Magnesium interference and different efficiencies of diastereoisomeric cluster formation in phenylalanine enantiomeric discrimination by the kinetic method

The kinetic method has been applied for determination of d-Phe/l-Phe enantiomeric ratio. Discrimination of enantiomers was inferred from product ion mass spectra of trimeric cluster ions containing the analyte (l,d-Phe), Cu²⁺ as a central metal and l-Trp as a chiral reference ligand. Unsatisfactory quantitative results achieved on an ion trap were rationalized by high-resolution mass spectrometry. The formation of Mg²⁺-containing cluster isobaric to trimeric cluster [Cu(l-Trp)₂Phe]⁺ was observed. Interference like this was identified as a possible reason for deterioration of quantitative low-resolution mass spectrometric analyses of real-world samples based on the kinetic method. Cation-exchanger was used for easy removal of magnesium from a sample and improvement of quantitation.Chiral dependence of formation of the Cu²⁺-containing trimeric cluster was also observed. Heterochiral diastereoisomeric ions were created less effectively.     

Silicone Nano/Microstructures Obtained in Ionic Polymerization

Summary: This work presents a novel surfactant-free method of preparation of silicone hollow nano/microstructures in water. New silicone monomer was synthesized by attaching the unsaturated fatty acid ester – methyl 10-undecenoate (UDM) to the commercial silicone monomer - 1,3,5,7-tetramethylcyclotetrasiloxane (D) using hydrosilylation reaction. The reaction was catalyzed by Karstedt's catalyst [Pt(0)-divinyltetramethyldisiloxane complex]. That modified monomer, tetra(11-methoxy-11-oxoundecyl)-tetramethylcyclotetrasiloxane (D), undergoes self-organization in water. The anionic ring-opening polymerization of D resulted in formation of the silicone polymer (poly-D). Both, the silicone monomer and the polymer were dispersed in aqueous medium using sonication. The structures in the dispersions were visualized by cryo-transmission electron microscopy (Cryo-TEM) and optical microscopy. The size of the particles was also determined from dynamic light scattering (DLS) measurements.     

Search for pair production of scalar top quarks decaying to a tau lepton and a b quark in pp over collisions at sqrt s=1.96 TeV

We search for pair production of supersymmetric top quarks (t over1), followed by R-parity violating decay t over1-->taub with a branching ratio beta, using 322 pb(-1) of pp over collisions at sqrt s=1.96 TeV collected by the upgraded Collider Detector at Fermilab. Two candidate events pass our final selection criteria, consistent with the standard model expectation. We set upper limits on the cross section sigma(t over1t over1) x beta2 as a function of the top-squark mass m(t over1). Assuming beta=1, we set a 95% confidence level limit m(t over1)>153 GeV/c2. The limits are also applicable to the case of a third-generation scalar leptoquark (LQ3) decaying LQ3-->taub.     

Search for resonant tt[overline] production in pp[overline] collisions at sqrt[s]=1.96 TeV

We report on a search for narrow-width particles decaying to a top and antitop quark pair. The data set used in the analysis corresponds to an integrated luminosity of 680 pb(-1) collected with the Collider Detector at Fermilab in run II. We present 95% confidence level upper limits on the cross section times branching ratio. Assuming a specific top-color-assisted technicolor production model, the leptophobic Z' with width Gamma(Z')=0.012M(Z'), we exclude the mass range M(Z')<725 GeV/c(2) at the 95% confidence level.     

First measurement of W boson production in association with a single Charm quark in pp collisions at sqrt(s)=1.96 TeV

We present the first measurement of the production cross section of a W boson with a single charm quark (c) in pp collisions at sqrt(s)=1.96 TeV, using soft muon tagging of c jets. In a data sample of approximately 1.8 fb(-1), recorded with the Collider Detector at Fermilab II detector at the Fermilab Tevatron, we select events with W+1 or 2 jets. We use the charge correlation between the W and the muon from the semileptonic decay of a charm hadron to extract the Wc signal. We measure sigma Wc(PTc >20 GeV/c,|eta c|<1.5) x BR(W-->l nu)=9.8+/-3.2 pb, in agreement with theoretical expectations.     

Lagerstandortoptimierung und Fuhrparkeinsatzplanung in der Konsumgüter-Industrie

Zusammenfassung Die vorliegende Studie wurde in Zusammenarbeit mit einem österreichischen Hersteller von Konsumgütern durchgeführt. Im Rahmen der langfristigen Planung war das gegenwärtige System von Auslieferungslägern auf seine Transportkostenintensität zu prüfen, um fallweise alternative Standortkombinationen zu entwickeln.Für jede ermittelte Standortkombination wurden die zugehörigen Kundenzonen mittels Cluster-analyse ermittelt und durch eine Grobtourenplanung in ein Belieferungsschema eingeordnet.Zur Kontrolle der Ergebnisse der Tourenplanung wurde parallel ein Mixed-Integer-Modell berechnet, dessen Ergebnisse denjenigen der Tourenplanung entsprechen:Bei ausschließlicher Berücksichtigung der variablen Transportkosten ist jeweils eine minimale Lageranzahl zu wählen, da die Fixkosten eines zusätzlichen Lagers in keinem Fall durch die Transportkostenverminderung kompensiert werden kann.

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Summary The study presented was implemented by an Austrian manufacturer of consumer goods, which are distributed to a large number of outlets.One goal of the study was to find warehouse locations which incurred minimal transportation cost. Additionally for each of the optimal locations customer zones were defined by means of cluster analysis. For all customers in a zone delivery routes were calculated. The results clearly show that the cost of additional warehouse locations cannot be offset by declining transportation cost. These findings were strengthened by comparison to a supporting Mixed-Integer-Model.

     

Chiral analysis of UV nonabsorbing compounds by capillary electrophoresis using macrocyclic antibiotics: 1. Separation of aspartic and glutamic acid enantiomers

Glycopeptide antibiotics, namely vancomycin or teicoplanin, were evaluated in capillary electrophoresis for the analysis of UV nonabsorbing compounds such as aspartic and glutamic acid enantiomers. Electrophoretic runs were performed in laboratory-made polyacrylamide-coated capillaries using the partial filling-counter current method in order to avoid the presence on the detector path of the absorbing chiral selector. The background electrolyte consisted of an aqueous or aqueous-organic buffer in the pH range of 4.5-6.5 of sorbic acid/histidine and the appropriate concentration of chiral selector. Several experimental parameters such as antibiotic concentration and type, buffer pH, organic modifier, type and concentration of absorbing co-ion (for the indirect UV detection) were studied in order to find the optimum conditions for the chiral resolution of the two underivatized amino acids in their enantiomers. Among the two investigated chiral selectors, vancomycin resulted to be the most useful chiral selector allowing relatively high chiral resolution of the studied compounds even at low concentration. The optimized method (10 mM sorbic acid/histidine, pH 5, and 10 mM of vancomycin) was used for the analysis of real samples such as teeth dentine and beer.     

N-Directed fluorination of unactivated Csp3–H bonds

Site-selective fluorination of aliphatic C–H bonds remains synthetically challenging. While directed C–H fluorination represents the most promising approach, the limited work conducted to date has enabled just a few functional groups as the arbiters of direction. Leveraging insights gained from both computations and experimentation, we enabled the use of the ubiquitous amine functional group as a handle for the directed C–H fluorination of Csp³–H bonds. By converting primary amines to adamantoyl-based fluoroamides, site-selective C–H fluorination proceeds under the influence of a simple iron catalyst in 20 minutes. Computational studies revealed a unique reaction coordinate for the catalytic process and offer an explanation for the high site selectivity.

By converting primary amines to adamantoyl-based fluoroamides, site-selective C–H fluorination proceeds under the influence of a simple iron catalyst in 20 minutes.

Due to the pervasiveness of fluorine atoms in industrially relevant small molecules, all practicing organic chemists appreciate the importance of this element. As a result of its unusual size and electronegativity, fluorine imparts unique physicochemical properties to pendant organic molecules.¹ For example, the strong C–F bond can prevent biological oxidation pathways, thereby thwarting rapid clearance and potentially improving pharmacokinetics of molecules.² Moreover, the installation of fluorine or trifluoromethyl groups, with their strong inductive effects,² can have a profound effect on the pK_a of nearby hydrogen atoms.³ These attributes, among others, have solidified the importance of fluorinated molecules in the medicinal,^1–4 material,⁵ and agrochemical⁶ industries. Yet, the same unique properties that make fluorine atoms attractive chemical modifiers also make their installation difficult. Consequently, new methods for site-selective fluorine incorporation remain highly desirable.⁷Methods to construct Csp²–F bonds traditionally make use of the Balz–Schiemann fluorodediazonization⁸ and halogen exchange (“Halex” process).⁹ Advances in transition metal-mediated fluorination have broadened access to Csp²–F-containing molecules,¹⁰ but methods to access aliphatic fluorides remain limited. Conventional methods to make Csp³–F bonds—such as nucleophilic displacement of alkyl halides¹¹ and deoxyfluorination¹²—can have limited functional group compatibility and unwanted side reactions. A more efficient route to form aliphatic C–F bonds would target the direct fluorination of Csp³–H bonds (Scheme 1).¹³Open in a separate windowScheme 1(a) Previous work on functional-group directed Csp³–H fluorination; (b) our approach to N-directed fluorination.Recent efforts with palladium catalysis employ conventional C–H-metallation strategies to target Csp³–H bonds for fluorination.¹⁴ Alternatively, radical H-atom abstraction can remove the transition metal from the C–H-cleavage step, thereby offering a promising approach for Csp³–H-bond functionalization.¹⁵ With undirected C–H fluorination,¹⁶ however, selectivity remains a challenge in molecules without strength-differentiated Csp³–H bonds.¹⁷ To overcome this, our group pioneered the directed fluorination of benzylic Csp³–H bonds through an iron-catalyzed process that involves 1,5 hydrogen-atom transfer (HAT) to cleave the desired Csp³–H bond.¹⁸ Since this work, other groups have demonstrated directed Csp³–H fluorination based on radical propagation that proceeds through an interrupted Hofmann–Löffler–Freytag (HLF)¹⁹ reaction (Scheme 1a). These examples employ various radical precursors such as enones,²⁰ ketones,²¹ hydroperoxides,²² and carboxamides²³ to direct fluorination to specific Csp³–H bonds. Since amines are ubiquitous in natural products and drugs, we sought to use amines as the building block of our directing group to achieve fluorination of unactivated Csp³–H bonds (Scheme 1b). By using amines as the starting point, one could use the approach in straightforward synthetic planning for the late-stage functionalization of remote C–H bonds.In the design phase of the project, we needed to devise a synthetically tractable N–F system that would enable 1,5-HAT and allow for fluorine transfer (Scheme 1b). To begin, we decided to examine common amine activating groups that would support 1,5-HAT while avoiding undesired radical reactions. The chosen activating group would provide the ideal steric and electronic properties to enable both N–F synthesis and N–F scission for 1,5-HAT. We first examined common acyl groups (e.g., acetyl-, benzoyl, and tosyl-based amides), but these proved unsatisfactory. For example, fluoroamide synthesis was either not achieved or low yielding, and the desired fluorine transfer proceeded with significant side reactions or returned starting material. We then turned our attention to more sterically hindered amides—which allow for higher yielding fluoroamide synthesis. For fluorine transfer, we hypothesized that the increased steric bulk could slow intermolecular H-atom transfer, thereby leading more efficient intramolecular 1,5-HAT. To that end, we were delighted that pivaloyl-based fluoroamide 1a proceeded in 64% yield to form product 2a (Scheme 2a). Interestingly, 7% of 1a underwent fluorination at the tert-butyl group of the pivaloyl—presumably through a 1,4-HAT reaction (2aa, Scheme 2a).²⁴ The problem is further exacerbated when the pivaloyl group is homologated by one methylene—providing only 7% yield of desired 2b with 32% of the fluorination taking place on the iso-pentyl group (2bb, Scheme 2a). In an attempt to “tie back” the pivaloyl group and prevent the undesired fluorination, we employed a cyclopropylmethyl-based fluoroamide but observed no improvement.Open in a separate windowScheme 2(a) The targeted 1,5-fluorination of unactivated aliphatic C–H bonds results in partial fluorination of the amine activating group; (b) DFT studies (uM06/cc-pVTZ(-f)-LACV3P**//uM06/LACVP** level of theory) identified the competing pathways responsible for alternate fluorination; (c) DFT (uM06/cc-pVTZ(-f)-LACV3P**//uM06/LACVP** level of theory) evaluation of adamantoylamides revealed higher transition state energy for 1,4-HAT due to restricted vibrational scissoring (d) adamantoyl-activated octylamine shows no fluorination of the activating group. ^{a 1}H-NMR yield using 1,3,5-trimethoxybenzene as an internal standard. ^{b 19}F-NMR yield using 4-fluorotoluene as an internal standard.At this point, 1a proved most promising for efficient fluorine transfer, as well as being the most synthetically accessible fluoroamide. The increased steric hindrance minimizes N-sulfonylation during fluorination with NFSI, a problem that plagued the synthesis of our previously targeted fluoroamides.¹⁸ Therefore, to further investigate how to improve fluorine transfer from 1a, we decided to model H-abstraction computationally.We hypothesized that the fluorinated side product 2aa was formed after 1,4-HAT. Since 1,4-HAT is rare,²⁴ we employed DFT (see ESI^† for details) to calculate the 5-membered and 6-memebered transition-states for 1,4- and 1,5-HAT, respectively. Surprisingly, we found that the barrier for 1,4 C–H abstraction in 1a was 18.7 kcal mol⁻¹, which was only 2.6 kcal mol⁻¹ higher in energy than the barrier calculated for 1,5 C–H abstraction in the same system (Scheme 2b). This suggested that both processes were competing at room temperature. We attributed the comparable barriers to the flexibility of the tert-butyl group, which undergoes vibrational scissoring to accommodate the C–H abstraction. The transition state distortion is modest and allows the molecule to maintain bond angles close to the ideal 109.5° (Scheme 2b). Based on this insight, we sought to limit the scissoring of the tert-butyl group and prevent the 1,4-HAT that leads to the undesired side product. After investigating several possible candidates, the underutilized adamantoyl group appeared promising. To evaluate the rigidity of adamantane, we calculated the barriers for 1,4- and 1,5-HAT for the adamantoyl-capped octylamine 1c (Scheme 2c). As expected, the barriers for 1,4- and 1,5-HAT differed significantly—with 1,4 C–H abstraction proceeding with a barrier of 25.1 kcal mol⁻¹ and the 1,5-HAT barely changed at 16.4 kcal mol⁻¹—an 8.7 kcal mol⁻¹ difference. Consequently, we synthesized 1c and subjected it to the reaction conditions. Excitingly, the adamantoyl-capped system produced desired product 2c in 75% yield with no fluorination of the adamantyl group (Scheme 2d).Using the newly devised adamantoyl-based fluoroamides, the reaction conditions were optimized. While a range of metal salts, ligands, and radical initiators were evaluated, Fe(OTf)₂ proved unique in catalyzing fluorine transfer with fluoroamides.¹⁸ Catalyst loading of 10 mol% allowed convenient setup and minor deviations above or below this loading had little effect on yield (see ESI^†). Increasing the temperature to 40 °C produced a slight increase in yield (entry 2, Table 1). Likewise, raising the temperature to 80 °C resulted in full conversion of the starting material in 20 minutes with 81% yield of the desired product (entry 3, Table 1). It should be noted that fluorine transfer occurs efficiently at a variety of temperatures with adjustments in reaction time (see ESI^†). Increasing the reaction concentration or changing the solvent resulted in decreased yield (entries 4 and 5, Table 1). Furthermore, the absence of Fe(OTf)₂ leads to no reaction and quantitative recovery of starting material, attesting to the stability of fluoroamides and the effectiveness of Fe(OTf)₂ (entry 6, Table 1).Optimization of pertinent reaction parameters

Charge-transfer biexciton annihilation in a donor–acceptor co-crystal yields high-energy long-lived charge carriers

Organic donor–acceptor (D–A) co-crystals have attracted much interest due to their important optical and electronic properties. Co-crystals having ⋯DADA⋯ π-stacked morphologies are especially interesting because photoexcitation produces a charge-transfer (CT) exciton, D˙⁺–A˙⁻, between adjacent D–A molecules. Although several studies have reported on the steady-state optical properties of this type of CT exciton, very few have measured the dynamics of its formation and decay in a single D–A co-crystal. We have co-crystallized a peri-xanthenoxanthene (PXX) donor with a N,N-bis(3-pentyl)-2,5,8,11-tetraphenylperylene-3,4:9,10-bis(dicarboximide) (Ph4PDI) acceptor to give an orthorhombic PXX–Ph4PDI ⋯DADA⋯ π-stacked co-crystal with a CT transition dipole moment that is perpendicular to the transition moments for S_n ← S₀ excitation of PXX and Ph4PDI. Using polarized, broadband, femtosecond pump–probe microscopy, we have determined that selective photoexcitation of Ph4PDI in the single co-crystal results in CT exciton formation within the 300 fs instrument response time. At early times (0.3 ≤ t ≤ 500 ps), the CT excitons decay with a t^−1/2 dependence, which is attributed to CT biexciton annihilation within the one-dimensional ⋯DADA⋯ π-stacks producing high-energy, long-lived (>8 ns) electron–hole pairs in the crystal. These energetic charge carriers may prove useful in applications ranging from photovoltaics and opto-electronics to photocatalysis.

Femtosecond transient absorption microscopy of donor–acceptor single co-crystals shows that photogenerated charge transfer excitons in one-dimensional donor–acceptor π stacks annihilate to produce high-energy, long-lived electrons and holes.