Enantioselectivity in the (salen)Mn-catalyzed asymmetric epoxidation reaction correlates directly with the electronic properties of the ligand substituents, with complexes bearing electron-donating substituents affording highest ee's. Several lines of evidence point to a single factorcontrol of the position of the transition state along the reaction coordinateas being responsible for the electronic effects on enantioselectivity. Analysis of the epoxidation of cis-β-deuteriostyrene reveals that electron-rich catalysts display a more pronounced secondary inverse isotope effect than electron-deficient catalysts. A strong correlation between ΔΔH ⧧ and the electronic character of the catalyst is also observed. The conclusion that enantioselectivity is tied to the position of a transition state along the reaction coordinate may hold general implications for the design of asymmetric catalysts, particularly those that effect reactions without substrate precoordination.

No abstract

The genetic background of T lymphocytes influences development of the T helper (TH) phenotype, resulting in either resistance or susceptibility of certain mouse strains to pathogens such as Leishmania major. With an in vitro model system, a difference in maintenance of responsiveness of T cells to interleukin-12 (IL-12) was detected between BALB/c and B10.D2 mice. Although naive T cells from both strains initially responded to IL-12, BALB/c T cells lost IL-12 responsiveness after stimulation with antigen in vitro, even when cocultured with B10.D2 T cells. Thus, susceptibility of BALB/c mice to infection with L. major may derive from the loss of the ability to generate IL-12-induced TH1 responses rather than from an IL-4-induced TH2 response.

Genetic background of the T cell can influence T helper (Th) phenotype development, with some murine strains (e.g., B1O.D2) favoring Thl development and others (e.g., BALB/c) favoring Th2 development. Recently we found that B1O.D2 exhibit an intrinsically greater capacity to maintain interleukin 12 (IL-12) responsiveness under neutral conditions in vitro compared with BALB/c T cells, allowing for prolonged capacity to undergo IL-12-induced Thl development. To begin identification of the loci controlling this genetic effect, we used a T-cell antigen receptor-transgenic system for in vitro analysis of intercrosses between BALB/c and B1O.D2 mice and have identified a locus on murine chromosome 11 that controls the maintenance of IL-12 responsiveness, and therefore the subsequent Thl/Th2 response. This chromosomal region is syntenic with a locus on human chromosome 5q31.1 shown to be associated with elevated serum IgE levels, suggesting that genetic control of Thl/Th2 differentiation in mouse, and of atopy development in humans, may be expressed through similar mechanisms.

No abstract