A bis-copper(II)-[D-βVal^3,7]ascidiacyclamide complex enveloping two square pyramids and sharing an apex atom from a...

The four azole rings place structural restrictions on ascidiacyclamide (ASC). As a result, the structure of ASC exists in an equilibrium between two major forms (i.e. folded and square). [D-βVal^3,7]Ascidiacyclamide (βASC) was synthesized by replacing two D-Val-Thz (Val is valine and Thz is thiazole) blocks with D-β-Valine (D-βVal-Thz). This modification expands the peptide ring; the original 24-membered macrocycle of ASC becomes a 26-membered ring. Circular dichroism (CD) spectra showed that, in solution, the structural equilibrium is maintained with βASC, but the folded form is dominant. A copper complex was prepared, namely [[D-βVal^3,7]ascidiacyclamide(2-)]aqua-μ-carbonato-dicopper(II) monohydrate, [Cu₂(C₃₈H₅₄N₈O₆S₂)(CO₃)(H₂O)]·H₂O, to determine the effect of the change in ring size on the coordinated structure. The obtained bis-Cu^II-βASC complex contains two water molecules and a carbonate anion. Two Cu^II ions are chelated by three N-donor atoms of two Thz-Ile-Oxz (Ile is isoleucine and Oxz is oxazoline) units. An O atom of the carbonate anion bridges two Cu^II ions, forming two square pyramids. These features are similar to the previously reported structure of the Cu^II-ASC complex, but the two pyramids are enveloped inside the peptide and share one apex. In the Cu^II-ASC complex, the apex of each square pyramid is an O atom of a water molecule, and the two pyramids are oriented toward the outside of the peptide. The incorporated β-amino acids of βASC make the space inside the peptide large enough to envelop the two square pyramids. The observed structural changes in the bis-Cu^II-βASC complex arising from ring expansion are particularly interesting in the context of the previously reported structure of the Cu^II-ASC complex.