The chemistry of reactive intermediates (guests) within the confined spaces of another species (host) presents interesting opportunities for the discovery of new reactions."] The reactive behavior of carbenes in constrained systems is expected to be very different from that of free carbenes in solution or in the gas phase. The "tight fit" between the structures of hosts and the guest carbenes should alter both inter-and intramolecular reactions. Furthermore, suitable cavity sizes will restrict the mobility of the entrapped carbenes, which are then anticipated to react more selectively.Carbene chemistry in different media has been studied extensively over the past decades.121 Nearly nothing, however, is known about carbenes generated in constrained systems. Although x-and fi-cyclodextrin (CD) have been the only molecules employed as hosts,[31 the intermediacy of carbenes or the corresponding carbenoids has not been firmly e~t a b l i s h e d .~~]The relatively stabler4] diazirine I derived from adamantaneIsl was chosen as the guest-carbene precursor and fi-CD as the molecular reaction vessel (see Scheme 1). Compound 1 was prepared according to the literature,['] purified by column chromatography (silica gel) under the exclusion of light, and shown to be pure by ' H N M R spectroscopy.The / K D complex of 1 (1 . p-CD) was synthesized (ratio of host: guest ca. 3: 1) and characterized. To avoid the replacement of entrapped guest molecules in the fi-CD cavity by solvent molecules, solid-state NMR spectroscopy was used for the characterization. Cross polarization/magic angle spinning (CP/MAS) 13C N M R spectra provide convincing evidence that an inclusion complex was formed.['] This is further supported by powder X-ray diffraction spectra of 1, P-CD, 1 P-CD, and a physical mixture of 1 and a-CD.Under the conditions of fast atom bombardment (FAB) mass spectrometry, however, the loosely bound complex does not survive, and only the (M -H)-peak of 8-CD is observed.I8]In addition, molecular modeling was used to gain information about the fit and possible position of 1 within the C D cavity.'" According to calculations carried out by using the SYBYL force field with default parameters, 1 is nearly completely submerged into the fl-CD cavity with the diazirine function at the wider rim of the truncated cone.

Acute pulmonary toxicity and tumor promotion by the food additive 2,6-di-tert-butyl-4-methylphenol (BHT) in mice are well documented. These effects have been attributed to either of two quinone methides, 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone (BHT-QM) formed through direct oxidation of BHT by pulmonary cytochrome P450 or a quinone methide formed by hydroxylation of a tert-butyl group of BHT (to form BHTOH) followed by oxidation of this metabolite to BHTOH-QM. BHTOH-QM is a more reactive electrophile compared to BHT-QM due to intramolecular interactions of the side-chain hydroxyl with the carbonyl oxygen. To further examine this bioactivation pathway, an analogue of BHTOH was prepared, 2-tert-butyl-6-(1'-hydroxy-1'-methyl)ethyl-4-methylphenol (BPPOH), that is structurally very similar to BHTOH but forms a quinone methide (BPPOH-QM) capable of more efficient intramolecular hydrogen bonding and, therefore, higher electrophilicity than BHTOH-QM. BPPOH-QM was synthesized and its reactivity with water, methanol, and glutathione determined to be >10-fold higher than that of BHTOH-QM. The conversions of BPPOH and BHTOH to quinone methides in lung microsomes from male BALB/cByJ mice were quantitatively similar, but in vivo the former was pneumotoxic at one-half of the dose required for the latter and one-eighth of the dose required for BHT, as determined by increased lung weight:body weight ratios following a single i.p. injection. Similar differences were found in the doses of BHT, BHTOH, or BPPOH required for tumor promotion after a single initiating dose of 3-methylcholanthrene followed by three weekly injections of the phenol. The downregulaton of calpain II, previously shown to accompany lung tumor promotion by BHT and BHTOH, also occurred with BPPOH. The correlation between biologic activities of these phenols and the reactivities of their corresponding quinone methides provides additional support for the role of BHTOH-QM as the principal metabolite responsible for the effects of BHT on mouse lung.

Type 1 diabetes results from the breakdown of peripheral tolerance. As regulators of T cell activation, antigen-presenting cells (APC) modulate peripheral tolerance and hence contribute to the immune dysregulation characteristic of insulin-dependent diabetes mellitus (IDDM). We initially observed an increased importance of NOD B cell APC function in a T cell priming assay as compared to non-autoimmune strains. Consistent with this increased APC function, we found that NF-‹ B nuclear translocation is increased in unmanipulated NOD and NOD.B10Sn-H2 b B cells and that, in addition, NOD B cells are more sensitive to NF-‹ Bactivating stimuli. We obtained similar results using NOD bone marrow-derived dendritic cell (BMDC) cultures. As costimulatory molecules have been shown to be NF-‹ B responsive, we examined the expression of these markers on NOD APC. Both B cells and BMDC expressed elevated levels of CD80 and CD40. Finally, NOD B cells provided better allostimulation than B cells from non-autoimmune strains. Therefore, hyperactivation of NF-‹ B and increased expression of CD80 and CD40 by NOD B cells and BMDC may be a contributing factor in the selection of effector T cells observed in IDDM.

Inclusion complexes of adamantane2-spiro-3'-diazirine (1) in different X-and Y-type zeolites (faujasite) have been prepared. These complexes were analyzed by FT-IR and '3C CP-MAS NMR spectroscopy. The guest-host complexes were irradiated with UV light in the solid state and the reaction products separated from the host and analyzed. Product ratios obtained in zeolites are totally different from those obtained by irradiation of 1 in solution or as a pure compound. In zeolites the main products isolated are 2A-dehydroadamantane (4) and 2-adamantanol (6). In addition, adamantanone (5) and adamantane are formed. While 2-adamantanol(6) is thought to be a product from an acid-catalyzed reaction, the strained 2,4-dehydroadamantane (4) derives from an intramolecular 1,3 C-H insertion of adamantanylidene (3). In stark contrast to reactions in solution, in zeolites the formation of adamantanone azine (7) resulting from an intermolecular reaction is only of minor significance.

No abstract