Synthesis and evaluation of sphinganine analogues of KRN7000 and OCH

[structures: see text] The phytosphingosine-containing alpha-galactosylceramides (alpha-GalCers), KRN7000 and OCH, have been shown to activate NKT cells via interaction with CD1d, a member of the CD1 family of antigen presenting proteins. Evidence from KRN7000 stimulation of NKT cells suggests that alpha-GalCers may have applications in the treatment or prevention of a range of viral, bacterial, and autoimmune conditions. Moreover, OCH, a truncated analogue of KRN7000, appears to induce a T(H)2 bias, which could have implications for the treatment of autoimmune and inflammatory conditions. We have prepared the direct sphinganine-containing analogues of KRN7000 and OCH, 1 and 2, and found them to be comparable in activity to the parent compounds in inducing the release of IL-2, IL-4, and IFNgamma. In addition, compound 2 leads to a cytokine bias similar to that seen with OCH. This is significant because sphinganines are more easily accessed than phytosphingosines, which should facilitate SAR studies.     

Cyclopropylcarbinyl --> homoallyl-type ring opening of ketyl radical anions. Structure/reactivity relationships and the contribution of solvent/counterion reorganization to the intrinsic barrier

[reaction: see text] Following a protocol developed by Mathivanan, Johnston, and Wayner (J. Phys. Chem. 1995, 99, 8190-8195), the radical anions of several cyclopropyl- and oxiranyl-containing carbonyl compounds were generated in an effort to measure the rate constants for their ring opening (k(o)) by laser flash photolysis. The results of these experiments are compared to those obtained from earlier electrochemical studies, and the combined data set is used to rationalize the kinetics of radical anion ring opening in a general context by using Saveant's theory pertaining to stepwise dissociative electron transfer (Acc. Chem. Res. 1993, 26, 455-461). Compared to cyclopropylcarbinyl --> homoallyl rearrangements of neutral free radicals, at comparable driving force, the radical anion ring openings are slightly slower. The small difference in rate is attributed to the contribution of an additional, approximately 2 kcal/mol, solvent reorganization component for the radical anion rearrangements. The solvent reorganization energy for ring opening of these radical anions is believed to be small because the negative charge does not move appreciably in the progression reactant --> transition state --> product.     

Electrochemical nucleation of gold nanoparticles in a polymer film at a liquid-liquid interface

Simultaneous nucleation of gold nanoparticles and polymerization of tyramine has been carried out at an immiscible electrolyte interface. By transferring the gold ion of tetraoctylammoniumtetracloroaurate (TOAAuCl(4)) from the organic to the aqueous phase, a fast homogeneous electron transfer from the tyramine monomer reduces the gold ion. Electropolymerization then proceeds, and gold nanoparticles form. The newly formed nanoparticles act as nucleation sites for the deposition of the oligomers/polymer (and possibly vice versa). This results in gold nanoparticles stabilized in a polytyramine matrix. The size of the nanoparticles is controlled by the concentration of oligomers/polymer in solution. The polymer nanoparticle composite film was analyzed with TEM, XPS, and AFM.     

Target identification for a promising anti-lupus drug

Target identification is one of the more difficult aspects of modern chemical genetics. In this issue of Chemistry & Biology, Johnson et al. provide a compelling case for going through the trouble. As a byproduct of their identification of the cellular target of an anti-lupus compound, they have uncovered a powerful tool for the characterization of a fascinating molecular machine, the F1F0-ATP synthase.     

Remarkably improved complexation of a bisparaquat by formation of a pseudocryptand-based [3]pseudorotaxane

Significant improvement of complexation of a bisparaquat guest was achieved by the formation of a pseudocryptand-based [3]pseudorotaxane.     

Fluorescence studies of the intra-cellular distribution of zinc bis(thiosemicarbazone) complexes in human cancer cells

The uptake of zinc bis(thiosemicarbazone) complexes in human cancer cells has been studied by fluorescence microscopy and the cellular distribution established, including the degree of uptake in the nucleus.     

Photochromism of a spirooxazine in the single crystalline phase

The single crystals of a closed form spirooxazine spiro[azahomoadamantane-isoquinolinoxazine] were found for the first time to undergo photocoloration processes consistent with photochromism in the single crystalline phase.     

Critical magnetic Prandtl number for small-scale dynamo

We report a series of numerical simulations showing that the critical magnetic Reynolds number Rm(c) for the nonhelical small-scale dynamo depends on the Reynolds number Re. Namely, the dynamo is shut down if the magnetic Prandtl number Pr(m)=Rm/Re is less than some critical value Pr(m,c)< approximately 1 even for Rm for which dynamo exists at Pr(m)> or =1. We argue that, in the limit of Re-->infinity, a finite Pr(m,c) may exist. The second possibility is that Pr(m,c)-->0 as Re--> infinity, while Rm(c) tends to a very large constant value inaccessible at current resolutions. If there is a finite Pr(m,c), the dynamo is sustainable only if magnetic fields can exist at scales smaller than the flow scale, i.e., it is always effectively a large-Pr(m) dynamo. If there is a finite Rm(c), our results provide a lower bound: Rm(c) greater, similar 220 for Pr(m)< or =1/8. This is larger than Rm in many planets and in all liquid-metal experiments.