Insights into the Acid-Base Properties of PtIV-Diazidodiam(m)inedihyroxido Complexes from Multinuclear NMR Spectroscopy

• Published in: Chemistry : a European journal 2011-10, Vol.17 (43), p.12051-12058
• Main Authors: Ronconi, Luca, Pizarro, Ana M., McQuitty, Ruth J., Sadler, Peter J.
• Format: Article
• Language: English
• Subjects: acid-base properties; anticancer complexes; bioinorganic chemistry; Cancer; Chemistry; NMR; NMR spectroscopy; Nuclear magnetic resonance; pKa values; platinum
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201002792

Platinum(IV) am(m)ine complexes are of interest as potential anticancer pro‐drugs, but there are few reports of their acid–base properties. We have studied the acid–base properties of three photoactivatable anticancer platinum(IV)‐diazidodiam(m)ine complexes (cis,trans,cis‐[PtIV(N3)2(OH)2(NH3)2], trans,trans,trans‐[PtIV(N3)2(OH)2(NH3)2], and cis,trans‐[PtIV(N3)2(OH)2(en)]) using multinuclear NMR methods and potentiometry. In particular, the combination of both direct and indirect techniques for the detection of 15N signals has allowed changes of the chemical shifts to be followed over the pH range 1–11; complementary 14N NMR studies have been also carried out. A distinct pKa value of approximately 3.4 was determined for all the investigated complexes, involving protonation/deprotonation reactions of one of the axial hydroxido groups, whereas a second pH‐dependent change for the three complexes at approximately pH 7.5 appears not to be associated with a loss of an am(m)ine or hydroxido proton from the complex. Our findings are discussed in comparison with the limited data available in the literature on related complexes. Which sites can (de)protonate? The acid–base properties of photoactivable platinum(IV) anticancer complexes have been investigated by multinuclear NMR methods and potentiometry; the pKa of approximately 3.4 can be assigned to the hydroxido ligands, but the second inflexion point at a pH of about 7.5 does not appear to involve net proton dissociation.