Detection of degradation products of chemical warfare agents by highly porous molecularly imprinted microspheres.

The multiplication of terrorist actions in the recent events is alarming and the detection of chemical warfare agents (CWAs) has become one of the highest research priorities in the fields of security and public health. The biomimetic properties of molecularly imprinted polymers (MIPs) render them attractive for molecular recognition as well as sensing purposes. The degradation products of easily hydrolysable organophosphorus nerve agents such as pinacolyl methylphosphonate (PMP), a hydrolysis by-product of soman, are often used as templates in MIP synthesis. In this study, we describe the first example of PMP-imprinted polymer microspheres synthesized by precipitation polymerization. This one-step process involves methacrylic acid (MAA) as the monomer and divinylbenzene (DVB) as the cross-linker, in a toluene/acetonitrile mixture. Subsequent morphological characterizations of the PMP-imprinted particles show that they have diameters between 1 and 10 mum (as opposed to 4-5 mum for the non-imprinted microspheres), surface areas of up to 680 m(2) g(-1) and high porosities with pore sizes smaller than 2 nm. The present investigation also evidences the imprinting effect via batch binding experiments and reports on the use of a novel fluorescence-based methodology, where 4-methylumbelliferone (4MU) is utilised as a sensing agent to determine the PMP concentration in solution.

Ability of carbazole salts, inhibitors of Alzheimer beta-amyloid fibril formation, to cross cellular membranes.

Alzheimer's disease is characterized by the presence of beta-amyloid fibril formation. The inhibition of this peptide accumulation may be a prevention method for Alzheimer's disease. Several classes of molecules have been reported to inhibit beta-amyloid fibril formation and among them carbazoles. However, very few studies have been performed to determine the destination of such molecules in vivo and especially if they can pass the blood brain barrier. The aim of this paper is to study whether carbazoles could pass the blood brain barrier, i.e. if they can circumvent ATP Binding Cassette (ABC) transporters such as P-glycoprotein (P-gp) and Multidrug Resistance-associated protein (MRP1) which efficiently limit drug brain uptake. For this purpose we have synthesized a fluorescent derivative of carbazole benzothiazolium iodide 1,2 disubstituted ethylene (referred as carbazole thiazole: CT), which can be easily detected and followed in the pre-trial study phases in cells or in tissue. We use cellular models overexpressing P-gp and MRP1. Our results show that: i) CT is able to cross membranes and to penetrate rapidly inside the cells, ii) CT is a P-gp substrate and consequently its accumulation in P-gp overexpressing cells is very low, iii) CT is a poor MRP1 substrate. In addition once inside the cells, CT rapidly binds to DNA and is then slowly reduced by intracellular reducing agents. In conclusion, the efficiency of carbazole derivatives in inhibiting the beta-amyloid formation in vivo could be highly compromised because, as P-gp substrates, they will probably not cross the blood brain barrier.