![]() ![]() ![]() Such chemical reduction is highly dependent on the levels of reducing agents present in body fluids and cells, which can be variable. ascorbic acid, intracellular glutathione). Increasing evidence suggests that for activity they require in vivo reduction to the corresponding platinum(II) species by biological reductants (e.g. Platinum(IV)-based anticancer drugs might be less toxic and more readily tolerated by normal cells. Platinum(IV) is a classically-inert low-spin d 6 metal ion. In this regard, there has long been interest in cytotoxic six-coordinate platinum(IV) analogues, especially since they are often effective against tumors resistant to cisplatin. 1 Thus, effort in designing new platinum drugs is aimed at making platinum-based therapy safer to patients, in particular by reducing or removing severe side effects, providing oral administration, and overcoming both intrinsic and acquired resistance. A second major drawback is tumor resistance, either acquired during cycles of therapy (as occurs in patients with, for instance, ovarian cancer) or intrinsic resistance (such as in patients with prostate, lung, or breast cancer). However, in spite of therapeutic success in the treatment of several types of tumors, their effectiveness is severely hindered by adverse side effects such as nausea, ototoxicity, neurotoxicity, myelosuppression, and nephrotoxicity. The platinum(II) complexes cisplatin, carboplatin, and oxaliplatin are currently approved drugs for the treatment of cancer. Our findings are discussed in comparison with the limited data available in the literature on related complexes. ![]() A distinct p K a 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. 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. We have studied the acid–base properties of three photoactivatable anticancer platinum(IV)-diazidodiam(m)ine complexes ( cis, trans, cis-, trans, trans, trans-, and cis, trans-) using multinuclear NMR methods and potentiometry. Platinum(IV) am(m)ine complexes are of interest as potential anticancer pro-drugs, but there are few reports of their acid–base properties. ![]()
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