Chelation step

We can now identify the major factors which play a role in the DNA-platination and chelation steps i) The nature and charge of the actual platinum species, ii) the bases to be platinated and their neighboring sequences, and iii) the nature of the nonleaving platinum ligands and their eventual interaction with the nucleic acid. To get a deeper insight into these parameters, in order to achieve selective DNA-platination, the study of oligonucleotide models is an appropriate approach. 

Fig. Oligonucleotides used to study the first platination, the monoadduct aquation, and the chelation steps involved in DNA-platination. The theoretical molecular electrostatic potentials, in kcal mol-1, of the 5 - and 3 -purines respectively, for each duplex structure are as follows II (TGGC) -249.5, -248.7 IV (TGGT) -249.5, -251.4 V (CGGT) -245.7, -251.4 ...

Aquation of the Chloro Monoadducts and Chelation Steps. The data are presented in Table 7. The chelation reactions were easily studied starting from the diaqua complex (Y = H20, Scheme 4) [99-102], Fewer experiments have been done starting from cis-[ PtC I (NH3)2 (H20) + [103],... 

Ab initio molecular-dynamics simulations, introduced by Car and Par-rinello [112], have the ambition to model biological systems in laboratoryrelevant conditions, i.e., either in solution or in solid phase (see, e.g., [113-115]). Recently, Carloni et al. [116] applied this method to a study of the first hydrolysis step of cisplatin. They were able to reproduce satisfactorily the free energy of activation and provided a model for the transition state. Their preliminary results, which include a model of the transition state for the chelation step of the reaction between the diaqua form of cisplatin, cA-[Pt(NH3)2(H20)2]2+, and d(GpG), seem to indicate that ab initio modeling of substitution reactions on heavy-metal centers may become possible in the near future. The main drawback of Car-Parrinello calculations - their considerable computer-time cost - can be expected to abate in the next years... 

A further investigation " deals with the anation of cw-[Co(en)2(H20)2] by quinolinic acid. At pH 4.05 quinolinic acid (H2A) behaves as a uninegative and bidentate (N, O) donor. A two-step reaction is observed the first step, is the replacement of one water and the second is the slower chelation step. Rate constants for both steps have been obtained and the ion-pair constant for the first step evaluated. 

M(dmf)6- (L-L)] " is an outer-sphere complex in which L-L resides in the second coordination sphere. Thus the data in Table 9.5 pertain to the first bond formation. The trends in lability closely follow those observed earlier for dmf exchange on [M(dmf)6], and the AV values are consistent with a dissociative mode of activation for the ligand substitution. In contrast the formation of ternary complexes of [Ni(nta)(H20)2] with amino acids is thought to involve a fast first bond formation with the chelating step being slow. " ... 

Copper(II) and zinc(II) are two of the more labile divalent metal ions and as a consequence the former is too labile for its water exchange rate to be determined by the NMR methods which utilize the paramagnetism of other divalent first-row transition metal ions, while the latter is diamagnetic and such NMR methods cannot be applied. However, it has been shown that water exchange rates and mechanisms can be deduced with reasonable reliability from simple ligand substitution studies, and this is one of the reasons for a recent variable-pressure spec-trophotometric SF study of the substitution of 2-chloro-l,10-phenanthroline on Cu(II) and Zn(II). The observed rate constants for the complexation reaction (kc) and the decomplexation reaction (k ) and their associated activation parameters for Cu(II) and Zn(II) are kc(298 K) = 1.1 x 10 and 1.1 x 10 dm mol" s", AH = 33.6 and 37.9 kJ mol", A5 = 3 and -2JK- mol", AV = 7.1 and 5.0 cm" mol", k 29S K) = 102 and 887 s", AH = 60.6 and 57.3 kJ mol", A5 = -3 and 4 J K" mol" and A V = 5.2 and 4.1 cm" mol". These data are consistent with the operation of an mechanism for the rate-determining first bond formation by 2-chloro-l,10-phenanthroline with the subsequent chelation step being faster [Eq. (18)]. For this mechanistic sequence (in which [M(H20)6 L-L] is an outer-sphere complex) it may be shown that the relationships in Eq. (19) apply. 

The formation of malonate and oxalate complexes from [Cr(OH2)6] + involves rate-determining chromium-water bond breaking in an ion-pair in each case. Activation parameters for these two reactions, for formation of the monoglycine complex, and for water exchange at chromium(iii) are all rather similar. The formation of edta complexes of chromium(iii) is more complicated, involving several water displacement and chelation steps. Rates and activation parameters are reported for the tridentate to quinquedentate conversion ... 

The effects of a variety of anions on chelation steps in the chromium(iii)-edta reaction have been studied. ... 

Most group A metal ions have the electronic configuration of the rare gases, and the interaction of the metal with a ligand is primarily electrostatic in nature. Because the charge density (oc charge radius) is small, the water molecules are weakly held and the rate of their loss is comparable with the diffusion-controlled value of around 10 —10 s. The complex formation rate-constant for an ion in this group is therefore approximately equal to the maximum possible value, unless chelation steps are important, and the stability of the complex is reflected in the dissociation rate constant. 

While all syntheses originally presented had been based on the strategy of coupling the biomolecule to a prochelator, a different approach has been presented by Peterson et al. (1999). This new way uses a solid phase bound peptide as anchor to build the chelator step by step (O Fig. 45.16). Solid phase synthesis offers many advantages one of the major advantages is that by-products may simply be washed away from the solid phase while the desired product stays bound. 

Formation reactions of chromium(iii)-carboxylate complexes often do not follow the normal kinetic pattern, as has been illustrated by the study of the reaction of [Cr(NH3)6(OH2)] + with amino-acids. Here reaction takes place exclusively by a carbon dioxide-catalysed pathway in which ammonia is displaced to give an intermediate carbonato-chelate. The ratedetermining step in the formation of chromium(rii)-edta complexes is a ligand interchange process. The dependence of rates on pH can be explained in terms of the relative reactivities of variously protonated forms of edta and of the [Cr(OH2)e] + and [Cr(OH2)s(OH)] + cations. The chelation step in the conversion of the quadridentate chromium(m)-edta complex to the quinquedentate form in aqueous solution has been studied over the pH range 0—12. From the rate-pH profile (see Figure) it is apparent that... 

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