Retinoids are ubiquitous signaling molecules that influence nearly every cell type, exert profound effects on development, and complement cancer chemotherapeutic regimens. All-trans retinoic acid (RA) and other active retinoids are generated from vitamin A (retinol), but key aspects of the signaling pathways required to produce active retinoids remain unclear. Retinoids generated by one cell type can affect nearby cells, so retinoids also function in intercellular communication. RA induces differentiation primarily by binding to RARs, transcription factors that associate with RXRs and bind RAREs in the nucleus. Binding of RA: (1) initiates changes in interactions of RAR/RXRs with co-repressor and co-activator proteins, activating transcription of primary target genes; (2) alters interactions with proteins that induce epigenetic changes; (3) induces transcription of genes encoding transcription factors and signaling proteins that further modify gene expression (e.g., FOX03A, Hoxa1, Sox9, TRAIL, UBE2D3); and (4) results in alterations in estrogen receptorα signaling. Proteins that bind at or near RAREs include Sin3a, N-CoR1, PRAME, Trim24, NRIP1, Ajuba, Zfp423, and MN1/TEL. Interactions among retinoids, RARs/RXRs, and these proteins explain in part the powerful effects of retinoids on stem cell differentiation. Studies of this retinol signaling cascade enhance our ability to understand and regulate stem cell differentiation for therapeutic and scientific purposes. In cancer chemotherapeutic regimens retinoids can promote tumor cell differentiation and/or induce proteins that sensitize tumors to drug combinations. Mechanistic studies of retinoid signaling continue to suggest novel drug targets and will improve therapeutic strategies for cancer and other diseases, such as immune-mediated inflammatory diseases.

Metal alloys with atomic scale ordering (ordered intermetallics) have emerged as a new class of high performance materials for mediating electrochemical reactions. However, ordered intermetallic nanostructures often require long synthesis times and/or high temperature annealing to form because a high-activation energy barrier for interdiffusion must be overcome for the constituent metals to equilibrate into ordered structures. Here we report the direct synthesis of metastable ordered intermetallic Pd31Bi12 at room-temperature in minutes via electrochemical deposition. Pd31Bi12 is highly active for the reduction of O2 to H2O, delivering specific activities over 35× higher than those of commercial Pt and Pd nanocatalysts, placing it as the most active Pd-based catalyst, to the best of our knowledge, reported under similar testing conditions. Stability tests demonstrate minimal loss of activity after 10,000 cycles, and a retention of intermetallic crystallinity. This study demonstrates a new method of preparing ordered intermetallics with extraordinary catalytic activity at room temperature, providing a new direction in catalyst discovery and synthesis.

Synthetic polymer approaches generally lack the ability to control the primary sequence, with sequence control referred to as the holy grail. Two click chemistry reactions were now combined to form nucleobase-containing sequence-controlled polymers in simple polymerization reactions. Two distinct approaches are used to form these click nucleic acid (CNA) polymers. These approaches employ thiol-ene and thiol-Michael reactions to form homopolymers of a single nucleobase (e.g., poly(A)n ) or homopolymers of specific repeating nucleobase sequences (e.g., poly(ATC)n). Furthermore, the incorporation of monofunctional thiol-terminated polymers into the polymerization system enables the preparation of multiblock copolymers in a single reaction vessel; the length of the diblock copolymer can be tuned by the stoichiometric ratio and/or the monomer functionality. These polymers are also used for organogel formation where complementary CNA-based polymers form reversible crosslinks.

Co-delivery of both chemotherapy drugs and siRNA from a single delivery vehicle can have a significant impact on cancer therapy due to the potential for overcoming issues such as drug resistance. However, the inherent chemical differences between charged nucleic acids and hydrophobic drugs have hindered entrapment of both components within a single carrier. While poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers have been used successfully for targeted delivery of chemotherapy drugs, loading of DNA or RNA has been poor. It is demonstrated that significant amounts of DNA can be encapsulated within PLGA-containing nanoparticles through the use of a new synthetic DNA analog, click nucleic acids (CNAs). First, triblock copolymers of PEG-CNA-PLGA are synthesized and then formulated into polymer nanoparticles from oil-in-water emulsions. The CNA-containing particles show high encapsulation of DNA complementary to the CNA sequence, whereas PEG-PLGA alone shows minimal DNA loading, and non-complementary DNA strands do not get encapsulated within the PEG-CNA-PLGA nanoparticles. Furthermore, the dye pyrene can be successfully co-loaded with DNA and lastly, a complex, larger DNA sequence that contains an overhang complementary to the CNA can also be encapsulated, demonstrating the potential utility of the CNA-containing particles as carriers for chemotherapy agents and gene silencers.

A carboxylated thiophene polymer-based chemiresistive device in a field-effect transistor (FET) configuration with unusual and enhanced responses to the widespread pollutants nitrogen dioxide (NO2) and ammonia (NH3) is described.

The development of high-performance-conjugated polymer-based gas sensors involves detailed structural tailoring such that high sensitivities are achieved without compromising the stability of the fabricated devices. In this work, we systematically developed a series of diketopyrrolopyrrole (DPP)-based polymer semiconductors by modifying the polymer backbone to achieve and rationalize enhancements in gas sensitivities and electronic stability in air. NO2- and NH3-responsive polymer-based organic field-effect transistors (OFETs) are described with improved air stability compared to all-thiophene conjugated polymers. Five DPP–fluorene-based polymers were synthesized and compared to two control polymers and used as active layers to detect a concentration of NO2 at least as low as 0.5 ppm. The hypothesis that the less electron-donating fluorene main-chain subunit would lead to increased signal/drift compared to thiophene and carbazole subunits was tested. The sensitivities exhibited a bias voltage-dependent behavior. The proportional on-current change of OFETs using a dithienyl DPP–fluorene polymer reached ∼614% for an exposure to 20 ppm of NO2 for 5 min, testing at a bias voltage of −33 V, among the higher reported NO2 sensitivities for conjugated polymers. Electronic and morphological studies reveal that introduction of the fluorene unit in the DPP backbone decreases the ease of backbone oxidation and induces traps in the thin films. The combination of thin-film morphology and oxidation potentials governs the gas-absorbing properties of these materials. The ratio of responses on exposure to NO2 and NH3 compared to drifts while taking the device through repeated gate voltage sweeps is the highest for two polymers incorporating electron-donating linkers connecting the DPP and thiophene units in the backbone, in this category of organic semiconductors. The responses to NO2 were much larger than that to NH3, indicating increased susceptibility to oxidizing vs reducing gases, and that the capability of oxidizing gases to induce additional charge density has a more dramatic electronic effect than when reducing gases create traps. This work demonstrates the capability of achieving improved stability with the retention of high sensitivity in conjugated polymer-based OFET sensors by modulating redox and morphological properties of polymer semiconductors by structural control.

No abstract

Characterizing doping effects in a conductive polymer and physical diffusion in a passive polymer were performed using a remote-gate field-effect transistor (RG FET) detection system that was able to measure the electrical potential perturbation of a polymer film coupled to the gate of a silicon FET. Poly­(3-hexylthiophene) (P3HT) film doped using various concentrations of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) solutions imposed additional positive potentials on the P3HT RG, resulting in a lower threshold voltage (V th) on the n-channel silicon FET. Changes in V th were related to the induced hole concentrations and hole mobility in P3HT films by using our V th shifting model for the RG FET. We discovered that the electron-donating P3HT and even inorganic materials, indium tin oxide and gold, showed similar electrical potential perturbations dependent on the concentration of F4TCNQ in overlying solutions as the dopant radical anions maximally covered the surfaces. This suggests that there are limited electroactive sites for F4TCNQ binding on electron donor surfaces which results in a similar number of positive charges in film materials forming dipoles with the F4TCNQ radical counteranions. The effect of electron acceptors such as 7,7,8,8-tetracyanoquinodimethane and tetracyanoethylene was compared to that of F4TCNQ in terms of V th shift using our analytical tool, with differences attributed to acceptor size and reduction potential. Meanwhile, this FET analysis tool offered a means of monitoring the physical diffusion of small molecules, exemplified by F4TCNQ, in the passive polymer polystyrene, driven by concentration gradients. The technique allows for nondestructive, nonspectroscopic, ambient characterization of electron donor–acceptor interactions at surfaces.