The reaction rate for dissociative adsorption of N2 on stepped Ru(0001): six-dimensional quantum calculations

Quantum-mechanical calculations of the reaction rate for dissociative adsorption of N2 on stepped Ru(0001) are presented. Converged six-dimensional quantum calculations for this heavy-atom reaction have been performed using the multiconfiguration time-dependent Hartree method. A potential-energy surface for the transition-state region is constructed from density-functional theory calculations using Shepard interpolation. The quantum results are in very good agreement with the results of the harmonic transition-state theory. In contrast to the findings of previous model calculations on similar systems, the tunneling effect is found to be small.     

New insights into an old reaction. High-resolution x-ray powder diffraction of Wiberg's aminoalane intermediate

In accordance with the procedure described by E. Wiberg, Me(3)Al-NH(3) was heated as a bulk material in inert atmosphere to give a colorless liquid which slowly loses methane. Close to the end of this elimination reaction, the melt crystallized to give a microcrystalline powder of (Me(2)AlNH(2))(x)(). The structure of this intermediate has been solved by the method of high-resolution X-ray powder diffraction. The compound crystallizes in the monoclinic space group C2/c with the cell parameters of a = 15.0047(6) A, b = 8.7500(2) A, c = 24.4702(8) A, and beta = 107.290(2) degrees, with eight trimers (Me(2)AlNH(2))(3) per unit cell. These trimers crystallize in a boat conformation in contrast to the known trimers of the same composition where a twist-boat conformation had been found by single crystal determination. Different conformers of (Me(2)AlNH(2))(3) have been investigated by theoretical methods (HF/6-31G(d), B3LYP/6-31G(d), B3LYP/6-311G(d,p), MP2(fc)/6-31G(d), and MP2(fc)/6-311G(d,p)). The twist-boat and the chair conformer correspond to minima at the potential energy surface, whereas the boat conformer corresponds to a first-order transition state (relative energies of 0.45-2.56 kJ/mol (boat) and 6.66-11.91 kJ/mol (chair)). Relaxed scans of the potential energy surface at the HF/6-31G(d) and B3LYP/6-31G(d) levels have shown that the boat conformer (C(s)() symmetry) connects two enantiomers of the twist-boat form (C(2) symmetry).     

Alkalimanganselenide und -telluride A2Mn3X4 – Synthese,Kristall- und Spinstruktur

Alkali Metal Manganese Selenides and Tellurides – Synthesis, Crystal and Spin Structures The compounds Rb₂Mn₃Se₄, Cs₂Mn₃Se₄, Rb₂Mn₃Te₄ and Cs₂Mn₃Te₄ were synthesized by the reaction of alkali metal carbonates with chalcogen and Mn or MnCO₃ in a stream of hydrogen charged with chalcogen. Structural investigations show that all compounds crystallize in isotypic atomic arrangements (Cs₂Mn₃S₄-type, space group Ibam, Z = 4). Additionally neutron diffraction experiments were carried out and yielded the spin structures of Rb₂Mn₃Se₄ and Cs₂Mn₃Se₄ (Shubnikov space group Ibam'). The structural related selenides ALiMnSe₂ and ALiZnSe₂ (A = K, Rb or Cs) were synthesized by analogous reactions. All these compounds are isotypic and crystallize in the BaZn₂P₂-structure type.     

Photodimers of a soluble tetracene derivative. excimer fluorescence from the head-to-head isomer

[reaction: see text] Irradiation of 5,12-didecyloxytetracene (1) leads to photodimers P(1) (planosymmetric) and P(2) (centrosymmetric). P(1) is characterized by naphthalene excimer fluorescence, whereas P(2) emits naphthalene monomer fluorescence.     

Ligand design by targeting a binding site water

Solvent reorganization is a major driving force of protein–ligand association, but the contribution of binding site waters to ligand affinity is poorly understood. We investigated how altered interactions with a water network can influence ligand binding to a receptor. A series of ligands of the A_2A adenosine receptor, which either interacted with or displaced an ordered binding site water, were studied experimentally and by molecular dynamics simulations. An analog of the endogenous ligand that was unable to hydrogen bond to the ordered water lost affinity and this activity cliff was captured by molecular dynamics simulations. Two compounds designed to displace the ordered water from the binding site were then synthesized and evaluated experimentally, leading to the discovery of an A_2A agonist with nanomolar activity. Calculation of the thermodynamic profiles resulting from introducing substituents that interacted with or displaced the ordered water showed that the gain of binding affinity was enthalpy driven. Detailed analysis of the energetics and binding site hydration networks revealed that the enthalpy change was governed by contributions that are commonly neglected in structure-based drug optimization. In particular, simulations suggested that displacement of water from a binding site to the bulk solvent can lead to large energy contributions. Our findings provide insights into the molecular driving forces of protein–ligand binding and strategies for rational drug design.

Solvent reorganization is a major driving force of protein–ligand association, but the contribution of binding site waters to ligand affinity is poorly understood.     

NMR solution structure of dsDNA containing a bicyclic D-arabino-configured nucleotide fixed in an O4'-endo sugar conformation

[3.2.0]bcANA is a D-arabino-configured bicyclic nucleotide with a 2'-O,3'-C-methylene bridge. We here present the high-resolution NMR structure of a [3.2.0]bcANA modified dsDNA nonamer with one modified nucleotide incorporated. NOE restraints were obtained by analysis of NOESY cross peak intensities using a full relaxation matrix approach, and subsequently these restraints were incorporated into a simulated annealing scheme for the structure determination. In addition, the furanose ring puckers of the deoxyribose moieties were determined by analysis of COSY cross peaks. The modified duplex adopts a B-like geometry with Watson-Crick base pairing in all base pairs and all glycosidic angles in the anti range. The stacking arrangement of the nucleobases appears to be unperturbed relative to the normal B-like arrangement. The 2'-O,3'-C-methylene bridge of the modified nucleotide is located at the brim of the major groove where it fits well into the B-type duplex framework. The sugar pucker of the [3.2.0]bcANA nucleotide is O4'-endo and this sugar conformation causes a change in the delta backbone angle relative to the C2'-endo deoxyribose sugar pucker. This change is absorbed locally by slight changes in the epsilon and zeta angles of the modified nucleotide. Overall, the [3.2.0]bcANA modifications fits very well into a B-like duplex framework and only small and local perturbations are observed relative to the unmodified dsDNA of identical base sequence.     

The amyloid-beta (Abeta) peptide pattern in cerebrospinal fluid in Alzheimer's disease: evidence of a novel carboxyterminally elongated Abeta peptide

The patterns of amyloid beta (Abeta) peptides in human cerebrospinal fluid (CSF) and brain homogenates were studied by surface-enhanced laser desorption/ionization (SELDI) time-of-flight (TOF) mass spectrometry, and the results were compared with those obtained by Abeta-SDS-PAGE/immunoblot. Apart from the peptides known in the literature to occur in the CSF, we postulate the existence of a novel, previously not described peptide, either Abeta1-45 or Abeta2-46. This peptide was observed exclusively in a pool of samples originating from patients with AD, i.e. CSF and postmortem brain homogenates, but not in either the pooled CSF samples nor the pooled brain homogenates of the non-demented controls. Similarly to our previous results, Abeta1-42 was decreased in the CSF in AD. Expectedly, brain homogenates of the control subjects did not show the presence of Abeta peptides. Compared with Abeta-SDS-PAGE/immunoblot, SELDI-TOF enabled more precise analysis of Abeta peptides in the human material. We conclude that SELDI-TOF offers a promising tool for dementia expression pattern profiling using a minute amount of a biological sample.     

Hexasubstituted donor-acceptor benzenes as nonlinear optically active molecules with multiple charge-transfer transitions

The synthesis of three novel nonlinear optical (NLO) chromophores with threefold symmetry, namely 1,3,5-tris(4-N,N-diethylaminophenyl)-2,4,6-tris(4-nitrophenyl)benzene (3), 1,3,5-tris(4-N,N-dihexylaminophenylbutadiynyl)-2,4,6-tris(4-nitrophenyl)benzene (13) and 1,3,5-tris(4-N,N-dihexylaminophenylethynyl)-2,4,6-tris(4-nitrophenylethynyl)benzene (4 b), is reported. We used the [Co(2)(CO)(8)]-catalysed trimerisation of 4-N,N-diethylamino-4'-nitrotolane (5) to prepare 3. The trimerisation experiment carried out with 1-(4-N,N-diethylaminophenyl)-6-(4-N,N-nitrophenyl)hexatriyne (6) and [Rh(PPh(3))(3)Cl] afforded 13. A stepwise approach was used to prepare 4 b. 1,3,5-Trichloro-2,4,6-triiodobenzene (8 b) was coupled with 4-nitrophenyl-acetylene (14) under Pd(0) catalysis to yield 1,3,5-trichloro-2,4,6-tris(4-nitrophenylethynyl)benzene (15). The coupling reaction of 15 with 4-N,N-dihexylaminophenylethynyltributylstannane (21) led to 4 b. X-ray investigations on 3, 4 b and 13 confirmed the structural assignments and revealed that the peripheral aryl rings in 4 b are less twisted around the connecting bonds than in 3 and 13. A large second-order polarisability (beta) of 4 b relative to 3 and 13 was determined by hyper-Rayleigh scattering (HRS). Compound 4 b represents an NLO chromophore with second-order polarisabily among the highest obtained so far for two-dimensional nondipolar NLO chromophores.     

Quantitative determination of phospholipids in amniotic fluid by high-performance liquid chromatography

Summary A new quantitative analytical method for the determination of phospholipids in amniotic fluid by high performance liquid chromatography (HPLC) is described. In addition to the main compounds, phosphatidylcholine (lecithin) and sphingomyelin, the so-called minor phospholipids, phosphatidylglycerol, phosphatidylinositol and phosphatidylethanolamine can also be determined. Separation is achieved using a guard-column of Lichrosorb Si 60 and an analytical column of Lichrosorb DIOL. Acetonitrile/water is used as mobile phase at an elevated temperature. By determining the recovery rates, the within-run and the between-run precision, it was shown that sufficient accuracy and precision could be achieved for all the parameters examined. The method is highly sensitive, the detection limit for sphingomyelin is 0.2 μg and 0.1 μg for all the other components. A single determination of 5 phospholipids in an amniotic fluid sample takes about two hours. By performing simultaneous extractions it is possible to analyse 5 samples per day.     

Relativistic theory for indirect nuclear spin–spin couplings within the polarization propagator approach

We present a relativistic theory for the nuclear spin–spin coupling tensor within the polarization propagator approach using the particle-hole Dirac–Coulomb–Breit Hamiltonian and the full four-component wave function. We give explicit expressions for the coupling tensor in the random-phase approximation, neglecting the Breit interaction. A purely relativistic perturbative electron–nuclear Hamiltonian is used and it is shown how the single relativistic contribution to the coupling tensor reduces to Ramsey's three second-order terms (Fermi contact, spin–dipole, and paramagnetic spin–orbit) in the nonrelativistic limit. The principal propagator becomes complex and the leading property integrals mix atomic orbitals of different parity. The well-known propagator expressions for the coupling tensor in the nonrelativistic limit is obtained neglecting terms of the order c^?n (n ? 1). © 1993 John Wiley & Sons, Inc.