Molecularly Imprinted Polymers

Man-Made Mimics of Antibodies and their Application in Analytical Chemistry

B. Sellergren

• Publisher: Elsevier Science
• Year: 2000
• Print ISBN: 9780444828378
• eBook ISBN: 9780080536804
• Topic: Physical Sciences
• Subtopic: Analytic Chemistry

This book is divided into 5 sections starting with an historic perspective and fundamental aspects on the synthesis and recognition by imprinted polymers. The second section contains 8 up-to-date overview chapters on current approaches to molecular and ion imprinting. This is followed by two chapters on new material morphologies and in the last two sections various analytical applications of imprinted polymers are given, with the last four chapters devoted to the promising field of imprinted polymers in chemical sensors.The authors of this volume have widely different backgrounds; mainly polymer chemistry, organic chemistry, biochemistry and analytical chemistry, which means that this book has an interdisciplinary character and should appeal to a broad audience.

Chapter 1

A historical perspective of the development of molecular imprinting

Håkan S. Andersson; Ian A. Nicholls

1.1 INTRODUCTION

Here we review the history of molecular imprinting, from the introduction of the technique in conjunction with silica matrices in 1931 until the beginning of the 1970s, when the technique was first applied to organic polymers. The theories used to explain the nature of the selective molecular recognition exhibited by imprinted silicas, the methods for their preparation, as well as the attempts to apply them for practical use, are discussed. Finally, a brief overview is given regarding the evolution of molecular imprinting in organic polymers.

Molecular imprinting is currently attracting wide interest from the scientific community as reflected in the 80 original papers published in the field during 1997 (Fig. 1.1). However, although interest in the technique is new, the concept itself has a long history. 1972 marked the start of molecular imprinting technology as we know it today, when the laboratories of Wulff [1] and Klotz [2] independently reported the preparation of organic polymers with predetermined ligand selectivities. Template molecules which were present during polymerisation, or derivatives thereof, were recognised by the resultant molecularly imprinted polymer (MIP). Nonetheless, some 40 papers describing conceptually similar approaches had appeared dating back to the early 1930s. This body of work pertains to the preparation of ligand-selective recognition sites in the inorganic matrix silica. The aim of this chapter is to review this “pre-history” of molecular imprinting, which serves as a reminder to us all that good science can be older than the time span covered by computer databases.

Fig. 1.1 Graphical representation illustrating the number of original papers published within the field of molecular imprinting between 1931 and 1997 [86].

1.2 POLYAKOV INVENTS MOLECULAR IMPRINTING

At the beginning of this century much effort was devoted to the development of new materials and techniques for application in chromatography [3]. Although it had already been described during the mid-19th century by Schönbein and Goppelsröder [4], it was not until the development of zonal chromatography by Tswett in 1906 [5] that its usefulness as a method for purifying and/or analysing single compounds from crude mixtures was truly highlighted.

Among the many scientists active in this field was the Soviet chemist M.V. Polyakov, who performed a series of investigations on silica for use in chromatography. Polyakov prepared his silica by the acidification of sodium silicate solutions, which after drying of the gelatinous silica polymer, afforded a rigid matrix. In a paper published in 1931 [6], the effects on silica pore structure of the presence of benzene, toluene or xylene during drying were reported. After 20–30 days of drying at room temperature, the additive was washed off using hot water. When H₂SO₄ was used as the polymerisation initiator (acidifying agent), a positive correlation was found between surface areas, e.g. load capacities, and the molecular weights of the respective additives. However, when (NH₄)₂CO₃ was instead used as the initiator, the results differed markedly from the above. When the silica was placed in a desiccator containing a beaker with one of the additives, the extent of adsorption of the different additives was shown to be dependent upon the structure of the additive present during the drying process (Table 1.1).

Table 1.1

Rebinding Data [6] for Silicas Prepared using (NH₄)₂CO₃ as the Acidifier

	Analyte, % adsorbed by silica
	Benzene	Toluene	Xylene
Gel prepared with:
Benzene	87.5	80.6	80.1
Toluene	88.5	87.2	86.7
Xylene	87.5	79	68.3

Polyakov concluded that differences in the rate and extent of silica polymerisation due to the weaker acidifier (NH₄)₂CO₃ were the key factors underlying the apparent selectivity. The effect was ascribed to alterations in the silica structure induced by the presence of the additive, which was anticipated to replace water molecules on the silica surface. Later work, published in 1933 [7] and 1937 [8], contained more detailed investigations of this selective molecular recognition phenomenon. Importantly, selectivity was suggested to arise from structural changes in the silica which were a consequence of the chemical nature of the additive. In other words, the additives were considered as templates which directly affected the resultant silica surfaces. To the best of our knowledge, this was the first time that experiments of this kind were accompanied by explanations of this nature.

Polyakov’s studies went largely unnoted by the scientific community, with only a handful of citations which were almost exclusively from other Eastern European scientists. Not deterred, Polyakov continued until the late 1950s [9,10] writing reviews of the area, though mainly devoted to establishing his founding role in the development of molecular imprinting.

1.3 THE CONTRIBUTIONS OF PAULING AND DICKEY

Over the years following Polyakov’s three papers, much attention was being focused on biochemical processes and the structures of biomolecules. Linus Pauling, at the Gates and Crellin Laboratories at the California Institute of Technology, Pasadena, was perhaps the most important contributor to the area at the time. After his work with valence bond theory, he shifted the direction of his research to the practical implications of the nature of the chemical bond, especially with respect to protein structure and function. The α-helix and β-sheet structures, the molecular-level explanation to sickle-cell anaemia, and an early transition-state theory of catalysis, were all products of his research [11]. In addition, he carefully examined the selectivity exhibited by antibodies. The following section describes Pauling’s efforts together with Frank Dickey, which constituted an independent development of molecular imprinting in silica matrices.

1.3.1 Theories of antibody formation

Mankind has for decades benefited from the in vitro use of antibodies. Nevertheless, the basic mechanisms of antibody formation in vivo have been known for less than 30 years, on account of the efforts of Burnet, Jerne, Talmadge and others [12,13]. Prior to the emergence of the clonal-selection theory, two divergent concepts evolved to explain the mechanism of antibody formation; the selective theory and the instructional theory (Fig. 1.2). The selective theory was first formulated in 1900 by Ehrlich [14], who postulated that a white blood cell’s surface bore various antibodies to one of which the antigen became chemically linked. The interaction would prompt the cell to produce copies of the selected antibody in great exc...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright page
• Preface
• List of contributors
• List of abbreviations
• Chapter 1: A historical perspective of the development of molecular imprinting
• Chapter 2: Fundamental aspects on the synthesis and characterisation of imprinted network polymers
• Chapter 3: Thermodynamic principles underlying molecularly imprinted polymer formulation and ligand recognition
• Chapter 4: Molecular imprinting with covalent or stoichiometric non-covalent interactions
• Chapter 5: The non-covalent approach to molecular imprinting
• Chapter 6: Metal-ion coordination in designing molecularly imprinted polymeric receptors
• Chapter 7: Covalent imprinting using sacrificial spacers
• Chapter 8: Molecular imprinting approaches using inorganic matrices
• Chapter 9: Imprinting polymerisation for recognition and separation of metal ions
• Chapter 10: Bio-imprinting: polymeric receptors with and for biological macromolecules
• Chapter 11: Surface imprinting of microorganisms
• Chapter 12: Polymerisation techniques for the formation of imprinted beads
• Chapter 13: Techniques for the in situ preparation of imprinted polymers
• Chapter 14: Application of molecularly imprinted polymers in competitive ligand binding assays for analysis of biological samples
• Chapter 15: Molecularly imprinted polymers in solid phase extractions
• Chapter 16: Capillary electrochromatography based on molecular imprinting
• Chapter 17: Molecularly imprinted polymers in enantiomer separations
• Chapter 18: Biomimetic electrochemical sensors based on molecular imprinting
• Chapter 19: Ionic sensors based on molecularly imprinted polymers
• Chapter 20: Toward optical sensors for biologically active molecules
• Chapter 21: Non-covalent molecularly imprinted sensors for vapours, polyaromatic hydrocarbons and complex mixtures
• Index