Design, synthesis, studies and evaluation of isatin-pyridine oximes hybrids as novel acetylcholinesterase reactivators.

Organophosphorus poisoning caused by some pesticides and nerve agents is a life-threating condition that must be swiftly addressed to avoid casualties. Despite the availability of medical countermeasures, the clinically available compounds lack a broad spectrum, are not effective towards all organophosphorus toxins, and have poor pharmacokinetics properties to allow them crossing the blood-brain barrier, hampering cholinesterase reactivation at the central nervous system. In this work, we designed and synthesised novel isatin derivatives, linked to a pyridinium 4-oxime moiety by an alkyl chain with improved calculated properties, and tested their reactivation potency against paraoxon- and NEMP-inhibited acetylcholinesterase in comparison to the standard antidote pralidoxime.

Quantum mechanical reference spectrum simulation for precursors and degradation products of chemicals relevant to the Chemical Weapons Convention.

A selection of acidic, alkaline and neutral degradation products relevant to the Chemical Weapons Convention was studied in wide range of pH conditions to determine their spin systems as well as spectral parameters. The pH dependence of chemical shifts and J couplings was parameterized using Henderson-Hasselbalch-based functions using dichloromethane as additional shift reference in TSP-d referenced spectra. The resulting parameters allowed calculation of precise chemical shifts and J coupling constants in arbitrary pH conditions.

Biodegradation of Organophosphorus Compounds Predicted by Enzymatic Process Using Molecular Modelling and Observed in Soil Samples Through Analytical Techniques and Microbiological Analysis: A Comparison.

Organophosphorus compounds (OP) are chemicals widely used as pesticides in different applications such as agriculture and public health (vector control), and some of the highly toxic forms have been used as chemical weapons. After application of OPs in an environment, they persist for a period, suffering a degradation process where the biotic factors are considered the most relevant forms. However, to date, the biodegradation of OP compounds is not well understood.