Tuning Reactivity of Platinum(II) Complexes
Tuning Reactivity of Platinum(II) Complexes Tuning Reactivity of Platinum(II) Complexes
σ-Donation According to classical explanation, the trans-effect causes electrostatic destabilisation of the ligand in the trans position and it is observable in the Pt–trans ligand bond length elongation through σ-donation. The trans ligand T and the leaving group (X) both share the metal dsp 2 orbital in the ground stat (Scheme 2.5). T 1 T 2 Pt (a) Scheme 2.5: A schematic diagram showing the difference in the Pt–X bond strengths for 38 Pt (b) a (a) weak and (b) strong σ-donor ligand T1 and T2, respectively. In (b) the strong trans σ-donor weakens the bond to the trans ligand (Pt–X). The stronger of the two contributes more electron density towards the shared orbital. If the trans ligand (T) is the stronger σ-donor, the Pt–T bond shortens while that of Pt–X is elongated and weakened as a result of less electron density being availed to this bond. Hence, in the normal trans-effect one bond shortens while the other lengthens. Bond cleavage of the weakened bond (Pt–X), trans to strong σ-donors occurs very fast during substitution reactions and as a result reduces the significance of nucleophilicity of the incoming ligand. π-back-donation or the π-Acceptor Effect Ligands such as CO and C2H4 stabilise the complex also by π-back-donation. It is the interaction of filled 5dxz or 5dxy orbital of the Pt metal (suppose the trans ligand lies on the x or y-axis) with empty π(px) or π(py) orbital of the ligand. Hence, π-back-donation increases the positive charge of the Pt(II) atom by a decrease of electron density in the xz or xy plane. This facilitates nucleophilic attack in the xz or xy plane and stabilises the corresponding five-coordinate transition state relative to the ground state by withdrawing the π-electron density of the metal into its own empty π*-orbitals as X X
shown in Figure 2.12 (b).The overall activation energy needed for substitution is reduced while the ground state energy remains unaffected. 56 Thus, the net effect of a strong π-acceptor ligand occupying a trans-position is to stabilise the trigonal- bipyramidal transition state by lowering the activation energy. This enhances the addition of the incoming ligand resulting in a rapid substitution reaction. The overall effect is called the trans-effect. Recent studies have reported that systematic variation of the π-acceptor effect of different ligands, substantially enhances reactivity of Pt(II) complexes. 33,57,58 A comparison of NBO charges 49 of cis- and trans-isomers of [Pt(NH3)2(C2H4)2] 2+ shows that a higher positive charge on the platinum atom is in the cis-isomer 33(b) since two orbitals (5dxz and 5dyz) are involved in π-backbonding. Only one (5dxz) orbital is available for the two π-back-donating ligands in the trans-isomer. It is clear changes in σ-donor, π-acceptor and steric properties of the cis ligand have opposite effects on reactivity of a complex. Until very recently, 33,59,60 studies on the effect of the σ-donor and π-acceptor properties of the cis ligand had not been separately investigated. In one of the studies, a replacement of the outer pyridyl unit by a phenyl group ( a strong σ- donor) in the cis position of [Pt(N-N-N)Cl] + complex, where N-N-N is a terpyridine ligand, led to a reduction in reactivity of the complex by a factor of about 16 when thiourea (TU) was the incoming ligand. 60 Whilst an extensive review of the current research is impossible to present here, efforts are being directed at developing a detailed understanding of the substitution behaviour of mono-, di- and trinuclear platinum-based anticancer drugs. In particular understanding the role of σ-donicity and π-acceptor properties of polydentated mononuclear Pt(II) complexes and the structural complexity of the bridging ligand in controlling reactivity at the Pt(II) metal centres constitutes a major challenge. The details of the objectives are given in Chapter one. 39
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shown in Figure 2.12 (b).The overall activation energy needed for substitution is<br />
reduced while the ground state energy remains unaffected. 56 Thus, the net effect <strong>of</strong> a<br />
strong π-acceptor ligand occupying a trans-position is to stabilise the trigonal-<br />
bipyramidal transition state by lowering the activation energy. This enhances the<br />
addition <strong>of</strong> the incoming ligand resulting in a rapid substitution reaction. The overall<br />
effect is called the trans-effect.<br />
Recent studies have reported that systematic variation <strong>of</strong> the π-acceptor effect <strong>of</strong><br />
different ligands, substantially enhances reactivity <strong>of</strong> Pt(<strong>II</strong>) complexes. 33,57,58 A<br />
comparison <strong>of</strong> NBO charges 49 <strong>of</strong> cis- and trans-isomers <strong>of</strong> [Pt(NH3)2(C2H4)2] 2+ shows<br />
that a higher positive charge on the platinum atom is in the cis-isomer 33(b) since two<br />
orbitals (5dxz and 5dyz) are involved in π-backbonding. Only one (5dxz) orbital is<br />
available for the two π-back-donating ligands in the trans-isomer. It is clear changes in<br />
σ-donor, π-acceptor and steric properties <strong>of</strong> the cis ligand have opposite effects on<br />
reactivity <strong>of</strong> a complex. Until very recently, 33,59,60 studies on the effect <strong>of</strong> the σ-donor<br />
and π-acceptor properties <strong>of</strong> the cis ligand had not been separately investigated. In one<br />
<strong>of</strong> the studies, a replacement <strong>of</strong> the outer pyridyl unit by a phenyl group ( a strong σ-<br />
donor) in the cis position <strong>of</strong> [Pt(N-N-N)Cl] + complex, where N-N-N is a terpyridine<br />
ligand, led to a reduction in reactivity <strong>of</strong> the complex by a factor <strong>of</strong> about 16 when<br />
thiourea (TU) was the incoming ligand. 60<br />
Whilst an extensive review <strong>of</strong> the current research is impossible to present here, efforts<br />
are being directed at developing a detailed understanding <strong>of</strong> the substitution behaviour<br />
<strong>of</strong> mono-, di- and trinuclear platinum-based anticancer drugs. In particular<br />
understanding the role <strong>of</strong> σ-donicity and π-acceptor properties <strong>of</strong> polydentated<br />
mononuclear Pt(<strong>II</strong>) complexes and the structural complexity <strong>of</strong> the bridging ligand in<br />
controlling reactivity at the Pt(<strong>II</strong>) metal centres constitutes a major challenge. The<br />
details <strong>of</strong> the objectives are given in Chapter one.<br />
39
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