Synthesis and Photochromic Properties of Diaryl [5]Helicene Derivatives.

Photoinduced tuning of aromaticity and correlative molecular properties has attracted enormous interest in recent years both for modulating photochromism properties and designing novel photochromic materials. Here, we report the synthesis and photochemical characterization of diaryl[5]helicene-based diarylethene molecular switches. 3,4-Bis(2,4-dimethyl-5-phenylthiophen-3-yl)dibenzo[c,g]phenanthrene derivative 1 a showed no photochromic reaction, whereas 3,4-bis(2-methyl-5-phenylthiophen-3-yl)dibenzo[c,g]phenanthrene derivative 2 a and 3,4-bis(5-methyl-2-phenylthiazol-4-yl)dibenzo[c,g]phenanthrene derivative 3 a exhibited reversible photochromism in different aprotic solvents with specific light irradiation. Meanwhile, the diarylethene compounds 2 a and 3 a underwent turn-off mode fluorescence photoswitching together with photoisomerization upon light irradiation. Remarkably, the photoinduced changes in the aromaticity of [5]helicene as a central ethene bridge along with the relative smaller activation energy and higher frequency factor facilitated the thermal bleaching rates of diarylethene switches 2 and 3 in solution. This research provides new insight for designing aromatic diarylethene photoswitches for reversible fluorescence switching, photoinduced changes in aromaticity and further fast thermal back reactions.

From Visible to Near-Infrared Light-Triggered Photochromism: Negative Photochromism.

Photochromic compounds, whose key molecular properties can be effectively modulated by light irradiation, have attracted significant attention for their potential applications in various research fields. The restriction of photoisomerization coloration induced by ultraviolet light limits their applications in the biomedical field and some other fields. Negative photochromism, wherein a relatively stable colored isomer transforms to a colorless metastable isomer under low-energy light irradiation, offers advantages in applications within materials science and life science. This review provides a summary of negatively photochromic compounds based on different molecular skeletons. Their corresponding design strategies and photochromic properties are presented to provide practical guidelines for future investigations. Negatively photochromic compounds can effectively expand the range of photochromic switches for future applications, offering unique properties such as responsiveness to visible to near-infrared light.

Comprehensive metabolism study of swertiamarin in rats using ultra high-performance liquid chromatography coupled with Quadrupole-Exactive Orbitrap mass spectrometry.

Swertiamarin, a natural ingredient with potent pharmacological activities in the iridoid glycoside family, had been reported to have significant therapeutic effects on a variety of human diseases.In this study, a systematic and efficient strategy based on UHPLC-Q-Exactive Orbitrap mass spectrometry was established to reveal the metabolic profile of swertiamarin in rat urine, plasma, and faeces.First of all, post-acquisition data-mining methods, including multiple mass defect filters (MMDFs) and high-resolution extracted ion chromatograms (HREICs), were developed to screen the metabolite candidates of swertiamarin from the complete mass scan data sets.Second, according to the diagnostic product ions (DPIs), neutral loss fragments (NLFs), chromatographic retention time, accurate mass measurement and calculated Clog P values, all metabolite candidates were rapidly identified.As a consequence, 49 metabolites altogether, including archetype compound, were preliminarily characterised. The corresponding in vivo biotransformation processes, such as dehydration, dehydrogenation, hydroxylation, hydrogenation, methylation, sulphonation, N-acetylcysteine (NAC) formation, N-heterocyclisation and their composite reactions, were all discovered in the study.In conclusion, our results not only detailedly elucidated many new metabolites and metabolic pathways of swertiamarin, but also provided a reference for further study of its pharmacological mechanism and evaluation of its safety.

[Effect of Danhong Injection on platelet metabolites based on metabonomics technology].

The effect of Danhong Injection on the endogenous metabolites of rabbit platelets was analyzed by the liquid chromatography-mass spectrometry( LC-MS) based metabonomic approach. Anti-platelet aggregation was detected after Danhong Injection treatment and the changes of platelet metabolites were analyzed by metabonomics. Principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) were performed to investigate the effect of Danhong Injection on endogenous metabolites of platelets,characterize the biomarkers,and explore the relevant pathways and the underlying mechanism. As demonstrated by the pharmacodynamic results,Danhong Injection of different doses and concentrations antagonized platelet aggregation in a dose-and concentration-dependent manner. In contrast to the control group,25 differential metabolites such as nicotinic acid,nicotinic acid riboside,and hypoxanthine were screened out after platelets were treated by Danhong Injection. These metabolites,serving as important biomarkers,were mainly enriched in the nicotinic acid-niacinamide metabolic pathway and purine metabolic pathway. This study explored the therapeutic mechanism of Danhong Injection from a microscopic perspective by metabonomics,which is expected to provide a new idea for the investigation of platelet-related mechanisms.

[Analysis and comparison of metabolic processes of salvianolic acid A and salvianolic acid B in rats based on UHPLC-LTQ-Orbitrap MS technology].

The metabolites of salvianolic acid A and salvianolic acid B in rats were analyzed and compared by ultra-high-perfor-mance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS). After the rats were administrated by gavage, plasma at different time points and urine within 24 hours were collected to be treated by solid phase extraction(SPE), then they were gradient eluted by Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) and 0.1% formic acid solution(A)-acetonitrile(B) mobile phase system, and finally all biological samples of rats were analyzed under negative ion scanning mode. By obtaining the accurate relative molecular mass and multi-level mass spectrometry information of metabolites, combined with the characteristic cleavage law of the reference standard and literature reports, a total of 30 metabolites, including salvianolic acid A and B, were identified. Among them, there were 24 metabolites derived from salvianolic acid A, with the main metabolic pathways including ester bond cleavage, dehydroxylation, decarboxylation, hydrogenation, methylation, hydroxylation, sulfonation, glucuronidation, and their multiple reactions. There were 15 metabolites of salvianolic acid B, and the main biotransformation pathways were five-membered ring cracking, ester bond cleavage, decarboxylation, dehydroxylation, hydrogenation, methylation, sulfonation, glucuronidation, and their compound reactions. In this study, the cross-metabolic profile of salvianolic acid A and B was elucidated completely, which would provide reference for further studies on the basis of pharmacodynamic substances and the exploration of pharmacological mechanism.

[Analysis of carnosic acid metabolites in rats by UHPLC-Q-Exactive MS].

A method of ultra-high performance liquid chromatography coupled with quadrupole/electrostatic field Obitrap high-resolution mass spectrometry(UHPLC-Q-Exactive MS) was established to comprehensively identify the metabolites of carnosic acid in rats. After oral gavage of carnosic acid CMC-Na suspension in rats, urine, plasma and feces samples were collected and pretreated by solid phase extraction(SPE). Acquity UPLC BEH C_(18 )column(2.1 mm×100 mm, 1.7 µm) was used with 0.1% formic acid solution(A)-acetonitrile(B) as the mobile phase for the gradient elution. Biological samples were analyzed by quadrupole/electrostatic field Obitrap high-resolution mass spectrometry in positive and negative ion mode. Based on the accurate molecular mass, fragment ion information, and related literature reports, a total of 28 compounds(including carnosic acid) were finally identified in rat samples. As a result, the main metabolic pathways of carnosic acid in rats are oxidation, hydroxylation, methylation, glucuronide conjugation, sulfate conjugation, S-cysteine conjugation, glutathione conjugation, demethylation, decarbonylation and their composite reactions. The study showed that the metabolism of carnosic acid in rats could be efficiently and comprehensively clarified by using UHPLC-Q-Exactive MS, providing a reference for clarifying the material basis and metabolic mechanism of carnosic acid.

Efficient Self-Contained Photoacid Generator System Based on Photochromic Terarylenes.

A series of highly sensitive neutral photoacid generators (PAGs) based on photochromic terarylenes was prepared. Like the example presented herein, these compounds show a subsequent thermal elimination of a Brønsted acid after a light-triggered 6π-electrocyclization, concomitant with the hexatriene aromatization. A novel type of molecular systems was developed, in which one thiazolyl moiety was replaced by a thienyl group. Depending on the solvents and on the nature of the acid source, the quantum yield (QY) for acid generation could reach up to 0.6. Comparative studies on the acid source clearly showed that aromatic leaving groups tend to extinguish the molecular system photoefficiency. A second type was also prepared, in which the nature of the hetero-aromatic rings were identical to our previous example, but their sequence was modified. Therefore, a second level of improvement was achieved in nonpolar solvents, pushing the QY value up to 0.7. Finally, we demonstrated the mesylic acid-releasing PAG as a photocatalyst in a chemically amplified positive resist system.

Dual Photochemical Bond Cleavage for a Diarylethene-Based Phototrigger Containing both Methanolic and Acetic Sources.

In this paper, we present a novel concept for "smarter" photolabile organic compounds combining not one but two caged functions. As proof of principle, this diarylethene-based compound possesses two inhibited chemical groups (OMe and OAc) and its efficient release in different solvents is reported. In low- to medium-polarity media, both MeOH and AcOH are released, with a slight preferential uncaging of AcOH except in 1,4-dioxane, where MeOH is preferentially released. In contrast, DMSO or DMF render AcOH release strongly dominating. DFT calculations of the corresponding photoreactive conformations not only afford strong support to the observed release of MeOH and AcOH but also qualitatively explain the preferential release of acid in terms of dispersive noncovalent interactions. Finally, mechanistic aspects are discussed on the bases of the spectroscopic observations and of the TD-DFT calculations.

Self-Contained Photoacid Generator Triggered by Photocyclization of Triangle Terarylene Backbone.

We herein propose a new type of efficient neutral photoacid generator. A photoinduced 6π-electrocyclization reaction of photochromic triangle terarylenes triggers subsequent release of a Brønsted acid, which took place from the photocyclized form. A H-atom and its conjugate base were introduced at both sides of a 6π-system to form the self-contained photoacid generator. UV irradiation to the 6π-system produces a cyclohexa-1,3-diene part with a H-atom and a conjugate base on the sp(3) C-atoms at 5- and 6-positions, respectively, which spontaneously release an acid molecule quantitatively forming a polyaromatic compound. A net quantum yield of photoacid generation as high as 0.52 under ambient conditions and a photoinitiated cationic polymerization of an epoxy monomer are demonstrated.

Doubly linked chiral phenanthrene oligomers for homogeneously π-extended helicenes with large effective conjugation length.

Helically twisted conductive nanocarbon materials are applicable to optoelectronic and electromagnetic molecular devices working on the nanometer scale. Herein, we report the synthesis of per-peri-perbenzo[5]- and [9]helicenes in addition to previously reported π-extended [7]helicene. The homogeneously π-extended helicenes can be regarded as helically fused oligo-phenanthrenes. The HOMO-LUMO gap decreased significantly from 2.14 to 1.15 eV with increasing helical length, suggesting the large effective conjugation length (ECL) of the π-extended helical framework. The large ECL of π-extended helicenes is attributed to the large orbital interactions between the phenanthrene subunits at the 9- and 10-positions, which form a polyene-like electronic structure. Based on the experimental results and DFT calculations, the ultrafast decay dynamics on the sub-picosecond timescale were attributed to the low-lying conical intersection.

Comprehensive Screening and Identification of Phillyrin Metabolites in Rats Based on UHPLC-Q-Exactive Mass Spectrometry Combined with Multi-Channel Data Mining.

Phillyrin, a well-known bisepoxylignan, has been shown to have many critical pharmacological activities. In this study, a novel strategy for the extensive acquisition and use of data was established based on UHPLC-Q-Exactive mass spectrometry to analyze and identify the in vivo metabolites of phillyrin and to elucidate the in vivo metabolic pathways of phillyrin. Among them, the generation of data sets was mainly due to multichannel data mining methods, such as high extracted ion chromatogram (HEIC), diagnostic product ion (DPI), and neutral loss filtering (NLF). A total of 60 metabolites (including the prototype compound) were identified in positive and negative ion modes based on intuitive and useful data such as the standard's cleavage rule, accurate molecular mass, and chromatographic retention time. The results showed that a series of biological reactions of phillyrin in vivo mainly included methylation, hydroxylation, hydrogenation, sulfonation, glucuronidation, demethylation, and dehydrogenation and their composite reactions. In summary, this study not only comprehensively explained the in vivo metabolism of phillyrin, but also proposed an effective strategy to quickly analyze and identify the metabolites of natural pharmaceutical ingredients in nature.

A self-contained photoacid generator for super acid based on photochromic terarylene.

A self-contained photoacid generator for super acid along with the photoinduced 6π-electrocyclization reaction of the terarylene backbone is demonstrated. The photoinitiated cationic polymerization of epoxy-monomers is achieved with an efficient photochemical quantum yield, Φacid = 0.47.

Photon-Quantitative 6π-Electrocyclization of a Diarylbenzo[b]thiophene in Polar Medium.

The high reactivity of 6π-electrocyclization in polar solvents has remained one of the important challenges for diarylethenes because of the emergence of a twisted intramolecular charge transfer (TICT) state at the excited state in such polar media, which usually quenches the photocyclization reaction. Herein we report on the preparation and highly efficient photocyclization of 2,3-diarylbenzo[b]thiophenes with nonsymmetric side-aryl units in a polar solvent. While the dithiazolylbenzo[b]thiophene showed a suppressed quantum yield of 6π-electrocyclization of 54 % in methanol, the replacement of a thiazole unit with a thiophene ring led to a photon-quantitative 6π-cyclization reaction. The nonsymmetrical modification into the side-aryl units was considered to enhance the CH/π interactions between side-aryl units to support a photoreactive conformation in methanol. The stabilization of the photochromic reactive conformation is expected to suppress the formation of the TICT state at the excited state, leading to highly efficient photoreactivity.