituted in just one step by any desired pendent arm, thus allowing access to complexes with finely tuned magnetic properties

A robust, high-sensitivity stealth probe for peptidases

International audienceA robust, modular fluorogenic probe system has been developed which allows the highly sensitive off–ON detection of aminopeptidase activity by releasing an exceptionally photostable, insoluble, phenolic ESIPT fluorophore. The probes generate no false positive signal in over 24 hours, but when activated give a signal within 10 minutes

3,5,7-Tripropyl-1-aza­adamantane-4,6,10-triol

The title compound, C18H33NO3, was prepared according to a highly diastereoselective hydrogenation procedure from 3,5,7-triallyl-1-aza­adamantane-4,6,10-trione. The crystal structure of the title compound contains two crystallographically independent mol­ecules (Z′ = 2), which are linked by inter­molecular hydrogen bonding into chains. In contrast to the aza­adamantanones, the aza­adamantanetriol core of the title compound does not show any particular C—C bond elongation

Magnetogenic probes that respond to chemical stimuli in an off–on mode

International audienceProbing chemical events can be achieved by several forms of readout. Very popular among designers of responsive probes is an optical/fluorescent output, and their operation in a truly binary off–on mode is greatly desired in view of the associated maximal signal-to-background ratio and detection simplicity. Promotion of another form of physical readout, a change in the magnetization of the sample, detectable for example by Magnetic Resonance Imaging, has been hampered by the inability to propose a molecular probe that is initially silent (off). This focus article discusses a recently proposed solution that consists in the design of suitable multi-dentate ligands whose diamagnetic ferrous complexes (off) turn into paramagnetic ones (on) in aqueous solution upon modification by an external chemical stimulus

Von Solarzellen bis zu Nanopartikeln, und immer wieder organische Synthese: die 48. Bürgenstock-Konferenz

International audienc

From Solar Cells to Nanoparticles and Lots of Organic Synthesis in Between: The 48th Bürgenstock Conference

International audienc

Etude de l'interaction amine tertiaire carbonyle en tant que mime de l'état de transition de la peptidolyse dans des inhibiteurs de peptidases aspartiques

LYON-ENS Sciences (693872304) / SudocSudocFranceF