Virtual Issue: Chemosensors

Abstract

Chemosensors are compounds that incorporate a receptor unit and a reporter unit in a single molecule. A chemosensor transforms the action of binding to a specific analyte into a readable signal. Chemosensors have enabled the study of molecular interactions in a range of different media and interfaces. This offers a non‐invasive approach to observe living biological samples in real time without the sample being destroyed. For example, fluorescence‐based chemosensors are designed to have a high sensitivity and specificity, allowing them to interact selectively with a single target within a complex biological environment. As a result, such chemosensors can be used for fluorescence imaging, allowing for high spatial and temporal resolution of biological samples. Consequently, chemosensors have been used for a broad range of applications including clinical diagnostics and for the detection of environmental, agriculture, and industrial pollutants, making them critically important for public health and safety.

The development of chemosensors is interdisciplinary, often involving a combination of organic and inorganic synthesis run in tandem with a variety of analytical techniques. Success, requires perseverance and hard work—by choosing chemosensor‐based research, you will never have a dull moment.

Fluorescence‐based chemosensors can be traced back 150 years to Goppelsroder, who reported a system for the detection of the Al³⁺ cations. Despite the significant progress made in chemosensor development, a number of challenges still exist, which include the detection of a wider spectrum of analytes. This could be in the form of new biomarkers or a particular pollutant in our air and water supplies. Moreover, an existing chemosensor may provide the desired result, but it may fall short of the selectivity or sensitivity required for use in practical applications. As a result, the improvement of existing chemosensors is needed to meet the demands of regulatory bodies, where increasingly stringent requirements are being imposed.

Look deep into nature, and then you will understand everything better

—Albert Einstein

Some current Reviews, including two from this virtual issue1, 2 highlight the importance of chemosensors for sensing a wide range of analytes such as anions, cations, neutral molecules, and gases.3 When designing a chemosensor, it is important to use host–guest interactions or a specific chemical reaction to invoke a change in measurable properties of the reporter. If the binding between the host and guest is non‐covalent and reversible, the probe is referred to as a chemosensor. If the interaction between the host and guest produces an irreversible chemical reaction, then it is referred to as a chemidosimeter (reaction based). Over the years, these two definitions have been used interchangeably and ambiguously. Therefore, for simplicity in this virtual special issue, we will consider all of them as “chemosensors”.

A seminal example of a reversible chemosensor was established by Shinkai and co‐workers, whereby the propensity of boronic acids to reversibly bind with 1,2‐diols was exploited. This enabled the detection of diol‐containing saccharides over a large pH range in aqueous media.4 In particular, fluorescence‐based boronate systems have been used in monitoring blood glucose levels.5 Interestingly, although the original system was published over 25 years ago, the binding mechanism has only recently been fully explained.6

Christopher J. Chang is a pioneer in the area of reaction‐based fluorescent chemosensors using established organic synthetic reactions as a chemical trigger to promote a change in fluorescence.7 The chemically reactive trigger must proceed with reasonable kinetics in aqueous solution and under complex biological conditions (pH, high salt content, and large concentration of reactive nucleophilic thiols). For a reaction‐based chemosensor to be effective, the reaction should be biorthogonal and any by‐products should be inert and non‐toxic.

Wong and co‐workers developed an excellent example of a reaction‐based chemosensor with a novel rhodol‐based fluorescence probe from the structural combination of rhodamine and fluorescein motifs. Through the modification of the functional group on the spiro‐ring, selectivity and sensitivity towards mercury(II) and hypochlorite ions was achieved, and confocal microscopy images of HeLa cells incubated with the probe displayed enhanced fluorescence intensity towards HClO, demonstrating the real‐world potential of the probe for in vivo HOCl detection.8

This exciting virtual issue also highlights a multitude of other important discoveries.9 Minamiki et al. constructed a reversible electrical bioassay for the label‐free and highly sensitive detection of a histidine‐rich protein (serum albumin) by using an organic field‐effect transistor (OFET) modified with a Ni^II–nitrilotriacetic acid monolayer (Ni^II‐nta) receptor unit. Lampard et al. prepared a number of reaction‐based boronate stilbene and oxazole chemosensors that produced a reasonable fluorescence response towards H₂O₂. Kim and co‐workers developed a two‐photon ratiometric fluorescent probe (SHP‐Cyto) for the direct quantitative in situ detection of cytosolic H₂O₂. The probe displayed a sensitive fluorescent color change in response to H₂O₂. The ratiometric two‐photon microscopic images with SHP‐Cyto revealed that H₂O₂ levels gradually increased from brain to kidney, skin, heart, lung, and then liver tissues. Jang and co‐workers constructed a reaction‐based chemosensor using a p‐toluenesulfonyl group, which produced a “turn‐on” response in the presence of several antioxidant amino acids and biothiols driven by light. Lee et al. prepared a new benzobisimidazolium derivative that exhibited strong fluorescence in the presence of F⁻ and CH₃CO₂ ⁻ in CH₃CN. Importantly, upon addition of a small amount of water, a significant fluorescence amplification with F⁻ was observed. Pascu and co‐workers developed novel water‐dispersible and luminescent carbon‐nanotube‐based hybrids. CdSe crystals were confined within single‐walled carbon nanotubes of varying dimensions and the exterior of the nanotubes were then functionalized using β‐d‐glucan. James and co‐workers developed benzoxaborole (BOB) hydrogels, which use the ability of boronic acids to reversibly bind to 1,2‐diols. These hydrogels demonstrated an enhanced binding affinity towards monosaccharides and, in particular, towards glucose.

In summary, this virtual issue in ChemistryOpen showcases a range of diverse chemosensors, clearly demonstrating the expansive nature of this highly interdisciplinary field. More importantly, many of the chemosensors reported could be developed into systems with real‐world applications.

Figure 1.

“We ride together, we die together. Bad boys for life.”—Det. Mike Lowrey (from the movie Bad Boys II, 2003).

Biographical Information

Adam C. Sedgwick graduated with a first‐class MChem in Chemistry for Drug Discovery from the University of Bath (UK) in 2014. During his undergraduate degree, he undertook an industrial placement at BioFocus (now Charles River), working as a Medicinal Chemist, synthesizing compound libraries for various drug‐discovery applications. He recently obtained his PhD from the University of Bath, developing novel sensors for the detection of reactive oxygen species.

Biographical Information

Tony D. James is a Professor at the University of Bath and a Fellow of the Royal Society of Chemistry and holds a prestigious Royal Society Wolfson Research Merit Award (2017–2022). He obtained his B.Sc. degree from the University of East Anglia (UK) in 1986, his Ph.D. degree in 1991 from the University of Victoria (Canada), and worked as a Postdoctoral Research Fellow in Japan from 1991 to 1995 with Seiji Shinkai. From 1995 to 2000, he was a Royal Society Research Fellow at the School of Chemistry at the University of Birmingham (UK) and moved to the Department of Chemistry at the University of Bath in September 2000. His research interests include molecular recognition, molecular self‐assembly, and sensor design.

A. C. Sedgwick, T. D. James, ChemistryOpen 2018, 7, 215.