Acidic centres on the inside

In general, two classes of acids have to be discussed Lewis and Brdnsted acids. In macrocycles, only a few Lewis acid centres have been incorporated, e.g. tin (Newcomb et al., 1987 Newcomb and Blanda, 1988 Blanda and Newcomb, 1989 Blanda et al., 1989) and boron (Reetz et al., 1991). Here we will discuss Brpnsted acids, starting with carboxylic acids. 

MACROCYCLES CONTAINING INTRA-ANNULAR CARBOXYLIC ACIDS 

Macrocycles with intra-annular carboxylic acid groups [33] have been synthesized by Cram and Reinhoudt. As for the analogous pyridinocrowns [9], the pATa values of the acids were measured in water at 22°C and at 25°C (Newcomb et al., 1977b Aarts et al., 1986). 

As for the pyridines [9] (see p. 73), the acidity of the acids [33] also depended on the ring size. The 18-membered ring [33b] had the largest pK but the pATa values of the 15-, 21- and 24-membered rings were also quite 

In another study (Adamic et al., 1986a,b), the influence of a solvent change on the pK values has been investigated for macrocyclic and non-macrocyclic acids [33] and [35] (see Table 16). Again the largest 

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Ethacrynic acid has been linked to the ruthenium(II)-arene frame via two different approaches. In one approach the acid is connected via an imidazole which coordinates to the ruthenium(II) centre, in place of the pta ligand in RAPTA-type compounds. In the second approach the ethacrynic acid is attached to the arene, via either an amide or ester linker, in such a way that it should be cleaved enzymatically once inside the active site of GST. The ability of the ruthenium complexes to inhibit GST Pl-1 activity was comparable or better than free ethacrynic acid whereas RAPTA-C, employed as a control, exhibited no inhibitory effect on GST Pl-1, even at high concentrations. 

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