Nickel−Cysteine Binding Supported by Phosphine Chelates

The effect of chelating phosphines was tested on the structure and pH-dependent stability of nickel−cysteine binding.
(1,2-Bis(diphenylphosphino)ethane (dppe) and 1,1,1-tris[(diphenylphosphino)methyl]ethane (triphos) were used with
three different cysteine derivatives (l-cysteine, Cys; l-cysteine ethyl ester, CysEt; cystamine, CysAm) to prepare
complexes of the form (dppe)NiCysRn+ and (triphos)NiCysRn+ (n = 0 for Cys; n = 1 for CysEt and CysAm).
Similar 31P {1H} NMR spectra for all (dppe)NiCysRn+ confirmed their square-planar P2NiSN coordination spheres.
The structure of [(dppe)NiCysAm]PF6 was also confirmed by single-crystal X-ray diffraction methods. The (triphos)NiCysAm+ and (triphos)NiCysEt+ complexes were fluxional at room temperature by 31P NMR. Upon cooling to −80
°C, all gave spectra consistent with a P2NiSN coordination sphere with the third phosphorus uncoordinated.
Temperature-dependent 31P NMR spectra showed that a trans P−Ni−S π interaction controlled the scrambling of
the coordinated triphos. In aqueous media, (dppe)NiCys was protonated at pH ∼ 4−5, leading to possible formation
of a nickel−cysteinethiol and eventual cysteine loss at pH < 3. The importance of N-terminus cysteine in such
complexes was demonstrated by preparing (dppe)NiCys-bead and trigonal-bipyramidal Tp*NiCys-bead complexes,
where Cys-bead represents cysteine anchored to polystyrene synthesis beads and Tp*- = hydrotris(3,5-dimethylpyrazolyl)borate. Importantly, results with these heterogeneous systems demonstrated the selectivity of
these nickel centers for cysteine over methionine and serine and most specifically for N-terminus cysteine. The
role of Ni−S π bonding in nickel−cysteine geometries will be discussed, including how these results suggest a
mechanism for the movement of electron density from nickel onto the backbone of coordinated cysteine.