Remarkable Improvement in Am3+ and Cm3+ Separation Using a Cooperative Counter Selectivity Strategy by a Combination of Branched Diglycolamides and Hydrophilic Polyaza-heterocycles.

Separation of Am3+ and Cm3+ is one of the most challenging problems in the back-end of the nuclear fuel cycle. In the present work, we exploited the cooperative effect of the opposite selectivity of hydrophobic branched DGA derivatives and hydrophobic N-donor heterocyclic ligands taken in two different phases to achieve improved separation behavior. A systematic study was performed using a series of DGA derivatives to understand the effect and the position of branching in the alkyl chains on the separation behavior of Am3+ and Cm3+. A separation factor (S.F.) value as high as 10 for Cm3+ over Am3+ was obtained in the case of TiBDGA (N,N,N',N'-tetra-iso-butyl diglycolamide) using SO3PhBTPhen ((phenanthroline-2,9-diyl)-1,2,4-triazine-5,5,6,6-tetrayltetrabenzenesulfonic acid) as the aqueous complexant, which is the highest reported value so far for the ligand-based separation of Am3+ and Cm3+ without involving any oxidation or reduction step. The high selectivity favoring Cm3+ ion extraction in the case of this DGA derivative is also explained with the help of computational studies.

Strongly Inhibited Spontaneous Emission of PbS Quantum Dots Covalently Bound to 3D Silicon Photonic Band Gap Crystals.

We present an optical study of the spontaneous emission of lead sulfide (PbS) nanocrystal quantum dots in 3D photonic band gap crystals made from silicon. The nanocrystals emit in the near-infrared range to be compatible with 3D silicon nanophotonics. The nanocrystals are covalently bound to polymer brush layers that are grafted from the Si-air interfaces inside the nanostructure by using surface-initiated atom transfer radical polymerization. The presence and position of the quantum dots were previously characterized by synchrotron X-ray fluorescence tomography. We report both continuous wave emission spectra and time-resolved, time-correlated single photon counting. In time-resolved measurements, we observe that the total emission rate greatly increases when the quantum dots are transferred from suspension to the silicon nanostructures, likely due to quenching (or increased nonradiative decay) that is tentatively attributed to the presence of Cu catalysts during the synthesis. In this regime, continuous wave emission spectra are known to be proportional to the radiative rate and thus to the local density of states. In spectra normalized to those taken on flat silicon outside the crystals, we observe a broad and deep stop band that we attribute to a 3D photonic band gap with a relative bandwidth of up to 26%. The shapes of the relative emission spectra match well with the theoretical density of states spectra calculated with plane-wave expansion. The observed inhibition is 4-30 times, similar to previously reported record inhibitions, yet for coincidental reasons. Our results are relevant to applications in photochemistry, sensing, photovoltaics, and efficient miniature light sources.

Distribution of polyelectrolytes and counterions upon polyelectrolyte complexation.

HYPOTHESIS: Understanding polyelectrolyte complexation remains limited due to the absence of a systematic methodology for analyzing the distribution of components between the polyelectrolyte complex (PEC) and the dilute phases. EXPERIMENTS: We developed a methodology based on NMR to quantify all components of solid-like PECs and their supernatant phases formed by mixing different ratios of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid)-sodium salt (PAA). This approach allowed for determining relative and absolute concentrations of polyelectrolytes in both phases by 1H NMR studies. Using 23Na and 35Cl NMR spectroscopy we measured the concentration of counterions in both phases. FINDINGS: Regardless of the mixing ratio of the polyelectrolytes the PEC is charge-stoichiometric, and any excess polyelectrolytes to achieve charge stoichiometry remains in the supernatant phase. The majority of counterions were found in the supernatant phase, confirming counterion release being a major thermodynamic driving force for PEC formation. The counterion concentrations in the PEC phase were approximately twice as high as in the supernatant phase. The complete mass balance of PEC formation could be determined and translated into a molecular picture. It appears that PAH is fully charged, while PAA is more protonated, so less charged, and some 10% extrinsic PAH-Cl- pairs are present in the complex.

Understanding the Interaction of Uranyl Cation with Two C-Pivot Tripodal Amides: Synthesis, Complexation, Microcalorimetry, and DFT Studies.

Complexation of uranyl ions with two structurally related C-pivotal tripodal amides with varying spacer lengths, synthesized for the first time, was studied by optical spectroscopy. In the tripodal amides, the coordination was through the carbonyl O atoms where the carbonyl groups were away from the central C-atom by three spacer atoms (LI) and four spacer atoms (LII), respectively. Increasing the spacer atoms going from LI to LII favors the complexation with the linear uranyl cations and results in stronger complex formation. The complexation heat between the uranyl cations and the two amide ligands was directly measured by microcalorimetric titrations. The complexation with both the ligands was driven by exothermic enthalpy and positive entropy changes. Formation of the complex proceeded by the replacement of water molecules from the primary coordination sphere of the uranyl cation. Both ligands formed bisolvated (ML2-type) complexes in which one unit of the ligand binds in a monodentate manner and the other in a bidentate mode. Density functional theory calculations further supported our experimental observations.

Selective Perchlorate Sensing Using Electrochemical Impedance Spectroscopy with Self-Assembled Monolayers of semiaza-Bambusurils.

In the last two decades, perchlorate salts have been identified as environmental pollutants and recognized as potential substances affecting human health. We describe self-assembled monolayers (SAMs) of novel semiaza-bambus[6]urils (semiaza-BUs) equipped with thioethers or disulfide (dithiolane) functionalities as surface-anchoring groups on gold electrodes. Cyclic voltammetry (CV) with Fe(CN)6 3-/4- as a redox probe, together with X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and ellipsometry, were employed to characterize the interactions at the interface between the anchoring groups and the metal substrate. Data showed that the anion receptors' packing on the gold strongly depends on the anchoring group. As a result, SAMs of BUs with lipoic amide side chains show a concentration-dependent layer thickness. The BU SAMs are extremely stable on repeated electrochemical potential scans and can selectively recognize perchlorate anions. Our electrochemical impedance spectroscopy (EIS) studies indicated that semiaza-BU equipped with the lipoic amide side chains binds perchlorate (2-100 mM) preferentially over other anions such as F- , Cl- , I- , AcO- , H2 PO4 - , HPO4 2- , SO4 2- , NO2 - , NO3 - , or CO3 2- . The resistance performance is 10 to 100 times more efficient than SAMs containing all other tested anions.

Utilizing the Oxygen Reduction Reaction in Particle Impact Electrochemistry: A Step toward Mediator-Free Digital Electrochemical Sensors.

The current blockade particle impact method opens a route toward highly parallelized single-entity electrochemical assays. An important limitation is, however, that a redox mediator must be present in the sample, which can detrimentally interfere with molecular recognition processes. Dissolved O2 that is naturally present in aqueous solutions under ambient conditions can in principle serve as a suitable mediator via the oxygen reduction reaction (ORR). Here, we demonstrate the validity of this concept by performing current blockade experiments to capture and detect individual microparticles at Pt microelectrodes using solely the ORR. The readout modality is independent of the absolute O2 concentration, allowing operation under varying conditions. We further determine how the trajectories of individual microparticles are influenced by the combination of electrophoresis and electroosmotic flows and how these can be utilized to provide continuous detection of cationic particles in water for environmental monitoring.

Receptor Density-Dependent Motility of Influenza Virus Particles on Surface Gradients.

Influenza viruses can move across the surface of host cells while interacting with their glycocalyx. This motility may assist in finding or forming locations for cell entry and thereby promote cellular uptake. Because the binding to and cleavage of cell surface receptors forms the driving force for the process, the surface-bound motility of influenza is expected to be dependent on the receptor density. Surface gradients with gradually varying receptor densities are thus a valuable tool to study binding and motility processes of influenza and can function as a mimic for local receptor density variations at the glycocalyx that may steer the directionality of a virus particle in finding the proper site of uptake. We have tracked individual influenza virus particles moving over surfaces with receptor density gradients. We analyzed the extracted virus tracks first at a general level to verify neuraminidase activity and subsequently with increasing detail to quantify the receptor density-dependent behavior on the level of individual virus particles. While a directional bias was not observed, most likely due to limitations of the steepness of the surface gradient, the surface mobility and the probability of sticking were found to be significantly dependent on receptor density. A combination of high surface mobility and high dissociation probability of influenza was observed at low receptor densities, while the opposite occurred at higher receptor densities. These properties result in an effective mechanism for finding high-receptor density patches, which are believed to be a key feature of potential locations for cell entry.

Recruitment of Receptors and Ligands in a Weakly Multivalent System with Omnipresent Signatures of Superselective Binding.

Recruitment of receptors at membrane interfaces is essential in biological recognition and uptake processes. The interactions that induce recruitment are typically weak at the level of individual interaction pairs, but are strong and selective at the level of recruited ensembles. Here, a model system is demonstrated, based on the supported lipid bilayer (SLB) that mimics the recruitment process induced by weakly multivalent interactions. The weak (mm range) histidine-nickel-nitrilotriacetate (His2 -NiNTA) pair is employed owing to its ease of implementation in both synthetic and biological systems. The recruitment of receptors (and ligands) induced by the binding of His2 -functionalized vesicles on NiNTA-terminated SLBs is investigated to identify the ligand densities necessary to achieve vesicle binding and receptor recruitment. Threshold values of ligand densities appear to occur in many binding characteristics: density of bound vesicles, size and receptor density of the contact area, and vesicle deformation. Such thresholds contrast the binding of strongly multivalent systems and constitute a clear signature of the superselective binding behavior predicted for weakly multivalent interactions. This model system provides quantitative insight into the binding valency and effects of competing energetic forces, such as deformation, depletion, and entropy cost of recruitment at different length scales.

Interface Engineering of "Clickable" Organic Electrochemical Transistors toward Biosensing Devices.

"Clickable" organic electrochemical transistors (OECTs) allow the reliable and straightforward functionalization of electronic devices through the well-known click chemistry toolbox. In this work, we study various aspects of the click chemistry-based interface engineering of "clickable" OECTs. First, different channel architectures are investigated, showing that PEDOT-N3 films can properly work as a channel of the transistors. Furthermore, the Cu(I)-catalyzed click reaction of ethynyl-ferrocene is studied under different reaction conditions, endowing the spatial control of the functionalization. The strain-promoted and catalyst-free cycloaddition of a dibenzocyclooctyne-derivatized poly-l-lysine (PLL-DBCO) is also performed on the OECTs and validated by a fiber optic (FO)-SPR setup. The further immobilization of an azido-modified HD22 aptamer yields OECT-based biosensors that are employed for the recognition of thrombin. Finally, their performance is evaluated against previously reported architectures, showing higher density of the immobilized HD22 aptamer, and originating similar KD values and higher maximum signal change upon analyte recognition.

Interplay of Depletion Forces and Biomolecular Recognition in the Hierarchical Assembly of Supramolecular Tubes.

Crowding effects have a profound impact on the hierarchical organization of cellular architectures. In the fields of systems chemistry and soft matter, this effect has not received much attention so far. Here, it is explored how poly(ethylene glycol) (PEG) as a crowding agent invokes depletion forces that act on synthetic supramolecular tubes. Hence, supramolecular tubes are pushed from their random orientation into hierarchically assembled bundles due to the PEG-induced crowded environment. The resulting morphology of formed bundled architectures can be tuned by the concentrations of both the supramolecular tubes and the PEG. The introduction of biotin groups at the surface of the tubes allows the engineering of biotin-streptavidin crosslinks between them. The order of introducing PEG and streptavidin in the system further affects the formed hierarchical assemblies, as well as their resistance toward dilution. The strategy described here provides a new route to establish hierarchically organized supramolecular architectures, combining crowding and specific biomolecular interactions, which shows the potential for controlling the structure of supramolecular materials and other soft matter systems.

Kinetic model for the dehydration of xylose to furfural from a boronate diester precursor.

A comprehensive kinetic model describes the dehydration of xylose starting from the boronate diester-protected xylose (PBA2X). The model incorporates (de)esterification of PBA2X, partitioning, and xylose dehydration, and aims to evaluate the effects of the solvent system on these steps. The model explores the effect of the water contents in monophasic solvent systems, and that of ionic strength and mixing in biphasic aqueous-organic systems. At low water content, hydrolysis of PBA2X is the rate-limiting step, while xylose dehydration is fast. Conversely, in a monophasic three-solvent system, where the water content is higher, complete hydrolysis of the diester is achieved quickly. Under biphasic conditions, xylose dehydration is fast at high ionic strengths, but the slower partitioning/hydrolysis of PBA2X results in an overall slower furfural production. Furthermore, the observed different but high, constant xylose-to-furfural selectivities observed experimentally are tentatively ascribed to a higher order of parallel side-product formation.

Aggregation Behavior of Nitrilotriacetamide (NTAmide) Ligands in Thorium(IV) Extraction from Acidic Medium: Small-Angle Neutron Scattering, Fourier Transform Infrared, and Theoretical Studies.

Two tripodal amides obtained from nitrilotriacetic acid with n-butyl and n-octyl alkyl chains (HBNTA(LI) and HONTA(LII), respectively) were studied for the extraction of Th(IV) ions from nitric acid medium. The effect of the diluent medium, i.e., n-dodecane alone and a mixture of n-dodecane and 1-decanol, onto aggregate formation were investigated using small angle neutron scattering (SANS) studies. In addition, the influence of the ligand structure, nitric acid, and Th(IV) loading onto ligand aggregation and third-phase formation tendency was discussed.The LI/LII exist as monomers (aggregarte radius for LI: 6.0 Å; LII:7.4 Å) in the presence of 1-decanol, whereas LII forms dimers (aggregarte radius for LII:9.3 Å; LI does not dissolve in n-dodecane) in the absence of 1-decanol. The aggregation number increases for both the ligands after HNO3 and Th(IV) loading. The maximum organic concentration (0.050 ± 0.004 M) of Th(IV) was reached without third-phase formation for 0.1 M LI/LII dissolved in 20% isodecanol +80% n-dodecane. The interaction of 1-decanol with LII and HNO3/Th(IV) with amidic oxygens of LI/LII results in shift of carbonyl stretching frequency, as shown by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) studies. The structural and bonding information of the Th-LI/LII complex were derived from the density functional theoretical (DFT) studies. The molecular dynamics (MD) simulations suggested that the aggregation behavior of the ligand in the present system is governed by the population of hydrogen bonds by phase modifier around the ligand molecules. Although the theoretical studies suggested higher Gibbs free energy of complexation for Th4+ ions with LI than LII, the extraction was found to be higher with the latter, possibly due to the higher lipophilicity and solubility of the Th-LII aggregate in the nonpolar media.

Kinetic characterization of SPR-based biomarker assays enables quality control, calibration free measurements and robust optimization for clinical application.

Biomarker measurements are essential for the early diagnosis of complex diseases. However, many current biomarker assays lack sensitivity and multiplexing capacity, work in a narrow detection range and importantly lack real time quality control opportunities, which hampers clinical translation. In this paper, we demonstrate a toolbox to kinetically characterize a biomarker measurement assay using Surface Plasmon Resonance imaging (SPRi) with ample opportunities for real time quality control by exploiting quantitative descriptions of the various biomolecular interactions. We show an accurate prediction of SPRi measurements at both low and high concentrations of various analytes with deviations <5% between actual measurements and predicted measurement. The biphasic binding sites model was accurate for fitting the experimental curves and enables optimal detection of heterophilic antibodies, cross-reactivity, spotting irregularities and/or other confounders. The toolbox can also be used to create a (simulated) calibration curve, enabling calibration-free measurements with good recovery, it allows for easy assay optimizations, and could help bridge the gap to bring new biomarker assays to the clinic.

Density Control over MBD2 Receptor-Coated Surfaces Provides Superselective Binding of Hypermethylated DNA.

Using the biomarker hypermethylated DNA (hmDNA) for cancer detection requires a pretreatment to isolate or concentrate hmDNA from nonmethylated DNA. Affinity chromatography using a methyl binding domain-2 (MBD2) protein can be used, but the relatively low enrichment selectivity of MBD2 limits its clinical applicability. Here, we developed a superselective, multivalent, MBD2-coated platform to improve the selectivity of hmDNA enrichment. The multivalent platform employs control over the MBD2 surface receptor density, which is shown to strongly affect the binding of DNA with varying degrees of methylation, improving both the selectivity and the affinity of DNAs with higher numbers of methylation sites. Histidine-10-tagged MBD2 was immobilized on gold surfaces with receptor density control by tuning the amount of nickel nitrilotriacetic acid (NiNTA)-functionalized thiols in a thiol-based self-assembled monolayer. The required MBD2 surface receptor densities for DNA surface binding decreases for DNA with higher degrees of methylation. Both higher degrees of superselectivity and surface coverages were observed upon DNA binding at increasing methylation levels. Adopting the findings of this study into hmDNA enrichment of clinical samples has the potential to become more selective and sensitive than current MBD2-based methods and, therefore, to improve cancer diagnostics.

Ring Ultramicroelectrodes for Current-Blockade Particle-Impact Electrochemistry.

In current-blockade impact electrochemistry, insulating particles are detected amperometrically as they impinge upon a micro- or nanoelectrode via a decrease in the faradaic current caused by a redox mediator. A limit of the method is that analytes of a given size yield a broad distribution of response amplitudes due to the inhomogeneities of the mediator flux at the electrode surface. Here, we overcome this limitation by introducing microfabricated ring-shaped electrodes with a width that is significantly smaller than the size of the target particles. We show that the relative step size is somewhat larger and exhibits a narrower distribution than at a conventional ultramicroelectrode of equal diameter.

Tailored Multivalent Targeting of Siglecs with Photosensitizing Liposome Nanocarriers.

The modification of surfaces with multiple ligands allows the formation of platforms for the study of multivalency in diverse processes. Herein we use this approach for the implementation of a photosensitizer (PS)-nanocarrier system that binds efficiently to siglec-10, a member of the CD33 family of siglecs (sialic acid (SA)-binding immunoglobulin-like lectins). In particular, a zinc phthalocyanine derivative bearing three SA moieties (PcSA) has been incorporated in the membrane of small unilamellar vesicles (SUVs), retaining its photophysical properties upon insertion into the SUV's membrane. The interaction of these biohybrid systems with human siglec-10-displaying supported lipid bilayers (SLBs) has shown the occurrence of weakly multivalent, superselective interactions between vesicle and SLB. The SLB therefore acts as an excellent cell membrane mimic, while the binding with PS-loaded SUVs shows the potential for targeting siglec-expressing cells with photosensitizing nanocarriers.

Targeted Positioning of Quantum Dots Inside 3D Silicon Photonic Crystals Revealed by Synchrotron X-ray Fluorescence Tomography.

It is a major outstanding goal in nanotechnology to precisely position functional nanoparticles, such as quantum dots, inside a three-dimensional (3D) nanostructure in order to realize innovative functions. Once the 3D positioning is performed, the challenge arises how to nondestructively verify where the nanoparticles reside in the 3D nanostructure. Here, we study 3D photonic band gap crystals made of Si that are infiltrated with PbS nanocrystal quantum dots. The nanocrystals are covalently bonded to polymer brush layers that are grafted to the Si-air interfaces inside the 3D nanostructure using surface-initiated atom transfer radical polymerization (SI-ATRP). The functionalized 3D nanostructures are probed by synchrotron X-ray fluorescence (SXRF) tomography that is performed at 17 keV photon energy to obtain large penetration depths and efficient excitation of the elements of interest. Spatial projection maps were obtained followed by tomographic reconstruction to obtain the 3D atom density distribution with 50 nm voxel size for all chemical elements probed: Cl, Cr, Cu, Ga, Br, and Pb. The quantum dots are found to be positioned inside the 3D nanostructure, and their positions correlate with the positions of elements characteristic of the polymer brush layer and the ATRP initiator. We conclude that X-ray fluorescence tomography is very well suited to nondestructively characterize 3D nanomaterials with photonic and other functionalities.

Au Nanoparticle-Based Amplified DNA Detection on Poly-l-lysine Monolayer-Functionalized Electrodes.

Affinity sensing of nucleic acids is among the most investigated areas in biosensing due to the growing importance of DNA diagnostics in healthcare research and clinical applications. Here, we report a simple electrochemical DNA detection layer, based on poly-l-lysine (PLL), in combination with gold nanoparticles (AuNPs) as a signal amplifier. The layer shows excellent reduction of non-specific binding and thereby high contrast between amplified and non-amplified signals with functionalized AuNPs; the relative change in current was 10-fold compared to the non-amplified signal. The present work may provide a general method for the detection of tumor markers based on electrochemical DNA sensing.

Multivalent Noncovalent Interfacing and Cross-Linking of Supramolecular Tubes.

Natural supramolecular filaments have the ability to cross-link with each other and to interface with the cellular membrane via biomolecular noncovalent interactions. This behavior allows them to form complex networks within as well as outside the cell, i.e., the cytoskeleton and the extracellular matrix, respectively. The potential of artificial supramolecular polymers to interact through specific noncovalent interactions has so far only seen limited exploration due to the dynamic nature of supramolecular interactions. Here, a system of synthetic supramolecular tubes that cross-link forming supramolecular networks, and at the same time bind to biomimetic surfaces by the aid of noncovalent streptavidin-biotin linkages, is demonstrated. The architecture of the networks can be engineered by controlling the density of the biotin moiety at the exterior of the tubes as well as by the concentration of the streptavidin. The presented strategy provides a pathway for designing adjustable artificial supramolecular superstructures, which can potentially yield more complex biomimetic adaptive materials.

Vesicle-based artificial cells: materials, construction methods and applications.

The construction of artificial cells with specific cell-mimicking functions helps to explore complex biological processes and cell functions in natural cell systems and provides an insight into the origins of life. Bottom-up methods are widely used for engineering artificial cells based on vesicles by the in vitro assembly of biomimetic materials. In this review, the design of artificial cells with a specific function is discussed, by considering the selection of synthetic materials and construction technologies. First, a range of biomimetic materials for artificial cells is reviewed, including lipid, polymeric and hybrid lipid/copolymer materials. Biomaterials extracted from natural cells are also covered in this part. Then, the formation of microscale, giant unilamellar vesicles (GUVs) is reviewed based on different technologies, including gentle hydration, electro-formation, phase transfer and microfluidic methods. Subsequently, applications of artificial cells based on single vesicles or vesicle networks are addressed for mimicking cell behaviors and signaling processes. Microreactors for synthetic biology and cell-cell communication are highlighted here as well. Finally, current challenges and future trends for the development and applications of artificial cells are described.