Identification of Structure–Activity Relationships from Screening a Structurally Compact DNA‐Encoded Chemical Library

Methods for the rapid and inexpensive discovery of hit compounds are essential for pharmaceutical research and DNA‐encoded chemical libraries represent promising tools for this purpose. We here report on the design and synthesis of DAL‐100K, a DNA‐encoded chemical library containing 103 200 structurally compact compounds. Affinity screening experiments and DNA‐sequencing analysis provided ligands with nanomolar affinities to several proteins, including prostate‐specific membrane antigen and tankyrase 1. Correlations of sequence counts with binding affinities and potencies of enzyme inhibition were observed and enabled the identification of structural features critical for activity. These results indicate that libraries of this type represent a useful source of small‐molecule binders for target proteins of pharmaceutical interest and information on structural features important for binding.     

Cocrystal Formation through Mechanochemistry: from Neat and Liquid‐Assisted Grinding to Polymer‐Assisted Grinding

Mechanochemistry is an effective method for the preparation of multicomponent crystal systems. In the present work, we propose an alternative to the established liquid‐assisted grinding (LAG) approach. Polymer‐assisted grinding (POLAG) is demonstrated to provide a new class of catalysts for improving reaction rate and increasing product diversity during mechanochemical cocrystallization reactions. We demonstrate that POLAG provides advantages comparable to the conventional liquid‐assisted process, whilst eliminating the risk of unwanted solvate formation as well as enabling control of resulting particle size. It represents a new approach for the development of functional materials through mechanochemistry, and possibly opens new routes toward the understanding of the mechanisms and pathways of mechanochemical cocrystal formation.     

Temperature effect on the structure and formation kinetics of vinyltriethoxysilane-derived organic/silica hybrids

The structure and formation kinetics of organic/silica hybrid species prepared from acid hydrolysis of vinyltriethoxisilane has been studied in situ by small-angle X-ray scattering (SAXS) at 298, 318, and 333 K in a strongly basic step of the process. The evolution of the SAXS intensity is compatible with the formation of linear chains which grow, coil, and branch to form polymeric macromolecules in solution. The SAXS data were analyzed by the scattering from a persistent chain model for polymeric macromolecules in solution using a modified branching Sharp and Bloomfield global function, which incorporates a branching probability typical of randomly and nonrandomly branched polycondensates, and in a particular case, it is also valid for polydisperse coils of linear chains. Growth of linear chains and coiling dominate the process up to the formation of likely monodisperse Gaussian coils or polydisperse coils of linear chains. The link probability to form a branching point is increased with time to form nonrandomly branched polycondensates in solution. The kinetics of the process is accelerated with temperature, but all the curves formed by the time evolution of the structural parameters in all temperatures can correspondingly be matched on a unique curve by using an appropriate time scaling factor. The activation energy of the process was evaluated as ΔE = 21 ± 1 kJ/mol. The characteristics of the kinetics are in favor of a complex overall mechanism controlled by both condensation reactions and dynamical forces driven by interfacial energy up to the final structure development of the hybrids.     

Efficient crystallization induced emissive materials based on a simple push-pull molecular structure

Solid state luminescent materials are the subject of ever growing interest both from a scientific and a technological point of view. Aggregation caused quenching (ACQ) processes however represent an obstacle to the development of most luminogens in the condensed phase. This is why particularly fascinating are those materials showing higher emission intensity in the solid state than in solution. Here we report on three 4-dialkylamino-2-benzylidene malonic acid dialkyl esters, very simple push-pull molecules, which are hardly emissive in solution and in the amorphous phase but become good emitters in the crystalline phase according to what has been indicated as crystallization induced emission (CIE). Thanks to combined emission and NMR spectroscopies at different temperatures on the prototype compound 4-dimethylamino-2-benzylidene malonic acid dimethyl ester in solution, we give full evidence that a restricted intramolecular rotation (RIR) phenomenon, in particular the hindered rotation around the aryl main axis of the compound, is at the origin of this behaviour. In addition, solid state photophysical and X-ray diffraction structural characterization allow us to identify J-dimeric interactions as responsible for the particularly intense emission of two of the three compounds. Moreover, by exploiting the compounds' acidochromic properties, applications in sensors and optoelectronics are envisaged.     

Ultra‐Small Plutonium Oxide Nanocrystals: An Innovative Material in Plutonium Science

Apart from its technological importance, plutonium (Pu) is also one of the most intriguing elements because of its non‐conventional physical properties and fascinating chemistry. Those fundamental aspects are particularly interesting when dealing with the challenging study of plutonium‐based nanomaterials. Here we show that ultra‐small (3.2±0.9 nm) and highly crystalline plutonium oxide (PuO₂) nanocrystals (NCs) can be synthesized by the thermal decomposition of plutonyl nitrate ([PuO₂(NO₃)₂] ? 3 H₂O) in a highly coordinating organic medium. This is the first example reporting on the preparation of significant quantities (several tens of milligrams) of PuO₂ NCs, in a controllable and reproducible manner. The structure and magnetic properties of PuO₂ NCs have been characterized by a wide variety of techniques (powder X‐ray diffraction (PXRD), X‐ray absorption fine structure (XAFS), X‐ray absorption near edge structure (XANES), TEM, IR, Raman, UV/Vis spectroscopies, and superconducting quantum interference device (SQUID) magnetometry). The current PuO₂ NCs constitute an innovative material for the study of challenging problems as diverse as the transport behavior of plutonium in the environment or size and shape effects on the physics of transuranium elements.     

Multiplexed Determination of Amino‐Terminal Pro‐B‐Type Natriuretic Peptide and C‐Reactive Protein Cardiac Biomarkers in Human Serum at a Disposable Electrochemical Magnetoimmunosensor

A rapid magnetoimmunosensor for the simultaneous determination of two cardiac biomarkers, amino‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and C‐reactive protein (CRP), in human serum is described. Specific capture antibodies were covalently immobilized onto carboxylic acid‐modified magnetic beads. The quantification of NT‐proBNP and CRP was performed by using indirect competitive and sandwich configurations, respectively, and horseradish peroxidase‐labeled tracers. The use of dual screen‐printed carbon electrodes allowed the achievement of simultaneous independent amperometric readout for each cardiac biomarker. The developed methodology showed very low limits of detection (0.47 ng mL^?1). An international standard for CRP serum spiked with NT‐proBNP was analyzed to evaluate the usefulness of the magnetoimmunosensor.