The existence of single-molecule surface-enhanced Raman spectroscopy (SMSERS) is proven by employing a frequency-domain approach. This is demonstrated using two isotopologues of Rhodamine 6G that offer unique vibrational signatures. When an average of one molecule was adsorbed per silver nanoparticle, only one isotopologue was typically observed under dry N2 environment. Additionally, the distribution of vibrational frequencies hidden under the ensemble average is revealed by examining the single-molecule spectra. Correlation with transmission electron microscopy reveals that SMSERS active aggregates are composed of multiple randomly sized and shaped nanoparticles. At higher coverage and in a humid environment, adsorbate interchange was detected. Using 2D cross correlation, vibrational modes from different isotopologues were anti-correlated, indicating that the dynamic behavior was from multiple molecules competing for a single hot spot. This allows hot-spot diffusion to be directly observed without analyzing the peak intensity fluctuations.

The synthesis, characterization, and oxidation reaction of a tropospherically relevant terpene bound to a glass surface are reported. Vibrational broadband sum frequency generation (SFG) is used to characterize the various terpene-modified glass surfaces and track their interaction with ozone. SFG spectra indicate that, although orientations of the surface-bound terpenes depend on the linker strategies employed, the CdC double bond is accessible to gas-phase ozone regardless of the strategy applied. Exposure of the terpene-functionalized surface to ppm levels of ozone at 1 atm and 300 K yields an initial reaction probability of approximately 1 × 10 -5 per surface collision, which is significantly higher than the corresponding gas-phase reaction involving 1-methyl-1-cyclohexene (5 × 10 -7 from gas-phase collision theory). The interaction of ozone with a saturated octyl silane-functionalized glass surface leads to a slight molecular reorientation, or tilting, of the terminal CH 3 groups on a much slower time scale. Our work demonstrates that SFG spectroscopy can be used to determine reaction probabilities of heterogeneous atmospheric reactions and bridges the gap between atmospheric chemistry and surface functionalization.

Embryonic signaling pathways, in particular those mediated by Wnt and TGF-b, are known to play key roles in tumor progression through the induction of epithelial-mesenchymal transition (EMT). Their simultaneous targeting could therefore represent a desirable anticancer strategy. On the basis of recent findings that both Wnt and TGF-b-associated pathways are regulated by Hippo signaling in mammalian cells, we reasoned that targeting the latter would be more effective in inhibiting EMT. In a search for such inhibitors, we identified a small molecule (C19) with remarkable inhibitory activity not only against Hippo, but also against Wnt and TGF-b pathways. C19 inhibited cancer cell migration, proliferation, and resistance to doxorubicin in vitro, and exerted strong antitumor activity in a mouse tumor model. Mechanistically, C19 induced GSK3-b-mediated degradation of the Hippo transducer TAZ, through activation of the Hippo kinases Mst/Lats and the tumor suppressor kinase AMPK upstream of the degradation complex. Overall, this study identified C19 as a multi-EMT pathway inhibitor with a unique mechanism of action. The findings that both AMPK and Mst/Lats mediate the antitumor activity of C19 shed light on a potential cross-talk between metabolic and organ size control pathways in regulating cancer progression. By simultaneously targeting these two pathways, C19 may represent a new type of agents to suppress cancer progression and/or its recurrence.