Unfavourable change

For soft cations, such as Ag+ and Pb2+, covalent contributions are much more important, and consequently the observed order of complex stabilities is quite different from that for alkali cations NH > O > S for Pb2+ and NH, S > O for Ag+. Dissection of the overall effect into enthalpy and entropy contributions (Table 15) reveals the complicated nature of the heteroatom effect. For K+ and Ba2+, the more favourable entropy contribution for N and S ligands is more than offset by the unfavourable change in enthalpy of binding. 

For Tl+ and Pb2+, the S ligands are much more stable with regard to the enthalpy, which difference is more than offset by the unfavourable change in entropy. For Ag+, N ligands are preferred to O ligands both from an enthalpy and from an entropy point of view. A detailed explanation of this rather different behaviour is not yet available. 

Moreover, unfavourable changes in intestinal bacteria can rednce their ability to inactivate carcinogens and, together with deficiencies of folic acid or methionine, predispose to colorectal cancer. 

Cells have a certain ability to keep the pH of their inner liquid within necessary limits, but if the reaction of the environment is too far outside these limits, they cannot defend themselves against unfavourable changes. Also their inner pH changes, which results in serious metabolic disorders. 

Macrocyclic Effect Host systems that are preorganised into a large cyclic shape form more stable complexes as there is no energetically unfavourable change in conformation in order to bind a guest. 

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