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Gold (Au) nanoparticles (NPs) are widely used in nanomedical applications as a carrier for molecules designed for different functionalities. Previous findings suggested that biological molecules, including amino acids, could contribute to the dissolution of Au NPs in physiological environments and that this phenomenon was size-dependent. We, therefore, investigated the interactions of L-cysteine with 5-nm Au NPs by means of time-of-flight secondary ion mass spectrometry (ToF-SIMS). This was achieved by loading Au NPs on a clean aluminum (Al) foil and immersing it in an aqueous solution containing L-cysteine. Upon rinsing off the excessive cysteine molecules, ToF-SIMS confirmed the formation of gold cysteine thiolate via the detection of not only the Au–S bond but also the hydrogenated gold cysteine thiolate molecular ion. The presence of NaCl or a 2-(N-morpholino)ethanesulfonic acid buffer disabled the detection of Au NPs on the Al foil. The detection of larger (50-nm) Au NPs was possible but resulted in weaker cysteine and gold signals, and no detected gold cysteine thiolate signals. Nano-gold specific adsorption of L-cysteine was also demonstrated by cyclic voltammetry using paraffine-impregnated graphite electrodes with deposited Au NPs. We demonstrate that the superior chemical selectivity and surface sensitivity of ToF-SIMS, via detection of elemental and molecular species, provide a unique ability to identify the adsorption of cysteine and formation of gold–cysteine bonds on Au NPs.


The authors thank the Swedish Research Council (Grant No. 2019-03657), the Swedish Foundation for Strategic Research (Grant No. FFL18-0173), the Swedish Steel Association Jernkontoret (Grant No. Stiftelsen Skandinaviska Malm 6-2020), the Canada Research Chairs Program (Grant No. 950–233099), the European Union Program MOST (Grant No. R-QSUa-65035), and the Ministry of Science and Higher Education of the Russian Federation in the Framework of Increase Competitiveness Program of NUST “MISiS” (Grant No. K2-2020-024) for financial support.


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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Citation of this paper:

Heng-Yong Nie, Elena Romanovskaia, Valentin Romanovski, Jonas Hedberg, and Yolanda S. Hedberg

, "Detection of gold cysteine thiolate complexes on gold nanoparticles with time-of-flight secondary ion mass spectrometry" , Biointerphases 16, 021005 (2021)

supplementary_information.pdf (790 kB)
Detection of gold cysteine thiolate complexes -figures

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