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The iodination of pyrimidines is usually carried out by using toxic reagents under acidic conditions, such as with sulfuric acid and nitric acid. To avoid toxic reagents, we developed a simple and eco-friendly approach for the iodination of pyrimidine derivatives under solvent-free conditions using solid iodine and AgNO3 as an electrophilic iodinating reagent. The advantages of this method are the relatively short reaction time (20–30 min), simple set-up procedure, high yields (70–98%), and environmentally friendly reaction conditions. Our novel approach for the iodination of pyrimidines, as well as a variety of their derivatives, will contribute to the development of nucleobase-related drug candidates.

Phosphatidylinositol phosphates (PtdInsPs) are ubiquitous membrane phospholipids that play diverse roles in cell growth and differentiation. To clarify the regulation mechanism acting on neurofilament light chain (NF-L) self assembly, we examined the effects of various PtdInsPs on this process. We found that PtdInsPs, including PI(4,5)P 2 , directly bind to the positively charged Arg 54 of murine NF-L, and this binding promotes NF-L self assembly in vitro . Mutant NF-L (R53A/R54A) proteins lacking binding affinity to PtdInsPs did not have the same effect, but the mutant NF-L proteins showed greater self assembly than the wild-type in the absence of any PtdInsP. These results collectively suggest that Arg 54 plays a pivotal role in NF-L self assembly by binding with PtdInsPs.

New colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 μ M ), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 n M , CT20126 induced 47% apoptosis among Jurkat T cells, whereas colchicine induced only 33% apoptosis. Our results suggest that the colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of colchicine or Taxol. Drug discovery: An alternative for halting tumor growth Colchicine's value as an anticancer drug is undercut by harmful side effects, but a related compound may offer a useful alternative. Cell division is facilitated by dynamic assembly and disassembly of tubulin protein into microtubule filaments, which ensure that each new cell receives a full set of chromosomes. Colchicine thwarts cancerous growth by forcing microtubule disassembly. Since it can also be toxic to patients, Jong-Soo Chang of Korea's Daejin University and colleagues characterized the anticancer effects of a colchicine derivative called CT20126. Unlike colchicine, CT20126 only transiently stimulates microtubule disassembly, and subsequently promotes aggregation of tubulin into unusually short, thick filaments. Nevertheless, CT20126 still proved a potent inhibitor of proliferation in cultured human cells, and triggered programmed cell death more efficiently than other microtubule-targeting drugs, highlighting its potential as a therapeutic candidate.

Growth factor stimulation induces Y783 phosphorylation of phosphoinositide-specific PLC-γ1, and the subsequent activation of this enzyme in a cellular signaling cascade. Previously, we showed that a double point mutation, Y509A/F510A, of PLC-γ1, abolished interactions with translational elongation factor 1-α. Here, we report that the Y509A/F510A mutant PLC-γ1 displayed extremely high levels of Y783 phosphorylation and enhanced catalytic activity, compared to wild-type PLC-γ1, upon treatment of COS7 cells with EGF. In quiescent COS7 cells, the Y509A/F510A mutant PLC-γ1 exhibited a constitutive hydrolytic activity, whereas the wild-type counterpart displayed a basal level of activity. Upon treatment of COS7 cells with EGF, the Y783F mutation in Y509A/F510A PLC-γ1 (Y509A/F510A/Y783F triple mutant) cells also led to an enhanced catalytic activity, whereas Y783F mutation alone displayed a basal level of activity. Our results collectively suggest that the Y509A/F510A mutant is more susceptible to receptor tyrosine kinase-induced Y783 phosphorylation than is wild-type PLC-γ1, but no longer requires Y783 phosphorylation step for the Y509A/F510A mutant PLC-γ1 activation in vivo .

Anion transporters based on small molecules have received attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis. However, a direct correlation between a change in cellular chloride anion concentration and cytotoxicity has not been established for synthetic ion carriers. Here we show that two pyridine diamide-strapped calix[4]pyrroles induce coupled chloride anion and sodium cation transport in both liposomal models and cells, and promote cell death by increasing intracellular chloride and sodium ion concentrations. Removing either ion from the extracellular media or blocking natural sodium channels with amiloride prevents this effect. Cell experiments show that the ion transporters induce the sodium chloride influx, which leads to an increased concentration of reactive oxygen species, release of cytochrome c from the mitochondria and apoptosis via caspase activation. However, they do not activate the caspase-independent apoptotic pathway associated with the apoptosis-inducing factor. Ion transporters, therefore, represent an attractive approach for regulating cellular processes that are normally controlled tightly by homeostasis. Anion transporters that disrupt cellular ion homeostasis could represent a new approach for generating therapeutic lead compounds. Now, two pyridine diamide-strapped calix[4]pyrroles have been shown to induce coupled chloride anion and sodium cation transport in liposomal models and cells. These compounds promote cell death by increasing intracellular chloride and sodium ion concentrations.

As the market for electric vehicles and portable electronic devices continues to grow rapidly, sodium-ion batteries (SIBs) have emerged as energy storage systems to replace lithium-ion batteries (LIBs). However, sodium-ion is heavier and larger than lithium-ion, resulting in volume expansion and slower ion transfer. It is necessary to find suitable anode materials with high capacity and stability. In addition, wearable electronics are starting to be commercialized, requiring a binder-free electrode used in flexible batteries. In this work, we synthesized nano flake-like VSe2 using organic precursor and combined it with MWCNT as carbonaceous material. VSe2@MWCNT was mixed homogenously using sonication and fabricated film electrodes without a binder and substrate via vacuum filter. The hybrid electrode exhibited high-rate capability and stable cycling performance with a discharge capacity of 469.1 mAhg−1 after 200 cycles. Furthermore, VSe2@MWCNT exhibited coulombic efficiency of ~99.7%, indicating good cycle stability. Additionally, VSe2@MWCNT showed a predominant 85.5% of capacitive contribution at a scan rate of 1 mVs−1 in sodiation/desodiation process. These results showed that VSe2@MWCNT is a suitable anode material for flexible SIBs.

A naphthalene imide (1) and a naphthalene (2) bearing two pyrrole units have been synthesized, respectively, as anion receptors. It was revealed by 1H NMR spectral studies carried out in CD3CN that receptors 1 and 2 bind various anions via hydrogen bonds using both C-H and N-H donors. Compared with receptor 2, receptor 1 shows higher affinity for the test anions because of the enhanced acidity of its pyrrole NH and naphthalene CH hydrogens by the electron-withdrawing imide substituent. Molecular mechanics computations demonstrate that the receptors contact the halide anions via only one of the two respective available N-H and C-H donors whereas they use all four donors for binding of the oxyanions such as dihydrogen phosphate and hydrogen pyrophosphate. Receptor 1, a push-pull conjugated system, displays a strong fluorescence centered at 625 nm, while receptor 2 exhibits an emission with a maximum peak at 408 nm. In contrast, upon exposure of receptors 1 and 2 to the anions in question, their fluorescence was noticeably quenched particularly with relatively basic anions including F−, H2PO4−, HP2O73−, and HCO3−.

Subcellular organelle-specific nanoparticles for simultaneous tumor targeting, imaging, and drug delivery are of enormous interest in cancer therapy. Herein, we report a selective mitochondria-targeting probe 1, which was synthesized by incorporating a triphenyl phosphine with a cyanostilbene and a long alkyl chain moiety. Probe 1 was found to display fluorescence via aggregation-induced emission （AIE）. The low molecular-weight cyanostilbene-based probe 1, with and without an anticancer drug, formed a narrow homogeneous nanorod with ca. 110 nm of length or nanopartides with ca. 20 nm diameter in aqueous media. The self-assembled cyanostilbene nanoparticles （N1） selectively accumulated in the mitochondria of cancer cells and emitted fluorescence. N1 was also able to deliver an anticancer drug, doxorubicin （DOX）, to the mitochondria with high efficiency. More importantl~ N1 exhibited highly selective cytotoxicity for cancer cells over normal cells. The great potential applications of this self-assembled nanoparticle to biological systems result from its ability to aggregate in the mitochondria. This aggregation led to a significant increase in the generation of intraceUular reactive oxygen species and to a decrease in the mitochondrial membrane potential in cancer cells. Furthermore, tumor tissue uptake experiments in mice proposed that the self-assembled N1 had the ability to internalize and deliver the anticancer drug into tumor tissues effectively. Moreover, both N1 and Nl-encapsulated doxorubicin （N1-DOX） effectively suppressed tumor growth in a xenograft model in vivo. Taken together, our findings indicate that applications of N1 as a mitochondrial targeting probe, drug delivery platform, and chemotherapeutic agent provide a unique strategy for potential image-guided therapy as well as a site-specific delivery system to cancer cells.

Sodium ion batteries (SIBs) have drawn interest as a lithium ion battery (LIB) alternative owing to their low price and low deposits. To commercialize SIBs similar to how LIBs already have been, it is necessary to develop improved anode materials that have high stability and capacity to operate over many and long cycles. This paper reports the development of homogeneous Sb2S3 nanorods (Sb2S3 NRs) on reduced graphene oxide (Sb2S3 NRs @rGO) as anode materials for SIBs. Based on this work, Sb2S3 NRs show a discharge capacity of 564.42 mAh/g at 100 mA/g current density after 100 cycles. In developing a composite with reduced graphene oxide, Sb2S3 NRs@rGO present better cycling performance with a discharge capacity of 769.05 mAh/g at the same condition. This achievement justifies the importance of developing Sb2S3 NRs and Sb2S3 NRs@rGO for SIBs.