Macrocyclic polyamines and their

MACROCYCLIC POLYAMINES AND THEIR METAL COMPLEXES A NOVEL TYPE OF ANTI-HIV AGENT... 

The present volume is the fourth in the series and covers the topics lithium in biology, the structure and function of ceruloplasmin, rhenium complexes in nuclear medicine, the anti-HIV activity of macrocyclic polyamines and their metal complexes, platinum anticancer dmgs, and functional model complexes for dinuclear phosphoesterase enzymes. The production of this volume has been overshadowed by a very sad event—the passing away of the senior editor, Professor Robert W. Hay. It was he who conceived the idea of producing this series and who more than anyone else has been responsible for its continuation. A tribute by one of his many friends, Dr. David Richens, is included in this Volume. 

Eiichi Kimura is retired from the Department of Medicinal Chemistry at Hiroshima University in Japan. His recent research interests have included the supramolecular chemistry of macrocyclic polyamines and their use in molecular recognition and as zinc-enzyme models. These interests have led to the development of fluorophore sensors for Zn(II) [8] use of macrocycles to effect selective recognition of anions [9], nucleobases in polynucleotides [10], thymidine mono- and diphosphate nucleotides (11), carbonic anhydrase and carboxypeptidase [12], and development of Zn(II)-macrocycle anti-HIV agents [13], In May 2004, he received a Purple Ribbon Award from the Emperor of Japan. 

Macrocyclic polyamines and their metal complexes 86PAC1461, 86PAC1511. 

Chart 1. Structure and abbreviated nomenclature of macrocyclic saturated polyamines and their relevant compounds. 

The characteristic property distinguishing macrocyclic polyamines from their linear counterparts is seen in successive protonation. One is the higher N basicity to the first proton and another is a sudden drop of N basicities in the later stages of protonation. Table 1 lists the protonation constants (Eq. 1) for the macrocyclic polyamines in comparison with the corresponding values for their linear homologues. When a linear triamine (e.g. dien) 36,37) is cyclized to, say, (9)aneN3, the basicity of the first amine increases (log Kt = 10.59 us 9.70), but the basicity of the second and especially the third amine diminish (log K2 = 6.88 vs 8.95, log K3 < 1 vs 4.25)36)... 

The calculated ligand field parameters are close to the values obtained for low-spin macrocyclic polyamines and clathrochelate boron-capped cobalt(III) tris-dioximates (see above). The ligand field strength in trichlorotin-capped cobalt(III) tris-dioximates is substantially higher than that in nonmacrocyclic and tribromotin-capped complexes and slightly exceeds that in their boron-capped analogs [44],... 

The first attempts at receptors for carboxylate concentrated on protonated polyazamacrocycles. These compounds bind their guests via a combination of electrostatic interactions and hydrogen bonds. An early example of a ditopic receptor composed of a macrocyclic polyamine and crown ether subunit was reported by Kimura. " The triprotonated form of 13 forms 1 1 complexes with zwitterionic compounds, such as glycine. 

The discovery of in vitro anti-HIV activity of macrocyclic polyamines by the Kimura and De Clercq groups led to development of a new type of effective anti-HIV agents. The results from the studies of the pharmacokinetics and their in vivo efficacy in a SCID-hu Thy/Liv mice are further encouraging indicators of their potential usefulness as new AIDS curing drugs. 

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