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Abstract New representatives of 2,4,7‐trisubstituted 9,9‐dialkyl‐9H‐fluorenes were prepared and used for crystallographic investigations as well as initial binding studies towards metal ions and carbohydrates. The binding studies, which included 1H NMR spectroscopic titrations and fluorescence measurements, demonstrated the ability of the tested fluorene‐based compounds to act as complexing agents for ionic and neutral substrates. Depending on the nature of the subunits of the fluorene derivatives, “turn on” or “turn off” fluorescent chemosensors can be developed. Compounds composed of 4,6‐dimethylpyridin‐2‐yl‐aminomethyl moieties have the potential to be used as sensitive “turn‐on” chemosensors for some metal ions.

The paper is a self-review of works on development of new approaches to formation of mimics of receptor and catalytic sites of biological macromolecules in the structure of highly cross-linked polymer membranes and thin films. The general strategy for formation of the binding sites in molecularly imprinted polymer (MIP) membranes and thin films was described. A selective recognition of a number of food toxins, endocrine disruptors and metabolites is based on the results of computational modeling data for the prediction and optimization of their structure. A strategy proposed for the design of the artificial binding sites in MIP membranes was supported by the research performed by the authors on development of a number of the MIP membrane-based affinity and catalytic biosensors for selective and sensitive measurement (detection limits 0.3–100 nM) of the target analytes. Novel versatile approaches aimed at improving sensitivity of the developed biosensor systems were discussed.

A method for encrypting messages using engineered bacteria and different fluorescently labeled synthetic receptors is described. We show that the binding of DNA-based artificial receptors to E. coli expressing His-tagged outer membrane protein C (His-OmpC) induces a Förster resonance energy transfer (FRET) between the dyes, which results in the generation of a unique fluorescence fingerprint. Because the bacteria continuously divide, the emission pattern generated by the modified bacteria dynamically changes, enabling the system to produce encryption keys that change with time. Thus, this development indicates the potential contribution of live-cell-based encryption systems to the emerging area of information protection at the molecular level.

Abstract A series of new 9,9‐diethylfluorenes consisting of three side‐arms each bearing a heterocyclic, bis(carboxymethyl)amino, bis(carbamoylmethyl)amino, bis(ethoxycarbonylmethyl)amino or an amino group were prepared on the basis of 2,4,7‐tris(bromomethyl)‐9,9‐diethylfluorene. Imidazolyl, benzimidazolyl, pyrazolyl, pyrrolyl, 1,3‐dioxoisoindolyl and pyridinium groups were taken into account as heterocyclic units, attached to the aromatic skeleton via −CH2−, −CH2NHCH2− or −CH2N=CH− linkers. In addition to the seventeen 2,4,7‐trisubstituted 9,9‐diethylfluorenes, two macrocyclic compounds were prepared on the basis of 2,7‐bis(aminomethyl)‐9,9‐diethylfluorene. The excellent yield of the macrocyclization reaction is worth a special mention. Both the acyclic and the macrocyclic fluorene‐based compounds have, among other things, the potential to act as artificial receptors for different substrates in analogy to the known receptors consisting of a benzene or biphenyl core.

Abstract Artificial receptor‐based protein assays have various attractive features such as a long‐term stability, a low‐cost production process, and the ease of tuning the target specificity. However, such protein sensors are still immature compared with conventional immunoassays. To enhance the application potential of synthetic sensing materials, organic field‐effect transistors (OFETs) are some of the suitable platforms for protein assays because of their solution processability, durability, and compact integration. Importantly, OFETs enable the electrical readout of the protein recognition phenomena of artificial receptors on sensing electrodes. Thus, we believe that OFETs functionalized with artificial protein receptors will be a powerful tool for the on‐site analyses of target proteins. In this Minireview, we summarize the recent progress of the OFET‐based protein assays including the rational design strategies for devices and sensing materials.

The detection of human serum albumin (HSA) is of significant clinical importance in disease diagnoses. In this work, polymer-based synthetic receptors are designed by incorporating Ag-ZnS microspheres in molecularly imprinted poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MIPs) for the gravimetric detection of HSA. Among different compositions of Ag-ZnS@MIPs, MIPs having methacrylic acid and ethylene glycol dimethacrylate volume ratio of 3:2 exhibit enhanced HSA sensitivity in the concentration range of 5–200 ng/mL. A remarkably low threshold limit of detection (LOD = 0.364 ng/mL) is achieved with quartz crystal microbalance (QCM) based gravimetric sensors. Furthermore, the Ag-ZnS@MIPs/QCM sensors show high selectivity for HSA compared to other proteins, e.g., bovine serum albumin (BSA), glycoprotein, ribonuclease, and lysozyme. Hence, the gravimetric quantification of HSA realizes a highly sensitive, selective, and label-free detection mechanism with a limit of quantification down to 1.1 ng/mL.

Molecularly imprinted polymers (MIPs) have gained growing interest among researchers worldwide, due to their key features that make these materials interesting candidates for implementation as receptors into sensor applications. In fact, MIP-based glucose sensors could overcome the stability issues associated with the enzymes present in commercial glucose devices. Various reports describe the successful development of glucose MIPs and their coupling to a wide variety of transducers for creating sensors that are able to detect glucose in various matrices. In this review, we have summarized and critically evaluated the different production methods of glucose MIPs and the different transducer technologies used in MIP-based glucose sensors, and analyzed these from a commercial point of view. In this way, this review sets out to highlight the most promising approaches in MIP-based sensing in terms of both manufacturing methods and readout technologies employed. In doing so, we aim at delineating potential future approaches and identifying potential obstacles that the MIP-sensing field may encounter in an attempt to penetrate the commercial, analytical market.

Sucrose is a primary metabolite in plants, a source of energy, a source of carbon atoms for growth and development, and a regulator of biochemical processes. Most of the traditional analytical chemistry methods for sucrose quantification in plants require sample treatment (with consequent tissue destruction) and complex facilities, that do not allow real-time sucrose quantification at ultra-low concentrations (nM to pM range) under in vivo conditions, limiting our understanding of sucrose roles in plant physiology across different plant tissues and cellular compartments. Some of the above-mentioned problems may be circumvented with the use of bio-compatible ligands for molecular recognition of sucrose. Nevertheless, problems such as the signal-noise ratio, stability, and selectivity are some of the main challenges limiting the use of molecular recognition methods for the in vivo quantification of sucrose. In this review, we provide a critical analysis of the existing analytical chemistry tools, biosensors, and synthetic ligands, for sucrose quantification and discuss the most promising paths to improve upon its limits of detection. Our goal is to highlight the criteria design need for real-time, in vivo, highly sensitive and selective sucrose sensing capabilities to enable further our understanding of living organisms, the development of new plant breeding strategies for increased crop productivity and sustainability, and ultimately to contribute to the overarching need for food security.

Abstract The design of a fully synthetic, chemical “apoptosis‐inducing receptor” (AIR) molecule is reported that is anchored into the lipid bilayer of cells, is activated by the incoming biological input, and responds with the release of a secondary messenger—a highly potent toxin for cell killing. The AIR molecule has four elements, namely, an exofacial trigger group, a bilayer anchor, a toxin as a secondary messenger, and a self‐immolative scaffold as a mechanism for signal transduction. Receptor installation into cells is established via a robust protocol with minimal cell handling. The synthetic receptor remains dormant in the engineered cells, but is effectively triggered externally by the addition of an activating biomolecule (enzyme) or in a mixed cell population through interaction with the surrounding cells. In 3D cell culture (spheroids), receptor activation is accessible for at least 5 days, which compares favorably with other state of the art receptor designs.

Abstract The newest generation of cell‐based technologies relies heavily on methods to communicate to the engineered cells using artificial receptors, specifically to deactivate the cells administered to a patient in the event of adverse effects. Herein, artificial synthetic internalizing receptors are engineered that function in mammalian cells in 2D and in 3D and afford targeted, specific intracellular drug delivery with nanomolar potency in the most challenging cell type, namely primary, donor‐derived T cells. Receptor design comprises a lipid bilayer anchor for receptor integration into cell membrane and a small xenobiotic molecule as a recognition ligand. Artificial receptors are successfully targeted by the corresponding antibody–drug conjugate (ADC) and exhibit efficient cargo cell entry with ensuing intracellular effects. Receptor integration into cells is fast and robust and affords targeted cell entry in under 2 h. Through a combination of the receptor design and the use of ADC, combined benefits previously made available by chimeric artificial receptors (performance in T cells) and the chemical counterpart (robustness and simplicity) in a single functional platform is achieved. Artificial synthetic receptors are poised to facilitate the maturation of engineered cells as tools of biotechnology and biomedicine.