Total synthesis of epothilone B, epothilone D, and cis- and trans-9,10-dehydroepothilone D

The phosphonium salt 35, representing one of the two principal subunits of the epothilones, was prepared from propargyl alcohol via heptenone 22. A Wittig reaction of the phosphorane from 35 with aldehyde 33, obtained from aldol condensation of ketone 27 with aldehyde 28, afforded 37. Seco acid 42 derived from 37 underwent lactonization to give cis-9,10-dehydroepothilone D (43) which was selectively reduced with diimide to yield epothilone D (4) and, after epoxidation, epothilone B (2). An alternative route to epothilone D employed alkyne 39, obtained from 33, in a Castro-Stephens reaction with allylic bromide 34 to furnish enyne 40. The latter was semi-hydrogenated to provide 37. Alkyne 46, prepared from alcohol 45, was converted to trans-vinylstannane 47 which, in a Stille coupling with allylic chloride 50, gave 51. Seco acid 52 derived from 51 underwent lactonization to give trans-9,10-dehydroepothilone D (54). Bioassay data comparing the antiproliferative activity and tubulin polymerization of 43 and 54 with epothilone B (2), epothilone D (4), and paclitaxel (7) showed that the synthetic analogues were less potent than their natural counterparts, although both retain full antiproliferative activity against a paclitaxel-resistant cell line. No significant difference in potency was noted between cis analogue 43 and its trans isomer 54.     

Direct observation of misfit dislocation glide on surfaces

Using scanning tunneling microscopy we have observed thermally induced dislocation glide in monolayer Cu films on Ru(0001) at room temperature. The motion is governed by a Peierls barrier that depends on the detailed structure of the dislocations, in particular upon whether the threading dislocations that terminate them are dissociated or not. Calculations based on the Frenkel-Kontorova model reproduce the threading dislocation structure and provide estimates of the Peierls barrier and dislocation stiffness which are consistent with experiment.     

Experimental evidence for a light and broad scalar resonance in D(+) --> pi(-)pi(+)pi(+) decay

From a sample of 1172 +/- 61 D(+)-->pi(-)pi(+)pi(+) decays, we find gamma(D(+)-->pi(-)pi(+)pi(+))/gamma(D(+)-->K-pi(+)pi(+)) = 0.0311 +/- 0.0018(+0.0016)(-0.0026). Using a coherent amplitude analysis to fit the Dalitz plot of these decays, we find strong evidence that a scalar resonance of mass 478(+24)(-23) +/- 17 MeV/c(2) and width 324(+42)(-40) +/- 21 MeV/c(2) accounts for approximately half of all decays.     

A new bound for the smallest

Let denote the number of primes and let denote the usual integral logarithm of . We prove that there are at least integer values of in the vicinity of with . This improves earlier bounds of Skewes, Lehman, and te Riele. We also plot more than 10000 values of in four different regions, including the regions discovered by Lehman, te Riele, and the authors of this paper, and a more distant region in the vicinity of , where appears to exceed by more than . The plots strongly suggest, although upper bounds derived to date for are not sufficient for a proof, that exceeds for at least integers in the vicinity of . If it is possible to improve our bound for by finding a sign change before , our first plot clearly delineates the potential candidates. Finally, we compute the logarithmic density of and find that as departs from the region in the vicinity of , the density is , and that it varies from this by no more than over the next integers. This should be compared to Rubinstein and Sarnak.

     

Multiple antiferromagnet/ferromagnet interfaces as a probe of grain-size-dependent exchange bias in polycrystalline Co/Fe50Mn50

We have used ferromagnet/antiferromagnet/ferromagnet trilayers and ferromagnet/antiferromagnet multilayers to probe the grain size dependence of exchange bias in polycrystalline Co/Fe₅₀Mn₅₀. X-ray diffraction and transmission electron microscopy show that the Fe₅₀Mn₅₀ (FeMn) grain size increases with increasing FeMn thickness in the Co (30 Å)/FeMn system. Hence, in Co(30 Å)/FeMn(t_AF Å)/Co(30 Å) trilayers the two Co layers sample different FeMn grain sizes at the two antiferromagnet/ferromagnet interfaces. For FeMn thicknesses above 100 Å, where simple bilayers have a thickness-independent exchange bias, we are therefore able to deduce the influence of FeMn grain size on the exchange bias and coercivity (and their temperature dependence) simply by measuring trilayer and multilayer samples with varying FeMn thicknesses. This can be done while maintaining the (1 1 1) orientation, and with little variation in interface roughness. Increasing the average grain size from 90 to 135 Å results in a fourfold decrease in exchange bias, following an inverse grain size dependence. We interpret the results as being due to a decrease in uncompensated spin density with increasing antiferromagnet grain size, further evidence for the importance of defect-generated uncompensated spins.     

Prediction of structure-dependent charge transfer rates for a Li atom outside a Si(0 0 1) surface

We investigate the broadening of the 2s energy level of a Li atom outside a Si(0 0 1) surface using a first principles approach. The covalent nature of the Si surface produces large variations in Li energy level widths as a function of lateral position across the surface. The widths above symmetric Si dimers are predicted to be much larger than above buckled Si dimers, suggesting that charge transfer will occur primarily above symmetric dimers. We discuss the ramifications of our results on the controversy surrounding the relative abundance of the buckled vs. symmetric dimers on the Si surface.     

Immobilized artificial membrane chromatography with mass spectrometric detection: a rapid method for screening drug-membrane interactions.

A high-performance liquid chromatography (HPLC)/electrospray ionization mass spectrometry method for measuring drug-membrane interactions was developed using immobilized artificial membrane (IAM) fast-screening mini-columns. The HPLC mobile phase consisted of phosphate-buffered saline (i.e., 5.0 mM phosphate buffer at pH 7.4, 1.35 mM KCl, and 68.5 mM NaCl) and acetonitrile. This method facilitated the measurement of IAM retention time of over ten compounds in one experiment, significantly reducing analysis time compared with the earlier IAM-HPLC method. The particular electrospray source used demonstrated the ability to tolerate the high salt-containing nonvolatile buffer used for retention time measurement.     

The Effect of Platinum on Diffusion Kinetics in β‐NiAl: Implications for Thermal Barrier Coating Lifetimes

Platinum is added to thermal barrier coatings (TBCs) as it is observed empirically to extend their lifetime, but the mechanism by which Pt acts is unknown. Since Pt has been proposed to alter diffusivities in NiAl, a key component of TBCs, we use first‐principles quantum mechanics calculations to investigate atomic level diffusion mechanisms. Here, we examine the effect of Pt on five previously proposed mechanisms for Ni diffusion in NiAl: next‐nearest‐neighbor jumps, the triple defect mechanism, and three variants of the six jump cycle. We predict that Pt increases the rate of Ni diffusion by stabilizing point defects and defect clusters that are diffusion intermediates. Previously, we predicted the triple defect mechanism to be a dominant Ni diffusion mechanism; it simultaneously results in long‐range Al diffusion in the opposite direction. Since Pt increases the rate of Ni diffusion, it also increases Al diffusion in NiAl, which may be key to extending the coating lifetime.