Tuning Reactivity of Platinum(II) Complexes

coordination to the soft Pt(II) centre. At pH 2.0, protonation of the released ammine
ligand serves as the driving force which prevents the reverse reaction. This step is
slower because of the steric hindrance of the coordinated thiourea and its σ-electron
donation toward the Pt(II) centre makes the metal centre less electrophilic, leading to
repulsion of the incoming nucleophile in the five-coordinate transition state. The release
of ammine has been detected in the reaction of cisplatin with methionine in blood 46 and
has also been reported in previous studies using S-donor nucleophiles TU and
glutathione for mononuclear analogues trans-[PtCl(NH3)3] + and trans-
[PtCl(NH3)2CH3NH2] + 47 and 1,1/c,c dinuclear complexes. 14,31(a),32
To confirm the stepwise mechanism proposed in Scheme 7.4, the reaction between
HexPt as a chloride and TU (at 2, 4, 6 equiv.) in D2O was monitored by 1 H and 195 Pt NMR
and the NMR spectra are recorded in Figures 7.4 & 7.5. An array of the (CH2)n protons of
the linker showing: δ /ppm Ha = 2.69 (CH2, 1/6), Hb = 1.72 (CH2, 2/5) and Hc = 1.40 (CH2,
3/4) in the absence of TU is recorded as a reference point provided as Figure 7.4 as
spectra “a”. During the course of substitution (refer to spectral array Figure 7.4), both Hb
and Hc resonances are shifted upfield, due to coordination of sulphur to the metal centre
consistent with the substitution of either chloro or ammine ligand by thiourea. The
broad multiplet resonance Ha underwent a downfield shift. The distinct broadened
multiplet resonance for Ha protons results from coordination of S to form PtN3S
intermediate species upon subsequent addition of larger amounts of TU to the complex
solution, which demonstrates further the sensitivity of the protons on the linker to
electronic changes at the Pt(II) centre upon coordination of the second TU moiety.
Kasherman et al. 47 have demonstrated that the formation of trans-[Pt(NH3)3TU] +2 from
the mononuclear complex trans-[PtCl(NH3)2L] + (where L = CH3NH2 or NH3) occurred in
the first 100 minutes, explaining why in the current study cleavage of the linker was not
observed. This is supported by the absence of the diagnostic triplet peak at 3.0 ppm
assigned to the free hexanediamine. 31(a)
16