We have synthesized and theoretically calculated 5-methylisoindolo[2,1- a ]quinoline derivatives as novel near-infrared absorption dyes via a ruthenium-catalyzed one-pot metathesis/oxidation/1,3-dipolar cycloaddition protocol. The reactivity in 1,3-dipolar cycloaddition was governed by the electronic effect of aromatic ring substituents. Substrates with an electron-withdrawing group on the aromatic ring afforded higher yields. The maximal absorption wavelength of 3,5-dimethyl-11-phenylisoindolo[2,1- a ]quinoline-7,10-dione and 11-(4-methoxyphenyl)-5-methylisoindolo[2,1- a ]quinoline-7,10-dione in MeOH increased to 736 and 737 nm, although that of 3a was 727 nm.

Balb/C nude and C.B-17 SCID mice were inoculated with salivary gland passaged cytomegalovirus (SG-MCMV) intraperitoneally. Dissemination of the virus in the systemic and ocular tissues was studied by the direct immunofluorescence test, and the virus growth in each tissue was titrated in mouse embryonic fibroblasts. The mode of viral spread was assessed by inhibiting macrophage function by silica and administering polyclonal murine anti-MCMV antibody in the circulation. The virus first reached the eyelid, conjunctiva, and cornea. Subsequently, it spread in the outer ocular muscles and chorioretinal layer. Ocular tissues were involved as part of a generalized infection. Abrogation of macrophage function by silica did not affect the outcome of the viral distribution. Administration of antibody prior to and 3 days after the viral infection prevented virus dissemination. Ocular CMV infection occurred initially at the anterior segment of the eye in an immunocompromised host. Free virus, not macrophage-bound virus, disseminated via the bloodstream.

Among the Arg-Gly-Asp (RGD)-containing sequences that are known to be cell-binding domains of fibronectin, 500 µg/ml of Arg-Gly-Asp-Ser (RGDS) and Gly-Arg-Gly-Asp-Ser showed 100% inhibition of the attachment of cultured lens epithelial cells (TOTL-86 cells), when they were added to culture medium and coincubated with the cells for 24 h whereas RGD at concentrations of 500, 1,000 and 2,000 µg/ml had no such activity. After 48 h of cocultivation of 800, 400 or 200 µg/ml of RGDS with TOTL-86 cells, the percentage of floating cells was 100, 30.1 or 11.1%, respectively. After 144 h of cocultivation with RGDS, the percentage of floating cells was 1.6,2.4 or 1.9%, respectively, indicating that RGDS was not cytotoxic to lens epithelial cells. However, replacing the medium with fresh medium containing new RGDS peptide resulted in floating of cells. We also studied the inhibitory effect of two other amino acid sequences that are found in cell-binding sites of the fibronectin molecule: Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (EILDVPST) and Arg-Glu-Asp-Val (REDV). At 500 and 1,000 µg/ml, respectively, neither EILDVPST nor REDV has an inhibitory effect on the attachment of TOTL-86 cells, while RGDS at a concentration of 500 µg/ml completely inhibited the attachment of the cells in 24 h of incubation.

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Cycloaddition catalyzed by transition metals such as rhodium (I) is an important way to synthesize functionalized molecules in medicinal chemistry. When the reagent has a saturated ring containing more than five carbons (or heavy atoms), the reaction can progress when the compound has an allenyl group, but not for a vinyl group. Here, we constructed two computational models for allenylcyclopentane-alkyne and vinylcyclopentane-alkyne, and obtained their reaction pathways using density functional theory (DFT). From the reaction pathways, we confirmed that the former model has a much lower reaction energy than the latter. We also found that the molecular orbitals of the transition state structure at the rate-controlling step contribute significantly to the difference in reactivity between the two models.