Recyclable self-assembly-supported catalytic system for orthoalkylation

[reaction: see text] A new recyclable supported catalyst system for orthoalkylation was devised using a self-assembly consisting of the barbiturate and 2,4,6-triaminopyrimidine H-bonding motifs. At high temperature, the system is completely homogeneous so as to give an efficient catalytic activity, while it is heterogenized at room temperature to form an insoluble solid phase for the easy recovery of the catalyst after the reaction.     

Dynamic identification of phosphopeptides using immobilized metal ion affinity chromatography enrichment, subsequent partial beta-elimination/chemical tagging and matrix-assisted laser desorption/ionization mass spectrometric analysis

The enrichment of phosphopeptides using immobilized metal ion affinity chromatography (IMAC) and subsequent mass spectrometric analysis is a powerful protocol for detecting phosphopeptides and analyzing their phosphorylation state. However, nonspecific binding peptides, such as acidic, nonphosphorylated peptides, often coelute and make analyses of mass spectra difficult. This study used a partial chemical tagging reaction of a phosphopeptide mixture, enriched by IMAC and contaminated with nonspecific binding peptides, following a modified beta-elimination/Michael addition method, and dynamic mass analysis of the resulting peptide pool. Mercaptoethanol was used as a chemical tag and nitrilotriacetic acid (NTA) immobilized on Sepharose beads was used for IMAC enrichment. The time-dependent dynamic mass analysis of the partially tagged reaction mixture detected intact phosphopeptides and their mercaptoethanol-tagged derivatives simultaneously by their mass difference (-20 Da for each phosphorylation site). The number of new peaks appearing with the mass shift gave the number of multiply phosphorylated sites in a phosphopeptide. Therefore, this partial chemical tagging/dynamic mass analysis method can be a powerful tool for rapid and efficient phosphopeptide identification and analysis of the phosphorylation state concurrently using only MS analysis data.     

Origins and predictions of stereoselective antibody catalysis: theoretical analysis of Diels-Alder catalysis by 39A11 and its germ-line antibody

The binding of enantiomeric haptens and transition states by the Schultz Diels-Alderase antibody 39A11 and its germ-line antibody were studied theoretically. The mechanisms by which one hapten and one transition state stereoisomer is recognized selectively are explored with docking simulations and quantum mechanical models. Transition states of the relevant Diels-Alder reaction were located with density functional theory. A prediction is made that the stereoselectivity of 39A11 will be achieved by two strategically placed hydrogen bonds and pi-stacking interactions of the maleimide with a binding-site tryptophan, arranged so as to coordinate one enantiomeric transition state. Binding of other ligands by antibody 39A11 and the germ-line antibody has also been investigated. The polyspecific nature of 39A11 and its germ-line precursor was found to originate from the general ability of the binding pockets to achieve hydrophobic binding of small organic substrates. Comparison of the highly homologous progesterone and Diels-Alderase antibodies (DB3, 1E9, and 39A11) highlights the fact that differences of several key residues in the binding pockets are sufficient to confer selectivity for different antigens.     

Notable coordination effects of 2-pyridinesulfonamides leading to efficient aziridination and selective aziridine ring opening

[reaction: see text] We have developed, on the basis of a chelation-strategy, an efficient copper-catalyzed aziridination protocol with the use of 5-methyl-2-pyridinesulfonamide and PhI(OAc)(2). The reaction proceeds smoothly under mild conditions to give aziridines in moderate to good yields in the absence of external ligands or bases. The coordination-assisted approach offers the additional benefits that efficient deprotection of the N-substituent and selective aziridine ring-opening are effectively achieved.     

Flux decline behaviors in dead-end microfiltration of activated sludge and its supernatant

The properties of dead-end microfiltration were explored under constant pressure using two types of activated sludge controlled under the condition of different air flow rates. The activated sludge cultured at the air flow rate of 0.15 L min⁻¹ (the anaerobic condition) exhibited a significant flux decline compared with the case of the air flow rate of 2.33 L min⁻¹ (the aerobic condition). It was found from the results of microfiltration of the supernatant separated by centrifugation that the constituents in the supernatant caused a major cake resistance in microfiltration of the activated sludge. The average specific filtration resistance for filtration of the activated sludge was closely consistent with that for filtration of the supernatant at low pressure (49 kPa). However, the cake resistance of the microbial floc in microfiltration of the activated sludge became substantial with increasing filtration pressure because of high compressibility of the microbial floc. Moreover, the foulant and the fouling mechanism in microfiltration of the supernatant were evaluated from both microfiltration test of the supernatant and microfiltration test of the filtrate collected thereby. As a result, the effects of the pore size and material of the microfiltration membrane on the flux decline behaviors in dead-end microfiltration were reasonably elucidated.     

Structure and reactivity of bis(silyl) dihydride complexes (PMe(3))(3)Ru(SiR(3))(2)(H)(2): model compounds and real intermediates in a dehydrogenative C-Si bond forming reaction

A series of stable complexes, (PMe(3))(3)Ru(SiR(3))(2)(H)(2) ((SiR(3))(2) = (SiH(2)Ph)(2), 3a; (SiHPh(2))(2), 3b; (SiMe(2)CH(2)CH(2)SiMe(2)), 3c), has been synthesized by the reaction of hydridosilanes with (PMe(3))(3)Ru(SiMe(3))H(3) or (PMe(3))(4)Ru(SiMe(3))H. Compounds 3a and 3c adopt overall pentagonal bipyramidal geometries in solution and the solid state, with phosphine and silyl ligands defining trigonal bipyramids and ruthenium hydrides arranged in the equatorial plane. Compound 3a exhibits meridional phosphines, with both silyl ligands equatorial, whereas the constraints of the chelate in 3c result in both axial and equatorial silyl environments and facial phosphines. Although there is no evidence for agostic Si-H interactions in 3a and 3b, the equatorial silyl group in 3c is in close contact with one hydride (1.81(4) A) and is moderately close to the other hydride (2.15(3) A) in the solid state and solution (nu(Ru.H.Si) = 1740 cm(-)(1) and nu(RuH) = 1940 cm(-)(1)). The analogous bis(silyl) dihydride, (PMe(3))(3)Ru(SiMe(3))(2)(H)(2) (3d), is not stable at room temperature, but can be generated in situ at low temperature from the 16e(-) complex (PMe(3))(3)Ru(SiMe(3))H (1) and HSiMe(3). Complexes 3b and 3d have been characterized by multinuclear, variable temperature NMR and appear to be isostructural with 3a. All four complexes exhibit dynamic NMR spectra, but the slow exchange limit could not be observed for 3c. Treatment of 1 with HSiMe(3) at room temperature leads to formation of (PMe(3))(3)Ru(SiMe(2)CH(2)SiMe(3))H(3) (4b) via a CH functionalization process critical to catalytic dehydrocoupling of HSiMe(3) at higher temperatures. Closer inspection of this reaction between -110 and -10 degrees C by NMR reveals a plethora of silyl hydride phosphine complexes formed by ligand redistribution prior to CH activation. Above ca. 0 degrees C this mixture converts cleanly via silane dehydrogenation to the very stable tris(phosphine) trihydride carbosilyl complex 4b. The structure of 4b was determined crystallographically and exhibits a tetrahedral P(3)Si environment around the metal with the three hydrides adjacent to silicon and capping the P(2)Si faces. Although strong Si.HRu interactions are not indicated in the structure or by IR, the HSi distances (2.00(4) - 2.09(4) A) and average coupling constant (J(SiH) = 25 Hz) suggest some degree of nonclassical SiH bonding in the RuH(3)Si moiety. The least hindered complex, 3a, reacts with carbon monoxide principally via an H(2) elimination pathway to yield mer-(PMe(3))(3)(CO)Ru(SiH(2)Ph)(2), with SiH elimination as a minor process. However, only SiH elimination and formation of (PMe(3))(3)(CO)Ru(SiR(3))H is observed for 3b-d. The most hindered bis(silyl) complex, 3d, is extremely labile and even in the absence of CO undergoes SiH reductive elimination to generate the 16e(-) species 1 (DeltaH(SiH)(-)(elim) = 11.0 +/- 0.6 kcal x mol(-)(1) and DeltaS(SiH)(-)(elim) = 40 +/- 2 cal x mol(-)(1) x K(-)(1); Delta = 9.2 +/- 0.8 kcal x mol(-)(1) and Delta = 9 +/- 3 cal x mol(-)(1).K(-)(1)). The minimum barrier for the H(2) reductive elimination can be estimated, and is higher than that for silane elimination at temperatures above ca. -50 degrees C. The thermodynamic preferences for oxidative additions to 1 are dominated by entropy contributions and steric effects. Addition of H(2) is by far most favorable, whereas the relative aptitudes for intramolecular silyl CH activation and intermolecular SiH addition are strongly dependent on temperature (DeltaH(SiH)(-)(add) = -11.0 +/- 0.6 kcal x mol(-)(1) and DeltaS(SiH)(-)(add) = -40 +/- 2 cal.mol(-)(1) x K(-)(1); DeltaH(beta)(-CH)(-)(add) = -2.7 +/- 0.3 kcal x mol(-)(1) and DeltaS(beta)(-CH)(-)(add) = -6 +/- 1 cal x mol(-)(1) x K(-)(1)). Kinetic preferences for oxidative additions to 1 - intermolecular SiH and intramolecular CH - have been also quantified: Delta = -1.8 +/- 0.8 kcal x mol(-)(1) and Delta = -31 +/- 3 cal x mol(-)(1).K(-)(1); Delta = 16.4 +/- 0.6 kcal x mol(-)(1) and Delta = -13 +/- 6 cal x mol(-)(1).K(-)(1). The relative enthalpies of activation (-)(1) x K(-)(1)). Kinetic preferences for oxidative additions to 1 - intermolecular SiH and intramolecular CH - have been also quantified: Delta (H)SiH(add) = 1.8 +/- 0.8 kcal x mol(-)(1) and Delta S((SiH-add) =31+/- 3 cal x mol(-)(1) x K(-)(1); Delta S (SiH -add) = 16.4 +/- 0.6 kcal x mol(-)(1) and =Delta S (SiH -CH -add) =13+/- 6 cal x mol(-)(1) x K(-)(1). The relative enthalpies of activation are interpreted in terms of strong SiH sigma-complex formation - and much weaker CH coordination - in the transition state for oxidative addition.     

Highly enantioselective synthesis of alpha-alkyl-alanines via the catalytic phase-transfer alkylation of 2-naphthyl aldimine tert-butyl ester by using O(9)-allyl-N(1)-2',3',4'-trifluorobenzylhydrocinchonidinium bromide

Systematic investigations to develop an efficient enantioselective synthetic method for alpha-alkyl-alanine by catalytic phase-transfer alkylation were performed. The alkylation of 2-naphthyl aldimine tert-butyl ester, 1E, with RbOH and O(9)-allyl-N-2',3',4'-trifluorobenzylhydrocinchonidinium bromide, 6, at -35 degrees C showed the highest enantioselectivities, up to 96% ee.     

Sustainable biorefinery processes using renewable deep eutectic solvents

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Determination of protein phosphorylation by extracellular signal-regulated kinase using capillary electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry

Extracellular signal-regulated kinase (ERK) is a key regulatory enzyme mediating cell responses to mitogenic stimulation and is one of the key components in linking growth factor receptor activation to serine/threonine protein phosphorylation processes. Phosphorylation reaction by ERK plays an important role in many signal transduction pathways. ERK phosphorylates numerous substrates such as MBP, microtubule-associated protein 2 (MAP2) and nuclear protein. In particular, MBP is a substrate commonly employed for the detection of ERK activity and contains the consensus primary sequence PRT97P. In this paper, we compared the degree of the phosphorylation reaction of MBP substrate peptides by ERK with the three different MBP substrate peptides, MBP1(KNIVTPRTPPPSQGK), MBP2(VPRTPGGRR) and MBP3(APRTPGGRR) in order to select an efficient substrate peptide for phosphorylation reaction by ERK. The results showed that the MBP3 peptide is the most efficient substrate for phosphorylation reaction by ERK. Using MBP3 peptide, the phosphorylation reaction of MBP by ERK was monitored with both matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and capillary electrophoresis (CE). Our results demonstrate the feasibility of the CE method, the method being a simple and reliable technique in determining and characterizing various kinds of enzyme reaction especially including kinase enzymes.