Structures, Electronics and Reactivity of Copper(II) Complexes of the Cyclic Pseudo-Peptides of the Ascidians

Abstract

Cyclic pseudo-peptides, derived from marine metabolites found in the genus Lissoclinum bistratum and Lissoclinum patella and produced by their symbiont Prochloron have attracted scientific interest in the last two decades. Their structural properties and solution dynamics were analyzed in detail, elaborate synthetic procedures for the natural products and synthetic derivatives were developed, the biosynthetic pathways were studied and it now is possible to produce them biosynthetically. A major focus in the last decade was on their Cu^II – more recently also on the Zn^II – coordination chemistry, as a number of studies have indicated that dinuclear Cu^II and Zn^II complexes of cyclic peptides may be involved in the ascidians’ metabolism. Solution equilibria of various derivatives of the synthetic ligands in presence of Cu^II were studied thoroughly and the solution structures were determined by EPR spectroscopy and spectra simulation in combination with molecular mechanics and DFT calculations. Recent in vitro studies indicate that the dicopper(II) complexes are phosphatase, glycosidase, lactamase and very efficient carbonic anhydrase model systems. First in vivo studies with a patellamide derivative containing an appended fluorescence tag suggest that Cu^II is coordinated to the patellamides in the Prochloron cells.

Part of this chapter is reproduced from the PhD thesis of A.E.