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A new class of N-confused porphyrin 1embedded with a carbazole subunit was prepared via [3 + 1] acid-catalyzed condensation of appropriate precursors. 1underwent smooth metal complexation with Pd(II) and Cu(II) salts to provide the corresponding diamagnetic 1-Pdand paramagnetic 1-Cu, respectively. The single-crystal X-ray structure of 1-Pdis evident with a square-planar Pd-center through C–H activation of inverted pyrrole. Superconducting quantum interference device analysis combined with electron paramagnetic resonance (EPR) results provided insights into the paramagnetic nature of 1-Cu. Further, a ratiometric enhancement of near-IR fluorescence at 746 nm was found to be reversible upon adding CN–and F–ions. The solid-state structure of 1-Pdconfirms that the anionic species is due to NH deprotonation.

A series of 5,10,15‐tris(pentafluorophenyl) doubly N‐confused bilanes were synthesized in a stepwise manner with the aid of sterically demanding N‐protecting groups, in which the difference in reactivity between regular pyrrole and N‐confused pyrrole plays a crucial role in the synthetic strategy. Some doubly N‐confused bilanes were converted into porphyrinoids or a unique 2:2 copper(II) complex with a helical structure. In addition, the conformations and electronic states of the doubly N‐confused bilanes were investigated theoretically, giving fruitful information about the effect of confusion on the bilane skeleton.

Mix and match: The title porphyrinoid has been synthesized and shows unique coordination chemistry by incorporating two different metals with different oxidation states (see figure). X‐ray crystallography was used to confirm that a rectangular conformation in both mono‐ and binuclear complexes was retained.

Background:Though an increased efficacy of carmustine and temozolomide (TMZ) has been demonstrated by inactivation of O6-methylguanine-DNAmethyltransferase(MGMT) with O6-benzyl-guanine (BG) in human pancreatic tumors refractive to alkylating agents, the regulatory mechanisms have not been explored. Methods:The effects of TMZ and BG on apoptosis, cell growth, the mitotic index, cell cycle distribution, and protein expression were studied byTUNEL, cell counting, flow cytometry, and Western blot analysis, respectively. Results:The wt-p53 human pancreatic tumor cell line Capan-2 and p53-efficient mouse embryonic fibroblasts (MEFs) were more responsive to treatment with TMZ + BG than mutant p53 Capan-1 and p53-null MEFs. S phase delay with a subsequent G2/M arrest was observed in Capans in response to BG + TMZ. The G1-to-S transition delay in Capan-2 was associated with p53-dependent apoptosis and was distinctly different from the presumed mismatch repair (MMR) killing operative during the G2/M arrest. The effect of p53on BG +TMZ toxicity was supported by a marked change in apoptosis when p53 function was restored/inactivated. There was an early induction of MMR proteins in p53-efficient lines. Conclusion:p53 provokes a classic proapoptotic response by delaying G1-to-S progression, but it may also facilitate cell killing by enhancing MMR-related cell cycle arrest and cell death.

Redox active hexaphyrins: Modified hexaphyrins with five mesolinks have been synthesized and characterized. These hexaphyrins not only exhibit conformational flexibility but also undergo facile redox interconversion between aromatic 26π and 28π non‐aromatic systems in accordance with (4n+2) Hückel's rule.

One of the predominant polymicrobial infections of humans is expressed clinically as periodontal disease. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia have been strongly implicated as members of a pathogenic consortium in the etiology of adult periodontitis. In this study we hypothesized that P. gingivalis, T. denticola, and T. forsythia are synergistic in terms of virulence potential and induce chronic periodontal inflammation that leads to alveolar bone resorption in a polymicrobial infection in rats. Groups of rats were infected with either P. gingivalis, T. denticola, or T. forsythia in monomicrobial infections or with all three species in polymicrobial oral infections with or without Fusobacterium nucleatum. PCR analyses of oral microbial samples demonstrated that rats infected with one bacterium were orally colonized by each of the bacteria during the study interval, and increased serum immunoglobulin G (IgG) antibody levels substantiated the interaction of the host with the infecting bacteria. PCR analyses of the rats with polymicrobial infections demonstrated that most rats were infected with P. gingivalis, T. denticola, and T. forsythia as a consortium. Furthermore, all rats exhibited a significant increase in the level of IgG antibody to the polymicrobial consortium. Radiographic measurement of alveolar bone resorption showed that rats infected with the polymicrobial consortium with or without F. nucleatum exhibited significantly increased alveolar bone resorption compared to the resorption in uninfected control rats, as well as the resorption in rats infected with one of the microbes. These results documented that P. gingivalis, T. denticola, and T. forsythia not only exist as a consortium that is associated with chronic periodontitis but also exhibit synergistic virulence resulting in the immunoinflammatory bone resorption characteristic of periodontitis.

The syntheses, characterization, and spectral properties of smaragdyrin–azobenzene conjugates are reported. Our synthetic strategy involves linking the azobenzene group in one of the precursors to a dipyrromethane subunit, which was achieved by reaction of azobenzenecarbaldehyde with pyrrole under TFA catalysis. A [3+2] acid-catalyzed oxidative coupling of this precursor with the tripyrrane moiety gave the expected smaragdyrin–azobenzene conjugates. The azobenzene is in the (E) conformation both in the precursor and in the smaragdyrin conjugates, as revealed by its single-crystal X-ray structure. Electronic absorption and emission spectral studies reveal the presence of a moderate electronic interaction between the azobenzene and smaragdyrin π-systems. Irradiation experiments at 360 nm reveal the presence of a reversible (E)/(Z) transformation of the azobenzene moiety in the precursors 3b and 4b. However, in the smaragdyrin conjugates the formation of the (Z) conformer leads to the decomposition of the macrocycle upon prolonged irradiation. Excitation at the azobenzene absorption results in the appearance of the emission band of smaragdyrin, thereby suggesting an energy transfer. The electrochemical data reveal that ring oxidations of the smaragdyrin macrocycle become harder upon azobenzene introduction, which suggests the electron-withdrawing nature of the azobenzene in these conjugates. A significant shortening of the N–N bond (0.067 Å) and elongation of the C–N bonds (0.055 and 0.069 Å) in 7a relative to the azobenzene–dipyrromethane precursor 4a clearly reveal a rearrangement of the electronic π-delocalization pathway in the smaragdyrin–azobenzene conjugates. RhI binds to one amino and one imino nitrogen atom in the smaragdyrin cavity to form a 1:1 complex. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

The synthesis and characterization of the first examples of core‐modified corrole dimers linked through the mesopositions are described. The dimers are obtained by a simple AgI‐ or FeIII‐catalyzed coupling reaction in near‐quantitative yields. The corroles obtained are metalated with metal ions, such as CuIIand NiII. The electronic‐absorption spectral studies reveal weak electronic interaction between the two subunits and the exciton coupling observed for the free‐base corrole dimer (1717 cm−1) is lower than that for the corresponding protonated derivative (4081 cm−1). The solution‐state structure derived from 1H and two‐dimensional NMR spectral studies reveals a noncoplanar arrangement of two corrole units. Geometry optimization at the B3LYP‐631G level also confirms the noncoplanar arrangement of corroles with a dihedral angle of 64.8° between two corrole planes. The electron paramagnetic resonance (EPR) and magnetic characterization studies on the paramagnetic copper‐metalated dimer indicate that both copper ions behave as independent spins without any noticeable interaction. Results of fluorescence studies reveal a bathochromic shift of about 60 nm upon dimerization. The first hyperpolarizability (β) measured by using the hyper Rayleigh scattering (HRS) method reveals doubling of the βvalues on progressing from monomer to dimer, attributed to enhanced π conjugation. The use of copper dimers in the photocleavage of DNA is also explored. It is shown that the bimetallic copper dimer selectively cleaves the nucleic acids without affecting the proteins, suggesting a possible application of the copper complex in the removal of nucleic acid contaminants from protein extracts through a simple photolytic pathway.

Spatially Fractionated high dose (Grid) Radiation Treatment (SFGRT) involves irradiation of bulky tumors with one high, grid-delivered, dose of 15 Gy followed by multiple consecutive doses of 2 Gy each. The goal of this study is to determine the effect of this treatment on serum ceramide content and to investigate possible involvement of ceramide in tumor regression after SFGRT. Serum ceramide and Secretory SMase (SSMase) were quantified in 11 patients before and at 24, 48 and 72 h after the dose of 15 Gy. Furthermore, LDL particles were isolated from the serum and their apoptotic ability was tested in human endothelial cells by TUNEL assay. Sixty seven per cent (6/8) of the patients with partial (PR) or complete (CR) response showed statistically significant increase in serum ceramide levels. Of the non-responders in the study, none showed an elevation in ceramide. S-SMase activity underwent similar changes. LDL particles from serum of patients collected 72 hours after SFGRT sensitized the endothelial cells to undergo apoptosis in response to 5 Gy radiation that by itself had only modest effect on cell death. Independent elevation of ceramide content of endothelial cells that were otherwise resistant to radiation-induced cell death also was sufficient to sensitize these cells to apoptosis. Serum S-SMase activity and ceramide content increase following SFGRT and correlate with the clinical response. Apparently, these changes are in the LDL-associated ceramide and may contribute to better tumor reduction after SFGRT, due to the ability of LDL–derived ceramide to sensitize endothelial cells for apoptosis.

A variety of cytokines especially TNF-α and TGF-β are known to be released in response to high dose radiation of tumors. However, these are not normally measurable in systemic circulation unless high levels of these cytokines are produced by tumor cells. This study was undertaken to see if circulating levels of these cytokines could be measured in the serum of patients treated with high dose spatially fractionated (GRID) radiation and to correlate the finding of these cytokines with clinical response to treatment. Thirty-four patients (31 patients had single treatment site and 3 patients had 2 treatment sites) treated with spatially fractionated (GRID) radiation were entered in this study. Serum samples were collected before treatment and at 24, 48 and 72 hours after GRID radiation. Sandwich enzyme linked immunosorbent assay (ELISA) was performed to estimate the levels of TNF-α and activated TGF-β1 proteins. Seven of 37 patients studied had no TNF-α protein before treatment but showed induction of TNF-α after GRID radiation. Three patients showed faint basal level of TNF-α protein before treatment and these levels were induced after treatment. Three patients showed a basal level of TNF-α protein before treatment and these levels decreased after treatment. In 21 cases no TNF-α protein was detected before or after treatment at the time points measured. In the case of TGF-β1 protein, 2 patients showed no TGF-β1 protein before GRID radiation and an induction of TGF-β1 protein was observed after treatment. Seven patients showed basal level of TGF-β1 protein prior to treatment and these levels were induced after treatment. Seventeen patients showed a basal level of TGF-β1 protein before treatment and these levels decreased after treatment. In 8 cases no TGF-β1 protein was detected before or after treatment. Complete clinical response (CR) to GRID therapy was seen in 12/37 (32%) treatment sites and partial response (PR) in 18/37 (49%) treatment sites. A strong correlation was observed between clinical CR rate and TNF-α induction. The rate of CR was 6/10 (60%) in patients where TNF-α was induced as compared to 6/27 (23%) treatment sites in patients where TNF-α induction was not seen (p = 0.029). No significant correlation with CR rate and TGF-β1 induction (44% vs. 28%, p = 0.36) was observed. High dose spatially fractionated (GRID) radiation results in significant induction of TNF-α that can be measured in serum of some patients 24 – 72 hours after radiation. Complete tumor response strongly correlated with the induction of TNF-α levels in the serum.

Activated iron electrodes have been prepared by electrochemical impregnation with both mercury and sulfur. The performance of such electrodes in 10 A h nickel/iron cells has revealed that the activation exerts only a marginal influence on the discharge capacity. By contrast, ageing of the activated electrodes is harmful to discharge performance.

1,4-Phenylene-linked cyclotrimer (3T) and cyclotetramer (4T) have been synthesized via Lewis acid-catalyzed self-condensation of appropriate precursors. Structural and Density Functional Theory (DFT) studies reveal the disruption of annulenic conjugation in both 3Tand 4Tby linking phenylene rings prevented them from global antiaromaticity. The single crystal X-ray structure of 4Treveals all the nitrogens are pointing toward the macrocyclic core with near-planar and square-shaped geometry, thus in sharp contrast to the ring-strained conformation of 3T.

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The objective of this report is to describe the characteristics of patients who develop infections associated with implantable cardioverter-defibrillators (ICDs) implanted with sternotomy and thoracotomy approaches. A retrospective chart review identified all patients who underwent ICD implantation at a university medical center from November 1982 through February 1990. Several patient and procedural variables were compared between infected patients and noninfected patients. One hundred fifty-seven patients underwent 202 ICD generator implantations (45 generator changes), and nine of these patients developed infection (4.5% per implantation and 5.7% per patient). Of the patient variables analyzed, a significant correlation (P < .0001) was made only with a diagnosis of diabetes mellitus: 36% of diabetics versus 3.9% of nondiabetics were infected. The only patientor procedure-specific variable that was found to correlate with the development of infection was the presence of diabetes mellitus.