Macrocyclic Polyamines Synthesis and Applications

Xiaoqi Yu, PhD, is Changjiang Chair professor and Dean of College of Chemistry, Sichuan University. He has received several awards, including The National Science Fund for Distinguished Young Scholars of China (2007). His research interests include biomedical materials chemistry (especially for non-viral gene and drug delivery vectors) and methodology of organic syntheses.

Ji Zhang, PhD is a professor in College of Chemistry, Sichuan University, China. His research focuses on nano-biomaterials, i.e. design, synthesis and establishment of novel non-viral gene and drug delivery systems and relative structure-activity relationship studies.

Preface ix

1 Introduction 1

1.1 Classification of Macrocyclic Polyamines 1

1.1.1 Aliphatic Macrocyclic Polyamines 1

1.1.2 Aromatic-ContainingMacrocyclic Polyamines 1

1.1.3 Macrocyclic Polyimines 2

1.1.4 Macrocyclic Polyamides 2

1.1.5 Cryptands 2

1.2 Properties of Macrocyclic Polyamines 3

1.2.1 Acid–Base Properties 3

1.2.2 Coordination Property 3

1.3 Applications of Macrocyclic Polyamines 4

References 5

2 SyntheticMethods for Macrocyclic Polyamines 7

2.1 Ring-Closure Modes 7

2.1.1 Intramolecular Cyclization 7

2.1.2 1 + 1 Cyclization 7

2.1.3 2 + 2 Cyclization 8

2.1.4 Other Cyclization Modes 8

2.2 The Synthesis of Saturated Macrocyclic Polyamines 9

2.2.1 Ring Closure Using Sulfonamides 9

2.2.2 The Removal of Tosyl Protecting Groups 11

2.2.3 The Use of Easily Removable Protecting Groups 12

2.2.4 Special Procedures for TetraazaMacrocyclic Compounds 13

2.3 Aromatic Subunit-Containing Polyazamacrocycles 14

2.3.1 Alkylation of Sulfonamide Salts with Dihalomethyl Arenes 15

2.3.2 Metal-Catalyzed N-arylation 16

2.4 Macrocyclic Polyimines (Schiff Bases) 18

2.4.1 Metal Template Reactions 18

2.4.1.1 Macrocyclic Schiff Bases without Aromatic Units 20

2.4.1.2 Macrocyclic Schiff Bases Containing Aromatic Units 21

2.4.2 Template-Free Cyclization 22

2.4.2.1 Condensation of Carbonyls with Aliphatic Diamines 23

2.4.2.2 Condensation of Carbonyls with Aromatic Diamines 25

2.5 Macrocyclic Amides 26

2.5.1 The Crab-Like Cyclization 26

2.5.2 Diacid-Diamine Condensation 29

2.6 Cryptands 33

2.6.1 Coupling of the Preformed Macrocycles 33

2.6.2 Direct Organic Synthesis 35

2.6.3 Spherical Cryptands 37

References 39

3 Chemical Nucleases Based on Macrocyclic Polyamines 45

3.1 Hydrolysis of Nucleic Acids 45

3.1.1 Metal Complexes of Macrocyclic Ligands 46

3.1.1.1 Lanthanide(III) Complexes 48

3.1.1.2 Transition Metal Complexes of Macrocyclic Ligands 51

3.1.1.3 Metal Complex–DNA Binder Conjugates 64

3.1.2 Metal-Free Macrocyclic Polyamines 67

3.2 Oxidative Cleavage of Nucleic Acids 70

3.2.1 Oxidative DNA Cleavage by Macrocyclic Polyamine Metallic Complexes 70

3.2.2 Oxidative DNA Cleavage by Metal-Free Macrocyclic Polyamines 74

3.3 Summary 76

References 76

4 Derivatives of Macrocyclic Polyamines as Nanovector Materials 83

4.1 Derivatives of MPAs as Nonviral Gene Vectors 83

4.1.1 Cationic Polymers 85

4.1.2 Lipids with Cationic MPA Headgroups 90

4.1.2.1 TACN-Based Lipids 91

4.1.2.2 Cyclen-Based Lipids 93

4.1.3 Other Types of Vectors 99

4.2 Multifunctional Materials for Both Drug Delivery and

Bio-Imaging 100

4.2.1 Gd Complexes 100

4.2.2 64Cu Complexes 103

4.2.3 Miscellaneous 104

4.3 Summary 104

References 105

5 Macrocyclic Polyamine Derivatives for Bio-Imaging 109

5.1 Typical Macrocyclic Polyamines for Magnetic Resonance Imaging (MRI) 111

5.1.1 DOTA and Its Derivatives 111

5.1.2 DO3A and Its Derivatives 118

5.1.3 PCTA and Its Derivatives 124

5.1.4 TETA and NOTA 126

5.2 Other Derivatives of Macrocyclic Polyamines for MRI 128

5.2.1 Phosphonate Macrocyclic Ligands 128

5.2.2 Ligands with Multiamide Arms 129

5.2.3 Ligands with Multihydroxy Arms 130

5.2.4 Other Types 131

5.3 MPAs for PET Imaging 133

References 135

6 Chemical Sensors Based on Macrocyclic Polyamines 141

6.1 Sensors for Metal Cations 141

6.1.1 Zn(II) and Cd(II) 141

6.1.2 Cu(II) and Pb(II) 147

6.1.3 Hg(II), Ag(I), and Others 149

6.2 Receptors for Anions 153

6.2.1 Phosphonates 153

6.2.2 Amino Acids 156

6.2.3 Other Anions 159

6.3 pH Indicator 162

6.4 Sensors for Bioactive Molecules 164

6.4.1 Small Molecules and Nucleotide 164

6.4.2 Proteins 169

6.4.3 Others 169

6.5 Summary 172

References 173

7 Other Applications of Macrocyclic Polyamines 177

7.1 Macrocyclic Polyamines as Ionophores 177

7.1.1 Macrocyclic Polyamines for Solvent Extraction and Membrane Transport of Metal Cations 177

7.1.2 Macrocyclic Polyamines for Solvent Extraction and Membrane Transport of Amino Acids and Their Derivatives 185

7.2 Macrocyclic Polyamines for Electrophoretic Separation 190

7.2.1 Macrocyclic Polyamines as Additives for Running Solution 191

7.2.2 Macrocyclic Polyamines for Open-Tubular CEC 193

7.2.3 Macrocyclic Polyamines as the Bonded Phase for Monolithic Columns 204

References 206

Index 209

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