7 research outputs found
Polysaccharide-Thickened Aqueous Fluoride Solutions for Rapid Destruction of the Nerve Agent VX. Introducing the Opportunity for Extensive Decontamination Scenarios
Among the chemical warfare agents,
the extremely toxic nerve agent
VX (<i>O</i>-ethyl <i>S</i>-2-(diisopropylamino)Âethyl
methylphosphonothioate) is a target of high importance in the development
of decontamination methods, due to its indefinite persistence on common
environmental surfaces. Liquid decontaminants are mostly characterized
by high corrosivity, usually offer poor coverage, and tend to flow
and accumulate in low areas. Therefore, the development of a noncorrosive
decontaminant, sufficiently viscous to resist dripping from the contaminated
surface, is necessary. In the present paper we studied different polysaccharides-thickened
fluoride aqueous solutions as noncorrosive decontaminants for rapid
and efficient VX degradation to the nontoxic product EMPA (ethyl methylphosphonic
acid). Polysaccharides are environmentally benign, natural, and inexpensive.
Other known decontaminants cannot be thickened by polysaccharides,
due to the sensitivity of the latter toward basic or oxidizing agents.
We found that the efficiency of VX degradation in these viscous solutions
in terms of kinetics and product identity is similar to that of KF
aqueous solutions. Guar gum (1.5 wt %) with 4 wt % KF was chosen for
further evaluation. The benign nature, rheological properties, adhering
capabilities to different surfaces, and decontamination from a porous
matrix were examined. This formulation showed promising properties
for implementation as a spray decontaminant for common and sensitive
environmental surfaces
Component Mobility by a Minute Quantity of the Appropriate Solvent as a Principal Motif in the Acceleration of Solid-Supported Reactions
The
effects solvents have on fluoride-promoted heterogeneous hydrolysis
and alcoholysis of various organo-phosphorus (OP) compounds on the
surface of KF/Al<sub>2</sub>O<sub>3</sub> are described. Solid-state
magic angle spinning NMR analyses and SEM microscopy have shown that
not only is the identity of the solvent important in these reactions
but also its quantity. That is, minimal solvent amounts are favored
and much more effective in such solid-supported reactions (and maybe
generally) than those featuring solvent-free or excess solvent (>50
wt %) conditions. The addition of a minute quantity of the correct
solvent (3â10 wt %, molar equivalent scale) avoids reagents
leaching from the matrix, permits mobility (mass transport) of the
reaction components and ensures their very high local concentration
in close proximity to the solid-support large porous surface area.
Accordingly, significant acceleration of reactions rates by orders
of magnitude is obtained. Fascinatingly, even challenging phosphoesters
with poor leaving groups, which were found to be very stable in the
presence of solvent-free KF/Al<sub>2</sub>O<sub>3</sub> or wetted
with excess water, were efficiently hydrolyzed with a minute amount
of this solvent
Difluoromethyl Bioisostere: Examining the âLipophilic Hydrogen Bond Donorâ Concept
There
is a growing interest in organic compounds containing the
difluoromethyl group, as it is considered a lipophilic hydrogen bond
donor that may act as a bioisostere of hydroxyl, thiol, or amine groups.
A series of difluoromethyl anisoles and thioanisoles was prepared
and their druglike properties, hydrogen bonding, and lipophilicity
were studied. The hydrogen bond acidity parameters <i>A</i> (0.085â0.126) were determined using Abrahamâs solute <sup>1</sup>H NMR analysis. It was found that the difluoromethyl group
acts as a hydrogen bond donor on a scale similar to that of thiophenol,
aniline, and amine groups but not as that of hydroxyl. Although difluoromethyl
is considered a lipophilicity enhancing group, the range of the experimental
Îlog <i>P</i>(waterâoctanol) values (log <i>P</i>(XCF<sub>2</sub>H) â log <i>P</i>(XCH<sub>3</sub>)) spanned from â0.1 to +0.4. For both parameters,
a linear correlation was found between the measured values and Hammett
Ï constants. These results may aid in the rational design of
drugs containing the difluoromethyl moiety
Species-specific lipophilicities of fluorinated diketones in complex equilibria systems and their potential as multifaceted reversible covalent warheads
Abstract Combined molecular, physicochemical and chemical properties of electrophilic warheads can be applied to create covalent drugs with diverse facets. Here we study these properties in fluorinated diketones (FDKs) and their multicomponent equilibrium systems in the presence of protic nucleophiles, revealing the potential of the CF2(CO)2 group to act as a multifaceted warhead for reversible covalent drugs. The equilibria compositions of various FDKs in water/octanol contain up to nine species. A simultaneous direct species-specific 19F-NMR-based log P determination of these complex equilibria systems was achieved and revealed in some cases lipophilic to hydrophilic shifts, indicating possible adaptation to different environments. This was also demonstrated in 19F-MAS-NMR-based water-membrane partitioning measurements. An interpretation of the results is suggested by the aid of a DFT study and 19F-DOSY-NMR spectroscopy. In dilute solutions, a model FDK reacted with protected cysteine to form two hemi-thioketal regioisomers, indicating possible flexible regio-reactivity of CF2(CO)2 warheads toward cysteine residues