Photo-induced versatile aliphatic C-H functionalization via electron donor-acceptor complex.

The ability to selectively introduce diverse functionality onto hydrocarbons is of substantial value in the synthesis of both small molecules and pharmaceuticals. In this endeavour, as a photocatalyst- and metal-free process, the electron donor-acceptor (EDA) strategy has not been well explored. Here we report an approach to aliphatic carbon-hydrogen bond diversification through an EDA complex constituted by HCl and SIV=O groups. As an efficient hydrogen atom transfer (HAT) reagent, chlorine radical can be produced via a proton-coupled electron transfer process in this system. Based on this unusual path, a photo-promoted versatile aliphatic C-H functionalization is developed without photo- and metal-catalysts, including thiolation, arylation, alkynylation, and allylation. This conversion has concise and ambient reaction conditions, good functional group tolerance, and substrate diversity, and provides an alternative solution for the high value-added utilization of bulk light alkanes.

Metal-Free C-S Bond Formation in Elemental Sulfur and Cyclobutanol Derivatives: The Synthesis of Substituted Thiophenes.

A general approach for the metal-free synthesis of thiophenes by tert-cyclobutanols and elemental sulfur has been developed. This protocol provides a strategy for constructing multisubstituted thiophene derivatives via C-S bond formation under air. This reaction shows good functionality tolerance under the reaction conditions, and the mechanism is validated by control experiments and density functional theory calculations.

Sequential Catalytic Annulations: Divergent Synthesis of Heterocycles through a Radical [1,4]-Oxygen Shift.

A radical [1,4]-oxygen-atom transfer has been realized by the reaction of linear alkyne-tethered ketoximes and ethynylbenziodoxolones (EBX) under sequential catalytic conditions. Mechanism studies indicate that the O atom transfer experiences a cascade O atom radical cyclization/alkynylation/N-O bond photocleavage and subsequent N,O-diradical rearrangement. By the diversification of catalytic sequences, a series of structurally important 3H-pyrrol-3-ones and chlorinated furo[3,2-b]pyrroles are divergently synthesized along with an O atom shift under the catalysis of Cu/Ir photosensitization and Cu/Ir photosensitization/AlCl3, respectively.

A small molecule fluorescent probe for mercury ion analysis in broad low pH range: Spectral, optical mechanism and application studies.

Development of new fluorescent probes for mercury ion analysis in environmental or living organism is undergoing quick growth due to its detrimental toxicity to environmental safety, ecological security, and human being. However, in most cases, the industrial waste water is acidic whereas it remains a great challenge to real-time monitor mercury ion directly at low pH using small molecule fluorescence probe. In this study, we have successfully designed and synthesized the Naph (1, 8-Naphthalimide derivative) -based small molecule probe termed as Naph-NSS capable of monitoring mercury ion in a broad range at low pH (from 2.0 to 7.0). The solid spectral studies demonstrated the high sensitivity and selectivity of the probe towards mercury ion among various species. After binding with Hg2+, the fluorescence of Naph-NSS greatly enhanced, and the mechanism of which was investigated by DFT studies. The probe was able to be loaded on paper strip for instant and fast detection of mercury ions. In addition, the probe is also suitable for detection of mercury ion in environmental samples, living cells and in vivo.

A tellura-Baeyer-Villiger oxidation: one-step transformation of tellurophene into chiral tellurinate lactone.

Baeyer-Villiger (BV) oxidation is a fundamental organic reaction, whereas the hetero-BV oxidation is uncharted. Herein, a tellura-BV oxidation is discovered. By oxidizing a tellurophene-embedded and electron-rich polycycle (1) with mCPBA or Oxone, an oxygen atom is inserted into the Te-C bond of the tellurophene to form tellurinate lactone mono-2. This reaction proceeds as follows: (i) 1 is oxidized to the tellurophene Te-oxide form (IM-1); (ii) IM-1 undergoes tellura-BV oxidation to give mono-2. Moreover, the hybrid trichalcogenasumanenes 7 and 8 are, respectively, converted to tellurinate lactones mono-9 and mono-10 under the same conditions, indicating that tellura-BV oxidation shows high chemoselectivity. Due to the strong secondary bonding interactions between the Te[double bond, length as m-dash]O groups on tellurinate lactones, mono-2, mono-9, and mono-10 are dimerized to form U-shaped polycycles 2, 9, and 10, respectively. Notably, mono-2, mono-9, mono-10, and their dimers show chirality. This work enables one-step transformation of tellurophene into tellurinate lactone and construction of intricate polycycles.

Tetrathiafulvalene-Fused Heterabuckybowl: Protonation-Induced Electron Transfer and Self-Sensitized Photooxidation.

The electron donor tetrathiafulvalene (D1 ) was fused onto the electron-rich heterabuckybowl trichalcogenasumanene (D2 ) through an electron-deficient pyrazine unit (A) to give 1 c, 1 d, 2 c, and 2 d, featuring the D1 -A-D2 structure. Both D1 and D2 play a pivotal role in intramolecular charge-transfer (ICT) transitions, consequently 1 c, 2 d, 2 c, and 2 d show a broad ICT band at 450-720 nm in steady state. They exhibit two charge-separated transient states, CS1 and CS2 , that appear in sequence. CS1 has a short lifetime (542 fs), and the D1 moiety on CS1 is in the radical cation state with an absorption maximum (λmax ) at 889 nm. CS1 then converts into CS2 (λmax , 1105 nm) through an ICT between D1 .+ and D2 , affording D1 (1-δ).+ and D2 δ.+ . Compounds 1 c, 1 d, 2 c, and 2 d show protonation-induced intramolecular electron transfer that leads to absorption at λ=700-1300 nm. Owing to the existence of an electron-rich C=C bond on the D1 moiety and in situ generation of 1 O2 by the pyrazine-fused D2 moiety, compounds 1 c, 1 d, 2 c, and 2 d display self-sensitized photooxidation in 50 s.

Efficient Construction of Near-Infrared Absorption Donor-Acceptor Copolymers with and without Pt(II)-Incorporation toward Broadband Nonlinear Optical Materials.

Organic nonlinear optical (NLO) materials have attracted immense scientific interest in various fields. Broadband NLO response extending to near-infrared (NIR) region is extremely important and remains challenging. Herein, two diketopyrrolopyrrole (DPP)-based donor-acceptor (D-A)-type π-conjugated copolymers with and without Pt(II) incorporation are rationally designed and synthesized toward broadband NLO response materials. The broad intramolecular charge transfer (ICT) absorption reaching 1000 nm due to the strong D-A interaction is well demonstrated by photophysical characterizations. The NLO properties of copolymers are studied using Z-scan technology. Owing to their extended π-conjugated D-A systems and near-infrared ICT absorption properties, both copolymers exhibit laser-induced NLO response to nanosecond as well as picosecond laser pulses upon the wavelengths of 532 and 1064 nm. Interestingly, introducing Pt(II) into the copolymer backbone can evidently improve the NLO property or unexpectedly switch the NLO response from saturable absorption to reverse saturable absorption. Meanwhile, both copolymers are successfully employed as optical limiting materials and exhibit broadband optical limiting abilities. Therefore, we present an efficient strategy toward broadband NLO materials, which may significantly facilitate the understanding of organic molecular structure-property relationship and promote their practical application.

Near-Infrared Fluorescence Probe for Evaluating Acetylcholinesterase Activity in PC12 Cells and In Situ Tracing AChE Distribution in Zebrafish.

Acetylcholinesterase (AChE) plays crucial roles in numerous physiological processes such as cell differentiation, cell apoptosis, and nerve tissue developments. Hence, it is highly necessary to design a fluorescent probe for monitoring AChE activity in complex living organisms. In this work, a near-infrared (NIR) off-on probe (CyN) was developed for AChE detection. CyN was exactly synthesized by introducing an N,N-dimethyl carbamyl moiety to hemicyanine (CyOH). AChE can "light up" strong NIR fluorescence through a cleavage special ester bond and transform CyN into CyOH. Moreover, CyN was qualified for imaging the dynamic change of AChE activity in PC12 cells with retinoic acid or hypoxia stimulation. In particular, the probe has been successfully applied for in situ tracing the intact distribution of AChE in living zebrafish. The observations indicate that major occurrence sites of endogenic AChE on zebrafish are the yolk sac and neuromasts. Overall, CyN shows great potential for use in AChE-related physiological studies.

A fast and specific fluorescent probe for thioredoxin reductase that works via disulphide bond cleavage.

Small molecule probes are indispensable tools to explore diverse cellular events. However, finding a specific probe of a target remains a high challenge. Here we report the discovery of Fast-TRFS, a specific and superfast fluorogenic probe of mammalian thioredoxin reductase, a ubiquitous enzyme involved in regulation of diverse cellular redox signaling pathways. By systematically examining the processes of fluorophore release and reduction of cyclic disulfides/diselenides by the enzyme, structural factors that determine the response rate and specificity of the probe are disclosed. Mechanistic studies reveal that the fluorescence signal is switched on by a simple reduction of the disulfide bond within the probe, which is in stark contrast to the sensing mechanism of published probes. The favorable properties of Fast-TRFS enable development of a high-throughput screening assay to discover inhibitors of thioredoxin reductase by using crude tissue extracts as a source of the enzyme.

Migratory Shift in Oxidative Cyclodehydrogenation Reaction of Tetraphenylethylenes Containing Electron-Rich THDTAP Moiety.

Four tetraphenylethylenes (2 a-d) containing an electron-rich 2,3,4,6-tetrahydro-1,6-dithia-3a-azaphenalene (THDTAP) moiety have been synthesized. The 2 a-d show aggregation-induced emission (AIE) with yellowish green photoluminescence (PL) in THF-H2 O (v/v, 1:9) solution and in the solid state. Compounds 2 a-d undergo 1,2-migratory shift in oxidative cyclodehydrogenation reactions to afford the unexpected products 3 a-d which display green PL in CH2 Cl2 solution and are non-emissive in the solid state. The PL intensities of 3 a-d are clearly enhanced in the presence of meta-chloroperoxybenzoic acid (mCPBA) owing to the oxidation of the S-atoms on the THDTAP moiety. In contrast, the PL of 2 a-d in THF-H2 O (v/v, 1:9) solution is quenched by adding mCPBA, ascribable to the oxidation of the C=C bond on the ethylene moiety. It is found that the absorption of 3 a-d is distinctly red-shifted from the UV/Vis region to the NIR region upon acidification, arising from the protonation of the N-atom on the THDTAP moiety. Furthermore, 3 a-d display nonlinear optical response (NLO) and optical limiting (OL) behaviour which is superior to that of the well-known OL material C60 .

Unusual Hypochlorous Acid (HClO) Recognition Mechanism Based on Chlorine-Oxygen Bond (Cl-O) Formation.

One of the most important endogenous reactive oxygen species, hypochlorous acid (HClO), is involved in numerous pathological and physiological processes. Herein, a near-infrared fluorescence probe (CyHR) was designed and synthesized for ultrafast (within 0.2 s), sensitive (limit of detection=39.44 nm), and selective response to HClO. The reaction mechanism was systematically analyzed by MS, 1 H NMR spectroscopy, HPLC-MS techniques, and theoretical calculations. The results indicated that HClO can be recognized by CyHR, which is based on chlorine-oxygen (Cl-O) bond formation. To the best of our knowledge, this study is the first to find Cl-O bonds among organic aromatic compounds, given that Cl-O bonds are common among inorganics. Through biological experiments, CyHR was successfully applied to image exogenous and endogenous HClO in macrophage cells (RAW 264.7). Thus, CyHR is a promising tool for HClO-related physiological and pathological studies and may provide a means for designing HClO-specific fluorescence probes.

Hydrogen bonding promoted simple and clean photo-induced reduction of C-X bond with isopropanol.

We herein report a simple and clean photo-induced metal-free reduction of C-X bond under an atmosphere of air at room temperature. Isopropanol is used as both the reducing reagent and solvent. Various functional groups (acids, esters, alcohols, anilines, phenols, indoles, pyridines, cyano and trifluoromethyl groups) and other heterocyclic compounds are tolerated. Different organic halides (including C-I, C-Br and C-Cl bonds) can be dehalogenated with moderate to excellent yields. Polyhalides are also reduced chemoselectively and efficiently. DFT calculation suggests a six-membered ring transition state via C-XH-O hydrogen bonding to decrease the activation energy.

Doping Sumanene with Both Chalcogens and Phosphorus(V): One-Step Synthesis, Coordination, and Selective Response Toward AgI.

Heterasumanenes 4-6 containing chalcogen (S, Se, and Te) and phosphorus atoms have been synthesized in a one-pot reaction from trichalcogenasumanenes 1-3 by replacing one chalcogen atom with a P=S unit. The P=S unit makes 4-6 almost planar and shrinks the HOMO-LUMO gap as compared to 1-3. The bonding between Ag+ and S atom on P=S brings about a distinct change to the optical properties of 4-6; 4 in particular shows a selective fluorescence response toward Ag+ with LOD of 0.21 µm. Compounds 4-6 form complexes with AgNO3 to be (4)2 ⋅AgNO3 , (5)2 ⋅AgNO3 , and (6)2 ⋅(AgNO3 )3 . In complexes, the coordination between Ag+ and P=S is observed, which leads to shrinkage of C-P and C-X (X=S, Se, Te) bond lengths. As a result, 4, 5, and 6 are all bowl-shaped in complexes with bowl-depths reaching to 0.66 Å, 0.42 Å, and 0.40 Å, respectively. There are Ag-Te dative bonds between Ag+ and Te atom on telluorophene in (6)2 ⋅(AgNO3 )3 .

Opening two benzene rings on trichalcogenasumanenes toward high performance organic optical-limiting materials.

Two flanking benzene rings on trichalcogenasumanenes (1a/1b) were opened upon oxidation, and the successive ring reconstruction afforded donor-acceptor type polycycles containing diimide units (3a/3b). 3a and 3b show excellent optical-limiting properties superior to C60.

Intermolecular interactions between σ- and π-holes of bromopentafluorobenzene and pyridine: computational and experimental investigations.

The characters of σ- and π-holes of bromopentafluorobenzene (C6F5Br) enable it to interact with an electron-rich atom or group like pyridine which possesses an electron lone-pair N atom and a π ring. Theoretical studies of intermolecular interactions between C6F5Br and C5H5N have been carried out at the M06-2X/aug-cc-pVDZ level without and with the counterpoise method, together with single point calculations at M06-2X/TZVP, wB97-XD/aug-cc-pVDZ and CCSD(T)/aug-cc-pVDZ levels. The σ- and π-holes of C6F5Br exhibiting positive electrostatic potentials make these sites favorably interact with the N atom and the π ring of C5H5N with negative electrostatic potentials, leading to five different dimers connected by a σ-holen bond, a σ-holeπ bond or a π-holeπ bond. Their geometrical structures, characteristics, nature and spectroscopy behaviors were systematically investigated. EDA analyses reveal that the driving forces in these dimers are different. NCI, QTAIM and NBO analyses confirm the existence of intermolecular interactions formed via σ- and π-holes of C6F5Br and the N atom and the π ring of C5H5N. The experimental IR and Raman spectra gave us important information about the formation of molecular complexes between C6F5Br and C5H5N. We expect that the results could provide valuable insights into the investigation of intermolecular interactions involving σ- and π-holes.

Linear σ-hole⋯CO⋯σ-hole intermolecular interactions between carbon monoxide and dihalogen molecules XY (X, Y=Cl, Br).

Carbon monoxide can interact with two dihalogen molecules XY (X, Y=Cl, Br) in the form of X(Y)⋯COX(Y)⋯CO⋯X(Y)X(Y) trimeric complex, and their nature and characteristics were investigated at MP2/aug-cc-pVDZ level without and with counterpoise method, together with single point calculations at CCSD(T)/aug-cc-pVDZ level. The optimized geometries, stretching modes and interaction energies of a series of X(Y)⋯COX(Y)⋯CO⋯X(Y)X(Y) trimeric complexes were obtained and discussed. The cooperativity in these complexes was evaluated. EDA analyses reveal that the electrostatic interaction is the dominant net driving force in each trimer, but the contributions of other interactions like exchange, dispersion and polarization interactions are also important. QTAIM and NCI analyses confirm the existence of attractive halogen-bonding interactions. Additionally, EDDMF analysis was employed for the component dimers of these trimers, which indicates that the formation of halogen-bonding interactions is closely related to the charge shift and the rearrangement of electronic density in the formation of these complexes. The results would provide valuable insight into for these linear halogen bonds.

Insights into the Diels-Alder Reaction between 3-Vinylindoles and Methyleneindolinone without and with the Assistance of Hydrogen-Bonding Catalyst Bisthiourea: Mechanism, Origin of Stereoselectivity, and Role of Catalyst.

The Diels-Alder reaction between 3-vinylindoles and methyleneindolinone can proceed both under catalyst-free conditions and with bisthiourea as the catalyst. The reaction with bisthiourea is much faster and results in higher stereoselectivity of the product. The reaction mechanism, origin of stereoselectivity, and role of the catalyst were elaborated based on quantum mechanical calculations and theoretical methods of reactivity indices, NCI, QTAIM, and distortion/interaction models. In the uncatalyzed reaction, the two C-C bonds that are formed undergo conversion from noncovalent to covalent bonding via a concerted asynchronous mechanism. The weak intermolecular interactions formed in the transition state play important roles. The difference between the interaction and distortion energies is responsible for the stereoselectivity. In the catalyzed reaction, bisthiourea induces both the diene and dienophile to approach it via weak intermolecular interactions, which greatly lowers the energy barrier of the reaction and leads to the product with excellent stereoselectivity. The possible pathways of this reaction were explored, which suggested that the formation of the two C-C bonds goes through either a stepwise or concerted asynchronous mechanism. These results detail the reaction mechanism and shed light on both the significant role of the bisthiourea catalyst and the origin of stereoselectivity for this type of Diels-Alder reaction and related ones.

A free-radical cascade methylation/cyclization of N-arylacrylamides and isocyanides with dicumyl peroxide.

A free-radical cascade methylation/cyclization of a wide range of N-arylacrylamides and isocyanides is demonstrated by using dicumyl peroxide as the methylating reagent, which provides a convenient and selective access to various methylated N-heterocycles such as oxindoles and phenanthridines.

Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma.

We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2) gemcitabine on Days 1 and 8 and 20 mg/m(2) cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2) DDP and 500 mg/m(2) 5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC-RT group were significantly higher than those observed in the Con-RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3-year OS, DFS and MFS rates between the Con-RT and the sPF-RT groups. The GC-RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC-RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.