Continuous-flow synthesis of ZIF-8 biocomposites with tunable particle size

Zeolitic Imidazolate Framework (ZIF) biocomposites show the capacity to protect and deliver bio-therapeutics. To date, the progress in this research area is based on laboratory batch methods. To further explore the potential of ZIF-biocomposites for application to biomedicine and biotechnology, the continuous production of ZIF-biocomposites of specific particle size is desirable. Here we report the first continuous flow synthetic method for the encapsulation of a model protein (bovine serum albumin, BSA) and a clinical therapeutic (α1-antitrypsin, AAT) in ZIF-8. We studied the in situ kinetics of nucleation, growth and crystallization of BSA@ZIF-8 by small angle X-ray scattering. By controlling the injection time of ethanol, we could quench the particle growth via ethanol-induced crystallization from amorphous particles to ZIF-8 crystals. The particle size of the biocomposite was tuned in the 40-100 nm range by varying residence time prior to introduction of ethanol. As a proof-of-concept, we used this protocol for the encapsulation of AAT in ZIF-8. Upon release of the bio therapeutic from the composite, the trypsin inhibitor function of AAT was preserved.Francesco Carraro, Jason D. Williams, Mercedes Linares‐Moreau, Chiara Parise ... Christian Doonan ... Paolo Falcaro ... et al

Acetylketene: Conformational isomerism and photochemistry. Matrix isolation infrared and ab initio studies

The s-Z and s-E conformers of acetylketene (5) were generated by flash vacuum pyrolysis (FVP) and matrix photolysis of precursors 1-4. Both conformers were characterized by low-temperature IR spectroscopy in argon, xenon, and nitrogen matrices. The observed frequencies and intensities are in excellent agrement with ab initio calculations at the MP2/6-31G* level. UV irradiation of s-Z/s-E-5 in nitrogen or xenon matrices allows the clean interconversion of conformers. Prolonged UV irradiation resulted in decarbonylation and formation of methylketene (7). However, the photolysis of argon matrix isolated 5 produced a new set of bands in the IR spectrum very close to the s-Z/s-E absorptions. Annealing of the matrix to 35 K removed these bands. This unusual phenomenon was shown to be due to a photochemically induced matrix site effect. Consistent with experimental observations, high-level calculations (QCISD(T)/6-311+G(2d,p)+ZPVE) predict that the s-Z and s-E conformers have virtually identical energies

Iminopropadienones, RN=C=C=C=O: Syntheses and reactions

Phenyliminopropadienone, PhN=C=C=C=O, is prepared and characterized, and init

Dipivaloylketene and Its Unusual Dimerization to a Permanently Stable α-Oxoketene

Dipivaloylketene (8) is obtained by flash vacuum pyrolysis of 5-tert-butyl-4-pivaloyl-2,3-dihydrofuran-2,3-dione (7) at temperatures between 250 and 500-degrees-C. It is stable in solution below 0-degrees-C and dimerizes at room temperature to 10, which involves an unusual [2+4] cycloaddition reaction between one alpha-oxoketene unit and the carbonyl double bond of a second molecule, thus preserving the ketene functionality. The structure of the highly hindered ketene 10 was proved by X-ray crystallography. This compound is stable for months in the open air at high humidity

Carboxy(vinyl)ketene intermediates in the thermolysis of methylthio- and methoxy-substituted Meldrum's acid derivatives

Journal of the Chemical Society. Perkin Transactions 23493-498JCPK

Reactions of Dipivaloylketene Dimer with Nucleophiles: New Access to the 2,6,9-Trioxabicyclo[3.3.1]nona-3,7-diene Ring System (Bridged Bis-Dioxines)

Novel and convenient methods to prepare several functionalized 2,6,9-trioxabicyclo[3.3.1]nonadienes (''bridged bis-dioxines'') 6, 10, 11, and 12 are described. In general, these are obtained by addition of nucleophiles to alpha-oxoketene 5 in a multistep reaction sequence, where the specific reaction pathway depends strongly on the type of nucleophile employed: Aromatic amines with electron-donating substituents afford the trioxabicyclononadienes 6, while with aliphatic amines or thiolates, 2 equiv of the corresponding dipivaloylacetamides 13 or thioesters 14, respectively, are formed. In the case of OH nucleophiles, the primary 1:1 adducts 8 are isolable, characterized by an X-ray analysis of 8a. Under acidic conditions, 8 can be cyclized to the bifunctionalized bis-dioxines 10. The bis-carboxylic acid 10c serves as a valuable intermediate to synthesize other derivatives, e.g. the bis-acid chloride 11 and the bis-ester 12. Mechanistic pathways leading to the various reaction products are discussed in detail and supported by semiempirical molecular orbital calculations using the AM1 method. The spontaneous formation of the bis-dioxine skeleton in the reaction 5 --> 6 is likely to proceed via an unusual [4 + 4] type tandem cyclization reaction