AbstactThe effect of V 2 O 5 addition on molybdates crystallization tendency, glass structure and chemical durability of aluminoborosilicate glass belonging to SiO 2 -B 2 O 3 -CaO-Na 2 O-Al 2 O 3 -MoO 3 system has been studied. The results confirm that V 2 O 5 addition can effectively suppress the crystallization tendency of powellite and enhance the molybdenum solubility in the glass. The MoO 3 solubility limit is found to be 2.8 mol% in the V 2 O 5 -containing aluminoborosilicate glass. Raman results reveal that V 2 O 5 addition seems to modify the local structural environment of isolated MoO 4 units and increase their chemical disorder in the glass, which is favored for molybdenum incorporation in the glass. The molar volume and glass transition temperature of samples are found to depend on V 2 O 5 content. Product consistency test (PCT) results show that the normalized leaching rates of the V 2 O 5 -containing aluminoborosilicate glass maintain at a fairly low level compared with standard borosilicate glassy waste form.
With
recent advances and success in several drugs designed to treat
acute and chronic diseases, targeted covalent inhibitors show a resurgence
in drug discovery. As covalent inhibition is time-dependent, the preferred
quantitative potency metric of irreversible inhibitors is the second-order
rate constant k
inact/K
i, rather than IC50. Here, we present the development
of a mass spectrometry-based platform for rapid kinetic analysis of
irreversible covalent inhibitors. Using a simple liquid handling robot
for automated sample preparation and a solid-phase extraction-based
RapidFire–MS system for rapid MS analysis, kinetic characterization
of covalent inhibitors was performed in high throughput both by intact
protein analysis and targeted multiple reaction monitoring (MRM).
In addition, a bimolecular reaction model was applied to extract k
inact/K
i in data
fitting, providing tremendous flexibility in the experimental design
to characterize covalent inhibitors with various properties. Using
KRASG12C inhibitors as a test case, the platform was demonstrated
to be effective for studying covalent inhibitors with a wide range
of k
inact/K
i values from single digit to 3 × 105 M–1 s–1.
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