Synthesis and coordination chemistry of topologically constrained azamacrocycles Timothy J. Hubin * Department of Natural Science, McPherson College, 1600 E. Euclid, P.O. Box 1402, McPherson, KS 67460, USA Received 22 July 2002; accepted 7 November 2002 Abstract Bridging superstructures added to small azamacrocycles, through the accompanying additional topological constraint, enhance the characteristic that makes azamacrocycles indispensable ligands for transition metal coordination including biomimetic chemistry: high complex stability. This review begins by briefly revisiting the coordination chemistry concepts leading to this advantage over less topologically complex ligands. Then, it details the approaches used to synthesize such bridged azamacrocycles, including direct organic synthesis, the use of templates, protection/deprotection chemistry, and various condensation reactions. The example of a specific ligand type and its transition metal complexes, which are useful for biomimetic applications, illustrates the potential of the field and lead to some general conclusions. # 2002 Elsevier Science B.V. All rights reserved. Keywords: Bridged macrocycle; Macrobicycle; Azamacrocycle; Topoligical constraint * Corresponding author. Tel.:  /1-620-241-0731x1795; fax:  /1-503-212-5746 E-mail address: hubint@mcpherson.edu (T.J. Hubin). Contents Abstract .......................................................................... 27 1. Factors for strong binding: molecular organization ............................................... 28 2. Methods for bridged azamacrocycle synthesis .................................................. 30 2.1 Defining the field .............................................................. 30 2.2 Direct organic synthesis ........................................................... 31 2.3 Template directed synthesis ......................................................... 32 2.4 Protection/deprotection synthesis ...................................................... 33 2.5 Condensation synthesis ........................................................... 35 2.6 Conclusions .................................................................. 38 3. A successful example ................................................................ 39 3.1 Choosing metal ions and topologically constrained ligands for biomimicry ............................... 39 3.2 Cross-bridged tetraazamacrocycle complexes for biomimicry ...................................... 41 3.2.1 Ligand solution behavior ...................................................... 41 3.2.2 Preparation of metal complexes .................................................. 42 3.2.3 Kinetic stability in acidic solution ................................................. 42 3.2.4 Solution behavior of a biomimetic complex ............................................ 43 3.2.5 Catalytic oxidation studies ..................................................... 44 3.2.6 Conclusions ............................................................. 44 References ......................................................................... 44 Coordination Chemistry Reviews 241 (2003) 27  /46 www.elsevier.com/locate/ccr 0010-8545/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved. PII:S0010-8545(02)00307-7