Molecular recognition: Supramolecular, polymeric and biomimetic coatings for chemical sensors and chromatographic columns

Complete control of the selective and reversible interaction of molecules from the gas or liquid phase at complementary recognition sites is of increasing interest for both basic science and practical applications. This recognition may occur at the surface or in the bulk of optimized chemically sensitive coatings. It is either monitored discontinuously by chromatography or continuously by a suitable sensor. The latter contains the optimized coating and converts the chemical information about concentrations of certain molecules by means of a certain transducer into an electronic signal. Generally speaking, these transducers form the essential part of ‘chemical sensors’; they monitor the molecular interactions at the chemically sensitive layer by changes in resistivity, impedance, mass, capacitance, work function, heat, electrochemical potential, optical thickness, or optical absorption in a certain spectral range. Three selected case studies of such molecular recognition devices which utilize supramolecular, polymeric, and biomimetic coatings are presented. Examples are given for both gas and liquid sensing devices. For simplification, because of its general applicability and its easy absolute calibration, particular emphasis is put on signal transduction via quartz crystal oscillators. The measurement principle is based on frequency changes which are directly correlated with mass changes and thus provide a particularly suitable signal transduction. The examples presented here concern systematic variations in the design of supramolecular cages, of selective interaction sites in polymeric matrices, and of covalently attached biomimetic recognition sites to monitor antibodies or enzyme interactions. Received: 11 August 1997 / Revised: 3 March 1998 / Accepted: 3 March 1998     

Supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids: synthesis, glucose-surfaced nanoparticles, and recognition with lectin

A new class of supramolecular and biomimetic glycopolymer/poly(epsilon-caprolactone)-based polypseudorotaxane/glycopolymer triblock copolymers (poly(D-gluconamidoethyl methacrylate)-PPR-poly(D-gluconamidoethyl methacrylate), PGAMA-PPR-PGAMA), exhibiting controlled molecular weights and low polydispersities, was synthesized by the combination of ring-opening polymerization of epsilon-caprolactone, supramolecular inclusion reaction, and direct atom transfer radical polymerization (ATRP) of unprotected D-gluconamidoethyl methacrylate (GAMA) glycomonomer. The PPR macroinitiator for ATRP was prepared by the inclusion complexation of biodegradable poly(epsilon-caprolactone) (PCL) with alpha-cyclodextrin (alpha-CD), in which the crystalline PCL segments were included into the hydrophobic alpha-CD cavities and their crystallization was completely suppressed. Moreover, the self-assembled aggregates from these triblock copolymers have a hydrophilic glycopolymer shell and an oligosaccharide threaded polypseudorotaxane core, which changed from spherical micelles to vesicles with the decreasing weight fraction of glycopolymer segments. Furthermore, it was demonstrated that these triblock copolymers had specific biomolecular recognition with concanavalin A (Con A) in comparison with bovine serum albumin (BSA). To the best of our knowledge, this is the first report that describes the synthesis of supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids and the fabrication of glucose-shelled and oligosaccharide-threaded polypseudorotaxane-cored aggregates. This hopefully provides a platform for targeted drug delivery and for studying the biomolecular recognition between sugar and lectin.     

Diatoms: self assembled silica nanostructures, and templates for bio/chemical sensors and biomimetic membranes

In this review we highlight recent advances in the understanding of biosilica production, biomodification of diatom frustules and their subsequent applications in bio/chemical sensors, and as a model membrane for filtration and separation.     

New polymeric chemical sensors for determination of lead ions

New polymeric electrochemical sensors for determining the content of lead were suggested. As the active substance of the polymeric membranes of the sensors was used N,N′-tetrabutyldipicolinamide, the compound exhibiting a high extractive capacity for heavy metal ions. The selectivity of the sensors with respect to lead ions in the presence of copper, cadmium, and zinc in a considerable excess was studied.     

Supramolecular complexes based on calixarenes: force field calculations and applications for chemical sensors

The inclusion of organic molecules to different calixarenes was investigated both experimentally and theoretically. Experimental data were obtained for various calixarenes of different thicknesses interacting with perchloroethylene, chloroform, benzene and toluene at different partial pressures and temperatures. The amount of included molecules was monitored by frequency responses of mass-sensitive bulk acoustic wave devices. To estimate ‘key-lock’ binding energies, the activation energy of desorption was determined experimentally from thermodesorption spectroscopy. The host/guest interaction energies were calculated theoretically with the TRIPOS force field approach which, in contrast to current quantum chemical approaches (MOPAC/AM1, MOPAC/PM3), gave satisfactory distance-dependent energy minima. Experimentally observed changes in the binding energies for the inclusion of C₂Cl₄, CHCl₃, CH₃C₅H₆ and C₆H₆ molecules in calixarenes agree surprisingly well with results with theoretical calculations.     

Nanoscale organic and polymeric field-effect transistors as chemical sensors

This article reviews recently published work concerning improved understanding of, and advancements in, organic and polymer semiconductor vapor-phase chemical sensing. Thin-film transistor sensors ranging in size from hundreds of microns down to a few nanometers are discussed, with comparisons made of sensing responses recorded at these different channel-length scales. The vapor-sensing behavior of nanoscale organic transistors is different from that of large-scale devices, because electrical transport in a nanoscale organic thin-film transistor depends on its morphological structure and interface properties (for example injection barrier) which could be modulated by delivery of analyte. Materials used in nanoscale devices, for example nanoparticles, nanotubes, and nanowires, are also briefly summarized in an attempt to introduce other relevant nano-transducers.      

Molecular recognition of cyclic-nucleotides and current sensors for their detection

This work briefly describes available sensors for cAMP and cGMP. Many sensors are based on derivatization of naturally occurring products such as immunoglobulins, protein kinases, etc. Only a few published works deal with chemosensors, which are built up by "total" chemical synthesis. This field stays opened for combinatorial chemist. The best sensors are protein kinases genetically modified with mutants of green fluorescent protein, which allow screening of entire cell cultures.     

Rational materials design of sorbent coatings for explosives: applications with chemical sensors

A series of chemoselective polymers had been designed and synthesized to enhance the sorption properties of polymer coated chemical sensors for polynitroaromatic analytes. To evaluate the effectiveness of the chemoselective coatings, a polynitroaromatic vapor test bed was utilized to challenge polymer coated surface acoustic wave (SAW) devices with different explosive vapors. Dinitrotoluene detection limits were determined to be in the <100 parts per trillion ranges. ATR-FTIR studies were used to determine the nature of the polymer-polynitroaromatic analyte interactions, and confirm the presence of hydrogen-bonding between polymer pendant groups and the nitro functional groups of polynitroaromatic explosive materials.     

Molecular recognition in homogeneous transition metal catalysis: a biomimetic strategy for high selectivity

Traditional methods for selectivity control in homogeneous transition metal catalysis either employ steric effects in a binding pocket or chelate control. In a supramolecular strategy, encapsulation of the substrate can provide useful shape and size selectivity. A fully developed molecular recognition strategy involving hydrogen bonding or solvophobic forces has given almost completely regioselective functionalization of remote, unactivated C-H bonds.     

Rapid bioanalysis with chemical sensors: novel strategies for devices and artificial recognition membranes

The increasing importance of biological analytes in chemistry has triggered the development of a vast number of techniques for rapidly assessing them. Aside from microbiological test methods, a wide range of analytical sensor and detection methods are being developed. Within this article, we review the literature on this topic from the last five years, stressing two main aspects of method development. The first aspect is the design of novel analytical strategies and transducers to generate signals more sensitively, more rapidly and more efficiently. Most of the progress in this field has focused on electrochemical detection, although novel approaches to optical and mass-sensitive measurements have been reported. Second, we provide an overview of two main approaches to creating artificial interaction layers for sensors based on tailored interaction sites in polymeric or biomimetic systems. The most prominent of these approaches is (molecular) imprinting, where selectivity is achieved by directly templating a polymer material with the target analyte or a model compound, thus achieving biomimetic interaction sites within both thin films and particles.     

Molecular modelling of host-guest interactions for mass sensitive chemical sensors

Paracyclophanes are effective coatings for mass sensitive chemical sensors. The enzyme analogue recognition can preferably be used to detect aromatic and halogenated hydrocarbons. Molecular modelling by the MM3 force field allows the prediction of an efficient analyte inclusion. Besides the necessary steric complementarity it could be shown that the interaction between the methyl groups of aromatic guests (e.g. toluene) and the aromatic walls of the host is essential for hostguest complexation. These phenomena get more pronounced if bicyclic cyclophanes are applied and these sensitive materials enable the detection of only a few ppm of toluene with SAW devices. Furtheron, the electron-rich diphenylether moieties of these hosts guarantee interactions with electron-deficiency analytes such as chlorinated hydrocarbons with a selectivity superior to that of the monocyclic materials.Dedicated to Professor Dr. Dr. h.c. mult. J.F.K. Huber on the occasion of his 70th birthday     

Modular domain structure: a biomimetic strategy for advanced polymeric materials

A long lasting challenge in polymer science is to design polymers that combine desired mechanical properties such as tensile strength, fracture toughness, and elasticity into one structure. A novel biomimetic modular polymer design is reported here to address this challenge. Following the molecular mechanism used in nature, modular polymers containing multiple loops were constructed by using precise and strong hydrogen bonding units. Single-molecule force-extension experiments revealed the sequential unfolding of loops as a chain is stretched. The excellent correlation between the single-molecule and the bulk properties successfully demonstrates our biomimetic concept of using modular domain structure to achieve advanced polymer properties.     

Lipophilic and immobilized anionic additives in solvent polymeric membranes of cation-selective chemical sensors

Lipophilic borate salts are frequently used as anionic additives in potentiometric and optical cation-selective sensors based on solvent polymeric membranes. The lifetime of such membranes may be limited owing to chemical decomposition and leaching of the components. Borate salts, in particular, are decomposed in the presence of acids in the membrane. Adequately substituted borate salts and sulphonic acids, such as sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, sodium tetrakis[3,5-bis(2-methoxyhexafluoro-2-propyl)phenyl]borate and dinonylnaphthalenesulphonic acid (DNSS), are shown to be sufficiently stable as membrane additives. Furthermore, lipoholic mobile or immoblizied sulphonic acids [DNNS or poly(2-acrylamido-2-methyl-1-propanesulphonic acid-co-styrene), respectively were also tested as anionic additives. Their influence on the selectivity behaviour of the sensor is attributed to their strong association with positively charged species in the membrane phase. It may be kept small by choosing ionophores that from stable complexes with the analyte.     

Silica-based monolithic columns versus conventional particle-packed columns for liquid chromatographic analysis of tetracycline, oxytetracycline and chlortetracycline

The rise of monolithic stationary phases offers to routine and research laboratories several advantages. In spite of their recent discovery, they have rapidly become highly popular separation media for liquid chromatography. Time reduction and economic reasons like e.g. a diminished use of mobile phase are the most important ones. At the same time, it was reported that these columns offer a faster and better separation. The aim of this article was to investigate the transferability of methods originally developed on conventional particle-packed C₁₈ columns (XTerra RP18 and Zorbax RX), onto the more recent monolithic columns. Both types, conventional particle-packed and monolithic columns, were able to separate tetracycline, oxytetracycline and chlortetracycline from their respective impurities with sufficient resolution, but showed remarkably shorter analysis times and lower backpressures, improving the lifetime of the column.     

Molecular recognition at the gas-solid interface: a powerful tool for chemical sensing

This tutorial review deals with the design of molecular receptors capable of molecular recognition at the gas-solid interface, to be used as selective layers in gas sensors. The key issue of specific versus nonspecific binding in the solid layer is discussed in terms of cavity inclusion and layer morphology. The combined use of mass spectrometry and crystal structure analysis provide accurate information on type, number, geometry and strength of receptor-analyte interactions in the gas phase and in the solid state. From these data, the gas sensing properties of a given receptor toward a single class of analytes can be anticipated.     

Metallized electrospun polymeric fibers for electrochemical sensors and actuators

Electrospun polymeric fibers present an emerging alternative for the development of flexible electronics, enabling applications in wearable sensors and biosensors for continuous monitoring, and actuators for tissue engineering. The possibility to prepare sub-micrometric polymeric scaffolds, their processing for increasing the conductivity, their modification with different materials, conductive polymers and biomolecules in order to obtain functional flexible electrodes, allows the development of innovative devices for healthcare, and biomedical applications. In this review, the impact of metallized electrospun polymeric fibers in electrochemical (bio)sensors and actuators is discussed. A relation between their structure and functionality is provided, alongside with an overview of the different methods to obtain functional conductive fibers.     

Surface-attached sensors for cation and anion recognition

The development of surface-attached sensors for cationic and anionic guests is of intense current research interest. In addition to the environmental flexibility, robustness and reusability of such devices, surface-confined sensors typically exhibit an amplified response to target analytes owing to preorganization of the receptor. Whereas redox-active cations may be sensed by studying the cyclic voltammetry of host–guest systems containing ion-selective receptors attached to an appropriate electrode, redox-inactive ionic species require the use of electrochemical impedance spectroscopy, with appropriately functionalized electrodes and redox probes. Alternatively, receptors may be constructed that incorporate an electrochemical or optical reporter group within their structure to provide a macroscopic response to the presence of an ionic guest. This critical review seeks to present an up-to-date, although necessarily selective, account of the progress in the field, and provides insights into possible future developments, including the utilization of receptor–nanoparticle conjugates and mechanically interlocked receptors.     

Molecular,Macromolecular, and Supramolecular Glucuronide Prodrugs: Lead Identified for Anticancer Prodrug Monotherapy

In this work, a tumor growth intervention by localized drug synthesis within the tumor volume, using the enzymatic repertoire of the tumor itself, is presented. Towards the overall success, molecular, macromolecular, and supramolecular glucuronide prodrugs were designed for a highly potent toxin, monomethyl auristatin E (MMAE). The lead candidate exhibited a fold difference in toxicity between the prodrug and the drug of 175, had an engineered mechanism to enhance the deliverable payload to tumours, and contained a highly potent toxin such that bioconversion of only a few prodrug molecules created a concentration of MMAE sufficient enough for efficient suppression of tumor growth. Each of these points is highly significant and together afford a safe, selective anticancer measure, making tumor‐targeted glucuronides attractive for translational medicine.