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Synthesis and Structural Properties of Patellamide A Derivatives and Their Copper (ii) Compounds
Author(s) -
Bernhardt Paul V.,
Comba Peter,
Fairlie David P.,
Gahan Lawrence R.,
Hanson Graeme R.,
Lötzbeyer Lutz
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20020402)8:7<1527::aid-chem1527>3.0.co;2-f
Subject(s) - copper , chemistry , thiazole , amide , crystallography , electron paramagnetic resonance , circular dichroism , stereochemistry , spectroscopy , nuclear magnetic resonance , organic chemistry , physics , quantum mechanics
The synthesis, characterization and copper( II ) coordination chemistry of three new cyclic peptide ligands, PatJ 1 ( cyclo ‐(Ile‐Thr‐(Gly)Thz‐Ile‐Thr‐(Gly)Thz)), PatJ 2 ( cyclo ‐(Ile‐Thr‐(Gly)Thz‐(D)‐Ile‐Thr‐(Gly)Thz)), and PatL ( cyclo ‐(Ile‐Ser‐(Gly)Thz‐Ile‐Ser‐(Gly)Thz)) are reported. All of these cyclic peptides and PatN ( cyclo ‐(Ile‐Ser‐(Gly)Thz‐Ile‐Thr‐(Gly)Thz)) are derivatives of patellamide A and have a [24]azacrown‐8 macrocyclic structure. All four synthetic cyclic peptides have two thiazole rings but, in contrast to patellamide A, no oxazoline rings. The molecular structure of PatJ 1 , determined by X‐ray crystallography, has a saddle conformation with two close‐to‐coparallel thiazole rings, very similar to the geometry of patellamide D. The two coordination sites of PatJ 1 with thiazole‐N and amide‐N donors are each well preorganized for transition metal ion binding. The coordination of copper (ii) was monitored by UV/Vis spectroscopy, and this reveals various (meta)stable mono‐ and dinuclear copper (ii) complexes whose stoichiometry was confirmed by mass spectra. Two types of dinuclear copper (ii) complexes, [Cu 2 (H 4 L)(OH 2 ) n ] 2+ ( n =6, 8) and [Cu 2 (H 2 L)(OH 2 ) n ] ( n =4, 6; L=PatN, PatL, PatJ 1 , PatJ 2 ) have been identified and analyzed structurally by EPR spectroscopy and a combination of spectra simulations and molecular mechanics calculations (MM‐EPR). The four structures are similar to each other and have a saddle conformation, that is, derived from the crystal structure of PatJ 1 by a twist of the two thiozole rings. The small but significant structural differences are characterized by the EPR simulations.