Synthesis of novel, simplified, C-7 substituted eleutheside analogues with potent microtubule-stabilizing activity

The synthesis of a number of novel, simplified, C-7 substituted eleutheside analogues with potent tubulin-assembling and microtubule-stabilizing properties is described, using ring closing metathesis as the key-step for obtaining the 6-10 fused bicyclic ring system. The RCM precursors were synthesized starting from aldehyde 3 [prepared in six steps on a multigram scale from R-(−)-carvone in 30% overall yield] via multiple stereoselective Hafner-Duthaler allyltitanations and/or Brown allylborations. ‘Second generation’ RCM-catalyst 15 gave the desired ring closed ten-membered carbocycles as single Z stereoisomers in good yields. The RCM stereochemical course (100% Z) is likely to reflect thermodynamic control. Molecular mechanics and semi-empirical calculations also show that the Z stereoisomers of these ten-membered carbocycles are consistently more stable than the E. The crucial role of the homoallylic and allylic substituents and of their protecting groups for the efficiency of the RCM reactions is discussed. In particular, we have found that p-methoxyphenyl (PMP) protected allylic alcohols, the products of a stereoselective oxyallylation, are compatible with the RCM reaction and give better yields than the corresponding free allylic alcohols. One of the simplified analogues of the natural product (44, lacking inter alia the C-4/C-7 ether bridge) retains potent microtubule-stabilizing activity. However, the cytotoxicity tests did not parallel the potent tubulin-assembling and microtubule-stabilizing properties: limited cytotoxicity was observed against three common tumor cell lines (human ovarian carcinoma, human colon carcinoma and human leukemia cell lines, IC₅₀ in the μM range), approximately two orders of magnitude less than paclitaxel (IC₅₀ in the nM range). The mechanism of cell cycle arrest induced by compound 44 is similar to that obtained with paclitaxel.     

Mössbauer effect studies of excited states of 155Gd

Mössbauer effect studies of the 60.0, 86.5 and 105.3 keV transitions of ¹⁵⁵Gd, yield the following nuclear parameters: $\text{τ}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{(60}\text{keV level}\text{) = 194 ± 15}\text{ps}$, $\text{g(87)}\text{g(0)}\text{= 1.235 ± 0.008}$, $\text{g(105)}\text{g(0)}\text{= 2.01 ± 0.05 or ?0.55 ± 0.05}$; $\text{Q(87)}\text{Q(0)}\text{= +0.087 ± 0.006}$ and $\text{Q(105)}\text{Q(0)}\text{= 1.00 ± 0.03}$ or $\text{Q(87)}\text{Q(0)}\text{= ?0.083 ± 0.008}$ and $\text{Q(105)}\text{Q(0)}\text{= = 1.16 ± 0.03}$. Theoretical considerations favour the first set of values of $\text{Q(87)}\text{Q(0)}$ and $\text{Q(105)}\text{Q(0)}$.     

Efficient simulations of gas-grain chemistry in interstellar clouds

Chemical reactions on dust grains are of crucial importance in interstellar chemistry because they produce molecular hydrogen and various organic molecules. Because of the submicron size of the grains and the low flux, the surface populations of reactive species are small and strongly fluctuate. Under these conditions rate equations fail and the master equation is needed for modeling these reactions. However, the number of equations grows exponentially with the number of reactive species, severely limiting its feasibility. Here we present a method which dramatically reduces the number of equations, thus enabling the incorporation of the master equation in models of interstellar chemistry.     

Regularization of diffusion tensor MRI via local coordinates

We propose a novel framework for regularization of symmetric positive-definite (SPD) tensors (e.g., diffusion tensors). This framework is based on differential geometry. The space of SPD matrices, P_n, is described as a Riemannian manifold that is parameterized via the Iwasawa coordinate system. Then, distances on P_n are measured in terms of a natural GL (n)-invariant Riemannian metric. Using the Beltrami framework we construct a set of coupled geometric PDEs with respect to the Iwasawa coordinates. Then, by means of the gradient descent method these equations define the regularization flow over P_n. It appears to be that the local coordinate approach via that coordinate system results in very simple numerics that leads to fast convergence of the algorithm. We demonstrate the efficiency of this algorithm on real volumetric DTI datasets. Results of fibers tractography before and afterthe regularization process arepresented. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Long radiative lifetimes of SO2 in a collision-free supersonic molecular beam

Radiative lifetimes and delayed laser-induced fluorescence spectra of cold SO₂ were measured in the range 3000–3150 Å in a differentially pumped collision-free supersonic beam. Lifetimes between 9 and 300 μs were obtained. We show the existence of high-density, low-intensity, and long-lifetime states in the vicinity of the strong spectral transitions.