Cyclodextrins

Properties and Industrial Applications

Sahar Amiri, Sanam Amiri

• Publisher: Wiley
• Year: 2017
• ISBN:
  9781119247920
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Industrial & Technical Chemistry

The comprehensive resource for understanding the structure, properties, and applications of cyclodextrins

Cyclodextrins: Properties and Industrial Applications is a comprehensive resource that includes information on cyclodextrins (CDs) structure, their properties, formation of inclusion complex with various compounds as well as their applications. The authors Sahar Amiri and Sanam Amiri, noted experts in the field of cyclodextrins, cover both the basic and applied science in chemistry, biology, and physics of CDs and offers scientists and engineers an understand of cyclodextrins.

Cyclodextrins are a family of cyclic oligosaccharides consisting of (?-1, 4)-linked ?-D-glucopyranose units. The formation of inclusion complex between CDs as host and guest molecules is based on non-covalent interaction such as hydrogen bonding or van der waals interactions and lead to the formation of supramolecular structures. These supramolecular structures can be used as macroinitiator for initiating various type of reactions. CDs are widely used in many industrial products such as pharmacy, food and flavours, chemistry, chromatography, catalysis, biotechnology, agriculture, cosmetics, hygiene, medicine, textiles, drug delivery, packing, separation processes, environment protection, fermentation, and catalysis. This important resource:

• Offers a basic understanding of cyclodextrins for researchers and engineers
• Includes information of the basic structure of cyclodextrins and their properties
• Reviews how cyclodextrins can be applied in a variety of fields including medicine, chemistry, textiles, packing, and many others
• Shows how encapsulate corrosion inhibitors became active in corrosive electrolytes to ensure delivery of the inhibitors to corrosion sites and long-term corrosion protection

Cyclodextrins offers research scientists and engineers a wealth of information about CDs with particular focus on how cyclodextrins are applied in various ways including in drug delivery, the food industry, and many other areas.

Chapter 1
Introduction

Cyclodextrins, also known as cycloamyloses, cyclomaltoses, or Schardinger dextrins, are cyclic oligosaccharides consisting of six, seven, eight, or more glucopyranose units composed of α-(1,4)-linked glucopyranose subunits synthesized from the enzymatic degradation of starch [1].

Cyclodextrins are chemically and physically stable macromolecules produced by intramolecular transglycosylation reaction from enzymatic degradation of starch with glucanotransferase (CGTase) enzyme [2]. Due to steric factors, cyclodextrins built by less than six glucopyranose units do not exist; however, cyclodextrins with more than eight glucopyranose units have been synthesized [3]. Because of chair conformation of glucopyranose unit, their molecular structure, and the lack of free rotation about the bonds connecting the glucopyranose units, CDs have a unique toroid or truncated cone shape with hydrophilic outer surface and hydrophobic cavity [4]. The most common ones are α, β, and γ cyclodextrins consisting of 6, 7, and 8 glucopyranose units that are crystalline, homogeneous, and nonhygroscopic substances produced by the enzymatic degradation of starch [5]. Glucosyltransferases of starch caused degradation of amylose fraction: one or several turns of the amylose helix are hydrolyzed off and their ends are joined together, thereby producing cyclic oligosaccharides. Per year using environmentally friendly technologies, thousands of tons of CDs are produced, with prices acceptable for most of the industrial purposes [6]. Absorption of CDs is negligible, so they are harmless; they have been widely used because of low toxicity both orally and intravenously. Unmodified CDs are completely resistant to β-amylase. α-Amylase is capable of hydrolyzing CDs only at a slow rate. After intravenous injections, CDs are mainly excreted in their intact form by renal filtration as they are minimally susceptible to hydrolytic cleavage or degradation by human enzymes [5, 7].

Chemical reactions of cyclodextrins led to intramolecular interactions based on noncovalent bonding such as hydrogen or van der Waals bonding and formed supramolecular structures. Specific structure of cyclodextrins with truncated shape causes the formation of complex between cyclodextrins and a wide range of molecules, which is called host–guest or inclusion complex. Formation of inclusion complex modifies or improves the physical, chemical, and/or biological characteristics of the guest molecule [8]. Because of negligible toxicity and also the formation of inclusion complex with various compounds, cyclodextrins can be used in various industrial products such as carriers, stabilizing agent, food and flavors, cosmetics, packing, textiles, separation processes, fermentation, catalysis, and drug delivery systems [9].

1.1 History of Cyclodextrins

CDs were first discovered in 1891, when in addition to reducing dextrins, a small amount of crystalline material was obtained from starch digestion of Bacillus amylobacter. Antoine Villiers worked on the action of enzymes on various carbohydrates, particularly using the butyric ferment Bacillus amylobacter on potato starch. He called this crystalline product “cellulosine.” After this period, Schardinger isolated two crystalline products in 1903 and isolated a new organism that was able to produce acetone and ethyl alcohol from sugar and starch-containing plant material [1]. By inoculating the amylaceous paste with the bacillus, a slightly acidic liquid with butyric-acid smell was formed. After purification of fractional precipitation, the dextrins (called so by Schardinger) presented very different optical rotation properties. It was difficult to hydrolyze them any further [10]. Crystalline structures of α- and β-cyclodextrin were determined by X-ray crystallography in 1942 [11]. In 1948–1950, the X-ray structure of γ-cyclodextrin was discovered and it was found that CDs can form inclusion complexes [12].

CDs are fractionalized to pure components by enzymic production. They were characterized physically and chemically by French [11] and Cramer in the 1950s [13]. Their ability to form inclusion complex was discovered by Cramer's group [14]. Various patents were published about application of CDs in drug formulations and protection of easily oxidizable substances against atmospheric oxidation, the enhancement of solubility of poorly soluble drugs, and reduction of the loss of highly volatile substances. In 1970, numerous industrial applications of cyclodextrins were discovered and industrial-scale production of CDs was started. Traditionally, three factors stood on the way of their industrial development: (i) high production costs; (ii) incomplete toxicological studies; and (iii) lack of sufficient scientific knowledge of native CDs and their derivatives [8].

From the 1980s, with a more accurate picture of their toxicity and better understanding of molecular encapsulation, several inclusion complexes appeared in market, especially in drug preparations, food industry, macromolecular chemistry [15–17], supramolecular chemistry [18, 19], catalysis [20, 21], membranes [22], foods [23], biotechnology [24], enzyme technology [25], cosmetics [26–28], pharmacy and medicine [29–32], textiles [28, 33, 34], chromatography [35, 36], agrochemistry [37], microencapsulation [38], nanotechnologies [39, 40], and analytical chemistry [41].

The most important and amazing property of CDs is their ability to form inclusion complexes with several hydrophobic and hydrophilic compounds [5, 42–44]. Cyclodextrins are truncated cone or torus rather than perfect cylinder because of the chair conformation of glucopyranose units. Secondary hydroxyl groups (C₂ and C₃) are located on the wider edge of the ring and the primary hydroxyl groups (C₆) on the other edge and the apolar C₃ and C₅ hydrogens and ether-like oxygens are at the inside of the torus-like molecules. Therefore, the outside of cyclodextrins is hydrophilic and inside is hydrophobic. CDs are water soluble, biocompatible in nature with hydrophilic outer surface and lipophilic cavity [4]. As a result of this cavity, cyclodextrins are able to form inclusion complexes with a wide variety of hydrophobic guest molecules. One or two guest molecules can be entrapped by one, two, or three cyclodextrins.

1.2 Cyclodextrin Properties

Cyclodextrins are crystalline, homogeneous, nonhygroscopic, nontoxic with truncated shape and are made up of glucopyranose units. They are classified into three common types: α-cyclodextrin (Schardinger's α-dextrin: cyclomaltohexaose, cyclohexaglucan, and cyclohexaamylose), β-cyclodextrin (Schardinger's β-dextrin: cyclomaltoheptaose, cycloheptaglucan, and cycloheptaamylose), and γ-cyclodextrin (Schardinger's γ-dextrin: cyclomaltooctaose, cyclooctaglucan, and cyclooctaamylose) and are referred to as first generation or parent cyclodextrins. α-, β-, and γ-CD are composed of six, seven, and eight α-(1,4)-linked glycosyl units, respectively (Figure 1.1) [4]. β-Cyclodextrin is the most accessible, priced the lowest, and generally the most useful. Their main properties are given in Table 1.1. On the side where the secondary hydroxyl groups are situated, the cavity is wider than on the other side where free rotation of the primary hydroxyls reduces the effective diameter of the cavity [45, 46].

Figure 1.1 Schematic diagram of cyclodextrins.

Table 1.1 Cyclodextrin properties

Property	α-Cyclodextrin	β-Cyclodextrin	γ-Cyclodextrin
Number of glucopyranose units	6	7	8
Molecular weight (g/mol)	972	1135	1297
Solubility in water at 25°C (%w/v)	14.5	1.85	23.2
Outer diameter (Å)	14.7	15.3	17.5
Cavity diameter (Å)	5.1	6.2	8.1
Height of torus (Å)	7.8	7.8	7.8
Cavity volume (Å^3)	174	262	427
Surface tension (MN/m)	71	71	71
Melting temperature range (°C)	255–260	255–265	240–245
Crystal water content (wt%)	10.2	13–15	8–18
Water molecules in cavity	6	11	17

All secondary hydroxyl groups are situated on one of the two edges of the ring, whereas all the primary hydroxyl groups are placed on the other edge, so CDs have a doughnut- or wreath-shaped truncated cone. CDs have high electron density and Lewis-base character because of nonbonding electron pairs of the glycosidic-oxygen bridges that are directed toward the inside of the cavity. H-bonds determined rigidity of CDs. In α-CD, one glucopyranose unit is in distorted position and H-bond belt is incomplete, but in β-CD, a complete secondary intramolecular H-bond is formed and causes rigid structure and lowest water solubility of β-CD among all CDs. The γ-CD is noncoplanar and more flexible; therefore, it is the most soluble of the three CDs [43, 47].

Depending on the type of cyclodextrin and the guest compound, cyclodextrins' inclusion complex has two main types of cr...

Table of contents

• Cover
• Title Page
• Copyright
• Dedication
• Table of Contents
• Preface
• Chapter 1: Introduction
• Chapter 2: Supramolecular Chemistry and Rotaxane
• Chapter 3: Smart Polymers
• Chapter 4: Basics of Corrosion
• Chapter 5: Phytochemicals
• Chapter 6: Cyclodextrins Application as Macroinitiator
• Chapter 7: Cyclodextrin Applications
• Index
• End User License Agreement