Continuous flow enzyme-catalyzed polymerization in a microreactor

Enzymes immobilized on solid supports are increasingly used for greener, more sustainable chemical transformation processes. Here, we used microreactors to study enzyme-catalyzed ring-opening polymerization of ε-caprolactone to polycaprolactone. A novel microreactor design enabled us to perform these heterogeneous reactions in continuous mode, in organic media, and at elevated temperatures. Using microreactors, we achieved faster polymerization and higher molecular mass compared to using batch reactors. While this study focused on polymerization reactions, it is evident that similar microreactor based platforms can readily be extended to other enzyme-based systems, for example, high-throughput screening of new enzymes and to precision measurements of new processes where continuous flow mode is preferred. This is the first reported demonstration of a solid supported enzyme-catalyzed polymerization reaction in continuous mode.     

New routes to 1-deoxy-(3,4-dihydro-7,8-dimethyl-2,4-dioxopyrimido[4,5-b]-quinolin-10(2H)yl)-D-ribitols (5-deazariboflavins)

The acid-catalyzed reaction of 6-(N-D-ribityl-3,4-xylidino)uracil ( 1 ) with trimethyl ortho-formate yields a bis(methoxymethylene) derivative ( 2 ), which is readily deprotected to give 5-deazariboflavin ( 3 ). Correspondingly, 5-methyl-5-deazariboflavin ( 6 ) is produced by cyclization of the tetraacetate of 1 with acetyl chloride in the presence of stannic chloride followed by deacetylation.     

Structure Elucidation of Triterpenoid Saponins Found in an Immunoadjuvant Preparation of Quillaja brasiliensis Using Mass Spectrometry and 1H and 13C NMR Spectroscopy

An immunoadjuvant preparation (named Fraction B) was obtained from the aqueous extract of Quillaja brasiliensis leaves, and further fractionated by consecutive separations with silica flash MPLC and reverse phase HPLC. Two compounds were isolated, and their structures elucidated using a combination of NMR spectroscopy and mass spectrometry. One of these compounds is a previously undescribed triterpene saponin (Qb1), which is an isomer of QS-21, the unique adjuvant saponin employed in human vaccines. The other compound is a triterpene saponin previously isolated from Quillaja saponaria bark, known as S13. The structure of Qb1 consists of a quillaic acid residue substituted with a β-d-Galp-(1→2)-[β-d-Xylp-(1→3)]-β-d-GlcpA trisaccharide at C3, and a β-d-Xylp-(1→4)-α-l-Rhap-(1→2)-[α-l-Arap-(1→3)]-β-d-Fucp moiety at C28. The oligosaccharide at C28 was further substituted at O4 of the fucosyl residue with an acyl group capped with a β-d-Xylp residue.     

Metallocycle synthesis accelerated by high pressure

Reaction of cis-[FeH₂(dmpe)₂](1) with diphenylbutadiyne results in an insertion into both of the iron-hydride bonds to form an iron metallocycle. Spectroscopic and crystallographic data of [Fe(PhHCC₂CHPh)(dmpe)₂] (3) show 1,4-diphenylbutatriene is symmetrically bound to the metal via the central double bond. The reaction to form the metallocyclic complex is greatly accelerated by application of external pressure. A 41% yield of (3) is isolated after two days at atmospheric pressure or after approximately 75 min at 800MPa.     

Oxygen adsorption on hydrated gold cluster anions: experiment and theory

The discovery that supported gold clusters act as highly efficient catalysts for low-temperature oxidation reactions has led to a great deal of work aimed at understanding the origins of the catalytic activity. Several studies have shown that the presence of trace moisture is required for the catalysts to function. Using near-atmospheric pressure flow reactor techniques, we have studied humidity and temperature effects on the reactivity of gas-phase gold cluster anions with O2. Near room temperature, the humid source produces abundant gold-hydroxy cluster anions, Au(N)OH(-), and these have a reversed O2 adsorption activity: Nonreactive bare gold clusters become active when in the form Au(N)OH(-), while active bare clusters are inactive when -OH is bound. The binding energies for the stable structures obtained from density functional calculations confirm fully these findings. Moreover, the theory provides evidence that electron-transfer induced by the binding of a OH group enhances the reactivity toward molecular oxygen for odd anionic gold clusters and suppresses the reactivity for the even ones. The temperature dependence of O2 addition to Au(3)OH(-) and Au(4)(-) indicates deviations from equilibrium control at temperatures below room temperature. The effects of humidity on gold cluster adsorption activity support the conclusion drawn for the mechanism of O2 adsorption on "dry" gold cluster anions and provides insight into the possible role of water in the enhanced activity of supported gold cluster catalysts.     

Anion sensing 'venus flytrap' hosts: a modular approach

A series of podands based on three hydrogen bonding 'arms' have been prepared and their affinities for simple inorganic anions measured.     

Stereoselective total syntheses and reassignment of stereochemistry of the freshwater cyanobacterial hepatotoxins cylindrospermopsin and 7-epicylindrospermopsin

A stereoselective total synthesis of the structure 1 proposed for the freshwater cyanobacterial heptatotoxin cylindrospermopsin has been accomplished in approximately 30 operations starting from commercially available 4-methoxypyridine. Utilizing methodology developed by Comins, the tetrasubstituted piperidine A-ring unit of the hepatotoxin was efficiently constructed. The two remaining stereocenters in the natural product were then set by a stereospecific intramolecular N-sulfinylurea Diels-Alder cyclization/Grignard ring opening/allylic sulfoxide [2,3]-sigmatropic rearrangement sequence previously developed in these laboratories, leading to key intermediate 29. The stereochemical assignment of alcohol 29, which contains all six of the stereogenic centers of the natural product, was confirmed by an X-ray crystal structure determination of a derivative. Installation of the D-ring uracil moiety was effected by using our new methodology developed for this purpose, and construction of the C-ring guanidine completed the total synthesis of racemic structure 1. However, the (1)H NMR data for this compound do not match that of cylindrospermopsin, but instead agree with the data reported for 7-epicylindrospermopsin, a minor toxic metabolite that co-occurs with cylindrospermopsin. Therefore, we propose a revision of the stereochemical assignments of these natural products such that cylindrospermopsin is now represented as structure 2 and 7-epicylindrospermopsin is 1. This reassignment was further confirmed by Mitsunobu inversion of the C-7 alcohol 51 to epimer 52, and conversion of this compound to tetracyclic diol 57, which has previously been transformed to cylindrospermopsin (2).     

Transition Metal‐Free Reduction of Activated Alkenes Using a Living Microorganism

Microorganisms can be programmed to perform chemical synthesis via metabolic engineering. However, despite an increasing interest in the use of de novo metabolic pathways and designer whole‐cells for small molecule synthesis, the inherent synthetic capabilities of native microorganisms remain underexplored. Herein, we report the use of unmodified E. coli BL21(DE3) cells for the reduction of keto‐acrylic compounds and apply this whole‐cell biotransformation to the synthesis of aminolevulinic acid from a lignin‐derived feedstock. The reduction reaction is rapid, chemo‐, and enantioselective, occurs under mild conditions (37 °C, aqueous media), and requires no toxic transition metals or external reductants. This study demonstrates the remarkable promiscuity of central metabolism in bacterial cells and how these processes can be leveraged for synthetic chemistry without the need for genetic manipulation.     

Liquid deposition patterning of conducting polymer ink onto hard and soft flexible substrates via dip-pen nanolithography

Ink formulations and protocols that enable the deposition and patterning of a conducting polymer (PEDOT:PSS) in the nanodomain have been developed. Significantly, we demonstrated the ability to pattern onto soft substrates such as silicone gum and polyethylene terephthalate (PET), which are materials of interest for low cost, flexible electronics. The deposition process and dimensions of the polymer patterns are found to be critically dependent on a number of parameters, including the pen design, ink properties, time after inking the pen, dwell time of the pen on the surface, and the nature of material substrate. By assessing these different parameters, an improved understanding of the ability to control the dimensions of individual PEDOT:PSS structures down to 600 nm in width and 10-80 nm in height within patterned arrays was obtained. This applicability of DPN for simple and nonreactive liquid deposition patterning of conducting polymers can lead to the fabrication of organic nanoelectronics or biosensors and complement the efforts of existing printing techniques such as inkjet and extrusion printing by scaling down conductive components to submicrometer and nanoscale dimensions.