Improvement of the rates associated to each loop of the cross-catalysis reaction is a strategy to shorten the analysis time and to potentially enhance the detection limit by better discriminating the specific from nonspecific responses. In the present case, the background amplification stems from the instability associated to Loop 2 (i.e., from NADH autoxidation or NADH-oxidase like activity of diaphorase) since the double masking of the probe makes it so stable that no nonspecific response can arise from Loop 1. It is therefore particularly relevant to find a strategy that aims at improving the global rate of Loop 2. To do so, a relatively straightforward method is to substitute the masked 1,4-NQH2 in P3 by an alternative faster redox cycling naphthohydroquinone. A series of different naphthoquinones were thus screened for their redox cycling properties and then compared to the 1,4-NQ (see SI and Figure for details). From this screening, three naphthoquinones were identified as a better redox cycler than the 1,4-NQ, i.e. the 2-amino-3-chloro-1,4-NQ, 1,2-NQ and 2-methoxy-1,4-NQ. The chemical stability of these three naphthoquinones in an aqueous buffered solution was also examined and the most stable was the 2-methoxy-1,4-NQ, showing almost no change in the absorbance spectra after several hours in a Tris buffer (graph C in Figure ). The chemical synthesis of the corresponding diboronic probe P4 was thus planned and successfully achieved (Scheme 1C). The long-term stability of a diluted solution of P4 was shown to be quite good (Figure and 2D), demonstrating a chemical stability of P4 at least as good as P3. Concerning the H2O2-mediated deprotection of P4 (Figure ), it was found a little slower than P3 (by a factor 6). We attribute this slower rate to the methoxy group in ortho position, which by steric effect can slow-down the nucleophilic attack of HO2 -.