Watching nanoparticles form: an in situ (small-/wide-angle X-ray scattering/total scattering) study of the growth of yttria-stabilised zirconia in supercritical fluids

Understanding nanoparticle-formation reactions requires multi-technique in situ characterisation, since no single characterisation technique provides adequate information. Here, the first combined small-angle X-ray scattering (SAXS)/wide-angle X-ray scattering (WAXS)/total-scattering study of nanoparticle formation is presented. We report on the formation and growth of yttria-stabilised zirconia (YSZ) under the extreme conditions of supercritical methanol for particles with Y(2)O(3) equivalent molar fractions of 0, 4, 8, 12 and 25 %. Simultaneous in situ SAXS and WAXS reveals a quick formation (seconds) of sub-nanometre amorphous material forming larger agglomerates with subsequent slow crystallisation (minutes) into nanocrystallites. The amount of yttria dopant is shown to strongly affect the crystallite size and unit-cell dimensions. At yttria-doping levels larger than 8 %, which is known to be the stoichiometry with maximum ionic conductivity, the strain on the crystal lattice is significantly increased. Time-resolved nanoparticle size distributions are calculated based on whole-powder-pattern modelling of the WAXS data, which reveals that concurrent with increasing average particle sizes, a broadening of the particle-size distributions occur. In situ total scattering provides structural insight into the sub-nanometre amorphous phase prior to crystallite growth, and the data reveal an atomic rearrangement from six-coordinated zirconium atoms in the initial amorphous clusters to eight-coordinated zirconia atoms in stable crystallites. Representative samples prepared ex situ and investigated by transmission electron microscopy confirm a transformation from an amorphous material to crystalline nanoparticles upon increased synthesis duration.     

Paramagnetic 19F chemical shift probes that respond selectively to calcium or citrate levels and signal ester hydrolysis

Paramagnetic magnetic resonance chemical shift probes containing a proximal CF(3) group have been characterised. Different systems have been created that report reversible changes in calcium ion concentrations in the millimolar regime, signal the presence of citrate selectively in competitive aqueous media and allow the monitoring of remote ester/amide hydrolysis in relayed, irreversible transformations. Chemical shift non-equivalence is amplified by the presence of the proximate lanthanide ion, with a mean separation between the CF(3) group and the metal ion of 6.4 ? found for a thulium complex, in an X-ray structure of the metal complex aqua adduct. The enhanced rate of longitudinal relaxation of the (19)F nucleus allows faster data acquisition.     

Understanding the formation and evolution of ceria nanoparticles under hydrothermal conditions

Supercritical growth: The formation and evolution of ceria nanoparticles during hydrothermal synthesis was investigated by in?situ total scattering and powder diffraction. The nucleation of pristine crystalline ceria nanoparticles originated from previously unknown cerium dimer complexes. The nanoparticle growth was highly accelerated under supercritical conditions.     

Combined muta- and semisynthesis: a powerful synthetic hybrid approach to access target specific antitumor agents based on ansamitocin P3

Access of four new tumor specific folic acid/ansamitocin conjugates is reported that relies on a synthetic strategy based on the combination of mutasynthesis and semisynthesis. Two bromo‐ansamitocin derivatives were prepared by mutasynthesis or by a modified fermentation protocol, respectively, that served as starting point for the semisynthetic introduction of an allyl amine linker under Stille conditions. A sequence of standard coupling steps introduced the pteroic acid/glutamic acid/cysteine unit to the modified ansamitocins. All new derivatives, including those that are expected to be generated after internalization of the folic acid/ansamitocin conjugates into the cancer cell and reductive cleavage of the disulfide linkage showed good to strong antiproliferative activity (IC₅₀ <10 nM ) for different cancer cell lines. Finally, the four conjugates were exposed to two cancer cell lines [cervix carcinoma, KB‐3‐1 (FR+) and lung carcinoma, A‐459 (FR?)], the latter devoid of the membrane‐bound folic acid receptor (FR?). All four conjugates showed strong antiproliferative activity for the FR+ cancer cell line but were inactive against the FR? cell line. The synthetic strategy pursued is based on the combination of mutasynthesis and semisynthesis and proved to be powerful for accessing new ansamitocin derivatives that are difficult to prepare by total synthesis.     

A tandem Diels–Alder/Mannich approach to the synthesis of AE and ABE ring analogues of Delphinium alkaloids

The one-pot TiCl₄ catalysed Diels–Alder/Mannich reaction of α-cyanoaminoacrylates with 2-silyloxy-1,4-butadienes gives 6-keto-3-azabicyclo[3.3.1]nonane-1-carboxylates. Reduction of the ketone and alkylation of the resultant alcohol gives 6-alkoxy-3-azabicyclo[3.3.1]nonanes mimicking the AE rings of a number of Delphinium and Aconitum alkaloids, with the same stereochemistry as the natural products.     

Hilbert’s Tenth Problem for function fields of varieties over algebraically closed fields of positive characteristic

Let K be the function field of a variety of dimension ?? 2 over an algebraically closed field of odd characteristic. Then Hilbert??s Tenth Problem for K is undecidable. This generalizes the result by Kim and Roush from 1992 that Hilbert??s Tenth Problem for the purely transcendental function field ${{{\overline{\mathbb{F}}_p}}(t_1,t_2)}$ is undecidable when p?>?2.     

Aqueous Synthesis of Triphenylphosphine-Modified Gold Nanoparticles for Synergistic In Vitro and In Vivo Photothermal Chemotherapy

Triphenylphosphine (TPP) surface-functionalized and F-108 Pluronic-stabilized gold nanoparticles (F-108@TPP-AuNPs) have been synthesized through a one-step approach, leading to well-defined (9.6±1.6 nm) and water-soluble nanoparticles by microwave heating an aqueous solution of TPP-Au^ICl in the presence of a Pluronic polymer under basic conditions. TPP release was negligible under physiological conditions, but enhanced significantly at an acidic pH (5.4) mimicking that of a cancer cell. Laser irradiation (532 nm) raised the temperature of an aqueous solution of F-108@TPP-AuNPs to 51.7 °C within 5 min, confirming efficient light-to-heat conversion capabilities without significant photodegradation. TEM confirmed intracellular localization of F-108@TPP-AuNPs in the cytosol, endosomes and lysosomes of HeLa cells. F-108@TPP-AuNPs were well tolerated by HeLa cells and zebrafish embryos at ambient temperatures and became toxic upon heat activation, suggesting synergistic interactions between heat and cytotoxic action by TPP.