Electrophilic Substitution of (Diamine)tetrahydroxoplatinum(IV) with Carboxylic Anhydrides. Synthesis and Characterization of (Diamine)platinum(IV) Complexes of Mixed Carboxylates

Abstract

A novel series of (diamine)platinum(IV) complexes of mixed carboxylates have been synthesized by electrophilic substitution of the tetrahydroxoplatinum(IV) complex (dach)Pt(OH)4 (dach = trans-(+/-)-1,2-diaminocyclohexane) with three different carboxylic anhydrides, pivalic, acetic, and trifluoroacetic anhydrides. Consecutive two-step acylations with two different carboxylic anhydrides in acetone or dichloromethane gave the mixed carboxylate complexes (dach)Pt(O2CR)x(O2CR')4 - x (R = C(CH3)3 or CF3, R' = CH3, x = 1-4) including all the possible stereoisomers, which could be separated and identified by means of HPLC, column chromatography, 1H NMR, and X-ray crystallography. From analysis of the reaction products we have found that the positions of electrophilic substitution of (dach)Pt(OH)4 were influenced by the kinds of carboxylic anhydrides exhibiting different electrophilicity or steric effects. The initial substitution by the first reactant occurs more favorably on axial OH, but in the case of pivalic anhydride, equatorial substitution is favored probably because of the bulkiness of the pivalate group. Such a result seems to be related to their stereochemical factors rather than to differences in electrophilicity. The lipophilicity of the title complexes was affected not only by the carbon numbers of substituents but also by the conformation of the resulting compound.

Synthesis and Characterization of Platinum(IV) Anticancer Drugs with Functionalized Aromatic Carboxylate Ligands: Influence of the Ligands on Drug Efficacies and Uptake

“…In addition, the carboxylate CO stretches in the Pt(IV) complexes were observed at lower frequencies (typically 50−100 cm -1 ) compared to those of the free acid, suggesting, as expected, a weakening in the CO bond. A similar trend has been observed in other reported trans -Pt(IV) carboxylate complexes. ,,, Negative mode NSI-MS was found to be very useful for the identification of complexes 3 − 8 . Using diluted methanolic solutions, the neutral compounds often yield the parent [M − H] - peak with the highest relative intensity along with other signature mass peaks attributable to either solvated or aggregated species.…”

“…The distances of the Pt-Cl, Pt-N, and Pt-O bonds in all the structures are similar and are not too different from those reported for Pt(IV) alkyl carboxylates. 19,20,23 Structurally, complex 8 is significantly different from 3, 4, or 7. The carboxylate bond adjacent to the Pt center is oriented almost perpendicular to the aromatic ring, in contrast to the carboxylate bonds of 3, 4, and 7, which are coplanar to their respective aromatic rings.…”

“…A similar trend has been observed in other reported trans-Pt(IV) carboxylate complexes. 15,16,19,20 Negative mode NSI-MS was found to be very useful for the identification of complexes 3-8. 21 Using diluted methanolic solutions, the neutral compounds often yield the parent [M -H]peak with the highest relative intensity along with other signature mass peaks attributable to either solvated or aggregated species.…”

The influence of a sugar-phosphate backbone on the cisplatin-bridged BpB? models of DNA purine bases. Quantum chemical calculations of Pt(ii) bonding characteristics

“…10,11 Six-coordinate platinum(IV) complexes were also extensively explored. [12][13][14][15][16] These complexes are relatively stable and can be passed through the digestive tract. After absorption in the bloodstream, they are metabolised and form four-coordinate Pt(II) cisplatin analogues.…”

Anticancer Platinum (IV) Prodrugs with Novel Modes of Activity

“…Platinum(IV) complexes containing mixed carboxylate ligands can be prepared using cis-[PtA 2 (OH) 4 ] as the precur-sor by exploiting the different reactivity of the hydroxyl groups towards carboxylic acids and their anhydrides [54][55]. For example, treatment of cis-[PtA 2 (OH) 4 ] with aliphatic acid anhydrides yielded cis-[PtA 2 (OCOR) 4 ] tetracarboxylate complexes [54], but reaction with aliphatic acids yielded cis,fac-[PtA 2 (OCOR) 3 (OH)] tricarboxylate species Fig.…”