Tower 1978

1978 yearbook of Westbrook College in Portland, Maine.https://dune.une.edu/wchc_yearbooks/1007/thumbnail.jp

Approaching the Frontier Between Fiber Devices and Single Molecule Devices in Redox Gated Junction

Charge transport in two conducting polymer [poly­(bithiophene) (PBT) and poly­(ethylenedioxythiophene) (PEDOT)] nanojunctions was investigated using two microelectrodes, separated by micrometric gap. Such junctions are redox gated and exhibit conductance switching between low and high resistance states at potential of 1.2 and 0 V, respectively. Devices with conductance between 100 and 500 nS in the oxidized state were easily obtained, indicating control of the charge transport within the whole micrometric gap by a limited number of wires (less than 100 oligomeric strands). <i>I</i>/<i>V</i> characteristics and steady state conductance measurements, for various gate potential, indicate that measured on/off ratios can be as high as 1000 despite the small number of strands controlling the charge transport properties of the devices. Finally, we show that generating nanojunctions whose smallest diameter is below 4 nm on a length close to the size of a polaron, or its localization length, makes it possible to reach the frontier between fiber devices and single molecule devices

Plasmon-Induced Conductance Switching of an Electroactive Conjugated Polymer Nanojunction

A plasmonic molecular electronic device, consisting of poly­(3,4-ethylenedioxythiophene) (PEDOT) nanowires bridging an ultramicroelectrode and an indium tin oxide (ITO) substrate covered by gold nanoparticles (Au NPs), has been developed. Light irradiation of this device has a dramatic impact on its conductance. Polymer strands, maintained electrochemically in their oxidized, conducting state, reversibly switch to their insulating state upon irradiation by visible-wavelength light, resulting in a sharp decrease in the conductance. The high-conductance state is restored when the light is turned off. Switching depends on the wavelength and the intensity of the incident light. It is due to reversible reduction of the nanosized region of PEDOT nanowires in contact with a gold NP and is attributed to plasmon-induced hot-electron injection into the PEDOT. The high/low conductance ratio can be as great as 1000, and switching requires low light intensity (220 W/m²). These results could open the way to the design of a new family of optoelectronic switches

Synthesis of CDDO–Amino Acid–Nitric Oxide Donor Trihybrids as Potential Antitumor Agents against Both Drug-Sensitive and Drug-Resistant Colon Cancer

Seventeen CDDO–amino acid–NO donor trihybrids (<b>4a</b>–<b>q</b>) were designed and synthesized. Biological evaluation indicated that the most active compound <b>4c</b> produced high levels of NO and inhibited the proliferation of drug-sensitive (HCT-8, IC₅₀ = 0.294 μM) and drug-resistant (HCT-8/5-FU, IC₅₀ = 0.232 μM) colon cancer cells, which were attenuated by an NO scavenger or typical substrate of PepT1. Furthermore, <b>4c</b> triggered HCT-8 and HCT-8/5-FU cell apoptosis more strongly than CDDO-Me, inhibited the HIF-1α, Stat3, AKT, and ERK signaling, and induced the nitration of P-gp, MRP1, and BCRP proteins in HCT-8/5-FU cells. Finally, <b>4c</b> had 4.36–5.53-fold less inhibitory activity against nontumor colon epithelial-like cells (CCD841, IC₅₀ = 1.282 μM) in vitro and inhibited the growth of implanted human drug-resistant colon cancers in mice more potently than CDDO-Me. Together, <b>4c</b> is a novel trihybrid with potent antitumor activity and may be a promising candidate for the treatment of drug-resistant colon cancer

Synthesis and Biological Evaluation of Novel Olean-28,13β-lactams as Potential Antiprostate Cancer Agents

γ-Lactam is an important structural motif in a large number of biologically active natural products and synthetic small pharmaceutical molecules. However, there is currently no effective approach to construct γ-lactam ring directly from natural rigid polycyclic amides. Herein, we report a facile methodology for synthesis of a new group of olean-28,13β-lactams (<b>10a</b>–<b>j</b>) from their corresponding amides, promoted by an easily available reagent 2,3-dichloro-5,6-dicyanobenzo­quinone (DDQ), through an intramolecular dehydrogenative C–N coupling reaction via a radical ion mechanism. Biological evaluation indicated that the most active lactam <b>10h</b> displayed potent antiproliferative activity against human cancer cells but 13.84- to 16.92-fold less inhibitory activity on noncancer cells in vitro. In addition, <b>10h</b> significantly inhibited the growth of implanted prostate cancer in vivo. Furthermore, <b>10h</b> induced cell cycle arrest and apoptosis and down-regulated the AKT/mTOR signaling in DU-145 cells. Finally, <b>10h</b> was more stable in rat plasma and human liver microsomes than CDDO-Me and had little hERG channel inhibitory activity. Collectively, <b>10h</b> may be a potential antiprostate cancer agent for further investigation

Discovery of New Monocarbonyl Ligustrazine–Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer

The elevation of oxidative stress preferentially in cancer cells by inhibiting thioredoxin reductase (TrxR) and/or enhancing reactive oxygen species (ROS) production has emerged as an effective strategy for selectively targeting cancer cells. In this study, we designed and synthesized 21 ligustrazine–curcumin hybrids (<b>10a</b>–<b>u</b>). Biological evaluation indicated that the most active compound <b>10d</b> significantly inhibited the proliferation of drug-sensitive (A549, SPC-A-1, LTEP-G-2) and drug-resistant (A549/DDP) lung cancer cells but had little effect on nontumor lung epithelial-like cells (HBE). Furthermore, <b>10d</b> suppressed the TrxR/Trx system and promoted intracellular ROS accumulation and cancer cell apoptosis. Additionally, <b>10d</b> inhibited the NF-κB, AKT, and ERK signaling, P-gp-mediated efflux of rhodamine 123, P-gp ATPase activity, and P-gp expression in A549/DDP cells. Finally, <b>10d</b> repressed the growth of implanted human drug-resistant lung cancer in mice. Together, <b>10d</b> acts a novel TrxR inhibitor and may be a promising candidate for intervention of lung cancer