Application of an asymmetric flow field flow fractionation multi-detector approach for metallic engineered nanoparticle characterization--prospects and limitations demonstrated on Au nanoparticles

In this work we discuss about the method development, applicability and limitations of an asymmetric flow field flow fractionation (A4F) system in combination with a multi-detector setup consisting of UV/vis, light scattering, and inductively coupled plasma mass spectrometry (ICPMS). The overall aim was to obtain a size dependent-, element specific-, and quantitative method appropriate for the characterization of metallic engineered nanoparticle (ENP) dispersions. Thus, systematic investigations of crucial method parameters were performed by employing well characterized Au nanoparticles (Au-NPs) as a defined model system.For good separation performance, the A4F flow-, membrane-, and carrier conditions were optimized. To obtain reliable size information, the use of laser light scattering based detectors was evaluated, where an online dynamic light scattering (DLS) detector showed good results for the investigated Au-NP up to a size of 80 nm in hydrodynamic diameter. To adapt large sensitivity differences of the various detectors, as well as to guarantee long term stability and minimum contamination of the mass spectrometer a split-flow concept for coupling ICPMS was evaluated. To test for reliable quantification, the ICPMS signal response of ionic Au standards was compared to that of Au-NP. Using proper stabilization with surfactants, no difference for concentrations of 1–50 μg Au L⁻¹ in the size range from 5 to 80 nm for citrate stabilized dispersions was observed. However, studies using different A4F channel membranes showed unspecific particle–membrane interaction resulting in retention time shifts and unspecific loss of nanoparticles, depending on the Au-NP system as well as membrane batch and type. Thus, reliable quantification and discrimination of ionic and particular species was performed using ICPMS in combination with ultracentrifugation instead of direct quantification with the A4F multi-detector setup.Figures of merit were obtained, by comparing the results from the multi detector approach outlined above, with results from batch-DLS and transmission electron microscopy (TEM). Furthermore, validation performed with certified NIST Au-NP showed excellent agreement. The developed methods show potential for characterization of other commonly used and important metallic engineered nanoparticles.     

The axiomatic power of Kolmogorov complexity

The famous Gödel incompleteness theorem states that for every consistent, recursive, and sufficiently rich formal theory T there exist true statements that are unprovable in T. Such statements would be natural candidates for being added as axioms, but how can we obtain them? One classical (and well studied) approach is to add to some theory T an axiom that claims the consistency of T  . In this paper we discuss another approach motivated by Chaitin's version of Gödel's theorem where axioms claiming the randomness (or incompressibility) of some strings are probabilistically added, and show that it is not really useful, in the sense that this does not help us prove new interesting theorems. This result answers a question recently asked by Lipton. The situation changes if we take into account the size of the proofs: randomly chosen axioms may help making proofs much shorter (unless NP=PSPACE$\mathrm{NP}=\mathrm{PSPACE}$).     

Regular Turán numbers and some Gan–Loh–Sudakov-type problems

Motivated by a Gan–Loh–Sudakov-type problem, we introduce the regular Turán numbers, a natural variation on the classical Turán numbers where we restrict ourselves to the class of regular graphs. Among other results, we prove a striking supersaturation version of Mantel's theorem in the case of a regular host graph of odd order. We also characterize the graphs for which the regular Turán numbers behave classically or otherwise.     

Productive Syntheses of Privileged Scaffolds Inspired by the Recognition of a Diels–Alder Pattern Common to Three Classes of Natural Products

Identification of a common Diels–Alder pattern in three classes of bioactive natural products led us to study the synthesis and cycloaddition of a new class of cyclic dienes readily available from β,γ-unsaturated lactams. A practical and readily scalable route to the parent p-methoxybenzyl-protected 6- and 7-membered β,γ-unsaturated lactams was developed. These were readily transformed into the corresponding O-silylated dienes, which were reacted with dimethyl and diethyl fumarate to yield stereoselectively highly functionalized bicyclic adducts. These exhibited unexpected and versatile transformations upon acid hydrolysis depending on the nature of the dienophile substituents and the acid catalyst. All reactions have been performed on multigram quantities. These transformations provide a convenient, economical, and easily scalable pathway for the rapid construction of functionally and stereochemically dense privileged scaffolds for the construction of libraries of natural products-inspired molecules of pharmacological relevance.     

A Three-Enzyme Cascade Reaction through Positional Assembly of Enzymes in a Polymersome Nanoreactor

Porous polymersomes based on block copolymers of isocyanopeptides and styrene have been used to anchor enzymes at three different locations, namely, in their lumen (glucose oxidase, GOx), in their bilayer membrane (Candida antarctica lipase B, CalB) and on their surface (horseradish peroxidase, HRP). The surface coupling was achieved by click chemistry between acetylene-functionalised anchors on the surface of the polymersomes and azido functions of HRP, which were introduced by using a direct diazo transfer reaction to lysine residues of the enzyme. To determine the encapsulation and conjugation efficiency of the enzymes, they were decorated with metal-ion labels and analysed by mass spectrometry. This revealed an almost quantitative immobilisation efficiency of HRP on the surface of the polymersomes and a more than statistical incorporation efficiency for CalB in the membrane and for GOx in the aqueous compartment. The enzyme-decorated polymersomes were studied as nanoreactors in which glucose acetate was converted by CalB to glucose, which was oxidised by GOx to gluconolactone in a second step. The hydrogen peroxide produced was used by HRP to oxidise 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) to ABTS^.+. Kinetic analysis revealed that the reaction step catalysed by HRP is the fastest in the cascade reaction.     

Plasmon interactions between gold nanoparticles in aqueous solution with controlled spatial separation

The effects of interparticle distance on the UV-visible absorption spectrum of gold nanocrystals aggregates in aqueous solution have been investigated. The aggregates were produced by ion-templated chelation of omega-mercaptocarboxylic acid ligands covalently attached to the nanoparticles surface. Variation of the ligand chain length provides control over the interparticle separation in the aggregates. The UV-visible spectra consist typically of a single particle band and a secondary band at higher wavelengths associated with the formation of aggregates in solution. The position of the latter depends on interparticle separation up to distances of approximately 8 nm, in accordance with existing models. Potential applications therefore include distance sensitive labels or proximity probes. Conversely, variation of the ligand length allows the preparation of nanostuctured materials with tuned optical properties.     

Radical CH Alkylation of BODIPY Dyes Using Potassium Trifluoroborates or Boronic Acids

A one‐step synthetic procedure for the radical C?H alkylation of BODIPY dyes has been developed. This new reaction generates alkyl radicals through the oxidation of boronic acids or potassium trifluoroborates and allows the synthesis of mono‐, di‐, tri‐, and tetraalkylated fluorophores in a good to excellent yield for a broad range of organoboron compounds. Using this protocol, multiple bulky alkyl groups can be introduced onto the BODIPY core thus creating solid‐state emissive BODIPY dyes.