Giving Gold Wings: Ultrabright and Fragmentation Free Mass Spectrometry Reporters for Barcoding, Bioconjugation Monitoring, and Data Storage

Abstract

The widespread application of laser desorption/ionization mass spectrometry (LDI‐MS) highlights the need for a bright and multiplexable labeling platform. While ligand‐capped Au nanoparticles (AuNPs) have emerged as a promising LDI‐MS contrast agent, the predominant thiol ligands suffer from low ion yields and extensive fragmentation. In this work, we develop a N‐heterocyclic carbene (NHC) ligand platform that enhances AuNP LDI‐MS performance. NHC scaffolds are tuned to generate barcoded AuNPs which, when benchmarked against thiol‐AuNPs, are bright mass tags and form unfragmented ions in high yield. To illustrate the transformative potential of NHC ligands, the mass tags were employed in three orthogonal applications: monitoring a bioconjugation reaction, performing multiplexed imaging, and storing and reading encoded information. These results demonstrate that NHC‐nanoparticle systems are an ideal platform for LDI‐MS and greatly broaden the scope of nanoparticle contrast agents.

Reactivity variance between stereoisomers of saturated N-heterocyclic carbenes on gold surfaces

“…LDI-MS is a highly efficient method for detecting NHCs on gold and for tracking subsequent chemical reactions. 51–53 The reason that this approach is so successful is that the NHCs do not fragment like thiols, and each gold ion binds two NHCs to form a cationic bis(NHC)gold( i ) complex. 51 LDI-MS analysis was carried for 6 , 7 , and 8 on gold mirror.…”

Seeking a Au–C stretch on gold nanoparticles with 13C-labeled N-heterocyclic carbenes

“…5 Advances in these applications are accelerating due to development of N-heterocyclic carbenes as an innovative surface passivation substrate for gold surfaces. [6][7][8][9][10] NHCs feature enhanced stability under a variety of thermal, chemical, and biological conditions compared to traditional surface ligands like thiols. 11,12 Given the myriad uses of NHC-functionalized gold nanoparticles, a fast and efficient method to determine chemisorption of the NHC to the AuNP is of paramount importance.To date, the primary method to determine chemisorption of NHCs to AuNPs is X-ray photoelectron spectroscopy (XPS).…”

“…19 Surface enhanced Raman spectroscopy of NHC-functionalized gold nanoparticles has rapidly developed since the discovery that gold complexes can be employed to append the NHCs to the AuNPs. 6,16,[20][21][22][23] Indeed, SERS measurements of NHCs on AuNPs have tracked post-synthetic modification on the nanoparticle surface 20 as well as monitoring ligand degradation in biological media. 21 Yet, despite the proven utility of SERS for characterizing NHCs on AuNPs, no SERS study of the Au-C bond for NHCs on AuNPs has been conducted.…”

“…Synthesis of the 13 C-labelled benzimidazole (1-1) and benzimidazolium salt (1-H)(I) proceeded via modified literature methods from commercially available 13 C-formyl labelled triethyl orthoformate in two steps (Scheme 1). 25 Synthesis of the gold complex (1-AuCl) is challenging, as a typical base used for these reactions, 6,20,23 potassium hexamethyldisilazane, generated an undesirable side product containing hexamethyldisilazane that could not be separated from the gold complex. Screening of alternative bases led to selection of potassium tertbutoxide, which, while slower to deprotonate (1-H)(I), cleanly generates the free carbene in THF at room temperature over two days.…”