Introduction

What is now proved was once only imagined

William Blake, 1757–1827

The recognition of a target molecule by a synthetically prepared receptor has captured the imagination of supramolecular chemists. Since its inception, research in this area has been instrumental in elucidating the mode of action of a great many biological events concerning recognition and catalysis. The importance of this work was underlined with the award of the Nobel Prize in Chemistry to Cram, Lehn and Peterson in 1987 "for their development and use of molecules with structure-specific interactions of high selectivity." Since then the diversity of compounds studied under the umbrella of supramolecular chemistry has grown significantly. Of particular interest are chemical molecular sensors, single molecules with the ability to both recognise and signal analytes in real time.

The development of coherent strategies for the selective binding of target molecules, by rationally designed synthetic receptors, remains one of chemistry's most sought after goals. The research conducted to this end is driven by a fundamental inquisitiveness and need to monitor compounds of industrial, environmental and biological significance.

Within our research groups we have exploited the interaction between boronic acids and diols. The primary interaction of a boronic acid with a diol is covalent and involves the rapid and reversible formation of a cyclic boronate ester. The array of hydroxyl groups present on saccharides provides an ideal scaffold for these interactions and has led to the development of boronic acid-based sensors for saccharides (Scheme 1).

Many synthetic receptors developed for neutral guests have relied on non-covalent interactions, such as hydrogen bonding, for recognition. It is the case, however, that in aqueous systems neutral guests may become heavily solvated. While biological systems have the capacity to expel water from their binding pockets and sequester analytes wholly, using non-covalent interactions, synthetic monomeric receptors have not yet been designed where hydrogen bonding has been able to compete with bulk water for low concentrations of monosaccharides. However, it should be pointed out that progress is being made in this area and recently Davis reported a hydrogen-bonding receptor capable of binding D-glucose in water with a weak but significant stability constant.

The capacity of boronic acid receptors to function effectively in water is reflected by the number of published sensory systems designed around them. The most popular class of the fluorescent boronic acid-based sensors utilise an amine group proximal to boron. The Lewis acid-ewis base interaction between the boronic acid and the neighbouring tertiary amine has a dual role. First, it enables molecular recognition to occur at neutral pH. Second, it can be used to communicate binding by modulating the intensity of fluorescence emission through photoinduced electron transfer (PET), introducing an "off-on" optical response to the sensor.

The quality of the research in this area, particularly in the past few years, has led to a significant advance in the understanding of the basic science behind the generic mode of action of this class of receptor. This book will therefore bring together and critique the contemporary scientific understanding of the fundamental processes involved in the molecular recognition of saccharides by boronic acids. It should be noted that a comprehensive overview of this nature has not been previously reported in the scientific literature. A literature review will then investigate the application of these sensory systems. Although this review cannot be exhaustive, it is our intention to illustrate the current state of play in the field.

The Molecular Recognition of Saccharides

The expression "fits like a glove" is an odd one, because there are many different types of gloves and only a few of them are going to fit the situation you are in.

Lemony Snicket

A Series of Unfortunate Events: The Grim Grotto: Book the Eleventh

2.1 Molecular Recognition

Molecular recognition lies at the very heart of sensor chemistry. The process itself involves the interaction between two substances, often termed as a host and a guest, a lock and a key or a receptor and a substrate. Importantly, recognition is not just denned as a binding event but requires selectivity between the host and the guest.

Selectivity between host and guest is a premise of compatibility. It arises between compounds with carefully matched electronic, geometric and polar elements. For synthetic receptors, the potential, therefore, exists to engineer receptors for any chosen analyte through judicious structural design and functional group complementarity. The power of this concept is illustrated within Nature. Biological systems have evolved with exquisitely constructed active-binding sites, sequestering guest molecules with near perfect selectivity.

Nevertheless, for the recognition event at a receptor to be of practical use, a further element is required. A channel of communication must be established between the receptor and the outside world. This additional quality converts a receptor into a sensor.

For a sensor to function, it must, therefore, permit selective binding to occur between host and guest and also report these binding events by generating a tangible signal. By performing these two fundamental tasks, sensors have the potential to relay information on the presence and location of important species in a quantifiable manner, bridging the gap between events occurring at the molecular level and our own (see Scheme 2).

Chemical sensors can be broadly categorised as either biosensors, or synthetic sensors. Biosensors make use of existing biological elements for recognition. Many of the physiologically important analytes already have corresponding biological receptors with intrinsically high selectivity and if these receptors can be connected to a signal transducer, a biosensor can be developed.

Synthetic sensors incorporate a synthetically prepared element for recognition. While biomimetic receptors have been prepared, with synthetic receptors mimicking the active sites in naturally occurring biological molecules, synthetic receptors can, and often are, designed entirely from first principles.

2.2 The Importance of Saccharides

2.2.1 Saccharides and Carbohydrates

In keeping with convention, the term saccharide is used within this book to refer broadly to polyhydroxylated carbohydrates. The product of photosynthesis, carbohydrates single-handedly account for the most prolific class of organic compounds that can be found on the surface of the Earth. Within biology they are of fundamental significance. In their most ubiquitous roles, they endow...