A general approach toward the synthesis of multi-functionalized diazapentacene derivatives 1, using 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene (TDCp, 2), a substituted benzene-1,2-diamine (ADA, ...6), and a naphthalene-1,4-dione (BQ, 3) as the building units, is described. The synthesis basically entails three operations: (i) oxidation of the dichloroetheno-bridge in the Diels-Alder cycloadduct 4 of TDCp and 3, (ii) condensation of the 1,2-diketone 5 thus generated with an ADA to give quinoxaline-fused polycyclic compounds 7, followed by (iii) an one-pot, three-reaction process keyed upon the base- or acid-catalyzed aromatization-driven Grob-type fragmentation to produce quinoxaline ring-embedded diazapentaceneesters 1. The diazapentacene derivative 1a underwent the nucleophilic aromatic ipso-amination with primary and secondary amines to afford the amino-substituted derivatives 12, which tend to self-assemble in solid state driven by the cofacial π-stacking interactions, demonstrated by the crystal packing structures of 12a and 12f.
Display omitted
•The multi-functionalized diazapentacene derivatives 1 can be synthesized by a general and flexible approach, using 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene, a substituted benzene-1,2-diamine, and a naphthalene-1,4-dione as the building units.•The diazapentacene derivatives 1 have an electronic structure exhibiting high electron affinity and are good candidates for n-type semiconducting material.•The diazapentacene derivatives 1 undergo the ipso-amination with electron-donating primary and secondary amines as nucleophiles, paving the way for exploring prospective application of synthesizing the D–π–A molecules (push–pull systems).
The U-shaped septuple-bridged 7,7orthocyclophanes (10Aa–c and 10Ca–c), side-walled with cofacial quinoxaline (QX) and benzoquinoxalinedione (BQXO) rings and mounted with N-(anthracen-9-ylmethyl)-, ...N-(naphthalen-2-ylmethyl)-, and N-(pyren-1-ylmethyl)succinimide ring, were, respectively, synthesized from the corresponding N-(4-methoxybenzyl)succinimide ring-incorporated, QX and benzoquinoxaline (BQX) ring-walled analogues molecular systems (1A and 1B). The synthesis involved oxidative removal of N-(4-methoxybenzyl) group from 1A and 1B with ceric ammonium nitrate (CAN), followed by Gabriel-type N-alkylation with a proper arylmethyl bromide. The BQX ring in 1B was found to be oxidized to BQXO ring in the CAN-oxidation step. The molecular cleft-like 7,7orthocyclophanes thus synthesized display a tendency of self-assembly chiefly driven by intermolecular π–π stacking interaction, forming V-shaped or linear tail-to-tail (wall-to-wall) dimers that further assemble in head-to-head (aryl-to-aryl) arrangement to form tetramers and polymers. The event of molecular assembly was investigated by concentration-variant 1H NMR spectroscopic and X-ray crystallographic analyses.
Display omitted
Background. This study tested the hypothesis that circulating microparticles (MPs) are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer ...(ES-NSCLC). Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1) platelet-derived activated MPs (PDAc-MPs), (2) platelet-derived apoptotic MPs (PDAp-MPs), (3) endothelial-derived activated MPs (EDAc-MPs), and (4) endothelial-derived apoptotic MPs (EDAp-MPs), were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1 ( n = 56 ) (one-year survivors) and patients who survived less than one year were categorized into group 2 ( n = 51 ) (one-year nonsurvivors). Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (all P < 0.05 ). Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1 ( P = 0.006 ) . Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (all P < 0.035 ). Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.
New rigid bicyclic N-anthrylsuccinimide 1a, 1b, 2a, and 2b were prepared. The Caryl–Nimide bond rotational barriers, intra/intermolecular arene–arene interactions, and photophysical properties were ...investigated. The rotational behaviors are more significantly controlled by the position of Caryl–Nimide connection than the sidewall framework. The fluorescence energy transfer (ΦET) in 1a and 1b was estimated to be 61% and 53%, respectively. The difference is attributed to the position of Caryl–Nimide connection, which directly influences the relative orientation of donor (naphthalene) and acceptor (anthracene).
Background. Endothelial-derived microparticles (EDMPs) and platelet-derived microparticles (PDMPs) have been reported to be increasing in various diseases including malignant diseases. Here, we ...investigated whether these MPs may be useful biomarkers for predicting lung cancer (LC) disease status, cell type, or metastasis. Methods and Results. One hundred and thirty LC patients were prospectively enrolled into the study between April 2011 and February 2012. Flow cytometric analysis demonstrated that the circulating levels of platelet-derived activated MPs (PDAc-MPs), platelet-derived apoptotic MPs (PDAp-MPs), endothelial-derived activated MPs (EDAc-MPs), and endothelial-derived apoptotic MPs (EDAp-MPs) were significantly higher in LC patients than in 30 age- and gender-matched normal control subjects (all P<0.05). Additionally, circulating level of PDAc-MPs was significantly lower (P=0.031), whereas the circulating levels of the other three biomarkers did not differ (all P>0.1) in early stage versus late stage LC patients. Furthermore, the circulating levels of the four types of MPs did not differ among patients with different disease statuses (i.e., disease controlled, disease progression, and disease without treatment, i.e., fresh case) (all P>0.2) or between patients with or without LC metastasis (all P>0.5). Moreover, only the circulating level of EDAp-MPs was significantly associated with the different cell types (i.e., squamous cell carcinoma, adenocarcinoma, and small cell carcinoma) of LC (P=0.045). Conclusion. Circulating MP levels are significantly increased in LC patients as compared with normal subjects. Among the MPs, only an increased level of EDAp-MPs was significantly associated with different LC cell types.
A series of semi-rigid N-phenylsuccinimides I (11Xy), N-arylmethylsuccinimides II (18Xy), and N,N′-(1,4-arylenebis(methylene))disuccinimides III (19XyX) walled by quinoxaline (QX), ...dimethylquinoxaline (diMQX), or benzoquinoxaline (BQX) ring were synthesized. Intramolecular π–π interactions in solution were detected by NMR and fluorescence spectroscopy, in terms of reciprocal anisotropic shielding and exciplex formation, respectively. The X-ray crystallographic analysis revealed the preferential conformations in solid state, which were compatible with the results of conformational studies by NMR and fluorescence spectroscopy. The results collectively indicated that 18Xy and 19XyX are driven by intramolecular π–π interactions in the mode of π-stacking (face-to-face) or T-shaped (edge-to-face) configuration to preferentially adopt the folded- and the double folded-conformation, respectively, where the spaced aromatic rings are oriented syn to each other in close proximity.
Display omitted
We report a three-step synthesis of 12 septuple-bridged 7,7orthocyclophanes
11 comprising (i) two quinoxaline-based sidewalls and (ii) a linker built-in with a succinimide ring that carries phenyl,
...p-methoxyphenyl,
p-hydroxyphenyl, or
p-methoxybenzyl appendants. The synthesis began from the Diels–Alder adduct of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene (
1) and succinimide ring-fused dioxatetracyclodecadiene
9, followed by ruthenium-promoted oxidation of dichloroetheno-bridges in the adduct to generate a bis-α-diketone, which was then condensed with an arene-1,2-diamine to construct sidewalls (phane parts), furnishing U-shaped septuple-bridged 7,7orthocyclophanes
11 embedding quinoxaline, dimethylquinoxaline, or benzoquinoxaline rings. Concentration-variant
1H NMR spectra of
N-
p-methoxybenzyl substituted orthocyclophanes (
11zd,
11xd, and
11yd) and single-crystal structures of four orthocyclophanes (
11xa,
11yd,
11zb, and
11zd) revealed that the U-shaped septuple-bridged 7,7orthocyclophanes
11 have a tendency of self-assembly, forming V-shaped dimeric entities driven chiefly by intermolecular π–π stacking interaction in both solid state and solution of high concentration.
Display omitted
A three-step synthesis of nineteen Z-shaped quadruple-bridged 6,6 and 6,4orthocyclophanes comprising two quinoxaline-based sidewalls are described. The synthesis began from the bis-Diels−Alder ...adducts
B1–
B3 followed by ruthenium-promoted oxidation of dichloroetheno-bridges in the adducts to generate a bis-α-diketones, which were then condensed with various arene-1,2-diamines (
9a–
g) to construct sidewalls (phane parts) of Z-shaped quadruple-bridged orthocyclophanes
D1-
3,
D2g, and
D3g. Single-crystal structures of six orthocyclophanes (
D1a,
D2a,
D2f,
D3f,
D2g-
α, and
D3g-
α) were obtained and revealed that the C
Ar−H⋯π and π⋯π stacking interactions between
N-containing arene rings are the major driving force for molecular assembly and crystal packing, in addition to the interactions involving the polar OCH
3 groups and the solvate molecules.
Display omitted
The U-shaped, multifunctionalized tetraetheno-bridged dicyclopentab,ianthracenediol 10 was synthesized to serve as a platform molecule. The molecule was prepared from the Diels−Alder adduct 5a of ...tricycloundecatriene 3 and bicyclo2.2.2octene-fused p-benzoquinone 4. Functionalization of 10 to construct crab-like molecules was achieved via the base-promoted bis-O-alkylation of two endo-oriented hydroxyl groups at termini in 10 with the following alkyl halides: allyl, propagyl, and benzyl bromides; 1-bromo- and 1-iodo-4-(bromomethyl)benzene; 9-(bromomethyl)anthracene; 1-(bromomethyl)pyrene; and isomeric bromomethylpyridines. Single-crystal X-ray structures were obtained for bis-phenyl (21) and bis-pyrenyl (25) crabs, and for the silver(I) complex (32 and 33) crabs. The silver(I) complex 32 from bis-o-pyridyl crab 30 is a 2+2 dimeric dimetallocyclophane, and 33 from bis-m-pyridyl crab 29 is a 1+1 metallo-bridged cyclophane. The self-assembled intramolecular π-stacking of pyrenyl rings in 25 with an interplanar distance of 3.40 Å and the consequent π−π interactions were revealed by the X-ray crystal structure and its luminescence property.
The development of an expedient synthesis toward quinoxaline ring-embedded polyacenoquinone esters with the generic structure A is demonstrated by the synthesis of penta- and hexacenoquinone esters. ...They are potential n-type small molecules, capable of undergoing successive reductions and self-assembling in face-to-face π-stacks.
PDF
