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This tutorial review summarizes recent progress in the design, synthesis, and multifunctional properties of fully conjugated macrocyclic π-systems. We focus on the π-expanded oligothiophene macrocycles after a short survey of macrocyclic conjugated loops and belts such as [n]cycloparaphenylenes, cyclic[n]para-phenylacetylenes, [4]cyclo-2,8-crysenylenes, and cyclo[n]thiophenes. Fully conjugated π-expanded oligothiophene macrocycles possess shape-persistent but sometimes pliable π-frames, and the electronic and optoelectronic properties of the macrocycles largely depend on the π-systems inserted into the oligothiophene macrocycles. Among them, the π-expanded oligothiophene macrocycle composed of 2,5-thienylenes, ethynylenes, and vinylenes is one of the most widely applicable macrocycles for constructing multifunctional π-systems. These π-expanded oligothiophene macrocycles from small to very large ring sizes can be prepared via a short step procedure, and their various solid state structures can be determined by X-ray analysis. Since these macrocycles have inner and outer domains, specific information concerning structural, electronic, and optical properties is expected. Furthermore, π-expanded oligothiophene macrocycles with alkyl substituents exhibit various morphologies depending on nanophase separation of molecules, and a morphological change is observed for the molecular switch.

Two isomers of a multifunctional π-expanded macrocyclic oligothiophene 8-mer, E,E-1 and Z,Z-1, were synthesized using a McMurry coupling of a dialdehyde composed of four 2,5-thienylene and three ethynylene units under high dilution conditions. On the other hand, cyclo[8](2,5-thienylene-ethynylene) 2 was synthesized by intramolecular Sonogashira cyclization of ethynyl bromide 5. From STM measurements, both E,E-1 and Z,Z-1 formed self-assembled monolayers at the solid-liquid interface to produce porous networks, and from X-ray analyses of E,E-1 and 2, both compounds had a round shape with a honeycomb stacked structure. E,E-1 formed various fibrous polymorphs due to nanophase separation of the macrorings. E,E-1 and Z,Z-1 in solution exhibited photochromism upon irradiation with visible and UV light, respectively, and this photoisomerization was confirmed by using STM. Furthermore, amorphous films of Z,Z-1 and E,E-1 showed photoisomerization, although single crystals, fibers, and square tubes of E,E-1 remained unchanged under similar conditions. E,E-1 with a 12.5-14.7 Å inner cavity incorporated fullerene C60 in the cavity in solution and the solid state to produce a Saturn-like complex, whose structure was determined by X-ray analysis. 2 also formed a Saturn-like complex with C60 in the solid state. These Saturn-like complexes are stabilized by van der Waals interactions between the sulfur atoms of 8-mer and C60. The complexes exhibited charge-transfer interactions in the solid state. Like E,E-1, Saturn-like complex E,E-1⊃C60 formed small cube and fiber structures depending on the solvent used, whereas those of Saturn-like complex 2⊃C60 were limited due to the rigidity of the macroring of 2.

Background: Several nested case-control studies have reported the potentially causal relationship between Helicobacter pylori infection and the development of gastric cancer. However, there has been no prospective study evaluating this issue. The purpose of this study is to examine the impact of H pylori infection on gastric cancer occurrence in a general Japanese population (Hisayama, Japan) stratified according to sex, using a prospective study design.Methods: A total of 2602 subjects aged 40 years or older (1070 men; mean age, 57 years; 1532 women; mean age, 59 years) without a history of gastrectomy or gastric cancer were classified according to the status of the serum IgG antibodies to H pylori and observed prospectively for 9 years from 1988. Results:Infection of H pylori was more common in men (71.5%) than in women (62.5%; PϽ.001). The ageadjusted incidence of gastric cancer for men (5.3 per 1000 person-years) was 4-fold higher than that for women (1.3; PϽ.001). In men, the age-adjusted incidence of gastric cancer was significantly higher in the subjects with H pylori infection than in those without it (6.2 vs 2.5; relative risk, 2.59 [95% confidence interval, 1.03-6.50]), whereas no significant difference was observed in women (1.2 vs 1.1; relative risk, 0.99 [95% confidence interval, 0.36-2.68]). These results were similar even after controlling for other risk factors in multivariate analysis. It was estimated that 40.1% of gastric cancers for men in this cohort were attributable to H pylori infection.Conclusion: A significant relationship exists between infection with H pylori and subsequent occurrence of gastric cancer for men but not for women in this Japanese population. Med. 2000;160:1962-1968 S INCE THE discovery of Helicobacter pylori in 1983, much research has focused on the relationship of this bacterium to gastric cancer. A number of clinical case-control studies have found positive associations between H pylori infection and gastric cancer. Arch Intern1 In addition, 8 prospective, nested case-control studies on this issue have since been reported. [2][3][4][5][6][7][8][9] Of these nested casecontrol studies, five [2][3][4]8,9 have shown a significant association between IgG seropositivity for H pylori and gastric cancer, and one 7 has shown that the risk of gastric cancer was significantly increased among subjects showing positive IgA antibodies against H pylori, but not among those showing positive IgG antibodies. Another 2 studies from Asian countries 5,6 have failed to reveal a significant relationship between IgG seropositivity and gastric cancer. Since all previous studies were of crosssectional or nested case-control design, the possibility of selection bias could not be ruled out, and the impact of H pylori infection on the development of gastric cancer in a general population could not be fully evaluated. Further, a number of additional factors that might influence gastric cancer, such as smoking habits, alcohol intake, history of peptic ulcer disease, and dietary factors, 10-14 shoul...

Background and Purpose-Glutathione (GSH) appears to have marked antioxidant activities and therefore may prevent cardiovascular disease (CVD). However, there are very few reports on this subject. In a community-based case-control study, we tested the hypothesis that low levels of plasma GSH are closely associated with CVD and its clinical types. Methods-The association between fasting plasma total GSH (tGSH) levels and CVD were assessed using conditional logistic regression analysis among 134 CVD cases and 435 age-and sex-matched healthy control subjects. Results-Mean tGSH concentrations were lower in all CVD cases than in the control subjects (3.06 versus 3.71 mol/L; Pϭ0.0001). Among the CVD types, both the cerebral infarction cases (2.98 versus 3.59 mol/L; Pϭ0.001) and cerebral hemorrhage cases (2.51 versus 3.43 mol/L; Pϭ0.0027) had significantly lower tGSH levels than the corresponding control groups had. The same tendency was observed for cases of subarachnoid hemorrhage (3.45 versus 3.83 mol/L; Pϭ0.36) and myocardial infarction (3.65 versus 3.77 mol/L; Pϭ0.69), but these differences were not statistically significant. After adjustment for other confounding factors, the risk of CVD was significantly lower in the third (adjusted odds ratio, 041; 95% CI, 0.21 to 0.77) and the fourth quartiles (adjusted odds ratio, 0.25; 95% CI, 0.12 to 0.51) than in the first. This association was most prominent in patients with lacunar infarction or cerebral hemorrhage. Conclusions-These findings suggest that reduced plasma tGSH levels are a risk factor for CVD, especially for cerebral small vessel disease.

Hypofunction of the N-methyl-D-aspartate (NMDA) receptor has been hypothesized to underlie the pathophysiology of schizophrenia, based on the observation that non-competitive antagonists of the NMDA receptor, such as phencyclidine, induce schizophrenia-like symptoms. Mice lacking the NR2A subunit of the NMDA receptor complex are known to display abnormal behaviour, similar to schizophrenic symptoms. The expression of NR2A starts at puberty, a period corresponding to the clinical onset of schizophrenia. This evidence suggests that the NR2A (GRIN2A) gene may play a role in the development of schizophrenia and disease phenotypes. In this study, we performed a genetic analysis of this gene in schizophrenia. Analysis of the GRIN2A gene detected four single nucleotide polymorphisms, and a variable (GT)(n) repeat in the promoter region of the gene. A case-control study (375 schizophrenics and 378 controls) demonstrated evidence of an association between the repeat polymorphism and the disease (P = 0.05, Mann-Whitney test), with longer alleles overly represented in patients. An in-vitro promoter assay revealed a length dependent inhibition of transcriptional activity by the (GT)(n) repeat, which was consistent with a receptor binding assay in postmortem brains. Significantly, the score of symptom severity in chronic patients correlated with repeat size (P = 0.01, Spearman's Rank test). These results illustrate a genotype-phenotype correlation in schizophrenia and suggest that the longer (GT)(n) stretch may act as a risk-conferring factor that worsens chronic outcome by reducing GRIN2A levels in the brain.

Multifunctional π-expanded macrocyclic oligothiophene 6-mer 1, as well as 9- (2) and 12-mers (3), was synthesized using a McMurry coupling reaction as the key step. The 6-mer 1 was converted to cyclo[6](2,5-thienylene-ethynylene) (4) by using a bromination-dehydrobromination procedure. From X-ray analysis, the crystal structures of nonplanar 1 and round-shaped 2 and 4 were elucidated. STM showed that 4 formed a self-assembled monolayer at the liquid/solid interface to produce a hexagonal porous network. Chemical oxidation of 1, 2, and 4 with 1 and 2 equiv of Fe(ClO4)3 produced 1(•+) and 1(2+), 2(•+) and 2(2+), and 4(•+) and 4(2+), respectively. Although oligothiophene radical cations containing β,β-disubstituted thiophenes usually do not form π-dimers, 4(•+) clearly formed a π-dimer owing to its planar, round shape. As for the dications of 1, 2, and 4, 1(2+), which has 34π-electrons, exhibited a large diatropic ring current effect, whereas 34π dication 4(2+) only showed a medium diatropic ring current effect. In contrast to 1(2+) and 4(2+), 52π dication 2(2+) had biradical cationic character instead of Hückel-type cyclic conjugation. Interestingly, 6-mer 1 showed polymorphism and unusual melting point behavior due to the number of stable conformations in the solid state. Single crystals of 1 melted at 176 °C, whereas an amorphous film of 1 crystallized in the temperature range of 80-83 °C to form a lamellarly stacked microcrystalline film, which melted at 139 °C. The polymorphism of 1 was applied to either fluorescence switching or switching of field effect transistor (FET) activity and electrical conductivity.

Excited-state dynamic planarization processes play a crucial role in determining exciton size in cyclic systems, as reported for π-conjugated linear oligomers. Herein, we report time-resolved fluorescence spectra and molecular dynamics simulations of π-conjugated cyclic oligothiophenes in which the number of subunits was chosen to show the size-dependent dynamic planarization in the vicinity of a ring-to-linear behavioral turning point. Analyses on the evolution of the total fluorescence intensity and the ratio between 0-1 to 0-0 vibronic bands suggest that excitons formed in a cyclic oligothiophene composed of six subunits fully delocalize over the cyclic carbon backbone, whereas those formed in larger systems fail to achieve complete delocalization. With the aid of molecular dynamics simulations, it is shown that distorted structures unfavorable for efficient exciton delocalization are more easily populated as the size of the cyclic system increases.