Highly convergent synthesis of a rebeccamycin analog with benzothioeno(2,3-a)pyrrolo(3,4-c)carbazole as the aglycone

A highly convergent, scalable synthesis of the rebeccamycin analog 2 was demonstrated in seven steps and 31% overall yield based on the N-protected building block dibromomaleimide 7. The practical synthesis of other two building blocks, 5,6-difluoro-3-benzothiopheneboronic acid 6 and 5,6-difluoroindole 8, is described.     

Impact of multiple re-use of anion-exchange chromatography media on virus removal

We evaluated viral clearance in multiply-cycled anion-exchange media run in flow-through mode. We found that anion-exchange columns do not lose viral clearance capacity after extensive re-use, if they are cleaned with recommended buffers that do not chemically degrade the media. In contrast, anion-exchange (AEX) columns that are not cleaned or are cleaned with buffers that chemically degrade the media lost viral clearance capacity after extended use. In these cases, other performance attributes that changed at the same time were increased band spreading, decreased DNA clearance and accumulating backpressure that prevented re-use past 80-120 cycles. Thus, our data suggests that flow through mode anion-exchange columns that are cleaned with recommended cleaning buffers, and periodically monitored for band spreading, DNA clearance and/or backpressure need not be re-evaluated for viral clearance at the end of the validated media lifetime.     

A modular approach to DNA-programmed self-assembly of macromolecular nanostructures

DNA-programmed organic reactions are new and powerful tools for assembling chemical compounds into predetermined complex structures and a brief review of their use is given. This approach is particular efficient for the selection and covalent coupling of multiple components. DNA-templated synthesis is used for polymerization of PNA tetramers and for copying of the connectivity information in DNA. Direct DNA-programmed multicomponent coupling of custom designed organic modules is described. The macromolecular structures obtained are highly conjugated potentially conducting nanoscaffolds. Some future developments in this area are discussed.     

Hinreichende Bedingungen für die Regularität einer komplexen Funktion

Ohne Zusammenfassung Die Ausführung dieser Arbeit wurde erm?glicht durch einen Beitrag aus dem Schweizerischen Nationalfonds.     

Tunable photonic crystal circuits: concepts and designs based on single-pore infiltration

We demonstrate that the infiltration of individual pores of certain two-dimensional photonic crystals with liquid crystals and (or) polymers provides an efficient platform for the realization of integrated photonic crystal circuitry. As an illustration of this principle, we present designs for monomode photonic crystal wave-guides and certain functional elements, such as waveguide bends, beam splitters, and waveguide intersections. These devices exhibit very low reflection over broad frequency ranges. In addition, we discuss the inherent tunability of these devices that originates in the tunability of the infiltrated material.     

Preparation of protein nanocrystals and their characterization by solid state NMR

Preparation of proteins in their crystalline state has been found to be important in producing stable therapeutic protein formulations, cross-linked enzyme crystals for application in industrial processes, generating novel porous media for separations, and of course in structure elucidation. Of these applications only X-ray crystallography requires large crystals, defined here as being crystals 100s of microns or greater in size. Smaller crystals have attractive attributes in many instances, and are just as useful in structure determination by solid state NMR (ssNMR) as are large crystals. In this paper we outline a simple set of procedures for preparing nanocrystalline protein samples for ssNMR or other applications and describe the characterization of their crystallinity by ssNMR and X-ray powder diffraction. The approach is demonstrated in application to five different proteins: ubiquitin, lysozyme, ribonuclease A, streptavidin, and cytochrome c. In all instances the nanocrystals produced are found to be highly crystalline as judged by natural abundance 13C ssNMR and optical and electron microscopy. We show for ubiquitin that nanocrystals prepared by rapid batch crystallization yield equivalent 13C ssNMR spectra to those of larger X-ray diffraction quality crystals. Single crystal and powder X-ray diffraction measurements are made to compare the degree of order present in polycrystalline, nanocrystalline, and lyophilized ubiquitin. Solid state 13C NMR is also used to show that ubiquitin nanocrystals are thermally robust, giving no indication of loss of local order after repeated temperature cycling between liquid nitrogen and room temperature. The methods developed are rapid and should scale well from the tenths of milligram to multi-gram scales, and as such should find wide utility in the preparation of protein nanocrystals for applications in catalysis, separations, and especially in sample preparation for structural studies using ssNMR.     

Blue alkali dinitrosomethanides: synthesis, structure, and bonding

Explosive alkali dinitrosomethanides (M[HC(NO)2]; M = Li, Na, K, Cs) were prepared in a new, simple, high-yielding synthetic procedure, fully characterized, and shown to be stable at ambient temperature. Alkali dinitrosomethanides are of widespread interest to pharmaceutical and materials scientists alike.     

D.C. Versus Copositive Bounds for Standard QP

The standard quadratic program (QPS) is min_xεΔx^TQx, where is the simplex Δ = {x ⩽ 0 ∣ ∑_i=1ⁿ x_i = 1}. QPS can be used to formulate combinatorial problems such as the maximum stable set problem, and also arises in global optimization algorithms for general quadratic programming when the search space is partitioned using simplices. One class of ‘d.c.’ (for ‘difference between convex’) bounds for QPS is based on writing Q=S−T, where S and T are both positive semidefinite, and bounding x^T Sx (convex on Δ) and −x^Tx (concave on Δ) separately. We show that the maximum possible such bound can be obtained by solving a semidefinite programming (SDP) problem. The dual of this SDP problem corresponds to adding a simple constraint to the well-known Shor relaxation of QPS. We show that the max d.c. bound is dominated by another known bound based on a copositive relaxation of QPS, also obtainable via SDP at comparable computational expense. We also discuss extensions of the d.c. bound to more general quadratic programming problems. For the application of QPS to bounding the stability number of a graph, we use a novel formulation of the Lovasz ϑ number to compare ϑ, Schrijver’s ϑ′, and the max d.c. bound.     

Locking lasers with large FM noise to high-Q cavities

We demonstrate that a laser can be directly locked to a cavity when the laser linewidth is much greater than the cavity linewidth. We lock an external-cavity diode laser with more than 1 MHz of added frequency noise to a 3.5 kHz wide cavity resonance. Our analog servo acquires lock even though the laser frequency sweeps through the cavity resonance in less than the cavity buildup time. Our theoretical analysis fully describes our measurements and explains why lock can be acquired.