In situ derivatization of Au nanoclusters via aurophilic interactions of a triphenylphosphine gold(i) salt with neurotransmitters and their rapid MALDI-TOF-MS detection in mice brain tissue extracts

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has attracted much attention for the detection of small molecules such as neurotransmitters due to its softness, high sensitivity, extensive compatibility and diverse mass analyzers. However, it has been really a difficult challenge to develop a highly specific organic compound as a matrix for the rapid, sensitive and selective detection of neurotransmitters. Herein, we report tris(triphenylphosphine)gold oxonium tetrafluoroborate ([Ph₃PAu]₃O⁺BF₄^-) for the first time as an efficient matrix for the rapid and simultaneous MALDI-MS detection of neurotransmitters. [Ph₃PAu]₃O⁺BF₄^- facilitates the in situ derivatization of gold nanoclusters (Au NCLs) during the interaction with neurotransmitters, which increases their ionization energy by absorbing more ultra-violet (UV) radiation during MALDI-TOF-MS detection. The results show that this [Ph₃PAu]₃O⁺BF₄^- matrix can exhibit a 10-fold faster response time compared to previously reported pyrylium matrices. In addition, [Ph₃PAu]₃O⁺BF₄^- can also provide the simultaneous derivatization of various neurotransmitters, including dopamine (DA), noradrenaline (NAd), serotonin (5-HT), γ-aminobutyric acid (GABA), histamine (H) and tyramine (TY), in mice brain tissue extracts, which can be detected in the MALDI-TOF-MS spectra.