Background:
Ischemic heart disease, cerebrovascular accident, and venous thromboembolism
have the presence of a thrombotic event in common and represent the most common
causes of death within the population.
Objective:
Since Schiff base copper(II) complexes are able to interact with polyphosphates
(PolyP), a procoagulant and potentially prothrombotic platelet agent, we investigated the antiplatelet
aggregating properties of two novel tridentate Schiff base ligands and their corresponding copper(
II) complexes.
Methods:
The Schiff base ligands (L1) and (L2), as well as their corresponding copper(II) complexes
(C1) and (C2), were synthesized and characterized by chemical analysis, X-ray diffraction,
mass spectrometry, and UV-Visible, IR and far IR spectroscopy. In addition, EPR studies were
carried out for (C1) and (C2), while (L1) and (L2) were further analyzed by 1H and 13C NMR.
Tests for antiplatelet aggregation activities of all of the four compounds were conducted.
Results:
X-ray diffraction studies show that (L1) and (L2) exist in the enol-imine tautomeric form
with a strong intramolecular hydrogen bond. NMR studies show that both ligands are found as
enol-imine tautomers in CDCl3 solution. In the solid state, the geometry around the copper(II) ion
in both (C1) and (C2) is square planar. EPR spectra suggest that the geometry of the complexes is
similar to that observed in the solid state by X-ray crystallography. Compound (C2) exhibited the
strongest antiplatelet aggregation activity.
Conclusion:
Schiff base copper(II) complexes, which are attracting increasing interest, could represent
a new approach to treat thrombosis by blocking the activity of PolyP with a potential anticoagulant
activity and, most importantly, demonstrating no adverse bleeding events.
γ-(S)-Trifluoromethyl proline: evaluation as a structural substitute of proline for solid state 19F-NMR peptide studies