Reaction of chloroauric acid with histidine in microdroplets yields a catalytic Au–(His)2 complex

Abstract

An aqueous solution containing histidine (His, 100 μM) and chloroauric acid (HAuCl₄, 10 μM) is electrosprayed (−4.5 kV) from a capillary (50 μm in diameter) with N₂ nebulizing gas (120 psi). The resulting microdroplets entered a mass spectrometer with a 2 cm flight path. The mass spectrum recorded in negative ion mode showed several peaks including the Au₅ nanocluster with the major one being [Au + 2His–2H]⁻, which is a catalytically active species. The reaction time was less 1 ms, and the yield of [Au + 2His–2H]⁻ was 76%. In contrast, the bulk reaction for the same concentration run at room temperature for 2 h did not produce this species but instead formed Au₁₀ nanocluster. When a solution of water and acetonitrile (1 : 1) containing indoline (100 mM) and the phenylacetylene (200 mM) as well as histidine and chloroauric acid at the same concentrations as above was electrosprayed, the mass spectrum showed the formation of the intermediate [Au + 2His + phenylacetylene + H]⁺. Upon collecting the microdroplets, the 4-methyl-4,6-diphenyl-1,2-dihydro-4H-pyrrolo[3,2,1-ij] quinolone product was observed by ¹H nuclear magnetic resonance and liquid chromatography with a yield of 44%. The microdroplet synthesis using the Au–(His)₂ complex as a catalyst was scaled up using room-temperature ultrasonic nebulization to produce the product at the rate of 35 mg min⁻¹, which is semi-preparative and demonstrates the promise of using microdroplet reactions for chemical synthesis.