Lability

Carvin, D.; Islam, S. A.; Sternberg, M. J. E.; Blundell, T. L.

doi:10.1107/97809553602060000679

International
Tables for
Crystallography
Volume F
Crystallography of biological macromolecules
Edited by M. G. Rossmann and E. Arnold

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International Tables for Crystallography (2006). Vol. F. ch. 12.1, p. 248 | 1 | 2 |

Section 12.1.3.2. Lability

D. Carvin,^a S. A. Islam,^b M. J. E. Sternberg^b and T. L. Blundell^c ^*

^a Biomolecular Modelling Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Field, London WC2A 3PX, England,^bInstitute of Cancer Research, 44 Lincoln's Inn Fields, London WC2A 3PX, England, and ^cDepartment of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, England
Correspondence e-mail: tom@cryst.bioc.cam.ac.uk

12.1.3.2. Lability

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The rates at which ligands enter and leave a metal complex are important in the formation of heavy-atom derivatives, especially the covalent complexes of mercury, gold and platinum. The rate-determining step in unimolecular S_N1 reactions is the expulsion of the leaving ligand from the metal complexes, which often proceeds relatively slowly. The intermediate complex, once formed, reacts with the entering ligand almost instantly. For S_N1 reactions, the rate is directly proportional to the intermediate complex concentration but independent of the ligand concentration. The bimolecular S_N2 mechanism involves attack by the ligand on the metal complex to form an intermediate complex, which then ejects the displaced ligand. The rate of reaction is proportional to the concentration of the initial species and the concentration of the nucleophile. S_N2 reaction rates are dependent on the nature of the leaving group and the attacking nucleophile in the following ways: $[ \eqalignno{ &\hbox{Relative rates of attack: } R\hbox{S}^{-} \gt \hbox{I}^{-} \gt \hbox{Br}^{-} \gt \hbox{NH}_{3} \gt \hbox{Cl}^{-} \gt R\hbox{O}^{-}\hbox{;} \cr &\hbox{Rate of leaving group: } \hbox{H}_{2}\hbox{O} \gt \hbox{Cl}^{-} \gt \hbox{NO}_{2}^{-} \gt \hbox{CN}^{-}.\cr}]$

Sulfur ligands are good nucleophiles but poor leaving groups. They form thermodynamically stable complexes. The rate of leaving is influenced by the trans effect in square-planar complexes of Au(III) and Pt(II). Thus groups in square-planar complexes trans to NH₃ are difficult to displace. This has implications for attempts to make derivatives of proteins in ammonium sulfate, where ligands may be replaced by NH₃.

Rates of reaction depend not only upon which ligands are present in a heavy-atom complex but also on the character of the metal. For example, $[\hbox{PtCl}_{4}^{2-}]$ , $[\hbox{AuCl}_{4}^{-}]$ and $[\hbox{PdCl}_{4}^{-}]$ have similar square-planar geometries (Petsko et al., 1978), but the rates of substitution vary: $[ \hbox{PdCl}_{4}^{-} \gt \hbox{PtCl}_{4}^{2-} \gt \hbox{AuCl}_{4}^{-}.]$ Thus, if the reaction between the protein and a palladium or platinum complex is proceeding too fast, a gold derivative might be investigated.

References

Petsko, G. A., Phillips, D. C., Williams, R. J. P. & Wilson, I. A. (1978). On the protein crystal chemistry of chloroplatinite ions: general principles and interactions with triose phosphate isomerase. J. Mol. Biol. 120, 345–359.Google Scholar

International Tables for Crystallography (2006). Vol. F. ch. 12.1, p. 248