Boronic acids have been extensively applied as versatile building blocks in constructing supramolecular architectures and other advanced materials. The on-surface boronic acid condensation reaction, particularly for forming boroxine-based two-dimensional (2D) networks or nanostructures, is a topic of great scientific interest.^[1,2] Despite its significance, elucidating the chemical dynamics of the on-surface boronic acid condensation reaction remains challenging for conventional analytical tools. In this presentation I will introduce a powerful label-free and non-destructive nanoanalytical technique called tip-enhanced Raman spectroscopy (TERS) and demonstrate its application to directly observe the formation of boroxine-based nanostructures in the 4-mercaptophenylboronic acid (4-MPBA) self-assembled monolayer (SAM) on a Au (111) surface, a study that was recently published in ACS Nano.^[3]

The 4-MPBA SAM forms through robust S-Au bonding between the molecules and the Au (111) substrate. A dehydration coupling reaction within the 4-MPBA adlayer, induced by thermal treatment, leads to molecular rearrangement and unique intermolecular binding on the surface. We systematically examine this dynamic process using hyperspectral TERS imaging, capturing the interplay of molecular dehydration and the reversible nature of the condensation process with remarkable sensitivity (See in  Fig. 1).  The a few nanometers spatial resolution of each pixel, enables the precise acquisition of chemical information from a localized area, facilitating the accurate monitoring of the reversible reaction and the assessment of its homogeneity.

Our experimental insights are complemented by density functional theory (DFT) modeling, which verifies the progression to boroxine ring formation and rules out alternative open-ring configurations, providing molecular-level understanding of the reaction mechanism. This study not only offers the first direct chemical imaging of boroxine nanostructures but also underscores the indispensable role of TERS in elucidating on-surface coupling reactions with exceptional sensitivity and resolution. Our findings demonstrate that label-free, non-destructive nanoanalysis via hyperspectral TERS imaging can facilitate a rational approach to on-surface architectural synthesis, thereby advancing the frontiers of surface science.

Fig. 1. Average spectra from hyperspectral TERS images illustrating the chemical evolution of the 4-MPBA adlayer on Au (111) through stages of dehydration and hydrolysis. TERS image step size: 50 nm.

[1] X. Li, Y. Zhang, Z. Shi et al., Nature Communications, 2024, 15, 1207

[2] G. Zhan, Z. F. Cai, K. Strutyński et al., Nature, 2022, 603, 835–840

[3] Y. Xia, K. Greis, C. Xu, N. Kumar, R. Zenobi, ACS nano, 2025, 19, 6511- 6519