A High-Affinity and Removable Iminium Dication Guest for Recycling of Cucurbit[7]uril Materials.

An iminium dication 1 was designed as a high-affinity and easily removable guest for cucurbit[7]uril (CB[7]). X-ray crystallographic analysis shows that maximized N+···O═C ion-dipole interactions and perfect packing coefficient are responsible for the high affinity of 1 for CB[7] (Ka > 1011 M-1). Under alkaline conditions, included 1 in CB[7]·1 is hydrolyzed into 2,6-adamantanedione and pyrrolidine that can be fully removed by further extraction, enabling the recycling of CB[7] materials.

Expected and unexpected photoreactions of 9-(10-)substituted anthracene derivatives in cucurbit[n]uril hosts.

By arranging substrates in a "reaction ready" state through noncovalent interactions, supramolecular nanoreactors/catalysts show high selectivity and/or rate acceleration features. Herein, we report the host-guest complexation of 9-(10-)substituted anthracene derivatives (G1-G3) with cucurbit[n]uril (CB[n], n = 8, 10), and the photoreactions of these derivatives in the presence of CB[n] hosts. Both CB[10] and CB[8] showed no obvious effects on the photoreaction of 9,10-disubstituted derivative G1. For G2 and G3, CB[10] operated as either a nanoreactor or catalyst (10%) for the photodimerization of two compounds with high selectivity and high yield. However, although CB[8] formed a 1 : 2 complex with G2, as also observed with CB[10], the photosolvolysis product (9-anthracenemethanol) was obtained quantitatively after photoirradiation of the CB[8]·2G2 complex. This unexpected photosolvolysis was rationalized by a plausible catalytic cycle in which anthracene acts as a photoremovable protecting group (PPG) and the carbonium ion intermediate is stabilized by CB[8].

Transgenic inhibition of astroglial NF-kappa B improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation.

In the CNS, the transcription factor NF-kappaB is a key regulator of inflammation and secondary injury processes. Following trauma or disease, the expression of NF-kappaB-dependent genes is activated, leading to both protective and detrimental effects. In this study, we show that transgenic inactivation of astroglial NF-kappaB (glial fibrillary acidic protein-IkappaB alpha-dominant-negative mice) resulted in reduced disease severity and improved functional recovery following experimental autoimmune encephalomyelitis. At the chronic stage of the disease, transgenic mice exhibited an overall higher presence of leukocytes in spinal cord and brain, and a markedly higher percentage of CD8(+)CD122(+) T regulatory cells compared with wild type, which correlated with the timing of clinical recovery. We also observed that expression of proinflammatory genes in both spinal cord and cerebellum was delayed and reduced, whereas the loss of neuronal-specific molecules essential for synaptic transmission was limited compared with wild-type mice. Furthermore, death of retinal ganglion cells in affected retinas was almost abolished, suggesting the activation of neuroprotective mechanisms. Our data indicate that inhibiting NF-kappaB in astrocytes results in neuroprotective effects following experimental autoimmune encephalomyelitis, directly implicating astrocytes in the pathophysiology of this disease.

Disruption of the beta2-integrin CD11d (alphaDbeta2) gene fails to protect against experimental autoimmune encephalomyelitis.

The fourth member of the beta(2)-integrin family of adhesion molecules, CD11d (alpha(D)beta(2)), is expressed on a wide variety of immune cells, however its function in autoimmune diseases, including EAE remains unknown. We induced EAE in wild-type and CD11d(-/-) C57BL/6 mice using myelin oligodendrocyte glycoprotein (MOG(35-55)) peptide. The clinical course and histopathology of EAE were identical in both groups of mice throughout the disease course. There were no significant differences in the infiltration of leukocyte subsets into the central nervous system or in the production of cytokines from T cells isolated from the spleen or spinal cord from both groups of mice. Our data demonstrate that CD11d is not required for the development of EAE and, to date, is the only beta(2)-integrin molecule whose deletion does not result in attenuated disease.