PQ probes with N-methylated triggers proved to have low solubility and irreproducible results above 25 µM in aqueous buffer with 1% DMSO. To address the challenge of the flat hydrophobic PQ without switching cargos, we used a basic N-methylpiperazinamide and a neutral morpholinamide as solubilising N-alkyl sidechains, to minimally crowd the redox-active site while being tracelessly removed upon cyclisation (Fig. ). The reproducibility of the resulting probes was greatly improved by their solubility, so we denoted the sidechains as 1 (piperazinamide, preferred; reliable to >250 µM), 2 (morpholinamide), or 3 (methyl).