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Download fileiClick Reactions of Square-Planar Palladium(II) and Platinum(II) Azido Complexes with Electron-Poor Alkynes: Metal-Dependent Preference for N1 vs N2 Triazolate Coordination and Kinetic Studies with 1H and 19F NMR Spectroscopy
journal contribution
posted on 08.08.2019, 19:15 authored by Kun Peng, Viviane Mawamba, Ellina Schulz, Mario Löhr, Carsten Hagemann, Ulrich SchatzschneiderTwo square-planar
palladium(II) and platinum(II) azido complexes [M(N3)(L)]
with L = N-phenyl-2-[1-(2-pyridinyl)ethylidene]hydrazine
carbothioamide reacted with four different electron-poor alkynes R–CC–R′
with R = R′ = COOCH3, COOEt, COOCH2CH2OCH3 or R = CF3, R′ = COOEt in
a [3 + 2] cycloaddition “iClick” reaction. The resulting
triazolate complexes [M(triazolateR,R’)(L)] were
isolated by simple precipitation and/or washing in high purity and
good yield. Six out of the eight new compounds feature the triazolate
ligand coordinated to the metal center via the N2 nitrogen atom, but
fortuitous solubility properties allowed isolation of the N1 isomer
in two cases from acetone. When the solvent was changed to DMSO, the
N1 → N2 isomerization could be studied by NMR spectroscopy
and took several days to complete. 19F NMR studies of the
iClick reaction with F3C–CC–COOEt
led to identification of a putative early linear intermediate in addition
to the N1 and N2 isomers, however with the latter as the final product.
Rate constants determined by 1H or 19F NMR spectroscopy
increased in the order Pd > Pt and CF3/COOEt > COOR/COOR
with R = CH3, Et, CH2CH2OCH3. The second-order rate constant k2 >
3.7 M–1 s–1 determined for the
reaction of [Pd(N3)(L)] with F3C–CC–COOEt
is the fastest observed for an iClick reaction so far and compares
favorably with that of the most evolved strained alkynes reported
for the SPAAC (strain-promoted azide–alkyne cycloaddition)
to date. Selected title compounds were evaluated for their anticancer
activity on the GaMG human glioblastoma brain cancer cell line and
gave EC50 values in the low micromolar range (2–16
μM). The potency of the Pd(II) complexes increased with the
chain length of the substituents in the 4- and 5-positions of the
triazolate ligand.
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Keywords
19 F NMR studiesSPAACEC 50 valuesglioblastoma brain cancer cell lineCOOEtPd19 F NMR spectroscopyCOORN 1 vs N 2 Triazolate CoordinationalkyneN 1 isomerN 2 nitrogen atomcycloaddition19 F NMR SpectroscopyN 2 isomersCH 2 CH 2 OCH 3CFSelected title compounds1 HiClick reactionCOOCH 2 CH 2 OCH 3complextriazolate ligandDMSO