Synthesis of Cembranoid Analogues through Ring‐Closing Metathesis of Terpenoid Precursors: A Challenge Regarding Ring‐Size Selectivity

A systematic study on ring‐closing metathesis with Grubbs II catalyst to cembranoid macrocycles is described. Acyclic terpenoids with a functional group X in the homoallylic position relative to an RCM active terminus and substituents R, R¹ directly attached to the other terminal double bond were prepared from geraniol derived trienes and fragments that are based on bromoalkenes and dimethyl malonate. Such terpenoids were suitable precursors, despite the presence of competing double bonds in their framework. The size of R and R¹ is crucial for successful macrocyclization. Whereas small alkyl substituents at the double bond directed the RCM towards six‐membered ring formation, cross metathesis leading to dimers dominated for bulkier alkyl groups. A similar result was obtained for precursors without functional group X. In the case of unsymmetrically substituted terpenoid precursor (R=Et, R¹=Me) with homoallylic OTBS or OMe group, the RCM could be controlled towards formation of macrocyclic cembranoids, which were isolated with excellent E‐selectivity. The role of the substituents was further studied by quantum chemical calculations of simplified model substrates. Based on these results a mechanistic rationale is proposed.     

Approximations of spectra of Schrödinger operators with complex potentials on ℝd

We study spectral approximations of Schrödinger operators T = ?Δ+Q with complex potentials on Ω = ?^d, or exterior domains Ω??^d, by domain truncation. Our weak assumptions cover wide classes of potentials Q for which T has discrete spectrum, of approximating domains Ω_n, and of boundary conditions on ?Ω_n such as mixed Dirichlet/Robin type. In particular, Re Q need not be bounded from below and Q may be singular. We prove generalized norm resolvent convergence and spectral exactness, i.e. approximation of all eigenvalues of T by those of the truncated operators T_n without spectral pollution. Moreover, we estimate the eigenvalue convergence rate and prove convergence of pseudospectra. Numerical computations for several examples, such as complex harmonic and cubic oscillators for d = 1,2,3, illustrate our results.     

Acoustic Radiation from a Finite Length Cylindrical Shell Excited by an Internal Acoustic Source: Solution Based on a Boundary Element Method and a Matched Asymptotic Expansion

This paper deals with acoustic radiation by a thin elastic shell, closed by two perfectly rigid discs, immersed in water and filled with air. The system is driven by an internal acoustic source. The shell has a length L, is clamped along one of its boundaries and is freely supported along the other boundary. Using the infinite domain Green's function, the radiated acoustic pressure is modeled by a hybrid layer potential (linear combination with nonreal coefficient of a simple layer and a double layer). Using Green's tensor of the in vacuo shell operator, the shell displacement is expressed as the sum of the field generated by the acoustic pressures and that due to boundary sources. Finally, the Green's function of the interior Neumann problem is used to express the acoustic pressure inside the shell in terms of the acoustic source and shell normal displacement: this representation fails for any frequency equal to one of the resonance frequencies of the shell interior. To overcome this, a light fluid approximation, which is allowed because the inner fluid is a gas, is adopted. Around each resonance frequency, an inner approximation is defined which matches the classical outer approximation. This revised version was published online in July 2006 with corrections to the Cover Date.     

Syntheses of N10‐substituted 7‐Arylpyrrolo[2,1‐c]‐[1,4]benzodiazepine‐5,11‐diones

Pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11‐dione and its 7‐bromo derivative were alkylated at the N10 atom applying various methods. The resulting products were subjected to Suzuki–Miyaura reactions using a catalyst system consisting of Pd(Cl)₂(PPh₃)₂ and sodium tert‐butanolate in toluene. Results of an X‐ray single crystal analysis are presented.     

Adsorption behavior of 4-methoxypyridine on gold nanoparticles

We demonstrate a phase transfer method to create stable colloidal solutions of Au nanoparticles with 4-methoxypyridine ligands. We then investigate the adsorption behavior of 4-methoxypyridine onto gold surfaces by Raman spectroscopy, DFT calculations, and (1)H NMR. In contrast to unsubstituted pyridine and the frequently used (N,N-dimethylamino)pyridine (DMAP), a flat adsorption of 4-methoxypyridine on gold was found.     

Synthesis,NMR‐Spectroscopy,and Molecular Structure of a Phosphonyl Ene Diamine

First examples of ene diamines with a phosphonate function at the C=C double bond were obtained by the reaction of dialkyl H‐phosphonates with bis(N‐tert‐butyl)‐diimine derived from glyoxal, [1,4‐bis(tert‐butyl)‐1,4‐diaza‐1,3‐butadiene], and isolated as hydrochlorides. Preferentially the cis‐diamine is formed. The new phosphonates are characterized by multinuclear NMR spectroscopy(¹H, ¹³C, ³¹P). In addition the methyl ester 8a was characterized by ^14,15N NMR spectroscopy as well as by several 2D NMR techniques and single‐crystal X‐ray diffraction, unequivocally establishing the ene diamine structure. In the crystal dimers of the cations are formed by P–O ··· H–N hydrogen bonding.     

Quantitative gel electrophoresis: new records in precision by elaborated staining and detection protocols

Gel electrophoresis (GE) is a very common analytical technique for proteome research and protein analysis. Despite being developed decades ago, there is still a considerable need to improve its precision. Using the fluorescence of Colloidal Coomassie Blue -stained proteins in near-infrared (NIR), the major error source caused by the unpredictable background staining is strongly reduced. This result was generalized for various types of detectors. Since GE is a multi-step procedure, standardization of every single step is required. After detailed analysis of all steps, the staining and destaining were identified as the major source of the remaining variation. By employing standardized protocols, pooled percent relative standard deviations of 1.2-3.1% for band intensities were achieved for one-dimensional separations in repetitive experiments. The analysis of variance suggests that the same batch of staining solution should be used for gels of one experimental series to minimize day-to-day variation and to obtain high precision.     

Accurate distance determination of nucleic acids via Förster resonance energy transfer: implications of dye linker length and rigidity

In Fo?rster resonance energy transfer (FRET) experiments, the donor (D) and acceptor (A) fluorophores are usually attached to the macromolecule of interest via long flexible linkers of up to 15 ? in length. This causes significant uncertainties in quantitative distance measurements and prevents experiments with short distances between the attachment points of the dyes due to possible dye-dye interactions. We present two approaches to overcome the above problems as demonstrated by FRET measurements for a series of dsDNA and dsRNA internally labeled with Alexa488 and Cy5 as D and A dye, respectively. First, we characterize the influence of linker length and flexibility on FRET for different dye linker types (long, intermediate, short) by analyzing fluorescence lifetime and anisotropy decays. For long linkers, we describe a straightforward procedure that allows for very high accuracy of FRET-based structure determination through proper consideration of the position distribution of the dye and of linker dynamics. The position distribution can be quickly calculated with geometric accessible volume (AV) simulations, provided that the local structure of RNA or DNA in the proximity of the dye is known and that the dye diffuses freely in the sterically allowed space. The AV approach provides results similar to molecular dynamics simulations (MD) and is fully consistent with experimental FRET data. In a benchmark study for ds A-RNA, an rmsd value of 1.3 ? is achieved. Considering the case of undefined dye environments or very short DA distances, we introduce short linkers with a propargyl or alkenyl unit for internal labeling of nucleic acids to minimize position uncertainties. Studies by ensemble time correlated single photon counting and single-molecule detection show that the nature of the linker strongly affects the radius of the dye's accessible volume (6-16 ?). For short propargyl linkers, heterogeneous dye environments are observed on the millisecond time scale. A detailed analysis of possible orientation effects (κ(2) problem) indicates that, for short linkers and unknown local environments, additional κ(2)-related uncertainties are clearly outweighed by better defined dye positions.     

Biogenesis of the unique 4',5'-dehydronucleoside of the uridyl peptide antibiotic pacidamycin

The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that act by inhibiting the clinically unexploited target translocase I, a key enzyme in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin 4',5'-dehydronucleoside portion is an essential pharmacophore. Here we show that the biosynthesis of the pacidamycin nucleoside in Streptomyces coeruleorubidus proceeds through three steps from uridine. The transformations involve oxidation of the 5'-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and dehydration by the Cupin-domain protein Pac13.