Low-temperature scanning tunneling microscopy (STM) is used to investigate the self-assembly behavior of small organic molecules on metal surfaces at ultra-high vacuum conditions. Additionally, the self-assembly behavior of molecules in rapidly evaporating solutions is investigated via electrospray ionization mass spectrometry (ESI–MS). This work is a systematic investigation of indole-derivative molecules in which the hydrogen-bond contacts are probed to observe how two-dimensional selfassembled morphologies change as a result of small changes to the chemical structure. Non-equilibrium methods of sample preparation are exploited in order to prepare complex assemblies that are otherwise not observed near equilibrium. Metastable cyclic pentamers are a common structural motif which are stabilized by secondary weak CH...O hydrogen bonds. It is observed in some cases that there are unusually intense oligomer peaks in the mass spectra, which correspond to enhanced stability of these oligomers as gas-phase ions. DFT calculations are done to study the energetics and calculate optimized geometries of these small-molecule oligomers. In addition, an active pharmaceutical is studied via STM and ESI–MS. Ordered, long-range packing of tetramers are observed on the gold surface and the mass spectrum exhibits a relatively intense tetramer peak; tetramers are not a motif that is present in any of the solid-state crystal polymorphs of carbamazepine. This work may shed light on the early stages of crystallization in which self-assembled structures form from evaporating droplets. In addition, these findings may contribute to the fundamental understanding between molecular structure and supramolecular structure, a question of interest in the fields of crystal engineering and supramolecular chemistry.