Ru(II), Os(II) and RH(III) complexes of PTA

A series of ruthenium, osmium and rhodium complexes utilizing pta, (1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane) and pta-Me+, its N-methyl derivative, have been synthesized. Their characterization by 1H and 31P NMR spectroscopy, ESI-MS and single crystal X-Ray diffraction are described. The mechanism of hydrolysis for [Ru(η6-C10H14)Cl2(pta)] has been studied and two watertype adducts, [Ru(η6-C10H14)Cl(OH2)(pta)][Cl] and [Ru(η6-C10H14)(OH2)2(pta)][Cl]2, have been characterized by 1H and 31P NMR spectroscopy and ESI-MS. The pKa of the pta moiety for the mono-aqua complex has been determined to be 2.33 ± 0.07, and the one of bis-aqua estimated to be between 2 and 2.1 units of pH. Although it was not possible to measure the pKa of the coordinated water, it is expected to be higher than 8 for the mono-aqua and 6.5 for the bis-qua complexes. The reactivity of the above described complexes towards guanine and adenine in which N9 position is blocked by a methyl or ribose substituent, has been investigated. The coordination of the complexes through the N7 center has been demonstrated by 1H NMR spectroscopy, and ESI-MS, which has also shown the formation of η2-(N6,N7) coordination mode for the adenine derivatives. The pKa for [Ru(η6-C10H14)Cl2(guanosine)(pta)] has been determined as 2.54 ± 0.03. A second model was devised based on a 14-mer strand (5'-ATACATGGTACATA-3') and ESI-MS has been used to demonstrate specific reactivity of the complexes. The interaction of pta and pta derivatives has been confirmed, however, no correlation between the reactivity toward the DNA strand and antineoplastic activity was found. Ruthenium, especially with hydrogen bonding capable substituents, is able to dissociate the arene group, which is not observed for the osmium cases, and it is believed that the water solubility of the arene, rather the strength of the arene – ruthenium bond plays more of a role.

6-Phosphoryl Picolinic Acids as Europium and Terbium Sensitizers

Julien Alexandre Andres, Anne-Sophie Chauvin

Three 6-phosphoryl picolinic acid (6PPA) derivatives were synthesized and used as europium and terbium sensitizers. Two of the three ligands (6-diethoxyphosphoryl picolinic acid (Hdeppa) and 6-monoethoxyphosphoryl picofinic acid (H(2)meppa)) are water-soluble, once complexed to lanthanide ions, while the third (6-dihydroxyphosphoryl picolinic acid (H(3)dhppa)) forms a precipitate. The stability constants of the phosphoryl-based complexes were found to be higher than the carboxylate analogue (dipicolinic acid, H(2)dpa). The main species are the [LnL(3)] complexes under strict stoichiometric conditions, confirmed by P-31 NMR spectroscopy, mass spectrometry and lifetime analyses. The photophysical measurements reveal that the emission intensity of [Eu(deppa)(3)] is maximal at pH 4.8, whereas for Eu(meppa)(3), the optimum pH is observed at 9.0. The lifetimes are all in the millisecond range and have confirmed the absence of water molecules in the first coordination sphere. The emissions of the terbium are always brighter than the corresponding europium within this phosphoryl series. The quantum yields of the phosphoryl containing complexes are lower than the carboxylate analogue (Ln(dpa)(3)), except for [Tb(deppa)(3)], which exhibits an interesting quantum yield of 40% in aqueous solution.

2011

Tetracarboxylatoplatinum(IV) complexes featuring monodentate leaving groups - A rational approach toward exploiting the platinum(IV) prodrug strategy

Hristo Plamenov Varbanov

A series of novel symmetrically and unsymmetrically coordinated platinum(IV) complexes with monodentate carboxylato ligands was synthesized. The compounds exhibit a general coordination sphere of [Pt(en)(OCOR)(2)(OCOR')(OCOR '')1, where the carboxylato ligands are represented by acetato and succinic acid monoester ligands. Dicarboxylatoplatinum(II) complexes were synthesized and oxidized symmetrically or unsymmetrically to obtain platinum(IV) complexes, which were subsequently carboxylated with noncyclic anhydrides. The compounds were investigated in detail by elemental analysis, mass spectrometry, infrared and multinuclear (H-1,C-13,N-15,Pt-195) NMR spectroscopy as well as by X-ray diffraction in some cases. The reduction behavior was followed by NMR spectroscopy, while stability and lipophilicity were examined by analytical reversed phase HPLC measurements. Cytotoxic properties were studied in three human cancer cell lines derived from cisplatin sensitive ovarian teratocarcinoma (CH1/PA-1), cisplatin insensitive colon carcinoma (SW480) and non-small cell lung cancer (A549). Thereby, the most lipophilic (yet water soluble) platinum(IV) complexes showed promising IC50 values in the low micromolar and even nanomolar range, demonstrating the significant advantage of using equatorially coordinated monodentate carboxylato ligands. (C) 2015 Elsevier Inc. All rights reserved.

Elsevier Science Inc2015

Cytotoxic Half-Sandwich Rh(III) and Ir(III) beta-Diketonates

Paul Joseph Dyson, Agnese Petrini, Tina Riedel, Rosario Scopelliti

A series of half-sandwich pentamethylcyclopentadienyl rhodium(III) and iridium(III) complexes [CpM(DBM/ HDB/AVB)Cl] and [CpM(DBM/HDB/AVB)(PTA)]-[SO3CF3], where Cp* = pentamethylcyclopentadienyl, the proligands DBMH = dibenzoylmethane, HDBH = o-hydroxydi-benzoylmethane, AVBH = avobenzone, and PTA = 1,3,5-triaza-7-phosphaadamantane, is reported. All the complexes were characterized by IR, H-1 and C-13 NMR spectroscopy, electrospray ionization mass spectrometry, elemental analysis, and DFT calculations. Five of the complexes have also been characterized in the solid-state by X-ray crystallography. The cytotoxicity of the complexes has been evaluated against human ovarian A2780 and A2780cisR cell lines and, with the only exception of complexes 1 and 2 that display a negligible cytotoxicity, exhibit moderate cytotoxicity toward both cancer cell lines. However, the complexes do not show cancer cell selectivity with respect to human embryonic kidney HEK293 cells.

American Chemical Society2017