The chemically diverse scaffolds in our library are likely to impact both active site binding affinity, as well as intrinsic reactivity of the chloroacetamide warhead. To account for changes in intrinsic reactivity, we measured the rate at which each chloroacetamide reacted with TNB 2-, a reduced form of Ellman's reagent (5,5-dithio-bis-2-nitrobenzoic acid, DTNB) using a previously reported colorimetric assay. The compounds in our library showed a wide range of reactivities, from compounds with no discernable reaction to rates around 1 M -1 s -1 (Figure and Table ). We also selected a few compounds spanning the reactivity spectrum and measured their rates of reaction with reduced glutathione (GSH), as GSH is commonly used as a biologically-relevant model thiol for reactivity studies (Figure ). The relative reactivities of these compounds showed good agreement between GSH and TNB 2-(Figure ). Juxtaposition of enzyme inhibition data from the pNPP dephosphorylation assay with thiol reactivity from the DTNB assay demonstrated that there was no significant correlation between reactivity towards PTPs and intrinsic thiol reactivity (Figure and Figure ). Thus, we reasoned that we could identify covalent fragments that inhibit PTPs without having excessive intrinsic reactivity that could undermine the downstream development of a drug molecule or chemoproteomic probe. The chloroacetamide fragment survey revealed a series of informative general trends, both with respect to the enzymes and the scaffold structures. As seen in our warhead survey, we observed substantially different degrees of inhibition of each phosphatase that was roughly inversely correlated with intrinsic catalytic activity (Figure ). On average across the library, HePTP and SHP1 were inactivated at a faster rate than other phosphatases, and both CD45 and CD148 were hard to inhibit. Notably, we observed unexpected correlations between the inhibition profiles of different phosphatase pairs (Figure ). PTP1B and SHP2 displayed the highest correlation, which was surprising, given the close sequence and structural homology between PTP1B and TCPTP and between SHP2 and SHP1. More nuanced enzyme-differentiating trends are discussed in the subsequent sections.