The Solution Structure of a Copper(II) Compound of a New Cyclic Octapeptide by EPR Spectroscopy and Force Field Calculations

A new cyclic octapeptide, cyclo(Ile-Ser-(Gly)Thz-Ile-Thr-(Gly)Thz) (PatN), related to patellamide A, has been synthesized and reacted with copper(II) and base to form mono- and dinuclear complexes. The coordination environments around copper(II) have been characterized by EPR spectroscopy. The solution structure of the thermodynamically most stable product, a purple dicopper(II) compound, has been examined by simulating weakly dipole−dipole coupled EPR spectra based upon structural parameters obtained from force field (MM and MD) calculations. The MM−EPR method produces a saddle-shaped structure for [Cu₂(PatN)(OH₂)₆] that is similar to the known solution structure of patellamide A and the known solid-state structure of [Cu₂(AscidH₂)CO₃(OH₂)₂]. Compared with the latter, [Cu₂(PatN)] has no carbonate bridge and a significantly flatter topology. The MM−EPR approach to solution-structure determination for paramagnetic metallopeptides may find wide applications to other metallopeptides and metalloproteins.