Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3.

Upatinib, a Janus kinase inhibitor drug, was developed by a biotech company to treat immune diseases. The compound tert-butyl (5-toluenesulfonyl-5h-pyrrole [2,3-b] pyrazine-2-yl) carbamate (ACT051-3) is an important intermediate of Upatinib. To date, the steady industrial production of this intermediate compound (ACT051-3) has not been reported. In this study, we described the specific synthesis method and process of the compound ACT051-3 in terms of laboratory synthesis, pilot scale-up, and industrial production. During the exploration of the process route for ACT051-3, many appropriate adjustments and improvements were made to the reaction conditions, finally leading to the successful development of the optimal industrial production process for ACT051-3. The reaction time was nearly doubled by changing the state of the potassium carbonate involved in the reaction, which greatly improved the reaction efficiency. Additionally, by introducing N,N-diisopropylethylamine (DIPEA) to the reaction, the amount of the expensive catalyst Pd(OAc)2 was reduced 2.5-fold, significantly lowering production costs, confirming the feasibility of this process route and the industrial production of ACT051-3, and satisfying market demand for this important intermediate.

Backbone Effects on the Thermoelectric Properties of Ultra-Small Bandgap Conjugated Polymers.

Conjugated polymers with narrower bandgaps usually induce higher carrier mobility, which is vital for the improved thermoelectric performance of polymeric materials. Herein, two indacenodithiophene (IDT) based donor-acceptor (D-A) conjugated polymers (PIDT-BBT and PIDTT-BBT) were designed and synthesized, both of which exhibited low-bandgaps. PIDTT-BBT showed a more planar backbone and carrier mobility that was two orders of magnitude higher (2.74 × 10-2 cm2V-1s-1) than that of PIDT-BBT (4.52 × 10-4 cm2V-1s-1). Both exhibited excellent thermoelectric performance after doping with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane, where PIDTT-BBT exhibited a larger conductivity (0.181 S cm-1) and a higher power factor (1.861 µW m-1 K-2) due to its higher carrier mobility. The maximum power factor of PIDTT-BBT reached 4.04 µW m-1 K-2 at 382 K. It is believed that conjugated polymers with a low bandgap are promising in the field of organic thermoelectric materials.

Effect of Side Chain Substituent Volume on Thermoelectric Properties of IDT-Based Conjugated Polymers.

A p-type thermoelectric conjugated polymer based on indacenodithiophene and benzothiadiazole is designed and synthesized by replacing normal aliphatic side chains (P1) with conjugated aromatic benzene substituents (P2). The introduced bulky substituent on P2 is detrimental to form the intensified packing of polymers, therefore, it hinders the efficient transporting of the charge carriers, eventually resulting in a lower conductivity compared to that of the polymers bearing aliphatic side chains (P1). These results reveal that the modification of side chains on conjugated polymers is crucial to rationally designed thermoelectric polymers with high performance.

Structure and Doping Optimization of IDT-Based Copolymers for Thermoelectrics.

π-conjugated backbones play a fundamental role in determining the thermoelectric (TE) properties of organic semiconductors. Understanding the relationship between the structure-property-function can help us screen valuable materials. In this study, we designed and synthesized a series of conjugated copolymers (P1, P2, and P3) based on an indacenodithiophene (IDT) building block. A copolymer (P3) with an alternating donor-acceptor (D-A) structure exhibits a narrower band gap and higher carrier mobility, which may be due to the D-A structure that helps reduce the charge carrier transport obstacles. In the end, its power factor reaches 4.91 µW m-1 K-2 at room temperature after doping, which is superior to those of non-D-A IDT-based copolymers (P1 and P2). These results indicate that moderate adjustment of the polymer backbone is an effective way to improve the TE properties of copolymers.

Boosting the Power Factor of Benzodithiophene Based Donor-Acceptor Copolymers/SWCNTs Composites through Doping.

In this study, a benzodithiophene (BDT)-based donor (D)-acceptor (A) polymer containing carbazole segment in the side-chain was designed and synthesized and the thermoelectric composites with 50 wt % of single walled carbon nanotubes (SWCNTs) were prepared via ultrasonication method. Strong interfacial interactions existed in both of the composites before and after immersing into the 2,3,5,6-Tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) solution as confirmed by UV-Vis-NIR, Raman, XRD and SEM characterizations. After doping the composites by F4TCNQ, the electrical conductivity of the composites increased from 120.32 S cm-1 to 1044.92 S cm-1 in the room temperature. With increasing the temperature, the electrical conductivities and Seebeck coefficients of the undoped composites both decreased significantly for the composites; the power factor at 475 K was only 6.8 µW m-1 K-2, which was about nine times smaller than the power factor at room temperature (55.9 µW m-1 K-2). In the case of doped composites, although the electrical conductivity was deceased from 1044.9 S cm-1 to 504.17 S cm-1, the Seebeck coefficient increased from 23.76 µV K-1 to 35.69 µW m-1 K-2, therefore, the power factors of the doped composites were almost no change with heating the composite films.

Preparation of Luminescent Thermotropic Liquid Crystal from Benzodiathiazole Derivatives.

Luminescent liquid crystal materials (LLCMs) have been a hot research topic in the field of fluorescent materials. In this study, we successfully designed and synthesized an intense fluorescence thermotropic liquid crystal material with a fluorescence quantum yield (Φ) of 0.26 in the solid state. Moreover, the alkyl chain attached to the terminus of the chromophore was able to promote the stability of electrochemical and thermal properties, which was beneficial to the device fabrication reproducibility and stability of the device performance.

Preparation and Thermoelectric Properties Study of Bipyridine-Containing Polyfluorene Derivative/SWCNT Composites.

Polymer/inorganic thermoelectric composites have witnessed rapid progress in recent years, but most of the studies have focused on the traditional conducting polymers. The limited structures of traditional conducting polymers restrain the development of organic thermoelectric composites. Herein, we report the preparation and thermoelectric properties of a series of composites films based on SWCNTs and bipyridine-containing polyfluorene derivatives. The value of the power factor around 12 µW m-1 K-2 was achieved for the composite F8bpy/SWCNTs with a mass ratio of 50/50, and the maximum value of 62.3 µW m-1 K-2 was obtained when the mass ratio reached 10/90. Moreover, taking advantage of the bipyridine unit could chelate various kinds of metal ions to form polymer complexes. The enhanced power factor of 87.3 µW m-1 K-2 was obtained for composite F8bpy-Ni/SWCNTs with a mass ratio of 50/50. Finally, the thermoelectric properties of the bipyridine-containing polyfluorene derivative/SWCNT composites were conveniently tuned by chelating with different metal ions.

Biodegradable nanoprobe based on MnO2 nanoflowers and graphene quantum dots for near infrared fluorescence imaging of glutathione in living cells.

Near infrared (NIR) emitting semiconductor quantum dots can be excellent fluorescent nanoprobes, but the poor biodegradability and potential toxicity limits their application. The authors describe a fluorescent system composed of graphene quantum dots (GQDs) as NIR emitters, and novel MnO2 nanoflowers as the fluorescence quenchers. The system is shown to be an activatable and biodegradable fluorescent nanoprobe for the "turn-on" detection of intracellular glutathione (GSH). The MnO2-GQDs nanoprobe is obtained by adsorbing GQDs onto the surface of MnO2 nanoflowers through electrostatic interaction. This results in the quenching of the NIR fluorescence of the GQDs. In the presence of GSH, the MnO2-GQDs nanoprobe is degraded and releases Mn2+ and free GQDs, respectively. This gives rise to increased fluorescence. The nanoprobe displays high sensitivity to GSH and with a 2.8 µM detection limit. It integrates the advantages of NIR fluorescence and biodegradability, selectivity, biocompatibility and membrane permeability. All this makes it a promising fluorescent nanoprobe for GSH and for cellular imaging of GSH as shown here for the case of MCF-7 cancer cells. Graphical abstract A biodegradable NIR fluorescence nanoprobe (MnO2-GQDs) for the "turn-on" detection of GSH in living cell was established, with the NIR GQD as the fluorescence reporter and the MnO2 nanoflower as the fluorescence quencher.

Synthesis of haptens and development of an indirect enzyme-linked immunosorbent assay for tris(2,3-dibromopropyl) isocyanurate.

A competitive indirect enzyme-linked immunosorbent assay (ciELISA) was developed for detection of tris(2,3-dibromopropyl) isocyanurate (TBC). Polyclonal antibodies against TBC were raised from synthesized haptens and then screened against various coating antigens. After optimization of the immunoassay conditions, the linear range and IC50 value of the assay were 0.30-100 and 5.17 µg/L, respectively, with little cross-reactivity (≤2%). Recovery of various samples (water, serum, soil) was tested and the values ranged from 68% to 110%. This ciELISA was also applied to determine TBC in the riverside soil of the Liuyang River, and the results were compared with the data obtained by UHPLC-MS/MS. The experimental assay results confirmed that this proposed immunoassay is a specific, sensitive, and reliable method for determination and monitoring of TBC.

1,3-Alternate conformer 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetra-kis-(4-methyl-sulfanylbenz-yloxy)-2,8,14,20-tetra-thia-calix[4]arene.

The title thia-calix[4]arene derivative, C72H80O4S8, adopts a 1,3-alternate conformation, where the four 4-methyl-sul-fan-yl-benzyl groups are located alternately at the two sides of a virtual plane defined by the four bridging S atoms. In the crystal, there are no significant inter-molecular inter-actions present. Some of the peripheral tert-butyl and methyl-sulfanyl groups are disordered over two positions. A region of disordered electron density, occupying voids of ca 700 Å(3) for an electron count of 124, was treated using the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155].

5,11,17,23-Tetra-kis(1,1-di-methyl-eth-yl)-26,28-di-hydroxy-calix[4]arene-25,27-mono-thia-crown-3.

The title calix[4]arene compound [systematic name: 3,9,15,34-tetra-tert-butyl-19,29-dioxa-24-thia-hexa-cyclo-[15.13.7.1(7,11).1(32,36).0(5,30).0(13,18)]nona-triaconta-1(30),2,4,7,9,11(39),13,15,17,32,34,36(38)-dodeca-ene-38,39-diol], C52H70O4S, displays a cone-like conformation, the opposite arene rings bridged by the mono-thia-crown-3 unit are nearly parallel [dihedral angle = 16.01 (18)°], whereas the other opposite arene rings are twisted to each other at an angle of 74.41 (17)°. Intra-molecular O-H⋯O hydrogen bonds help to stabilize the mol-ecular structure. In the crystal, a C-H⋯π inter-action occurs. One of the tert-butyl groups is disordered over two sets of sites with a site-occupancy ratio of 0.70:0.30.

Modulated dye retention for the signal-on fluorometric determination of acetylcholinesterase inhibitor.

A novel fluorometric assay method based on target-induced signal on was developed for acetylcholinesterase (AChE) inhibitor with obviously improved detection sensitivity. In this method, the AChE molecules catalyzed the hydrolysis of acetylthiocholine (ATCl) to form thiocholine, which in turn can specifically react with fluorescent squaraine derivative, a specific chemodosimeter for thiol-containing compounds, resulting in fluorescence quenching and offering a low fluorometric background for the further detection of AChE inhibitor. In the presence of AChE inhibitor, the catalytic hydrolysis of ATCl is blocked, and then the squaraine derivative remains intact and shows signal-on fluorescence. The amount of the remaining fluorescent squaraine derivative is positively correlated with that of the AChE inhibitor in solution. This new designed sensing system shows an obviously improved sensitivity toward target with a detection limit of 5 pg mL(-1) (0.018 nM) for the AChE inhibitor, comparing favorably with previously reported fluorometric methods. To our best knowledge, this new method is the first example of fluorometric enzymatic assay for AChE inhibitors based on such a signal-on principle and using a specific reaction, which has potential to offer an effective strategy for the detection of AChE inhibitors.

Bifunctional fluoroionphore-ionic liquid hybrid for toxic heavy metal ions: improving its performance via the synergistic extraction strategy.

Several heavy metal ions (HMIs), such as Cd(2+), Pb(2+), and Hg(2+), are highly toxic even at very low concentrations. Although a large number of fluoroionphores have been synthesized for HMIs, only a few of them show detection limits that are below the maximum contamination levels in drinking water (usually in the nM range), and few of them can simultaneously detect and remove HMIs. In this work, we report a new fluoroionphore-ionic liquid hybrid-based strategy to improve the performance of classic fluoroionphores via a synergistic extraction effect and realize simultaneous instrument-free detection and removal of HMIs. As a proof-of-concept, Hg(2+) was chosen as a model HMI, and a rhodamine thiospirolactam was chosen as a model fluoroionphore to construct bifunctional fluoroionphore-ionic liquid hybrid 1. The new sensing system could provide obviously improved sensitivity by simply increasing the aqueous-to-ionic liquid phase volume ratio to 10:1, resulting in a detection limit of 800 pM for Hg(2+), and afford extraction efficiencies larger than 99% for Hg(2+). The novel strategy provides a general platform for highly sensitive detection and removal of various HMIs in aqueous samples and holds promise for environmental and biomedical applications.

Cationic recognition by tert-butylcalix[4]arene-functionalized nanoprobes.

A nanoparticle-based strategy has been demonstrated using structurally-tailored tert-butylcalixarenes immobilized on gold nanoparticles to tune the guest access to the calixarene cone cavity for cationic recognition. This strategy exploits the interparticle charge-induced aggregation upon selective capture of metal cations into the nanoparticle-immobilized tert-butylcalixarenes, which produces calorimetric changes for the detection. A possible pathway for the binding of M(n+) into the t-BCA structure and the interparticle interaction is proposed for the formation of an electric double layer inducing the interparticle association responsible for the red-shifted surface plasmon resonance band of the nanoparticles. The value of this class of calorimetric nanoprobes will be in the area of designing advanced host-guest probes using a variety of calixarene ligands for ionic recognition in a simplistic detection format.

Clicking fluoroionophores onto mesoporous silicas: a universal strategy toward efficient fluorescent surface sensors for metal ions.

Mesoporous SBA-15 silica is an excellent support for constructing fluorescent surface sensors. In this letter, we reported a two-step surface reaction involved strategy to construct efficient fluorescent surface sensors for metal ions by clicking fluoroionophores onto azide-functionalized SBA-15. Our experimental results indicate that such a strategy exhibits an obviously higher loading efficiency within commercial SBA-15 than a previously reported strategy. As a proof-of-concept, a newly designed alkyne-functionalized Hg(2+) fluoroionophore was grafted onto SBA-15 to form a fluorescent Hg(2+) surface sensor. It shows improved sensitivity and selectivity than the fluoroionophore itself working in the solution phase with a detection limit of 2.0 x 10(-8) M for Hg(2+).