Insights into the electronic structure of Cu(II) bound to an imidazole analogue of westiellamide.

Three synthetic analogues of westiallamide, H3L(wa), have previously been synthesized (H3L(1-3)) that have a common backbone (derived from l-valine) with H3L(wa) but differ in their heterocyclic rings (imidazole, oxazole, thiazole, and oxazoline). Herein we explore in detail through high-resolution pulsed electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy in conjunction with density functional theory (DFT) the geometric and electronic structures of the mono- and dinuclear Cu(II) complexes of these cyclic pseudo hexapeptides. Orientation-selective hyperfine sublevel correlation, electron nuclear double resonance, and three-pulse electron spin echo envelope modulation spectroscopy of [Cu(II)(H2L(1))(MeOH)2](+) reveal delocalization of the unpaired electron spin onto the ligating and distal nitrogens of the coordinated heterocyclic rings and that they are magnetically inequivalent.

Cyclic peptide marine metabolites and CuII.

Cyclic pseudo-peptides derived from marine metabolites of the genus Lissoclinum bistratum and Lissoclinum patella have attracted scientific interest in the last two decades. Their structural properties and solution dynamics have been analyzed in detail, elaborate synthetic procedures for the natural products and synthetic derivatives developed, the biosynthetic pathways studied and it now is possible to produce them biosynthetically. Initially, these macrocyclic ligands were studied due to their medicinal and pharmaceutical potential - some of the isolated cyclic pseudo-peptides show high cytotoxic and antiviral activity.

Cu(II) coordination chemistry of patellamide derivatives: possible biological functions of cyclic pseudopeptides.

Two synthetic derivatives of the naturally occurring cyclic pseudooctapeptides patellamide  A-F and ascidiacyclamide, that is, H(4)pat(2), H(4)pat(3), as well as their Cu(II) complexes are described. These cyclic peptide derivatives differ from the naturally occurring macrocycles by the variation of the incorporated heterocyclic donor groups and the configuration of the amino acids connecting the heterocycles. The exchange of the oxazoline and thiazole groups by dimethylimidazoles or methyloxazoles leads to more rigid macrocycles, and the changes in the configuration of the side chains leads to significant differences in the folding of the cyclic peptides.

Synthesis and Cu(II) coordination chemistry of a patellamide derivative: consequences of the change from the natural thiazole/oxazoline to the artificial imidazole heterocycles.

The synthesis and Cu(II) coordination chemistry of the cyclic pseudo-octapeptide H(4)pat(1), a dimethyl-imidazole analogue of naturally occurring cyclic peptides (patellamide A-F, ascidiacyclamide) is reported. Substitution of the oxazoline and thiazole heterocycles by dimethyl-imidazoles leads to a slightly different structure of the macrocycle in the solid state. The Cu(II) coordination chemistry of H(4)pat(1), monitored with high-resolution electrospray mass spectrometry, spectrophotometric titrations, and EPR spectroscopy, revealed the presence of both mono- and dinuclear Cu(II) complexes.

Complex formation and stability of westiellamide derivatives with copper(II).

The CuII coordination chemistry of three synthetic analogues of westiellamide (H3Lwa) with an [18]azacrown-6 macrocyclic structure and imidazole (H3L1), oxazole (H3L2), or thiazole (H3L3) heterocyclic donors in addition to the peptide groups, is reported. The Nheterocycle-Npeptide-N(heterocycle) binding sites are highly preorganized for the coordination to CuII ions. The stability constants of mono- and dinuclear CuII complexes of H3L1, H3L2, and H3L3, obtained by isothermal titration microcalorimetry, are reported.