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Hydrogen–deuterium exchange of the carbon-bound protons of thiazole coordinated to PtII in complexes 1, 2 and 3, has been measured in aqueous buffer solutions, at 60 °C, by 1H NMR spectroscopy. Analysis of the rate data indicates that PtII enhances exchange of C(2)–H by a factor of ca. 106, with respect to the neutral substrate, but is ca. 103–104 times less effective compared to H+ or Et+. Exchange of C(5)–H is enhanced ca. 6 × 103 by PtII relative to the neutral heterocycle; an effect much less than that for C(2)–H exchange. We also report the first quantitative measurement of C(4)–H exchange in a thiazole moiety, as observed in 1 under moderate conditions (pD 8.69 and 60 °C, k2= 2.54 dm3 mol–1s–1). The C(5)–H exchange process in complex 1 is moderately faster than C(4)–H exchange, a result opposite to that expected on the basis of an inductive/field effect by PtII. This is ascribed to the enhanced stabilization of the carbanionic intermediate at C(5) by the adjacent sulfur atom which is absent in the carbanion at C(4). This factor overrides the inductive/field effect of PtII, and accounts for the order of reactivity observed in this study, C(2)–H C(5)H > C(4)–H.

Hydrogen-deuterium exchange of the carbon-bound C(8)-H protons of the inosine residues in tetrakis(inosine)platinum(ii) chloride, S, with Pt binding at N(7), was studied in aqueous buffer solutions at 60 degrees C by (1)H NMR spectroscopy. The kinetics at all four C(8) sites as a function of pD of the D(2)O/OD(-) medium was measured through the disappearance of the C(8)-H signal, which yielded the pseudo first-order rate constant for exchange, k(obs). Plots of k(obs)versus [OD(-)] showed curvature reminiscent of saturation type kinetics and indicative of competitive deprotonation of N(1)-H sites. In contrast, the analogous N(1)-methylated cis-bis(1-methylinosine)diammineplatinum(ii) chloride leads to a linear k(obs)versus [OD(-)] plot. The potentiometrically determined macroscopic composite N(1)-H ionization constant was further dissected into the successive microscopic N(1)-H acidity constants of the four inosine residues of the complex S. The k(obs) values were also deconvoluted into individual rate constants k(ex) (i.e.k(0), k(1), k(2), k(3) for exchange of the successively deprotonated inosine moieties, S, S(1), S(2), S(3), it being assumed that S(4) where all four inosine ligands are deprotonated at N(1) is unreactive ("immunized") to exchange. The k(ex) values show a progressive attenuation in Pt activation of H-D exchange along the series, k(0), k(1), k(2), k(3). The k(ex) data thus generated, together with the deconvoluted individual pK(a) values allow the construction of the plot, log k(ex) [C(8)-H] vs. pK(a) [N(H)-1]. Remarkably, this plot exhibits good linearity (R(2) = 0.99), which accords this as a linear free energy relationship (LFER). The large negative slope value (-2.3) of this LFER reflects the high sensitivity of transmission of electron density from the ionized N(1) via Pt and/or through space to the remaining C(8)-H sites. This is to our knowledge the first instance in which a LFER is generated through modulation of a structure in a single molecule. One can anticipate that this approach may lead to: (1) predicting N-H acidity; (2) C-H H-D exchange susceptibility in a range of metal-biomolecule complexes; (3) their carbon acidity.