A new paclitaxel prodrug for use in ADEPT strategy

A new paclitaxel prodrug intended for use in Antibody-Directed Prodrug Therapy (ADEPT) or Prodrug Monotherapy (PMT) has been prepared. This prodrug was originally designed to be activated into the drug by human beta-glucuronidase. In order to enhance the liberation rate of paclitaxel, an elongated spacer system including a nitro-aromatic derivative and a N,N'-methylethylenediamine was incorporated between the sugar moiety and the drug. Indeed, this new prodrug proved to be activated significantly faster than a former paclitaxel prodrug containing a conventional spacer.     

Determination of unreacted 2,4-toluene diisocyanate (2,4TDI) and 2,6-toluene diisocyanate (2,6TDI) in foams at ultratrace level by using HPLC-CIS-MS-MS

Isocyanates can cause occupational asthma. By using available HPLC-UVF methods, isocyanates can be quantified only at levels above 1% of the Permissible Exposure Limits (PEL). Once sensitized, workers can react to concentrations below these limits of detection (LOD) making these methods insufficiently sensitive to adequately evaluate trace amounts of isocyanates present in air or in materials at safe levels for sensitized workers. This article describes a novel method for isocyanate analysis allowing the quantification of 2,4TDI and 2,6TDI monomers at very low concentrations using HPLC-CIS-MS-MS. The method's sensitivity increases with a decrease in the alkali radius. The LOD is 0.039 ng mL(-1) for 2,4TDI and 0.100 ng mL(-1) for 2,6TDI in solution when lithium is the alkali adduct, which is 20 times more sensitive than HPLC-UVF method. This new method allows determination in foam at levels of 0.078 ng g(-1) for 2,4TDI and 0.200 ng g(-1) for 2,6TDI respectively, for a 0.5 g foam sample. This is more than 100 times more sensitive than other methods for determining free monomers in solid materials. Analytical reproducibility and precision are better than 92% and 93% for both diisocyanate monomers. The use of HPLC-UVF conventional method failed to detect unreacted isocyanates in foam samples, but TDI monomers were quantified by HPLC-CIS-MS-MS.     

A rare earth-DOTA-binding antibody: probe properties and binding affinity across the lanthanide series

An antibody that binds rare earth complexes selectively could be used as a docking station for a set of probe molecules, of particular interest for medical imaging and therapy. The rare earths are rich in probe properties, such as the paramagnetism of Gd, the luminescence of Tb and Eu, and the nuclear properties of Lu and Y. We find that antibody 2D12.5, initially developed to bind analogues of Y-DOTA (1,4,7,10-tetraazacyclododecane-N,N',N' ',N' '-tetraacetic acid) for radiotherapy, binds not only Y-DOTA analogues but also analogous DOTA complexes of all of the lanthanides. Surprisingly, chelates of some metals such as Gd3+ bind more tightly than the original Y3+ complex. When the shape of the complex is perturbed by either increasing or decreasing the radius of the lanthanide ion, the thermodynamic stability of the protein-ligand complex changes in a regular fashion. The behavior of DeltaDeltaG as a function of ionic radius fits a parabola, as might be expected for a system that behaves in a thermodynamically elastic way. The broad specificity and high affinity of this antibody for all rare earth-DOTA complexes make it particularly interesting for applications that take advantage of the unique characteristics of lanthanides. For example, UV excitation of the Tb-DOTA-2D12.5 complex leads to energy transfer from aromatic side chains of the antibody to bound Tb-DOTA, enhancing green terbium luminescence >104 relative to unbound Tb-DOTA.     

A multi-component reaction (MCR) approach to the synthesis of highly diverse polymers with polypeptide-like features

A new strategy for the combinatorial synthesis of new materials has been developed through the consecutive application of an Ugi 4CC reaction and a ring-opening metathesis polymerization (ROMP) reaction. Norbornenyl aldehydes and carboxylic acids could be used in the Ugi MCR to give highly diverse monomers that were converted to the corresponding polymers by exposure to the second-generation Grubbs' catalyst. These polymers have structural features reminiscent of polypeptides and the process could be extended to the preparation of chiral materials.     

Dwork cohomology and algebraic ${\Cal D}$-modules

Using local cohomology and algebraic -Modules, we generalize a comparison theorem between relative de Rham cohomology and Dwork cohomology due to N. Katz, P. Monsky, A. Adolphson and S. Sperber. Received June 10, 1999 / Published online July 20, 2000     

Parametric generation of twin photons in vertical triple microcavities

We report the realization of a monolithic vertical-cavity, surface emitting micro-optical parametric conversion nanostructure, triply resonant with the parametric frequencies, allowing parametric oscillation with ultra-low pump power threshold. The photonic phase-space naturally provides triple resonance for the parametric frequencies, together with built-in cavity phase-matching for the pump wave at normal incidence. Parametric oscillation is observed in both the strong and weak exciton–photon coupling regime, allowing a high operating temperature. Signal and idler beams can be collected at 0° or at finite angles. The OPO threshold is low enough to envisage the realization of an all-semiconductor electrically-pumped micro-parametric oscillator. To cite this article: C. Diederichs et al., C. R. Physique 8 (2007).     

Porous 3-D honeycomb architecture by self-assembly of helical H-bonded molecular tapes

Enantiopure dipeptide-derived 1,3,5-triazepan-2,6-diones and form H-bonded 3(1) helical molecular tapes with P chirality in the solid state; in the case of , these columnar tapes self-assemble through aromatic-aromatic interactions to give hollow tubular structures.