Isolation and Total Synthesis of Bromoiesol sulfates, Antitrypanosomal arylethers from a Salileptolyngbya sp. Marine Cyanobacterium.

Bromoiesol sulfates A (1) and B (2), new polyhalogenated aryl sulfates, were isolated from a Salileptolyngbya sp. marine cyanobacterium along with their hydrolyzed compounds, bromoiesols A (3) and B (4). To pick up the candidates of their structures, we used Small Molecule Accurate Recognition Technology (SMART), an artificial intelligence-based structure-prediction tool, and their structures were elucidated on the basis of single-crystal X-ray diffraction analysis of bromoiesols (3 and 4). In addition, to verify the structures, the total synthesis of bromoiesol A sulfate (1) and bromoiesol A (3) was achieved. The bromoiesol family, especially bromoiesols (3 and 4), selectively inhibited the growth of the bloodstream form of Trypanosoma brucei rhodesiense, the causative agent of human African sleeping sickness.

5,12-Diacetyl-5,12-dihydroquinoxalino[2,3-b]quinoxalines: Solid-State Fluorescence, AIE Properties, and Orbital Switching by Substituent Effect.

The compound 5,12-diacetyl-5,12-dihydroquinoxalino[2,3-b]quinoxaline 1 a and its derivatives were prepared, and their solid- and solution-state spectroscopic properties were studied; 1 a shows stronger fluorescence in solution than in the solid state due to aggregation caused by self-quenching. Phenyl- or alkoxy-substituted derivatives 1 b-d show solid-state fluorescence with moderate quantum yields of about Φ=0.12-0.15, although the corresponding values are 0.01-0.07 in solution. The spectroscopic properties of alkoxy-substituted derivatives were hardly changed compared to 1 a and 1 b, although 1 a and 1 b have similar absorption and fluorescence maxima in solution and in the solid state. DFT calculations indicate that orbital switching occurs between HOMO and HOMO-1 and HOMO-2 due to orbital interactions with introduced substituents. Crystal structure analysis revealed that the molecules have bent structures around tertiary nitrogen atoms and form a characteristic dimeric structure.

Magnetic Interactions through a Nonconjugated Framework Observed in Back-to-Back Connected Triazinyl-Nitroxyl Biradical Derivatives.

Three hetero-biradical derivatives, with the structure of a back-to-back connected benzotriazinyl and tetramethyl or tetraethylisoindoline N-oxyl sharing a common benzo ring, 3-tert-butyl-1-phenyl-1,4,6,8-tetrahydro-6,6,8,8-tetramethyl-pyrrolo[4,5-g]-1,2,4-benzotriazin-4-yl-7-oxyl (1-tBu), 1,3-diphenyl-1,4,6,8-tetrahydro-6,6,8,8-tetramethyl-pyrrolo[4,5-g]-1,2,4-benzotriazin-4-yl-7-oxyl (1-Ph), and 3-tert-butyl-1-phenyl-1,4,6,8-tetrahydro-6,6,8,8-tetraethyl-pyrrolo[4,5-g]-1,2,4-benzotriazin-4-yl-7-oxyl (2-tBu), were synthesized and characterized by single-crystal X-ray analyses, variable-temperature magnetic susceptibility studies, and DFT calculations. Temperature dependences of the magnetic susceptibilities of 1-tBu, 1-Ph, and 2-tBu exhibit broad maxima at 70, 71, and 43 K, respectively. Although these radical derivatives form a columnar or chained assembly in the solid state, magnetic measurements of diluted samples in the polymer matrices and computational results imply that the magnetic properties of the polycrystalline sample can be explained by a two-spin system with an intramolecular antiferromagnetic interaction. The magnetic behavior can be reproduced by using the Bleaney-Bowers model, with 2J=-80.0 cm-1 for 1-tBu, 2J=-77.1 cm-1 for 1-Ph, and 2J=-48.9 cm-1 for 2-tBu. The moderately strong intramolecular antiferromagnetic interactions can be interpreted by a through-bond interaction through the nonconjugated framework and/or through-space interactions based on molecular orbital theory. The strong distance dependency between the N-O spin site and vinylic carbon atoms indicates that the orbital interaction plays an important role in the intramolecular magnetic interaction. The reduced magnetic interaction in 2-tBu relative to those of 1-tBu and 1-Ph can be attributed to restricted rotation of the tetraethyl group.

Synthesis and Magnetic Properties of Stable Radical Derivatives Carrying a Phenylacetylene Unit.

A nitronyl nitroxide derivative, 2-phenylethynyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl-3-oxide (1), and two verdazyl derivatives carrying a phenylacetylene unit, 1,5-diphenyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (2) and 1,5-diisopropyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (3), were synthesized and their packing structures were studied by X-ray crystallographic analysis and magnetically characterized in the solid state. While 1 and 3 had an isolated doublet spin state, 2 formed an antiferromagnetically coupled pair (2J/kB = -118 K). Density functional theory (DFT) calculations reveal that the spin density polarized in the phenyl group decreases as the dihedral angle between the phenyl ring and radical plane increases.

In Silico Study, Synthesis, and Cytotoxic Activities of Porphyrin Derivatives.

Five known porphyrins, 5,10,15,20-tetrakis(p-tolyl)porphyrin (TTP), 5,10,15,20-tetrakis(p-bromophenyl)porphyrin (TBrPP), 5,10,15,20-tetrakis(p-aminophenyl)porphyrin (TAPP), 5,10,15-tris(tolyl)-20-mono(p-nitrophenyl)porphyrin (TrTMNP), 5,10,15-tris(tolyl)-20-mono(p-aminophenyl)porphyrin (TrTMAP), and three novel porphyrin derivatives, 5,15-di-[bis(3,4-ethylcarboxymethylenoxy)phenyl]-10,20-di(p-tolyl)porphyrin (DBECPDTP), 5,10-di-[bis(3,4-ethylcarboxymethylenoxy)phenyl]-15,20-di-(methylpyrazole-4-yl)porphyrin (cDBECPDPzP), 5,15-di-[bis(3,4-ethylcarboxymethylenoxy)phenyl]-10,20-di-(methylpyrazole-4-yl)porphyrin (DBECPDPzP), were used to study their interaction with protein targets (in silico study), and were synthesized. Their cytotoxic activities against cancer cell lines were tested using 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay. The interaction of porphyrin derivatives with carbonic anhydrase IX (CAIX) and REV-ERBß proteins were studied by molecular docking and molecular dynamic simulation. In silico study results reveal that DBECPDPzP and TrTMNP showed the highest binding interaction with REV- ERBß and CAIX, respectively, and both complexes of DBECPDPzP-REV-ERBß and TrTMNP-CAIX showed good and comparable stability during molecular dynamic simulation. The studied porphyrins have selective growth inhibition activities against tested cancer cells and are categorized as marginally active compounds based on their IC50.

Magnetic Interaction Observed in Hetero Biradical Derivatives Containing a 2,2,5,5-Tetramethylpyrrolin-1-yloxyl Unit as a Localized Spin Center.

The magneto-structural correlation of hetero biradical derivatives containing a 2,2,5,5-tetramethylpyrrolin-1-yloxyl unit as a localized spin center and a verdazyl or nitronyl nitroxide radical is reported. The magnetic susceptibility measurement revealed that the verdazyl attached biradical 1 exhibits ferromagnetic interaction, whereas antiferromagnetic interaction is observed for nitronyl nitroxide attached biradical 2. An EPR study in toluene glass matrix suggests that both 1 and 2 have a ground triplet state. DFT calculations predict that there is intramolecular ferromagnetic interaction for both biradicals. The computation also suggests that the intramolecular magnetic interaction is weaker with larger dihedral angle between pyrroline ring and verdazyl ring/O-N-C-N-O plane of nitronyl nitroxide. The computations of model compounds 3 and 4 suggest that spin polarization on vinylic moiety without distribution of SOMO might be an essential condition for the intramolecular ferromagnetic interaction.

Wurster's Blue-type cation radicals framed in a 5,10-dihydrobenzo[a]indolo[2,3-c]carbazole (BIC) skeleton: dual electrochromism with drastic changes in UV/Vis/NIR and fluorescence.

Electron-donating dihydrobenzindolocarbazoles (BICs) 1 a-c, which adopt planar disk-shaped geometries, were prepared by gold(I)-catalyzed cyclization as a key step. Due to the presence of a 1,4-phenylenediamine (PD) moiety in the framework, they undergo reversible one-electron oxidation to the corresponding Wurster's Blue (WB)-type species that exhibits NIR absorptions up to λ=1200 nm. In the case of the N,N'-dimethyl derivative, cation radical 1 c(+.) is stable enough to be isolated as a salt and X-ray analysis indicated paraquinoid-type bond alternation in the WB core unit, whereas the bond lengths in the peripheral benzene rings are identical to those in the neutral donor. Upon electrochemical interconversion, the redox pairs of 1 a-c and 1 a-c(+.) exhibited an electrochromic response in the UV/Vis/NIR region, which was accompanied by a drastic change in the fluorescence spectrum because only neutral donors 1 a-c are highly emissive (Φ(F) : 0.7-0.8).

7,7,8,8-Tetraaryl-o-quinodimethane stabilized by dibenzo annulation: a helical π-electron system that exhibits electrochromic and unique chiroptical properties.

When two benzene rings are fused to a tetraaryl-o-quinodimethane skeleton, sterically hindered helical molecules 1 acquire a high thermodynamic stability. Because the tetraarylbutadiene subunit contains electron-donating alkoxy groups, 1 undergo reversible two-electron oxidation to 2(2+), which can be isolated as deeply colored stable salts. Intramolecular transfer of the point chirality (e.g., sec-butyl) on the aryl groups to helicity induces a diastereomeric preference in dications 2 b(2+) and 2 c(2+), which represents an efficient method for enhancing circular-dichroism signals. Thus, those redox pairs can serve as new electrochiroptical response systems. X-ray analysis of dication 2(2+) revealed π-π stacking interaction of the diarylmethylium moieties, which is also present in solution. The stacking geometry is the key contributor to the chirosolvatochromic response.

[Impact of iterative reconstruction on shape reproducibility of three-dimensional computed tomography].

The purpose of this study was to evaluate the effect of an iterative reconstruction method (IR) on shape reproducibility in three-dimensional (3D) computed tomography images. We used an IR (sinogram-affirmed iterative reconstruction: SAFIRE) implemented in a 64-channel multi slice computed tomography system (Siemens, SOMATOM Definition AS). We scanned a simulated vessel phantom with 180-HU vessel contrast at various radiation doses and reconstructed axial images of filtered back projection (FBP) and SAFIRE. Then we reconstructed multi-planar reconstruction (MPR) and volume rendering (VR) images from the axial images. Roundness was evaluated from MPR images and vessel surface roughness was evaluated from pixel value profiles of a vessel in VR images and visual evaluation by radiological technologists. In comparison on equivalent dose, the roundness and roughness were improved with increase of SAFIRE strength level. However, in comparison on equivalent noise (standard deviation: SD) of axial images, SAFIRE strength levels of 2 to 5 were significantly inferior to FBP (p<0.05). SAFIRE strength of 1 with a dose reduction of 19% maintained the shape reproducibility in all evaluations. Therefore, it would be not appropriate to use the SD of axial image as index for the dose reduction rate determination of 3D-CT images.

[Investigation of vessel visibility in the iterative reconstruction method in coronary computed tomography angiography using simulated vessel phantom].

Iterative reconstruction methods can reduce the noise of computed tomography (CT) images, which are expected to contribute to the reduction of patient dose CT examinations. The purpose of this study was to investigate impact of an iterative reconstruction method (iDose(4), Philips Healthcare) on vessel visibility in coronary CT angiography (CTA) by using phantom studies. A simulated phantom was scanned by a CT system (iCT, Philips Healthcare), and the axial images were reconstructed by filtered back projection (FBP) and given a level of 1 to 7 (L1-L7) of the iterative reconstruction (IR). The vessel visibility was evaluated by a quantitative analysis using profiles across a 1.5-mm diameter simulated vessel as well as visual evaluation for multi planar reformation (MPR) images and volume rendering (VR) images in terms of the normalized-rank method with analysis of variance. The peak CT value of the profiles decreased with IR level and full width at half maximum of the profile also decreased with the IR level. For normalized-rank method, there was no statistical difference between FBP and L1 (20% dose reduction) for both MPR and VR images. The IR levels higher than L1 sacrificed the spatial resolution for the 1.5-mm simulated vessel, and their visual vessel visibilities were significantly inferior to that of the FBP.