The formation of HGCs with the gold-bound 1 was investigated using TERS, and DFT calculations were performed to gain a better understanding of this system. The optimization of 1 on an Au(111) slab (more details in Methods and SI) revealed the expected binding of the host via all seven thiol groups, despite the mismatch in symmetry with the gold substrate (Figure ), and is consistent with the complete loss of the ν(S-H) band in the TER spectra of 1 on Au (see Figure ). Formation of the HGCs was first computed at the DFT level of theory for all guests in the gas phase (more details in SI and Figures S5, S6 and S7), which gave binding energies between 1 host and the guests of -2.03 eV (guest 4) and -2.17 eV (guests 2 and 3). On the Au(111) surface, the binding energies between guests and surface-bound 1 were found to be between -4.31 eV and -4.89 eV, which reveals a dramatic increase in adsorption energy into the cyclodextrin cavity. This large increase in the adsorption energy is related to delocalization of electronic states of the guest molecules and the gold substrate (see Figure and S9), which is evidenced by significant mixing of gold and guest orbitals. The strong interactions and delocalization of electronic states indicate that oxidation or reduction of electroactive guests (2 and 3) can be easily achieved.