Small molecules as inhibitors of cyclin-dependent kinases

Cell division (mitosis) is one of the basic requirements for multicellular oranisms. The capability of a cell to replicate enables a complex assembly to be created. Faulty regulation of the control mechanism in the cell cycle leads to an excessive cell proliferation and is the cause of cancer. The key position of the cyclin-dependent kinases (CDKs) and their direct partners, as well as the fact that the majority of malign illnesses show defects in at least one of these key players of the cell cycle, is of great interest for the development of low-molecular-weight CDK inhibitors. In this Review an overview of the different structural classes of ATP-competitive inhibitors of CDKs are given, whose devlopment was aimed at battling cancer. The Review shows how far the development of selective CDK inhibitors has progressed and to what extent the expectations for such drugs have so far been fulfilled.     

Intrazeolite photooxygenation of chiral alkenes. Control of facial selectivity by confinement and cation-π interactions

Depending on the nature of the substituents on the stereogenic carbon atom, the ene reaction of singlet oxygen with several chiral alkenes by confinement within thionin-supported zeolite NaY, may exhibit significant changes on facial selectivity by comparison to their photooxygenation reaction in solution. It is proposed that, apart from the conformational consequences as a result of the alkene confinement within the zeolite cavities, a synergism between Na⁺-π interactions and singlet oxygen-Na⁺ interactions plays a significant role in the transition states of ene hydroperoxidation. Within NaY, the diastereoselectivity may significantly depend on the site selectivity, as probed through specific deuterium labelling of trisubstituted alkenes bearing a gem-dimethyl group. In certain cases, a remote stereogenic centre relative to the reacting double bond may induce enhanced diastereoselection and regioselectivity.     

Remarkable change of the diastereoselection in the dye-sensitized ene hydroperoxidation of chiral alkenes by zeolite confinement

[reaction: see text] The ene reaction of singlet oxygen with chiral trisubstituted alkenes bearing an alkyl and a phenyl group at the stereogenic center is erythro diastereoselective in solution and threo diastereoselective if carried out within zeolite Na-Y. The change of the diastereoselection trend by zeolite confinement is attributed to a synergism of steric effects and cation-pi interactions.     

Computational studies on the thermal decomposition and isomerization of CHBr2O radical

The unimolecular decomposition study of dibromomethoxy radical, CHBr₂O, and its isomeric hydroxy dibromomethyl radical, CBr₂OH, is carried out using ab initio electronic molecular structure methods. Three kinds of reaction pathways are examined, C–H and C–Br bond scissions, intramolecular three-center HBr elimination and isomerization. Based on the ab initio results, energy-specific rate coefficients k(E) and thermal rate constants k(T,P) are evaluated using RRKM theory and master equation numerical analysis. Relevance to existing experimental evidence is discussed.     

Magnetic structure of the europium fulleride ferromagnet Eu(6)C(60)

The powder neutron diffraction technique has been used for the direct observation of magnetic scattering below a Curie temperature of approximately 14 K in the fullerene-based molecular ferromagnet Eu6C60. Europium is in the divalent state with a magnetic moment of 7.1(3) muB per atom, and the configurational symmetry of the magnetic structure is body-centered cubic. Close contacts between Eu2+ and neighboring C60 units provide the signature of orbital hybridization, which can evidently account for the conducting and magnetic properties of the material.     

Magnetic enhancement and magnetic reduction in binary clusters of transition metal atoms

Electronic and magnetic properties of small binary clusters containing one or two transition metal atoms are investigated using ab initio calculations with a view to explain the experimentally observed magnetic enhancement/reduction in these systems. As the present investigations do not rely on spin-orbit effects, our results reveal the enhancement or reduction in the magnetic moment to depend on two main factors; namely geometry and, most importantly, the d-band filling. The results can be used as a guide in the experimental synthesis of high density magnetic grains.     

Ab initio molecular orbital and RRKM calculations of the thermal decomposition of CH2BrO radical

A theoretical study of the thermal decomposition and isomerization channels of bromomethoxy radical is carried out using ab initio molecular orbital methods and RRKM theory. Three kinds of reaction pathways are examined, bond scission, intramolecular three-center HBr elimination and isomerization. Energy-specific rate coefficients k(E) and thermal rate constants k(T,P) are evaluated using the ab initio data and RRKM theory. Relevance to existing experimental evidence is discussed.     

On aggregate composite indicators

In this paper it is shown that the unweighted arithmetic average is the theoretically consistent scheme to aggregate composite indicators, derived from the benefit-of-the-doubt model, across decision-making units.