Versatile automatic stopped-flow system for routine analysis

A versatile, automatic stopped-flow system featuring a mixing module and real-time data collection and treatment is presented. The mixing module is compatible with a number of spectrophotometers and spectrofluorimeters. The fast reaction between iron(III) and thiocyanate is used to evaluate the performance of the system and to develop a routine procedure for the determination of iron in wines, with a reaction time of 3 s. The calibration is linear over the range 1–30 μg ml^?1, with a r.s.d. of 0.9% (n = 11) for 10 μg Fe ml^?1 and a high sample throughput (120 h^?1) is achieved.     

The magic number nine-atom alkali halide cluster ion. Is the nine-atom planar structure the most stable?

The question of whether the cubic structures proposed for the alkali halide cluster ions are the most stable has been re-examined. Geometry/energy optimization calculations were performed on other candidate structures for the [M(MX)₄]⁺ species. The square-planar structure was found to be more than 3 eV lower in energy than a proposed quasi-octahedral structure. The relative energies of the square-planar and other structures for a series of nine-atom alkali halide cluster ions are found to correlate with published experimental data.     

Spec2D: a structure elucidation system based on 1H NMR and H-H COSY spectra in organic chemistry

A system for structure elucidation based on proton NMR spectra has been developed. The system, named Spec2D (system for spectra from 2D-NMR), incorporates 1H NMR and H-H correlation spectroscopy (COSY) spectral information obtained from 2D-NMR experiments. 2D-NMR is important for the structure elucidation because it provides information about the relationships among differently situated protons in the structures of unknown compounds. The system uses the concepts of molecular graphs. The improved representation of substructures as well as several novel algorithms for structure generation have been devised to solve the combinatorial problem and to reduce the processing time. Spec2D consists of a knowledge base, an analysis module, and a candidate structure generator module. Spec2D proposes candidate structures from only 1H NMR and H-H COSY spectral information of an unknown compound without any 13C NMR spectral or structural information, such as molecular formulas. Spec2D has the capability to propose the "new" structure of an unknown compound, if the corresponding substructures are included in the knowledge base.     

The contributions of molecular framework to IMS collision cross-sections of gas-phase peptide ions

Molecular dynamics (MD) is an essential tool for correlating collision cross-section data determined by ion mobility spectrometry (IMS) with candidate (calculated) structures. Conventional methods used for ion structure determination rely on comparing the measured cross-sections with the calculated collision cross-section for the lowest energy structure(s) taken from a large pool of candidate structures generated through multiple tiers of simulated annealing. We are developing methods to evaluate candidate structures from an ensemble of many conformations rather than the lowest energy structure. Here, we describe computational simulations and clustering methods to assign backbone conformations for singly-protonated ions of the model peptide (NH₂-Met-Ile-Phe-Ala-Gly-Ile-Lys-COOH) formed by both MALDI and ESI, and compare the structures of MIFAGIK derivatives to test the ‘sensitivity’ of the cluster analysis method. Cluster analysis suggests that [MIFAGIK + H]⁺ ions formed by MALDI have a predominantly turn structure even though the low-energy ions prefer partial helical conformers. Although the ions formed by ESI have collision cross-sections that are different from those formed by MALDI, the results of cluster analysis indicate that the ions backbone structures are similar. Chemical modifications (N-acetyl, methylester as well as addition of Boc or Fmoc groups) to MIFAGIK alter the distribution of various conformers; the most dramatic changes are observed for the [M + Na]⁺ ion, which show a strong preference for random coil conformers owing to the strong solvation by the backbone amide groups.     

NMR structural characterization from one‐bond 13C?13C couplings: Complete assignment of a hydrogen‐poor depsidone

The connectivity, conformation, tautomeric form, and dynamics of a new depsidone (perisalazinic acid) were characterized using one‐bond ¹³C? ¹³C NMR scalar couplings (¹J_CC) obtained from the INADEQUATE experiment. Characterization of perisalazinic acid using more conventional NMR techniques is problematic due to the extremely limited number of C? H protons present. In the present study, 81 candidate structures were considered and a best fit structure was selected by comparing computed ¹J_CC values for each candidate to 15 experimental values. Of the six flexible moieties in perisalazinic acid, three are adequately represented by a single orientation stabilized by intramolecular hydrogen bonding. The three remaining groups are present as mixtures of conformers with two sites consisting of a pair of conformations and another disordered over six orientations. This study demonstrates the feasibility of complete three‐dimensional structural characterization of an unknown using only theoretical and experimental ¹J_CC values.     

Nucleic acid sequence design via efficient ensemble defect optimization

We describe an algorithm for designing the sequence of one or more interacting nucleic acid strands intended to adopt a target secondary structure at equilibrium. Sequence design is formulated as an optimization problem with the goal of reducing the ensemble defect below a user‐specified stop condition. For a candidate sequence and a given target secondary structure, the ensemble defect is the average number of incorrectly paired nucleotides at equilibrium evaluated over the ensemble of unpseudoknotted secondary structures. To reduce the computational cost of accepting or rejecting mutations to a random initial sequence, candidate mutations are evaluated on the leaf nodes of a tree‐decomposition of the target structure. During leaf optimization, defect‐weighted mutation sampling is used to select each candidate mutation position with probability proportional to its contribution to the ensemble defect of the leaf. As subsequences are merged moving up the tree, emergent structural defects resulting from crosstalk between sibling sequences are eliminated via reoptimization within the defective subtree starting from new random subsequences. Using a Θ(N³) dynamic program to evaluate the ensemble defect of a target structure with N nucleotides, this hierarchical approach implies an asymptotic optimality bound on design time: for sufficiently large N, the cost of sequence design is bounded below by 4/3 the cost of a single evaluation of the ensemble defect for the full sequence. Hence, the design algorithm has time complexity Ω(N³). For target structures containing N ∈{100,200,400,800,1600,3200} nucleotides and duplex stems ranging from 1 to 30 base pairs, RNA sequence designs at 37°C typically succeed in satisfying a stop condition with ensemble defect less than N/100. Empirically, the sequence design algorithm exhibits asymptotic optimality and the exponent in the time complexity bound is sharp. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011     

Asymmetric flow catalysis: Mix-and-go solid-phase Nd/Na catalyst for expeditious enantioselective access to a key intermediate of AZD7594

An anti-selective catalytic asymmetric nitroaldol reaction was implemented in a continuous-flow reaction platform for the synthesis of a key intermediate of a drug candidate. The requisite solid-phase catalyst was readily prepared by mixing an amide-based chiral ligand and inexpensive inorganic salts, NdCl₃?6H₂O and NaO^tBu, without covalent bond linkages. The flow system was operated with 2-Me-THF as the eluent for ca. 400 h to provide a crude nitroaldol adduct in a highly stereoselective manner with no work-up procedure, reaching turnover number over 1600. Facile reduction of the nitro group of the product afforded a key intermediate of AZD7594, a therapeutic candidate for asthma and chronic obstructive pulmonary disease.     

Olefin copolymerization with metallocene catalysts. I. Comparison of catalysts

A number of metallocene/methylaluminoxane (MAO) catalysts have been compared for ethylene/propylene copolymerizations to find relationship between the polymerization activities, copolymer structures, and copolymerization reactivity ratio with the catalyst structures. Stereorigid racemic ethylene bis (indenyl) zirconium dichloride and the tetrahydro derivative exhibit very high activity of 10 ⁷ g (mol Zr h bar)^?1, giving copolymers having comonomer compositions about the same as the feed compositions, molecular weights increasing with the increase of ethylene in the feed, random incorporation of comonomers, and narrow molecular weight distribution indicative of a single catalytic species. Nonbridged bis (indenyl) zirconium behaved differently, favoring the incorporation of ethylene over propylene, producing copolymers whose molecular weight decreases with the increase of ethylene in the feed, broad molecular weight distribution, and a methanol soluble fraction. This catalyst system contains two or more active species. Simple methallocene catalysts have much lower polymerization activities. C_pTiCl₂/MAO produced copolymers with tendency toward alternation, whereas Cp₂HfCl₂/MAO gave copolymer containing short blocks of monomers.     

Untersuchungen an oxidischen Katalysatoren. XLII. Redoxverhalten des Nickels in NiNa?Y-Zeolithen 4. Einfluß der Zusammensetzung auf die Reduzierbarkeit von Nickel in NiNa?Y-Zeolithen

Studies on Oxide Catalysts. XLii. Redox Behaviour of Nickel in Zeolites NiNa? Y. 4. Influence of Composition on the Reducibility of Nickel in Zeolites NiNa? Y By chemical analysis (reaction with K₂Cr₂O₇) and ESCA investigations we determined the degree of reduction in reduced samples NiNa-Y as function of the mole ratio SiO₂/Al₂O₃ (module), of the Ni²⁺ degree of exchange and the kind of the second cations. (NH₄₊, Ca²+, Co²+, and Nd³+) in the temperature region of 620–770 K. The degree of nickel reduction increases with increasing module, decreasing degree of exchange and decreasing number of Brönsted acidic centres. This behaviour is caused by the influence of the interaction between cations Ni²⁺ and zeolite lattice on the reduction equilibrium.     

Extensive flow-injection dilution for in-line sample pretreatment: Comparison between Single-Stage and Dual-Stage Modules

A flow-injection single-stage dilution module is compared with a dual-stage dilution module. Each stage consists of a fixed loop injector, a stirred mixing chamber and a pulse-free pumping system. The precision of both systems is rather insensitive to flow rate and is better than 2% r.s.d. at dispersion coefficients up to 10⁶. The dual-stage dilution module provides superior performance over a large range of dispersion coefficients at higher throughput and offers much more versatility for sample pretreatment. The single-stage dilution module is usually a sufficiently powerful inline sample pretreatment for flow injection analyzers as well as for other kinds of chemical analyzers.     

Carbon-13 n.m.r. spectra of branched carboxylic acids and their derivatives

¹³C n.m.r. spectra have been measured for 39 compounds with branched structures including carboxylic acids, their methyl and ethyl esters, nitriles and chlorinated esters. The results obtained indicate that the ¹³ C n.m.r. technique is applicable to structure assignment of acids and their derivatives containing various numbers of substituents on the chain. The dependence of the carboxylic carbon chemical shift on the number and structure of α-positioned substituents has been determined. Calculation of the chemical shifts for branched carboxylic acids, esters and nitriles from the corresponding increments using the additivity scheme is shown to be possible in principle.     

Design and performance of a miniature TDCR counting system

A portable liquid scintillation counting system based on the triple-to-double coincidence ratio (TDCR) method was developed at Sofia University “St. Kliment Ohridski”. The system consists of a miniature TDCR counter with cylindrical optical chamber and a specialized TDCR counting module named nanoTDCR. The nanoTDCR module is produced by the labZY company and provides several important new TDCR counting functionalities like: individual extending-type dead-time in each channel; simultaneous counting with two different extendable dead-times and two different coincidence windows and simultaneous TDCR counting and spectrum acquisition. The performance of the new system was tested in benchmark comparisons with the LNHB’s primary TDCR counting system of activity measurements of ²⁴¹Am, ³H, ¹⁴C and ⁶³Ni. Good agreement between the two systems was observed.     

Standard-geometry chains fitted to X-ray derived structures: Validation of the rigid-geometry approximation. II. Systematic searches for short loops in proteins: Applications to bovine pancreatic ribonuclease A and human lysozyme

A rigid-geometry approach to protein conformational searches has been used to calculate stable structures for localized regions of the molecules bovine pancreatic ribonuclease A and human lysozyme. The search method is essentially an application of the local deformation algorithm of Gō and Scheraga [Macromolecules, 3 , 178–187 (1970)]. A series of local chain deformations is produced in the polypeptide chain. The deformations are screened to eliminate structures having serious atomic overlaps or energetically unreasonable backbone dihedral angles. The remaining structures are refined by energy minimization and the rms deviations of the energy-minimized structures, relative to the native structures, are calculated. The correlation between low rms deviation and low energy is reasonably good, indicating that this method should be useful in generating a small number of candidate structures for further energy refinement. Further applications to proteins with an unknown structure, such as homology-based modeling applications, should now be amenable to this type of procedure.     

Graph-theoretical analysis of the bonding topology in polyhedral organic cations

It is shown that in several cases where planar delocalisation in organic cations would result in the formation of an anti-aromatic system, polyhedral delocalisation is the form of bonding actually preferred. This explains, for instance, why organic cations in such cases adopt cage-like structures. A full graph-theoretical analysis, similar to one previously published¹² for polyhedral boranes, carboranes and metal clusters, indicates that the nido structure for (CH)₅⁺ may readily be accounted for. Moreover, in the case of the dication (CH)₆²⁺ the fact that its energy minimum also corresponds to a nido structure is explained. In fact, no closo- or arachno-type structures appear to be possible for organic cations. A number of structural predictions concerning these species are given in the conclusion.     

Interactions in a phosphate—water—cation system

SCF ab initio study of the system dimethylphosphate anion—water—Na⁺ in the supermolecule approach shows the competitivity of the through-water binding of Na⁺ to a phosphodiester linkage with its direct interaction. Confirmation of this situation is seen in a number of crystal structures of mono- and oligonucleotides.     

Gas chromatography with ballistic heating and ultrafast cooling of column

An overview of the existing methods for minimization of the analysis time in gas chromatography (GC) is presented and a new system for fast temperature programming and very fast cooling down is evaluated. In this study, a system of coaxial tubes, a heating/cooling module (HC-M), was developed and studied with a capillary column placed inside the HC-M. The module itself was heated by a GC oven and cooled down by an external cooling medium. The HC-M was heated at rates of up to 330 °C min⁻¹ and cooled at the rate of 6000 °C min⁻¹. The GC system was prepared for the next run within a few seconds. The HC-M permits good separation reproducibility, comparable with that of a conventional GC, expressed in terms of relative retention times and peak areas of analytes reproducibilities. The HC-M can be used within any commercial gas chromatograph.     

Laser properties of holmium and erbium in thorium-, zinc- and yttrium-based fluoride glass

Optical properties of Ho(III)- and Er(III)-doped thorium-, zinc- and yttrium-based fluoride glasses are determined. Due to the large number of luminescent levels, it is possible to determine the multiphonon relaxation rates even for energy gaps smaller than 1900 cm⁻. Peak cross sections for laser action and threshold powers for infrared laser emissions are calculated and compared with literature data. It is shown that addition of other lanthanides significantly decreases the threshold power for laser action. The results indicate that a rare-earth-doped fluoride glass is a promising candidate for an integrated fiber optics system in which the rare earth laser is a part of the fiber.     

Structure and properties of 2,2-dihydroxymalonates of trivalent Y, lanthanides, Pu and Am

The M-O bond lengths in the lanthanide series show a well-known behaviour due to lanthanide contraction, including so-called “gadolinium break”. All three bond lengths show a good linear correlation with Shannon ionic radii for Y³⁺ and Ln³⁺ ions with coordination number 9. Nevertheless, the slopes of these dependences are different (0.957(16) for OH-groups, 0.85(2) for carboxylate groups and 1.080(17) for water molecules) and differ from unity due to a layer nature of the structures. The ionic radii for Pu³⁺ and Am³⁺ with coordination number 9 are absent in the Shannon system of ionic radii. From our data, we can propose the values 1.172 and 1.156 Å for Pu³⁺, and Am³⁺, respectively. In all crystals the structure is stabilized through extensive hydrogen bonding involving carboxylic and hydroxyl groups and water molecules.