Immobilized DNA switches as electronic sensors for picomolar detection of plasma proteins

The sensing principle of a new class of DNA conformational switches (deoxyribosensors) is based on the incorporation of an aptamer as the receptor, whose altered conformation upon analyte binding switches on the conductivity of an adjacent helical conduction path, leading to an increase in the measured electrical signal through the sensor. We report herein the rational design and biochemical testing of candidate deoxyribosensors for the detection and quantitation of a plasma protein, thrombin, followed by surface immobilization of the optimized sensor and its electrochemical testing in both a near-physiological buffer solution and in diluted blood serum. The very high detection sensitivity (in the picomolar range) and specificity, as well as the adaptability of deoxyribosensors for the detection of diverse molecular analytes both small and macromolecular, make this novel sensing methodology an extremely promising one. Such synthetic and robust DNA-based electronic sensors should find broad application in the rapid, miniaturized, and automated on-chip detection of many biomedically relevant substances (such as metabolites, toxins, and disease and tumor markers) as well as of environmental contaminants.     

Ion-mediated conformational switches

Molecular switches are ubiquitous in Nature and provide the basis of many forms of transport and signalling. Single synthetic molecules that change conformation, and thus function, reversibly in a stimulus-dependent manner are of great interest not only to chemists but society in general; myriad applications exist in storage, display, sensing and medicine. Here we describe recent developments in the area of ion-mediated switching.     

Nonlinear optical molecular switches as selective cation sensors

This work demonstrates that the recognition of cations by molecular switches can give rise to large contrasts of the second-order nonlinear optical (NLO) properties, which can therefore be used as a powerful and multi-usage detection tool. The proof of concept is given by evidencing, by means of ab initio calculations, the ability of spiropyran/merocyanine systems to selectively detect alkali, alkaline earth, and transition-metal cations.     

Anthryl-doped conjugated polyelectrolytes as aggregation-based sensors for nonquenching multicationic analytes

The fluorescence-based detection of nonquenching, multicationic small molecules has been demonstrated using a blue-emitting, polyanionic poly(p-phenylene ethynylene) (PPE) doped with green-emitting exciton traps (anthryl units). Multicationic amines (spermine, spermidine, and neomycin) were found to effectively induce the formation of tightly associated aggregates between the polymer chains in solution. This analyte-induced aggregation, which was accompanied by enhanced exciton migration in the PPE, ultimately led to a visually noticeable blue-to-green fluorescence color change in the solution. The aggregation-based sensor exhibited poor sensitivity toward dicationic and monocationic amines, demonstrating that a conjugated polyelectrolyte sensor relying on nonspecific, electrostatic interactions may still attain a certain level of selectivity.     

Chemical functionalization of single-walled carbon nanotube field-effect transistors as switches and sensors

Because of the one-dimensional (1D) nanostructural nature of single-walled carbon nanotubes (SWNTs) and their advantages of chemical flexibility and sensitivity arising from the susceptibility of their active surfaces to interacting species, great effort has been made to integrate carbon nanotube field-effect transistors (NTFETs) into functional optoelectronic devices capable of converting external stimuli to easily detectable electrical signals. In this Review article, we aim to capture recent advances of rational design and chemical functionalization of NTFETs for the purpose of switching or biosensing applications. To provide a deeper understanding of the device responses to analytes, this review will also survey the proposed sensing mechanisms. As demonstrated by these remarkable examples, the concept of combining the proper selection of functional molecular materials and molecular self-assembly with device micro/nanofabrication offers attractive new prospects for constructing NTFET-based molecular optoelectronic devices with desired functionalities.     

Azobenzenes as light-controlled molecular electronic switches in nanoscale metal-molecule-metal junctions

Conductance switching associated with the photoisomerization of azobenzene-based (Azo) molecules was observed in nanoscopic metal-molecule-metal junctions. The junctions were formed by using a conducting atomic force microscope (C-AFM) approach, where a metallic AFM tip was used to electrically contact a gold-supported Azo self-assembled monolayer. The measured 30-fold increase in conductance is consistent with the expected decrease in tunneling barrier length resulting from the conformational change of the Azo molecule.     

trans-2-(Azaarylsulfanyl)cyclohexanol derivatives as potential pH-triggered conformational switches

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Trans-3,4-diacetoxypiperidine as a model for novel pH-triggered conformational switches

An acid-induced conformational flip of trans-3,4-diacetoxy-1-benzylpiperidine has been determined by ¹H NMR. It occurs while the apparent pH (pD) of the d₄-methanol solution decreases from 6 to 3. Due to an intramolecular hydrogen bond, the conformer with axial position of both acetoxy groups becomes strongly predominant. The separation of the acetoxy groups increases drastically. Thus, in similar structures an incorporated trans-3,4-disubstituted piperidine moiety can serve as a conformational pH-trigger when equipped with substituents designed to perform certain geometry-dependent functions, for example, as cation chelators or as lipid tails. The power of this trigger was estimated as ∼10 kJ/mol.     

Rigidization,preorientation and electronic decoupling--the 'magic triangle' for the design of highly efficient fluorescent sensors and switches

One of the key interests in the recent development of fluorescent molecular sensors and switches is the realization of systems that show strong signal changes as a response to the chemical trigger. Aiming at rational probe design, this article compiles and compares different promising strategies to extract those supramolecular and photophysical features that allow the construction of molecular devices suitable for efficient signaling. The examples comprise fluorescence 'OFF'-'ON' as well as 'ON'-'OFF' operative systems and the mechanisms, properties, and limitations of the different design concepts are discussed.     

Protein conformational switches: from nature to design

Protein conformational switches alter their shape upon receiving an input signal, such as ligand binding, chemical modification, or change in environment. The apparent simplicity of this transformation--which can be carried out by a molecule as small as a thousand atoms or so--belies its critical importance to the life of the cell as well as its capacity for engineering by humans. In the realm of molecular switches, proteins are unique because they are capable of performing a variety of biological functions. Switchable proteins are therefore of high interest to the fields of biology, biotechnology, and medicine. These molecules are beginning to be exploited as the core machinery behind a new generation of biosensors, functionally regulated enzymes, and "smart" biomaterials that react to their surroundings. As inspirations for these designs, researchers continue to analyze existing examples of allosteric proteins. Recent years have also witnessed the development of new methodologies for introducing conformational change into proteins that previously had none. Herein we review examples of both natural and engineered protein switches in the context of four basic modes of conformational change: rigid-body domain movement, limited structural rearrangement, global fold switching, and folding-unfolding. Our purpose is to highlight examples that can potentially serve as platforms for the design of custom switches. Accordingly, we focus on inducible conformational changes that are substantial enough to produce a functional response (e.g., in a second protein to which it is fused), yet are relatively simple, structurally well-characterized, and amenable to protein engineering efforts.     

Linear, redox modified DNA probes as electrochemical DNA sensors

We show here that hybridization-linked changes in the dynamics of a redox-modified, electrode-bound linear (as opposed to stem-loop) probe DNA produce large changes in Faradaic current, allowing for the ready detection of target oligonucleotides.     

Aptamer conformational switch as sensitive electrochemical biosensor for potassium ion recognition

We report the first use of an electrochemical aptasensor for selective potassium recognition, based on a conformational change, affording an electric signal transduced electrochemically by square wave voltammetry or electrochemical impedance spectroscopy.     

Photo-controllable electronic switches based on azopyridine derivatives

Stable photo-controllable electronic switches based on new light-sensitive azopyridines are reported herein. Such systems produce notable variations in the cathodic current density on working at low reduction potentials when UV light falls on them. The appropriate design of the azopyridine chromophore allows modulating the response time of the final opto-electronic switch.     

Metal-directed thiophene-carboxylate-based nickel(II) complexes as multifunctional electrochemical and fluorescent sensors for detecting different analytes

Transition Metal Chemistry - To investigate the effect of the sites of S-atoms in thiophene carboxylates on the structures of coordination polymers, two thiophene-mono-carboxylic acids...     

Transition metal-based chiroptical switches for nanoscale electronics and sensors

Efficient metal-based chiroptical switches have been designed that are capable of achieving multiple stable and reversible states. Studies in this field have yielded a variety of complex molecular devices whose conformations are controllable by many triggering mechanisms including pressure, solvent, counter ion, redox state, and photoinduction. Many of the systems are monitored with precision using circular dichroism spectroscopy. This review aims to provide a brief background of the development of these systems and a comprehensive overview of recently developed metal-based chiroptical switches. Potential applications in electronics and sensor technologies are discussed.     

Colloidal particle motion as a diagnostic of DNA conformational transitions

Tethered particle motion is an experimental technique to monitor conformational changes in single molecules of DNA in real time, by observing the position fluctuations of a micrometer-size particle attached to the DNA. This article reviews some recent work on theoretical problems inherent in the interpretation of TPM experiments, both in equilibrium and dynamical aspects.     

Highly sensitive WO3 hollow-sphere gas sensors

In this paper, we describe how WO(3) hollow spheres have been synthesized in solution phase by the controlled hydrolysis of WCl(6) using novel carbon microspheres as the templates. All of the products were characterized by X-ray powder diffraction (XRD), scanning electronic microscopy (SEM), and transmission electron microscopy (TEM). The as-synthesized spheres had large diameters of about 400 nm and thin shells of about 30 nm composed of numerous small nanocrystals. Prompted by the porous structure and small crystal size of the shell wall, we constructed WO(3) hollow-sphere gas sensors and found that these sensors had good sensitivity to alcohol, acetone, CS(2), and other organic gases.     

Polymeric membranes conditioning for sensors applications: mechanism and influence on analytes detection

In this work, we studied an ion-exchange membrane based on an inert polymer skeleton in which it is dispersed and anchored a molecule with charged groups able to discriminate and bind positive or negatively charged ions present in a sample. In order to be ready to work, electromembranes need a complex procedure called activation or conditioning. Although most of the known literature looks at the subject from an electrochemical point of view, we put forward a structural approach. Membrane conditioning, in fact, is considered a required step to improve sensor performances and to allow the collection of reproducible data. Even if this operation is carefully followed by all the operators working with sensors equipped with a membrane, it looks like that a thoroughly explanation of the working mechanism and a detailed balance of cost and gains has still not been carried out. As a consequence, we suggest a bulk or membrane approach, where the landscape is mainly characterized by the long-range structure of the membrane itself. Our findings suggest that membrane conditioning has to be carried out carefully and the advantages of this pre-treatment can be appreciated especially for very low concentration measurements. The need for the conditioning mainly results from the necessity of a complete permeation of all the different tortuous channels constituting the membrane itself.