An Entry to Novel Platinum Complexes: Carboxylation of Dihydroxoplatinum(IV) Complexes with Succinic Anhydride and Subsequent Derivatization

Abstract

An improved carboxylation method of (OC‐6‐33)‐dichloro(ethane‐1,2‐diamine)dihydroxyplatinum(IV) based on succinic anhydride is reported. Reaction of the uncoordinated carboxylic acid with simple amines and alcohols leads to the corresponding amides and esters in the presence of 1,1′‐carbonyldiimidazole. The resulting new complexes are characterized by IR, 1H, 13C, 15N, and 195Pt NMR spectroscopy, mass spectrometry, and elemental analysis. This reaction provides an entry to a new class of kinetically inert platinum(IV) complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Tuning of lipophilicity and cytotoxic potency by structural variation of anticancer platinum(IV) complexes

“…For these studies, a series of nine bis(carboxylato)platinum(IV) complexes (Fig. 2) was chosen that covers a broad range of cytotoxicity and lipophilicity [17][18][19].…”

“…The platinum(IV) complexes were synthesized following a published procedure [17][18][19]. Sodium dodecyl sulfate (SDS), dodecanophenone, 1-butanol and sodium monohydrogenphosphate were purchased from Sigma-Aldrich (Vienna, Austria).…”

“…or phthalic anhydride as carboxylation agents [14][15][16][17][18][19] resulted in bis (carboxylato)platinum(IV) complexes, displaying two free and uncoordinated carboxylic acid groups, therefore opening up the possibility for further functionalization of the axial ligands. Derivatization of the axial ligands is of great importance, when taking into account, that these ligands are released during the activation of the platinum(IV) complex in the body.…”

“…Recently, we reported on the synthesis, characterization and cytotoxicity of a series of bis(carboxylato)platinum(IV) complexes with exceptionally high antiproliferative properties using succinic and glutaric anhydride as carboxylation agents [17][18][19]. Further derivatization was performed using amines and alcohols, which resulted in formation of the corresponding amides or esters, respectively.…”

What do we know about the reduction of Pt(IV) pro-drugs?

“…This results in expansion of the coordination sphere by adding hydroxido or chlorido ligands to the axial positions (Fig 3). The axial hydroxido ligands can be carboxylated (or carbamated) thereby providing an entry to the preparation of a whole range of axial ligands [37][38][39]. The octahedral platinum(IV) complexes are substitution-inert, so reactions with biological nucleophiles, including cysteine and methionine, are extremely slow.…”