Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10

We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents

Probing of an Adsorbate-Specific Excited State on an Organic Insulating Surface by Two-Photon Photoemission Spectroscopy

In this study, we investigate the photoexcited electronic states of ferrocene (Fc) molecules adsorbed on an organic insulating surface by two-photon photoemission spectroscopy. This insulating layer, composed of a decanethiolate self-assembled monolayer formed on an Au(111) substrate, enables us to probe the electronically excited states localized at the adsorbed Fc molecules. The adsorbate-specific state is resonantly excited by photons at 4.57 eV, which is 0.5 eV smaller than the energy of the first molecular Rydberg state of free Fc in the gas phase. This result indicates that the electrons are bound to both the excited hole formed in the adsorbate and the positive image charge induced in the substrate. The hybridized electronic characteristics of the adsorbate-specific state are responsible for the strong transition selectivity and short lifetime of the excited state

Energy Level Alignment of Organic Molecules with Chemically Modified Alkanethiolate Self-Assembled Monolayers

We have employed two-photon photoemission spectroscopy to nondestructively resolve the unoccupied energy levels of fullerene C₆₀ molecules deposited on alkanethiolate self-assembled monolayers (SAMs). By fluorine substitution of the hydrogen atoms in the alkyl chain, the work function (WF) increased from 4.3 eV for the alkanethiolate-SAM (H-SAM) to 5.7 eV for the fluorine-substituted SAM (F-SAM), owing to the formation of surface dipole layers. When C₆₀ is deposited on the H-SAM and F-SAM, the energy positions of the unoccupied/occupied levels of C₆₀ are pinned to the vacuum level (Fermi level (<i>E</i>_F) + WF). As a result of the energy level alignment, on the F-SAM, the relative energy from <i>E</i>_F of the highest occupied molecular orbital of C₆₀ almost equals that of the lowest unoccupied molecular orbital, implying that the C₆₀ film on the F-SAM exhibits both p- and n-type (ambipolar) charge transport properties, while C₆₀ is known as a typical n-type semiconductor. The energetics are preserved even with multilayered C₆₀ films at least up to ∼5 nm in thickness, showing that the dipole layers induced by SAMs are robust against molecular overlayers. Such a spectroscopic study on the energy levels for organic films will be of importance for further development of organic thin film devices

Charge Transfer Complexation of Ta-Encapsulating Ta@Si₁₆ Superatom with C₆₀

The tantalum-encapsulating Si₁₆ cage nanocluster superatom (Ta@Si₁₆) has been a promising candidate for a building block of nanocluster-based functional materials. Its chemical states of Ta@Si₁₆ deposited on an electron acceptable C₆₀ fullerene film were evaluated by X-ray and ultraviolet photoelectron spectroscopies (XPS and UPS, respectively). XPS results for Si, Ta, and C showed that Ta@Si₁₆ combines with a single C₆₀ molecule to form the superatomic charge transfer (CT) complex, (Ta@Si₁₆)⁺C₆₀^–. The high thermal and chemical robustness of the superatomic CT complex has been revealed by the XPS and UPS measurements conducted before and after heat treatment and oxygen exposure. Even when heated to 720 K or subjected to ambient oxygen, Ta@Si₁₆ retained its original framework, forming oxides of Ta@Si₁₆ superatom

Charge Separation at the Molecular Monolayer Surface: Observation and Control of the Dynamics

Charge separation dynamics relevant to an electron transfer have been revealed by time- and angle-resolved two-photon photoemission spectroscopy for an <i>n</i>-alkanethiolate self-assembled monolayer (SAM) on a Au(111) surface fabricated by a chemical-wet process. The electron was photoexcited into an image potential state located at 3.7 eV above the Fermi level (<i>E</i>_F), and it survived well for more than 100 ps on dodecanethiolate (C12)-SAM. The degree of electron separation is precisely controlled by selecting the length of the alkyl chain (C10–C18). We have also evaluated molecular conductivity at the specific electron energy of <i>E</i>_F + 3.7 eV. The tunneling decay parameter, β, was fitted by β_90 K = 0.097 Å^–1 and β_RT = 0.13 Å^–1. These values were one order smaller than that at around <i>E</i>_F by conventional contact probe methods

Molecular-Scale and Wide-Energy-Range Tunneling Spectroscopy on Self-Assembled Monolayers of Alkanethiol Molecules

The electronic properties of alkanethiol self-assembled monolayers (alkanethiolate SAMs) associated with their molecular-scale geometry are investigated using scanning tunneling microscopy and spectroscopy (STM/STS). We have selectively formed the three types of alkanethiolate SAMs with standing-up, lying-down, and lattice-gas phases by precise thermal annealing of the SAMs which are conventionally prepared by depositing alkanethiol molecules onto Au(111) surface in solution. The empty and filled states of each SAM are evaluated over a wide energy range covering 6 eV above/below the Fermi level (<i>E</i>_F) using two types of STS on the basis of tunneling current–voltage and distance–voltage measurements. Electronic states originating from rigid covalent bonds between the thiol group and substrate surface are observed near <i>E</i>_F in the standing-up and lying-down phases but not in the lattice-gas phase. These states contribute to electrical conduction in the tunneling junction at a low bias voltage. At a higher energy, a highly conductive state stemming from the alkyl chain and an image potential state (IPS) formed in a vacuum gap appear in all phases. The IPS shifts toward a higher energy through the change in the geometry of the SAM from the standing-up phase to the lattice-gas phase through the lying-down phase. This is explained by the increasing work function of alkanethiolate/Au(111) with decreasing density of surface molecules