Biphenyl- and Fluorene-Based <i>o</i>‑Carboranyl Compounds: Alteration of Photophysical Properties by Distortion of Biphenyl Rings

Four biphenyl- and fluorene-based <i>o</i>-carboranyl compounds, 4-[2-(<i>p</i>-<i>n</i>-butylphenyl)-1-<i>o</i>-carboran-1-yl]­biphenyl (<b>1B</b>), 4,4″-bis­[2-(<i>p</i>-<i>n</i>-butylphenyl)-1-<i>o</i>-carboran-1-yl]­biphenyl (<b>2B</b>), 2-[2-(<i>p</i>-<i>n</i>-butylphenyl)-1-<i>o</i>-carboran-1-yl]­fluorene (<b>1F</b>), and 2,7-bis­[2-(<i>p</i>-<i>n</i>-butylphenyl)-1-<i>o</i>-carboran-1-yl]­fluorene (<b>2F</b>), were prepared and fully characterized by multinuclear NMR spectroscopy and elemental analysis. The crystal structures of <b>1B</b> and <b>2B</b>, analyzed by single-crystal X-ray diffraction, exhibited distinct distortions of the central biphenyl rings with dihedral angles of 44.2 and 33.1°. In photoluminescence measurements, fluorene-based carboranyl compounds in the rigid state (e.g., in solution at 77 K and as films) exhibited a noticeable emission in the low-energy region below 400 nm. <b>1F</b> displayed a low-energy emissive trace in solution at ambient temperature, whereas biphenyl-based carboranes mainly exhibited high-energy emissions above 400 nm. TD-DFT calculations on the first excited singlet (S₁) state of each compound suggested that the emission in the low-energy region involves intramolecular charge transfer (ICT) between the carborane and central phenylene rings, indicating that the radiative decay of these ICT bands could be enhanced by preventing the distortion of the central biphenyl groups. Furthermore, less distortion on the biphenyl rings of the biphenyl-based analogues at S₁ in the optimized structures supports that these phenylenes must be flat for the formation of stable excited states. Comparison of the quantum efficiency (Φ_PL) and radiative decay constants (<i>k</i>_r) of the <i>o</i>-carboranes also reveals definitively that the structural features of the biphenyl groups can have a decisive effect on those photophysical properties

Biphenyl- and Fluorene-Based <i>o</i>‑Carboranyl Compounds: Alteration of Photophysical Properties by Distortion of Biphenyl Rings

Four biphenyl- and fluorene-based <i>o</i>-carboranyl compounds, 4-[2-(<i>p</i>-<i>n</i>-butylphenyl)-1-<i>o</i>-carboran-1-yl]­biphenyl (<b>1B</b>), 4,4″-bis­[2-(<i>p</i>-<i>n</i>-butylphenyl)-1-<i>o</i>-carboran-1-yl]­biphenyl (<b>2B</b>), 2-[2-(<i>p</i>-<i>n</i>-butylphenyl)-1-<i>o</i>-carboran-1-yl]­fluorene (<b>1F</b>), and 2,7-bis­[2-(<i>p</i>-<i>n</i>-butylphenyl)-1-<i>o</i>-carboran-1-yl]­fluorene (<b>2F</b>), were prepared and fully characterized by multinuclear NMR spectroscopy and elemental analysis. The crystal structures of <b>1B</b> and <b>2B</b>, analyzed by single-crystal X-ray diffraction, exhibited distinct distortions of the central biphenyl rings with dihedral angles of 44.2 and 33.1°. In photoluminescence measurements, fluorene-based carboranyl compounds in the rigid state (e.g., in solution at 77 K and as films) exhibited a noticeable emission in the low-energy region below 400 nm. <b>1F</b> displayed a low-energy emissive trace in solution at ambient temperature, whereas biphenyl-based carboranes mainly exhibited high-energy emissions above 400 nm. TD-DFT calculations on the first excited singlet (S₁) state of each compound suggested that the emission in the low-energy region involves intramolecular charge transfer (ICT) between the carborane and central phenylene rings, indicating that the radiative decay of these ICT bands could be enhanced by preventing the distortion of the central biphenyl groups. Furthermore, less distortion on the biphenyl rings of the biphenyl-based analogues at S₁ in the optimized structures supports that these phenylenes must be flat for the formation of stable excited states. Comparison of the quantum efficiency (Φ_PL) and radiative decay constants (<i>k</i>_r) of the <i>o</i>-carboranes also reveals definitively that the structural features of the biphenyl groups can have a decisive effect on those photophysical properties

Diagnostic Significance of Serum HMGB1 in Colorectal Carcinomas

<div><p>High mobility group box 1 protein (HMGB1), a nuclear protein, can be translocated to the cytoplasm and secreted in colon cancer cells. However, the diagnostic significance of HMGB1 has not been evaluated in colorectal carcinomas. For this purpose, we have screened the expression and secretion of HMGB1 in 10 colon cancer cell lines and 1 control cell line and found that HMGB1 was detected in the culture medium. To evaluate the diagnostic value of HMGB1, we performed an enzyme-linked immunosorbent assay to measure HMGB1 levels and compared them to carcinoembryonic antigen (CEA) levels in the serum samples of 219 colorectal carcinoma patients and 75 healthy control subjects. We found that the serum HMGB1 level was increased by 1.5-fold in patients with colorectal carcinoma compared to those in healthy controls. When HMGB1 and CEA levels were compared, HMGB1 had similar efficacy as CEA regarding cancer detection (the sensitivity was 20.1% for HMGB1 vs. 25.6% for CEA, and the specificity was 96% for HMGB1 vs. 90.7% for CEA). Moreover, the diagnostic accuracy of HMGB1 for stage I cancer was significantly higher than that of CEA (sensitivity: 41.2% vs. 5.9%; specificity: 96% vs. 90.7). When we combined HMGB1 and CEA, the overall diagnostic sensitivity was higher than that of CEA alone (42% vs. 25.6%), and the diagnostic sensitivity for stage I was also elevated (47% vs. 5.9%). However, the prognosis of patients was not related with serum HMGB1 concentrations. Our findings indicate that serum HMGB1 levels are increased in a subset of colorectal carcinomas, suggesting their potential utility as a supportive diagnostic marker for colorectal carcinomas.</p> </div

The demographics of 75 healthy control subjects and 219 colorectal cancer patients according to age and gender.

<p>The demographics of 75 healthy control subjects and 219 colorectal cancer patients according to age and gender.</p

Correlation plot generated with serum CEA and HMGB1 levels.

<p>To assess the relationship between serum CEA and HMGB1 levels for the correlation, we used the Spearman's rho method to determine the correlation coefficient r. (A) Correlation plot of 75 healthy subjects for CEA and HMGB1 serum expression levels. The correlation coefficient r was 0.414 (P = 0.0002) for the two values in healthy control group showing these two markers were positively correlated with each other. The X axis represents CEA levels and the Y axis represents HMGB1 levels, respectively. (B) Correlation plot of 219 colorectal carcinoma patients for CEA and HMGB1 serum expression levels. The correlation coefficient r was −0.0275 (P = 0.6858) for the two values in cancer patients demonstrating that these two markers seems to be negatively correlated with each other despite its low accuracy for this tendency. The X axis represents CEA levels and the Y axis represents HMGB1 levels, respectively.</p

Clinicopathologic features of 219 colorectal cancer patients according to serum HMGB1 levels.

a<p>The cutoff value of HMGB1 was determined by MedCalc software using a previously published algorithm <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034318#pone.0034318-DeLong1" target="_blank">[44]</a>.</p>b<p>The cutoff value of CEA was determined by the level practically used to diagnose CRC <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034318#pone.0034318-Wanebo1" target="_blank">[39]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034318#pone.0034318-Chen1" target="_blank">[45]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034318#pone.0034318-Moertel1" target="_blank">[46]</a>.</p>c<p>MSI, microsatellite-instable cancer.</p>d<p>MSS, microsatellite-stable cancer.</p>e<p>The information of tumor metastasis was followed up over 5 years after surgery.</p

ROC curves generated with serum CEA and HMGB1 levels.

<p>To certify the utility of HMGB1 in the diagnosis of colorectal cancer, we used the ROC method to determine cutoff values. (A) ROC curve for HMGB1. At the cutoff value of 58.2 ng/mL, the sensitivity and specificity were 20.1% and 96%, respectively. Overall AUC was 0.580. (B) ROC curve for the CEA. The sensitivity and specificity were 25.6% and 90.7%, respectively. Overall AUC was 0.581. (C) ROC curve for the combination of HMGB1 and CEA. The sensitivity and specificity were 42.0% and 86.7%, respectively. Overall AUC was 0.643. (D) Comparison of combination of HMGB1 and CEA with CEA alone for stage I colorectal cancer. The overall AUC was higher for the combination of these two markers than for CEA alone. All of the reference lines were determined when the AUC was 0.5.</p

Summary of receiver operating curve methods for HMGB1 and CEA.

<p>Summary of receiver operating curve methods for HMGB1 and CEA.</p

A pilot study on particle emission from printer paper shredders

<p>This project investigated airborne particle releases derived from paper shredding. The characteristics of these emissions have not been studied previously. The objective of this project was to characterize released particles in terms of particle size distribution, particle mass and number concentration, particle morphology and chemical composition, as well as the structure of paper fibers. A significant amount of paper particles were found in the close vicinity of an unenclosed paper shredder during shredding and the manual manipulation of shredded paper. The particle release from shredding using two types of printer paper, two types of shredders, and various shredding frequencies was measured inside the shredder basket. The particles released from paper shredding were found to be in the nanometer to micrometer size ranges, and the particles contained calcium and other metal elements. Manual stirring of shredded paper released the highest particle concentration as measured at the opening of the container. Shredding with 30-s intervals increased the duration of airborne particle release as compared to intermittent shredding. Multiple quantitative analyses were employed to evaluate released particles at various particle size ranges. Two real-time instruments which measured thoracic (<10 μm) and respirable (<4 μm) particle sizes showed comparable concentrations measured inside and outside of the shredder basket.</p> <p>Copyright © 2017 American Association for Aerosol Research</p

HMGB1 is secreted from colon cancer cells and detected in the blood of cancer patients.

<p>HMGB1 in the culture media of colon cancer cells (A) and the sera of colorectal cancer patients (B) exhibited varying degrees of HMGB1 secretion. Culture media were collected, concentrated using a specified column, and the blood samples were depleted of the six most abundant proteins using a MARS column. (A) Normal colon fibroblast cell line CCD18Co did not secrete visible amounts of HMGB1 in the culture media; however most tumor cells secreted HMGB1 with slight differences between tumor cells. Coomassie Brilliant Blue staining indicated that equal amounts of proteins were loaded onto SDS-PAGE gels. (B) Human serum proteins were depleted, and HMGB1 secretion was examined. HMGB1 secretion was observed in both healthy controls and colorectal cancer patients, but elevated serum HMGB1 levels were noted in cancer patients. The numbers provided for the cases match those in our tissue bank database. N represents normal healthy controls, and T represents colorectal carcinoma tumor patients. Coomassie Brilliant Blue staining indicated that equal amounts of proteins were loaded onto SDS-PAGE gels. The ratio of HMGB1∶CBB was calculated by TINA program and depicted under the images.</p