Coordination-Driven Self-Assembly Using Ditopic Pyridyl-Pyrazolyl Donor and p-Cymene Ru(II) Acceptors: [2]Catenane Synthesis and Anticancer Activities.

Coordination-driven self-assembly of m-bis[3-(4-pyridyl)pyrazolyl]xylene (L) and [(p-cymene)2Ru2(OO∩OO)2(OTf)2] (A1) (OO∩OO = 6,11-dioxido-5,12-naphthacenedione) in methanol resulted in a mixture of [2]catenane 1 and macrocycle 2, and self-assembly in nitromethane resulted in pure macrocycle 2, whereas the coordination-driven self-assembly of L and similar acceptors [(p-cymene)2Ru2(OO∩OO)2(OTf)2] [OO∩OO = 5,8-dioxido-1,4-naphthoquinonnato (A2); 2,5-dioxido-1,4-benzoquinonato (A3); oxalato (A4)] resulted in the formations of monomeric macrocycles 3-5, respectively. All self-assembled macrocycles were obtained in excellent yields (>90%) as triflate salts and were fully characterized by multinuclear NMR, elemental analysis, and electrospray ionization mass spectrometry (ESI-MS). The structures of [2]catenane 1 and macrocycles 5 were confirmed by single-crystal X-ray diffraction analysis. The X-ray structure of 1 confirmed an edge-to-face interaction between the tetracene moiety in parallel-displaced π-π stacks (3.5 Å), and CH···π (2.5 Å) stabilizes the [2]catenane topology. Macrocycles 2-5 were assessed for anticancer activities using human cancer cell lines of different origins, and the macrocycle 3 was found to exhibit the best inhibitory effect and to do so in a dose-dependent manner. Further examination with the Tali apoptosis assay suggested the growth inhibitory effect of 3 involved the induction of the programmed cell death, and this suggestion was supported by observations of PARP and caspase 3 cleavage after treating cells with 3. In addition, exposure to 3 increased the expression of Bax and repressed the expression of Bcl-2, thus indicating the involvement of macrocycle 3 upstream of Bax and Bcl-2 in the apoptotic signaling pathway. Macrocycle 3 also tended to repress metastasis as evidenced by changes in the transcriptional expressions E- and N-cadherin (markers of metastasis). Furthermore, a stability assay demonstrated macrocycle 3 remained stable at high concentration.

Coordination-Driven Self-Assembly and Anticancer Potency Studies of Ruthenium-Cobalt-Based Heterometallic Rectangles.

Three new cobalt-ruthenium heterometallic molecular rectangles, 1-3, were synthesized through the coordination-driven self-assembly of a new cobalt sandwich donor, (η5 -Cp)Co[C4 -trans-Ph2 (4-Py)2 ] (L; Cp: cyclopentyl; Py: pyridine), and one of three dinuclear precursors, [(p-cymene)2 Ru2 (OO∩OO)2 Cl2 ] [OO∩OO: oxalato (A1 ), 5,8-dioxido-1,4-naphthoquinone (A2 ), or 6,11-dioxido-5,12-naphthacenedione (A3 )]. All of the self-assembled architectures were isolated in very good yield (92-94 %) and were fully characterized by spectroscopic analysis; the molecular structures of 2 and 3 were determined by single-crystal X-ray diffraction analysis. The anticancer activities of bimetallic rectangles 1-3 were evaluated with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, an autophagy assay, and Western blotting. Rectangles 1-3 showed higher cytotoxicity than doxorubicin in AGS human gastric carcinoma cells. In addition, the autophagic activities and apoptotic cell death ratios were increased in AGS cells by treatment with 1-3; the rectangles induced autophagosome formation by promoting LC3-I to LC3-II conversion and apoptotic cell death by increasing caspase-3/7 activity. Our results suggest that rectangles 1-3 induce gastric cancer cell death by modulating autophagy and apoptosis and that they have potential use as agents for the treatment of human gastric cancer.

Effects of different rhBMP-2 release profiles in defect areas around dental implants on bone regeneration.

This study was undertaken to evaluate the effects of different rhBMP-2 release profiles in defect areas around dental implants on osseointegration and bone regeneration. Four beagle dogs (13-15 kg) were used. The defect was 3 mm deep and there was a 1 mm gap around the implant. Each of the four implants was installed on the right and left mandibular alveolar ridges. After the implants were placed, experimental groups were applied to the surrounding defect area (n = 8 in each group, the control group was not treated). The inject group was injected with rhBMP-2 solution directly. In the gel group, rhBMP-2 mixed with a hydrogel matrix was applied. In the particle-gel group, rhBMP-2-embedded poly(lactic-co-glycolic acid)(PLGA) microparticles mixed with hydrogel matrix were applied to maintain consistent release. Sequential fluorescent labeling and histological analysis were performed to evaluate the new bone formation and osseointegration in the defect area. In the control group, larger marginal bone loss was detected as compared with the other groups (P < 0.05). The gel group showed significantly higher levels of BIC in the buccal and lingual defect areas compared with the other groups (P < 0.05). New-bone percentages in the inject and gel groups formed more new bone than in the particle-gel and control groups (P < 0.05). Despite the limitations of this study, the use of only hydrogel, which allows early release of rhBMP-2 followed by consistent extended release, showed better bone formation and osseointegration than simple injection or PLGA microparticles with hydrogel matrix.

A case of solitary fibrous pleura tumor associated with severe hypoglycemia: doege-potter syndrome.

Solitary fibrous tumor of the pleura (SFTP) is a rare primary intrathoracic tumor that arises from mesenchymal tissue underlying the mesothelial layer of the pleura. It usually has an indolent clinical course. The hypoglycemia that accompanies SFTP was first described by Doege and Potter independently in 1930, hence the eponym Doege-Potter syndrome (DPS). The incidence of DPS is reported to be ~4%. In this report, we present a typical case of DPS that was cured through complete surgical resection.

Coordination-driven self-assembly of an iridium-cornered prismatic cage and encapsulation of three heteroguests in its large cavity.

A hollow iridium-cornered prismatic cage was self-assembled without the assistance of any template. The cage was found to be capable of encapsulating heteroguest's triplet in its perfect sized cavity, producing the first demonstration of quintuple structure by an octahedral metal cornered prismatic cage.

Anticancer potency studies of coordination driven self-assembled arene­Ru-based metalla-bowls.

New tetranuclear cationic metalla-bowls 5­7 with the general formula [Ru4(p-cymene)4(N∩N)2(OO∩OO)2]4+ (N∩N=2,6-bis(N-(4-pyridyl carbamoyl)pyridine, OO∩OO=2,5-dihydroxy-1,4-benzoquinonato (5), OO∩OO=5,8-dioxydo-1,4-naphthaquinonato (6), OO∩OO=hoxonato (7)) were prepared by the reaction of the respective dinuclear ruthenium complexes 2­4 with a bispyridine amide donor ligand 1 in methanol in the presence of AgO3SCF3.These new molecular metalla-bowls were fully characterized by analytical techniques including elemental analysis as well as 1H and 13C NMR and HR-ESI-MS spectroscopy. The structure of metalla-bowl 6 was determined from X-ray crystal diffraction data. A UV/visible study was also carried out for the entire suite of new complexes. As with recent studies of similar arene­Ru complexes, the inhibition of cell growth by metalla-bowls was established against SK-hep-1 (liver cancer), AGS (gastric cancer), and HCT-15 (colorectal cancer) human cancer cell lines. Inhibition of cell growth by 6 was found to be considerably stronger against all cancer cell lines than the anticancer drugs, doxorubicin and cisplatin. In particular, in colorectal cancer cells, expression of the cancer suppressor genes APC and p53 was increased following exposure to 6.