Sensitized terbium(III) macrocyclic-phthalimide complexes as luminescent pH switches.

Four new macrocyclic-phthalimide ligands were synthesised via the coupling of N-(3-bromopropyl)phthalimide either to cyclen (1,4,7,10-tetraazacyclododecane) itself or its carboxylate-functionalized analogues, and photophysical studies were carried out on their corresponding Tb(III) complexes in aqueous media as a function of pH. Luminescence intensities of Tb·L1a­Tb·L3a were in 'switched off' mode under acidic conditions (pH < 4), and were activated on progression to basic conditions as the phthalimido functions therein were hydrolysed to their corresponding phthalamates Tb·L1b­Tb·L3b. Emission of phthalamate-based macrocyclic Tb(III) complexes Tb·L1b­Tb·L3b was in 'switched on' mode between pH 4 and 11, exhibiting high quantum yields (Φ) and long lifetimes (τ) of the order of milliseconds at pH ~ 6. Tb(III) emissions were found to decline with increasing number of chromophores. The values of Φ and τ were 46% and 2.4 ms respectively for Tb·L1b at pH ~ 6 when activated. This is the best pH-dependent sensor based on a Tb(III) complex reported to date, benefiting from the macrocyclic architecture of the ligand.

A chemically unlocked binary molecular switch.

A highly luminescent and sensitive terbium complex of a ligand comprising of a phthalimide group appended to a DO3A moiety is an active pH sensor that is conditional on its previous pH.

¹H NMR study of monocrotaline and its metabolites in human blood.

Monocrotaline (MCT) is a naturally occurring hepatotoxic pyrrolizidine alkaloid found in plants. This investigation is aimed at furthering the understanding of the role of blood in mediating the transport of MCT and its reactive metabolites in humans. Reactions of monocrotaline and its metabolites, dehydromonocrotaline (DHM), retronecine (RET) and dehydroretronecine (DHR) with human blood plasma, red blood cells (RBCs), and whole blood were studied in vitro by proton nuclear magnetic resonance spectroscopy. In plasma MCT remained intact and weakly associated with plasma proteins, and DHM was rapidly hydrolyzed releasing necic and lactone acids, and the reactive pyrrolic metabolite. MCT and its metabolite DHM were internalized in RBCs to the extent of 46.0% and 48.9% respectively in 30 min. No polymerization of DHR was observed when incubated with plasma and RBCs. The data clearly showed that both human plasma and RBCs could be the carriers for the transportation of MCT and its metabolites, DHM, RET and DHR between organs and could stabilise the reactive MCT metabolite DHR.

Synthesis and characterisation of a novel tubulin-directed DO3A-colchicine conjugate with potential theranostic features.

Colchicine is a known tubulin binding agent enabling necrosis in tumors. A novel tubulin-directed DO3A-colchicine conjugate and its Gd(III) complex were prepared from N-deacetylcolchicine, coupling alkaloid and polyaza-alicyclic functions via a peptide coupling methodology. The longitudinal proton relaxivity of the Gd(III) complex in water at 4.7 T is 2.86 mM(-1) s(-1) and a similar efficacy as colchicine towards ovarian carcinoma cells in vitro.