posted on 2014-08-04, 00:00authored byAviran Amir, Alon Ezra, Linda J. W. Shimon, Bilha Fischer
Bis(dialkyl/aryl-phosphorothioyl)amide
(BPA) derivatives are versatile
ligands known by their high metal-ion affinity and selectivity. Here,
we synthesized related chelators based on bis(1,3,2-dithia/dioxaphospholane-2-sulfide)amide
(BTPA/BOPA) scaffolds targeting the chelation of soft metal ions.
Crystal structures of BTPA compounds 6 (N–R3NH+) and 8 (NEt) revealed a gauche geometry, while BOPA compound 7 (N–R3NH+) exhibited an anti-geometry. Solid-state 31P magic-angle spinning NMR spectra
of BTPA 6-Hg(II) and 6-Zn(II) complexes
imply a square planar or tetrahedral geometry of the former and a
distorted tetrahedral geometry of the latter, while both BTPA 6-Ni(II) and BOPA 7-Ni(II) complexes possibly
form a polymeric structure. In Cu(I)-H2O2 system
(Fenton reaction conditions) BTPA compounds 6, 8, and 10 (NCH2Ph) were identified
as most potent antioxidants (IC50 32, 56, and 29 μM,
respectively), whereas BOPA analogues 7, 9 (NEt), and 11 (NCH2Ph) were found to be
poor antioxidants. In Fe(II)-H2O2 system, IC50 values for both BTPA and BOPA compounds exceeded 500 μM
indicating high selectivity to Cu(I) versus the borderline Fe(II)-ion.
Neither BTPA nor BOPA derivatives showed radical scavenging properties
in H2O2 photolysis, implying that inhibition
of the Cu(I)-induced Fenton reaction by both BTPA and BOPA analogues
occurred predominantly through Cu(I)-chelation. In addition, NMR-monitored
Cu(I)- and Zn(II)-titration of BTPA compounds 8 and 10 showed their high selectivity to a soft metal ion, Cu(I),
as compared to a borderline metal ion, Zn(II). In summary, lipophilic
BTPA analogues are promising highly selective Cu(I) ion chelators.