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1.
J Gen Virol ; 102(4)2021 04.
Article in English | MEDLINE | ID: mdl-33891534

ABSTRACT

A small-scale study with Mosi-guard Natural spray, an insect repellent containing Citriodiol, was performed to determine if it has virucidal activity against SARS-CoV-2. A liquid test examined the activity of the insect repellent and the individual components for virucidal activity. A surface contact test looked at the activity of the insect repellent when impregnated on a latex surface as a synthetic skin for potential topical prophylactic application. Both Mosi-guard Natural spray and Citriodiol, as well as other components of the repellent, had virucidal activity in the liquid contact test. On a latex surface used to simulate treated skin, the titre of SARS-CoV-2 was less over time on the Mosi-guard Natural-treated surface but virus was still recovered.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Insect Repellents/therapeutic use , SARS-CoV-2/drug effects , Humans , Plant Extracts/therapeutic use
2.
Dalton Trans ; 47(8): 2568-2574, 2018 Feb 20.
Article in English | MEDLINE | ID: mdl-29384545

ABSTRACT

The cooperative effect of both NHC and metal centre has been found to destroy chemical warfare agent (CWA) simulants. Choice of both the metal and NHC is key to these transformations as simple, monodentate N-heterocyclic carbenes in combination with silver or vanadium can promote stoichiometric destruction, whilst bidentate, aryloxide-tethered NHC complexes of silver and alkali metals promote breakdown under mild heating. Iron-NHC complexes generated in situ are competent catalysts for the destruction of each of the three targetted CWA simulants.

3.
J Am Chem Soc ; 131(28): 9746-55, 2009 Jul 22.
Article in English | MEDLINE | ID: mdl-19555102

ABSTRACT

The rates of catalytic oxidative decontamination of the chemical warfare agent (CWA) sulfur mustard (HD, bis(2-chlororethyl) sulfide) and a range (chloroethyl) sulfide simulants of variable lipophilicity have been examined using a hydrogen peroxide-based microemulsion system. SANS (small-angle neutron scattering), SAXS (small-angle X-ray scattering), PGSE-NMR (pulsed-gradient spin-echo NMR), fluorescence quenching, and electrospray mass spectroscopy (ESI-MS) were implemented to examine the distribution of HD, its simulants, and their oxidation/hydrolysis products in a model oil-in-water microemulsion. These measurements not only present a means of interpreting decontamination rates but also a rationale for the design of oxidation catalysts for these toxic materials. Here we show that by localizing manganese-Schiff base catalysts at the oil droplet-water interface or within the droplet core, a range of (chloroethyl) sulfides, including HD, spanning some 7 orders of octanol-water partition coefficient (K(ow)), may be oxidized with equal efficacy using dilute (5 wt. % of aqueous phase) hydrogen peroxide as a noncorrosive, environmentally benign oxidant (e.g., t(1/2) (HD) approximately 18 s, (2-chloroethyl phenyl sulfide, C(6)H(5)SCH(2)CH(2)Cl) approximately 15 s, (thiodiglycol, S(CH(2)CH(2)OH)(2)) approximately 19 s {20 degrees C}). Our observations demonstrate that by programming catalyst lipophilicity to colocalize catalyst and substrate, the inherent compartmentalization of the microemulsion can be exploited to achieve enhanced rates of reaction or to exert control over product selectivity. A combination of SANS, ESI-MS and fluorescence quenching measurements indicate that the enhanced catalytic activity is due to the locus of the catalyst and not a result of partial hydrolysis of the substrate.


Subject(s)
Chemical Warfare Agents/chemistry , Decontamination/methods , Mustard Gas/chemistry , Catalysis , Chemical Warfare Agents/isolation & purification , Emulsions , Kinetics , Magnetic Resonance Spectroscopy , Mustard Gas/isolation & purification , Neutron Diffraction , Oils/chemistry , Oxidation-Reduction , Scattering, Small Angle , Solubility , Surface Properties , Water/chemistry
4.
J Med Chem ; 49(1): 246-55, 2006 Jan 12.
Article in English | MEDLINE | ID: mdl-16392809

ABSTRACT

Enzymes that efficiently hydrolyze highly toxic organophosphorus nerve agents could potentially be used as medical countermeasures. As sufficiently active enzymes are currently unknown, we synthesized twelve fluorogenic analogues of organophosphorus nerve agents with the 3-chloro-7-oxy-4-methylcoumarin leaving group as probes for high-throughput enzyme screening. This set included analogues of the pesticides paraoxon, parathion, and dimefox, and the nerve agents DFP, tabun, sarin, cyclosarin, soman, VX, and Russian-VX. Data from inhibition of acetylcholinesterase, in vivo toxicity tests of a representative analogue (cyclosarin), and kinetic studies with phosphotriesterase (PTE) from Pseudomonas diminuta, and a mammalian serum paraoxonase (PON1), confirmed that the analogues mimic the parent nerve agents effectively. They are suitable tools for high-throughput screens for the directed evolution of efficient nerve agent organophosphatases.


Subject(s)
Acetylcholinesterase/drug effects , Chemical Warfare Agents/chemistry , Cholinesterase Inhibitors/chemistry , Fluorescent Dyes/chemistry , Organophosphorus Compounds/chemistry , Organothiophosphorus Compounds/toxicity , Phosphoric Triester Hydrolases/chemistry , Animals , Aryldialkylphosphatase/chemistry , Chemical Warfare Agents/toxicity , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/toxicity , Coumarins/chemistry , Drug Evaluation, Preclinical/methods , Guinea Pigs , Hydrolysis , Kinetics , Male , Molecular Structure , Organophosphorus Compounds/chemical synthesis , Organophosphorus Compounds/toxicity , Organothiophosphorus Compounds/chemistry , Pesticides/chemistry , Structure-Activity Relationship
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