Helix-to-Disc Conversion of Thia[6]helicenes into Coronenes Facilitated by Sulfur Oxidation and Fluorination.

Helicenes, with their unique helical structures, have long captured the interest of synthetic chemists, not only as end products, but also as versatile platforms for further chemical transformations. However, transforming [6]helicene into planar coronene typically requires harsh conditions and poses significant challenges. Herein, we demonstrate that replacing the terminal benzene ring of [6]helicene with a thiophene ring enables its photochemical transformation into coronene. Sulfur oxidation of the thiophene ring enables the corresponding thermal transformation, and the terminal tetrafluorination of the opposite benzene ring further accelerates this process, yielding 1,2-difluorocoronene, as confirmed by X-ray crystallography. The transformation begins with an intramolecular Diels-Alder reaction, whose activation energy is significantly lowered by these structural changes. Our findings underscore the utility of strategic modifications such as sulfur oxidation and fluorination in promoting this "helix-to-disc" conversion and opening new avenues for synthesizing functional polycyclic aromatics.

Hypoxia suppresses stretch-induced elongation and orientation of macrophages.

BACKGROUND: Cells in the arterial wall are normally subjected to approximately 10% cyclic stretch due to pulsatile blood flow. In addition, cells in the walls of abdominal aortic aneurysms (AAA) experience hypoxic conditions caused by the accumulation of intraluminal thrombus. Such combined stimulation by hypoxia and stretch can induce abnormal functions in macrophages that infiltrate into the AAA walls; however, the details of these effects are unknown. OBJECTIVE: The aim of this study is to know the influence of a combination of cyclic stretch and hypoxia on the macrophage morphology. METHODS: Morphological changes, such as aspect ratio and orientation, in macrophages exposed to 10% cyclic stretch and 2.2% O2 hypoxia during 24 h were evaluated with usage of ImageJ software. We also assessed expression of hypoxia-inducible factor-α (HIF-1α), an intracellular signaling factor, in macrophages by western blotting. RESULTS: The results indicate that hypoxia significantly suppresses stretch-induced orientation in the direction of the stretch and elongation of macrophages. We also found that the combination of cyclic stretch and hypoxia significantly increased HIF-1α expression. CONCLUSIONS: These results suggest that hypoxia suppresses morphological responses of macrophages to cyclic stretch by elevating HIF-1α expression.

Combined stimulation with cyclic stretching and hypoxia increases production of matrix metalloproteinase-9 and cytokines by macrophages.

Macrophages in the vessel wall of advanced abdominal aortic aneurysms (AAAs) are subjected to cyclic stretching and hypoxia because of pulsatile blood flow and intraluminal thrombi, respectively. It is possible that these conditions induce abnormal changes in macrophage functions, such as increased production of matrix metalloproteinase-2 (MMP-2), MMP-9, and inflammatory cytokines, leading to weakening of the aortic wall through excessive extracellular matrix disruption. Here we show the effects of cyclic stretching and hypoxia on the production of MMP-9 and inflammatory cytokines by macrophages. Gelatin zymography revealed that MMP-9 production by macrophages was significantly increased by 5% and 10% cyclic stretching under hypoxia (2.2% O(2)). Using enzyme-linked immunosorbent assay, we also evaluated the production of 12 different inflammatory cytokines and found that there was a tendency toward higher expressions of interleukin-8 and tumor necrosis factor-α by macrophages subjected to 10% cyclic stretching under normoxia and hypoxia. Next, we evaluated apoptosis of smooth muscle cells (SMCs) in medium conditioned by macrophages cultured under the 2 conditions described above. SMC apoptosis increased significantly when exposed to media harvested from macrophages subjected to 10% cyclic stretching under normoxia and hypoxia. On the basis of these results, we believe that macrophages produce cytokines that induce SMC apoptosis. Our results suggest that the combination of cyclic stretching and hypoxia stimulates MMP-9 and cytokine production in macrophages, which may result in weakening of AAA walls.