Genome projects and the functional-genomic era

The problems we face today in public health as a result of the -- fortunately -- increasing age of people and the requirements of developing countries create an urgent need for new and innovative approaches in medicine and in agronomics. Genomic and functional genomic approaches have a great potential to at least partially solve these problems in the future. Important progress has been made by procedures to decode genomic information of humans, but also of other key organisms. The basic comprehension of genomic information (and its transfer) should now give us the possibility to pursue the next important step in life science eventually leading to a basic understanding of biological information flow; the elucidation of the function of all genes and correlative products encoded in the genome, as well as the discovery of their interactions in a molecular context and the response to environmental factors. As a result of the sequencing projects, we are now able to ask important questions about sequence variation and can start to comprehensively study the function of expressed genes on different levels such as RNA, protein or the cell in a systematic context including underlying networks. In this article we review and comment on current trends in large-scale systematic biological research. A particular emphasis is put on technology developments that can provide means to accomplish the tasks of future lines of functional genomics.     

Surface step structure of Ag13OsO6, experimental evidence for Ag13 cluster building blocks

The surface of single crystal Ag(13)OsO(6) has been investigated using atomic force microscopy. Growth spirals with very large flat terraces, separated by steps of equal height, have been observed. The measured step height of approximately 6.7 Angstrom corresponds to the diameter of one Ag13-icosahedron and identifies the cluster as the key structural building block.     

Site-specific dissociation of DNA bases by slow electrons at early stages of irradiation

At the very early time of irradiation, ballistic secondary electrons are produced as the most abundant of the radiolytic species directly within DNA or its environment. Here, we demonstrate the propensity of such low-energy (<3 eV) electrons to damage DNA bases via an effective loss of hydrogen located at the specific nitrogen positions. Since this site is directly implicated in the bonding of nucleobases within DNA and since dehydrogenation of the nucleic acid bases has been observed to be the predominant dissociative channel, the present findings foreshadow significant implications for the initial molecular processes leading to genotoxicity in living cells following unwanted or intended exposure to ionizing radiation (e.g., sunbathing, air travel, radiotherapy, etc.).     

Catalysis of nucleophilic aromatic substitutions in the 2,6,8-trisubstituted purines and application in the synthesis of combinatorial libraries

The following paper summarizes our work on compound libraries of 2,6,8-trisubstituted purines. This synthesis route on a polystyrene support begins with 2,6-dichloro purine making extensive use of catalysis. During the synthesis the polymer bound purines were brominated selectively on C8. The substitution reaction of C6-Cl by amines was found to be acid catalyzed. The substitution of C2-Cl by amines and aryls, as well as the substitution of a C8-Br by aryls, alkenyl and alkynyl groups can be catalyzed by transition metals. Under some bromination conditions novel selective oxidative transformations of 2-amino groups in 2,6-diamino purines have been found.     

Micellization of amphiphilic block copolymers and use of their micelles as nanosized reaction vessels

Amphiphilic block copolymers made by a variety of techniques form in selective solvents micelles of well defined size and shape. We report on the underlying principles of micelle formation, as revealed by light scattering experiments. In addition, we will delineate some applications of these block-copolymer micelles where we focus on two technological relevant cases, namely the stabilization of polymer particles in low cohesion energy environments as well as the stabilization of metal and semiconductor colloids inside specially functionalized block copolymer micelles. In the latter case, stable hybride materials are obtained where the properties both of the polymer and the inorganic are added in a synergistic way. First data on special catalytic properties, the generation of superparamagnetic materials, and special colloids with optical functionality are presented.     

Ligand versus metal protonation of an iron hydrogenase active site mimic

The protonation behavior of the iron hydrogenase active-site mimic [Fe2(mu-adt)(CO)4(PMe3)2] (1; adt=N-benzyl-azadithiolate) has been investigated by spectroscopic, electrochemical, and computational methods. The combination of an adt bridge and electron-donating phosphine ligands allows protonation of either the adt nitrogen to give [Fe2(mu-Hadt)(CO)4(PMe3)2]+ ([1 H]+), the Fe-Fe bond to give [Fe2(mu-adt)(mu-H)(CO)4(PMe3)2]+ ([1 Hy]+), or both sites simultaneously to give [Fe2(mu-Hadt)(mu-H)(CO)4(PMe3)2]2+ ([1 HHy]2 +). Complex 1 and its protonation products have been characterized in acetonitrile solution by IR, (1)H, and (31)P NMR spectroscopy. The solution structures of all protonation states feature a basal/basal orientation of the phosphine ligands, which contrasts with the basal/apical structure of 1 in the solid state. Density functional calculations have been performed on all protonation states and a comparison between calculated and experimental spectra confirms the structural assignments. The ligand protonated complex [1 H]+ (pKa=12) is the initial, metastable protonation product while the hydride [1 Hy]+ (pKa=15) is the thermodynamically stable singly protonated form. Tautomerization of cation [1 H]+ to [1 Hy]+ does not occur spontaneously. However, it can be catalyzed by HCl (k=2.2 m(-1) s(-1)), which results in the selective formation of cation [1 Hy]+. The protonations of the two basic sites have strong mutual effects on their basicities such that the hydride (pK(a)=8) and the ammonium proton (pK(a)=5) of the doubly protonated cationic complex [1 HHy]2+ are considerably more acidic than in the singly protonated analogues. The formation of dication [1 HHy]2+ from cation [1 H]+ is exceptionally slow with perchloric or trifluoromethanesulfonic acid (k=0.15 m(-1) s(-1)), while the dication is formed substantially faster (k>10(2) m(-1) s(-1)) with hydrobromic acid. Electrochemically, 1 undergoes irreversible reduction at -2.2 V versus ferrocene, and this potential shifts to -1.6, -1.1, and -1.0 V for the cationic complexes [1 H]+, [1 Hy]+, and [1 HHy]2+, respectively, upon protonation. The doubly protonated form [1 HHy]2+ is reduced at less negative potential than all previously reported hydrogenase models, although catalytic proton reduction at this potential is characterized by slow turnover.