From Natural to Rationally Designed Artificial Enediynes: Towards New Anticancer Antibiotics Activable at Will - Polyynes: Synthesis, Properties, and Applications - page 472

19.5.2 M ETAL -I ON C OORDINATION
The design of enediyne systems stable and unreactive until activated by a
metal ion is extremely intriguing from a pharmaceutical point of view.
Various research groups have found that the coordination of metal ions to
suitable substituted enediynes can modulate their reactivity due to
conformational and electronic changes in their structure. Conformational
changes are observed, for example, in the work by Ko ¨ nig and Rutters, 112
where the enediyne system 114, equipped with two crown ether moieties, is
alternatively transformed in a bis sodium complex 115 or in a sandwich
potassium complex 116, and the effects of the coordination on the
cycloaromatization process is investigated. However, the results are
disappointing, since the cycloaromatization process begins at temperatures
higher than the metal-free counterpart (Scheme 19.31).
SCHEME 19.31
Conformational changes are observed also in the 1,2-aryldiyne system
117 bearing two phosphine groups at its extremities synthesized by Warner
et al.: 113 in this case the complexation to ions such as Pd 2 þ and Pt 2 þ
activates the Bergman rearrangement, while Hg 2 þ stabilizes the aryldiyne
moiety ( Scheme 19.32 ) . The author proposes that not only conformational
changes, but also electronic effects, may contribute to the reactivity.
Electronic effects are observed in a third example by Wang and Finn: 114