Protein hormones exhibit high biological specificity and are therefore regarded as valuable targets for pharmaceutical research and development. The schematically represented hormone interleukin-4 is of particular importance because of its pivotal role in the genesis of allergy and asthma. The recent elucidation of the structure and function of the hormone/receptor complex has opened up new approaches for therapeutic intervention.

A toxic determinant of the human skin disease the Buruli ulcer, which is caused by Mycobacterium ulcerans, has been identified for the first time as containing two polyketides. The novel structures of these twelve-membered macrolides (one of which is shown) reveal an unusual biosynthesis, in which two type 1 polyketide synthases (PKS) have to be involved. There is also evidence that the polyketide toxin might represent the first of a family of virulence factors associated with other mycobacterial diseases, such as leprosy and tuberculosis.

A functional role of a D-amino acid in the mammalian brain has been proven for the first time. Unlike the L-amino acids, the D-amino acids are not taken up with food or stereospecifically biosynthesized. Instead, they are formed by racemization from their L congeners, a process which is enzymatically catalyzed by racemases (see scheme). A serine racemase has now been isolated and cloned. It is a potential new target for neuroactive drugs.

Since it was first reported in 1899 the Baeyer–Villiger reaction has become an important reaction in organic synthesis. The stereoelectronic components of this reaction have been difficult to observe because of the conformational mobility of the Criegee intermediate. Simply placing a fluorine substituent such that it interacts with the O−O bond of the peroxyester in this intermediate permits the observation of the primary stereoelectronic effect. Lactone 1 (see reaction scheme) is formed with 90 % selectivity, which demonstrates preferential migration of the equatorially substituted carbon and is in agreement with the primary stereoelectronic effect.

A Cayley tree is the structural motif of the dendrimerlike supramolecular structure that is formed by self-assembly of the bile salt sodium deoxycholate (NaDC) with the β-cyclodextrin trimer T (see schematic picture). This is the first example of dendritic growth by a cyclodextrin complex.

Binaphthol is a well-loved and much-studied chiral molecule, but until now the structures of its synthetically useful lithiated derivatives have been overlooked. However, these lithium alkoxides form unexpected helical polymers and chiral clusters (see picture) in the solid state.

The Lewis acid catalyzed cyclization of squalene analogues which are constrained at the 11,12 bond leads to products with BCD ring structures typical of terpenoids. The structure of the product given in the example in Equation (1) was determined by X-ray diffraction studies.

Hybrid molecular orbital/molecular mechanics calculations are used to determine the origin of the “anti-lock-and-key” behavior in asymmetric catalytic hydrogenation. The computations provide a simple model to explain this behavior (see scheme), and agree with all relevant empirical data.

Early intermediates along the stepwise multi-insertions of CO, ethene, or methyl acrylate into the palladium–carbon bond of cationic palladium(II) complexes such as 1, which is stabilized by a P,O chelate, have been isolated under ambiant conditions. The crystallographically characterized CO–ethene coupling product 2 reversibly inserts further CO to give the isolated intermediate 3 (not shown), which affords 4 or 5 upon insertion of ethene or methyl acrylate, respectively.

Narrow band gaps and high electron affinities are associated with the new oligomers containing thiophene-1-oxide and thiophene-dioxide that have been prepared by zirconocene coupling methods. A series of oligomers with 3–11 rings (X=2 H, S, and S(=O)₂; see picture) allow the electronic properties of conjugated chains to be investigated. Of particular note is that the less electron-withdrawing sulfoxide group results in the narrowest band gap.

Potent and selective antagonists of the vitronectin receptor α_Vβ₃ (for example, 1) were obtained by incorporation of a central purine scaffold into RGD peptidomimetics. The ease of derivatization of the purine building block holds promise for many future uses of this scaffold in peptidomimetic chemistry.

A very convenient route for the acylation of alcohols is provided by using a Bi(OTf)₃ catalyst [Eq. (1)]. In this protocol hindered and functionalized alcohols are acylated at 25°C, and solvents can be employed without purification. R=primary, secondary, tertiary alkyl, aryl; R′=Me, Ph, tBu.

Inversion at the leaving group in a substitution reaction is implied in the reaction of 1 with borohydride at room temperature. The trapping of 2 leads to 3, even though the stable monoprotonated ion is 4.

The binding of the HIV-1 surface glycoprotein gp120 to several glycosphingolipids, reconstituted into planar lipid bilayers (see scheme; small circle= 2-oleoyl-1-palmitoylphosphatidylcholine (POPC), arrow=glycosylceramide recognition element; left: low and right: high protein concentrations), has been quantitatively measured under equilibrium conditions. Complex binding behavior was observed, which suggests that the induced aggregation of gp120 molecules at a ligand-bearing membrane surface may be an important step in the mechanism of HIV-1 infection of a host cell.

A high-spin ground state S>8 is obtained through ferromagnetic coupling in a Fe^IIFe complex that models the electronic properties of Prussian blue. The picture shows the postulated core structure for this heptanuclear complex.

Even systems with integer spins such as [L₂Mn(μ-O)(μ-phBO₂)₂](PF₆)₂ (1, S=3; L=1,4,7-trimethyl-1,4,7-triazacyclononane, phBO₂=phenyl boronic acid)—a model for the high oxidation states in several manganese-containing metalloproteins—can be studied in detail by high-field and high-frequency EPR spectroscopy (see picture, spectra recorded at 285 GHz). In association with low-frequency EPR and magnetization measurements, a complete analysis of the magnetic properties of 1 was obtained.

The square hole for the round peg: The first two members of a new family of tetrametallic cyclophanes (1; M=Mn^I, Re^I), which feature rectangular cavities, have been synthesized and characterized. Both of the luminescent compounds behave as mesoporous materials in a thin film and display high capacities and substantial affinities towards the uptake of selected volatile organic compounds.

Playing two roles at once, chiral amines from L-proline or D-mannitol act as protecting groups and as chiral auxiliaries in the [2+2] cycloaddition of formaldehyde hydrazones, such as 1, to ketenes. This strategy, based on the stability of the hydrazones as methanimines and on the development of a new oxidative cleavage of hydrazides, provides a short entry to enantiopure 4-unsubstituted 3-alkoxy- and 3-aminoazetidinones with desired configurations. X=OBn, N(CO₂Bn)Bn; Bn=benzyl; MMPP=magnesium monoperoxyphthalate.

A macrocycle-linked polymer architecture that involves thiophene linkages between the phthalocyanine rings (see picture) has been found to have conductivities three orders of magnitude higher than previously investigated macrocycle-linked materials. Rigid three-dimensional iptycene scaffolds were used to prevent aggregation of the macrocycles, and yield highly soluble monomers with a cleft around the axial coordination sites of the metal center.

The ready addition of CO to [(Cp*ReH₂)₂B₄H₄] (1) results in the cleavage of a B−B bond and formation of the structurally characterized isomers cis- and trans-2. The B−B bond is reformed, with loss of H₂, on mild thermolysis to generate complex 3.

Up to one hundred thousand equivalents of a variety of low-strain cyclic olefins, such as cyclooctadiene, cyclooctene, and several functionalized and sterically hindered derivatives, were polymerized by using highly active ruthenium-based ring-opening metathesis polymerization (ROMP) catalysts [Eq. (1)]. Efficient syntheses of other polymeric structures were also accomplished.

Unlike the usual exo-selective Pauson–Khand cyclization of allylic-substituted 1,6-enynes, the reaction of 1,6-enynes with γ-oxygenated α,β-unsaturated sulfone structures occurs with high endo stereoselectivity. As the starting enynes are available in enantiopure form and the sulfonyl group can be easily eliminated, this procedure constitutes a stereocomplementary approach to the asymmetric synthesis of bicyclo[3.3.0]oct-1-en-3-ones [Eq. (1)].

The thiolate-bridged diruthenium complexes [Cp*RuCl(μ₂-SR)₂RuCp*Cl] (Cp*=η⁵-C₅Me₅; R=Me, Et, nPr) have been found to be effective catalysts for the cyclization of α,ω-diynes to produce the corresponding endocyclic (Z)-1-en-3-ynes in moderate to high yields with complete stereoselectivities (see scheme).

Temperature dependent electrical conductivity is seen in [{Ag(C₅H₄NS)}_n] (1). This inorganic polymer with a lamella structure and a graphite-like array of silver(I) ions (see picture) is prepared by the treatment of AgBF₄ with pyridine-2-thiol in DMF at 0°C. However, the same reaction in CH₃CN at room temperature generates the layered polymer [{Ag₅(C₅H₄NS)₄(C₅H₅NS)BF₄}_n] (2).

Linear polymeric polyanions (see picture) are assembled from lacunary polyoxotungstate building blocks and lanthanide cations. Given the large number of lanthanide and lacunary polyoxoanions available, a considerable variety of new materials is now accessible.

The appearance of a bright yellow color signals the inclusion of a halide ion (X=Cl, Br, I) into the dicopper(II) cryptate 1 in aqueous solution at pH 5.2. The X⁻ ion bridges the two metal centers, as is shown by the crystal structure of the bromide inclusion complex. At pH 8, X⁻ is replaced by the smaller OH⁻ ion, and the solution turns emerald green. The cage can adjust its intermetallic cavity to include polyatomic anions as large as N₃⁻ and NCS⁻.

Adjusting the pore size and volume of molecular sieve MCM-41 over a very wide range is possible through simple hydrothermal treatment of “off the shelf”, as-synthesized materials in a decyldimethylamine (DMDA)–water emulsion (see schematic representation). The amine/silica ratio as well as the time and temperature of the treatment are the main parameters that control the pore size expansion process.

The base-catalyzed cyclization of 1,2-bis(phosphanyl)ethane with trivinylphosphane on a pentamethylcyclopentadienyl iron template results in the high-yield synthesis of the first triphosphacyclononane derivative containing one vinyl-functionalized and two secondary phosphanes. The vinyl triphosphacyclononane is readily hydrogenated and alkylated to give the tritertiary 1,4,7-triethyltriphosphane macrocycle 1.

Chromogenic and electrochemical recognition are combined in the calix[4]arenecrown-4 1: 1) Conformational changes upon complexation of Na⁺ or K⁺ influence the through-space exciton coupling between the two diametrically arranged thienylene analogues of p-terphenoquinone used as the chromophores, and a color change results. 2) Complexation also causes an anodic shift in the oxidation and reduction potentials of 1.

The NMR analysis of high-temperature reactions, even at temperatures over 800 K, has been carried out with the aid of a specially designed apparatus. The reaction studied was the catalytic methane aromatization on a molybdenum-modified ZSM-5 catalyst. The experiments could be performed under conditions identical to those used in the real catalytic process.

Unexpectedly, not interested in sulfur: the antiarthritic complex [Au(PEt₃)Cl] (1) reacts with crystals of cyclophilin-3 (Cyp-3), a peptidyl prolyl isomerase enzyme linked to cellular stress responses, to form an N_ε-bound [AuPEt₃]⁺ adduct with the active site residue His 133, despite the presence of four Cys thiol groups in the protein. Complex 1 is a potent inhibitor of the enzyme (IC₅₀=14 nM).

NO and NO₂ associated as the asymmetric N₂O₃ conformer compete with water molecules for coordination with sodium cations of the sodium–water clusters in supercages of the Na-Y zeolite. This reactive NO_x adsorption is reversible (see picture), not sensitive to SO₂, and presents an alternative method for the removal of NO_x from lean-burn exhaust gas without the formation of surface nitrates.

Very high inversion barriers for a pyramidal nitrogen atom have been found for the sterically hindered 1,2,4-oxadiazolidines 1 (R¹, R²=CH₃) and 2 (R¹=COOCH₃, R²=CH₂CH₃, only one enantiomer is shown). The synthesis and NMR studies of the diastereomerization of 2 are described, as well as the determination of the enantiomerization barrier of 1 by stopped-flow multidimensional gas chromatography (sfMDGC).

Relying on only interbase hydrophobic packing for bonding, several unnatural nucleobases similar to 1 can form selective and stable self-pairs in duplex DNA. These unnatural nucleobases should make it possible to increase the stringency and information content of hybridization or encoding experiments.

Double addition of the phosphinidene complex [PhPW(CO)₅] to 2,5-dimethyl-2,4-hexadiene led to the first bisphosphiranes. The s-trans conformation of the intermediate vinylphosphiranes prevents rearrangements and epimerizations, but does not hamper a second addition (see scheme).

Complete saturation of the complexation capacity of cyclodextrins (CDs) is not required for micellization to take place. Investigation of the competition between micellization and complexation of surfactant monomers with β-CD (shown schematically) shows the presence of a high concentration of uncomplexed β-CD in equilibrium with the micellar system. This concentration increases with the length of the hydrocarbon chain of the surfactant.

Enantiopure and highly functionalized cyclohexanes may be accessed in a single step and with high stereocontrol from the 7-oxo-2-enimides 1 with use of the title reactions (see scheme). The bifunctional substrates 1 are available by a thermal [3.3]-sigmatropic rearrangement of aldol products. X_c=chiral auxiliary; M=Cu, Al.

Cleavage of the aldehyde C=O bond takes place in the zirconocene- and AlCl₃-mediated cyclization of two molecules of an alkyne with an aldehyde to afford cyclopentadiene derivatives [Eq. (1)]. Only one of the possible positional double-bond isomers is formed. The same method can also be used to couple two different alkynes with an aldehyde.

A section of the gallium high-pressure modification GaIII is represented by the metalloid cluster core (see picture) of the Ga₂₆ cluster anion, which forms along with further gallium cluster compounds, in a reaction of sonochemically prepared “Ga₂I₃” with [Li(thf)₃{Si(SiMe₃)₃}].