Synthesis and reactivity of platinum(II) triphenylphosphino complexes with aromatic aldoximes

trans-[Pt(μ-Cl)Cl(PPh3)]2 reacted with arylaldoximes in 1,2-dichloroethane to afford [PtCl2(PPh3){N(OH)=CHAr}] (Ar = 3,4-dimethoxyphenyl, 1-naphthyl, 9-anthryl) where aldoxime ligands are N-coordinated to platinum. The obtained complexes are soluble in chlorinated solvents, where they afford equilibrium mixtures of cis,trans and/or (E),(Z) isomers. Equilibria in solution were studied by 31P-NMR spectroscopy and solid state structural data were obtained by single crystal X ray diffraction studies. The reactivity of [PtCl2(PPh3){N(OH)=CHAr}] complexes with basic aqueous solutions was studied, under liquid-liquid phase transfer catalysis conditions. The outcome of the reaction depends on the stereochemistry of the precursors: cis,(Z)-isomers promptly undergo cyclization to the corresponding dinuclear derivatives [Pt{μ-(2-N,O)}- {N(O)=CHAr}Cl(PPh3)]2, where two aldoximate ligands symmetrically bridge two metal centers

Synthesis and reactivity of cytotoxic platinum(II) complexes of bidentate oximes: a step towards the functionalization of bioactive complexes

Two new platinum(II) complexes bearing triphenylphosphine and bidentate oxime ligands [Pt(Cl)(PPh3){(κ2-N,O)-(1{C(R)=N(OH)-2(O)C10H6})}] (R = H, Me) were synthesized in good yields from trans-[PtCl(μ-Cl)(PPh3)]2. The structure of [Pt(Cl)(PPh3){(κ2-N,O)-(1{CH=N(OH)-2(O)C10H6})}] was determined by single-crystal X-ray diffraction. Both complexes showed good antiproliferative properties in vitro against HeLa, A2780, and A2780cis cancer cell lines. They reacted cleanly with alkylating agents in the presence of aqueous bases under phase-transfer catalysis conditions to afford the corresponding O-alkylation products [Pt(Cl)(PPh3){(κ2-N,O)-(1{HC=N(OR′)-2(O)C10H6})}] [R′ = CH2CH2Cl, CH2Ph, (CH2)4Br] in good yields

Sintesi, reattivita e caratterizzazione di composti quadrato planari di Pt(II), contenenti trifenilfosfina ed ossime aromatiche.

Sulla base di quanto esposto e nell’ambito di una linea di ricerca già avviata in precedenza, in questo lavoro di tesi verranno preparati composti di Pt(II) caratterizzati dal legante trifenilfosfina ed ossime aromatiche. I leganti arilaldossimici verranno preparati sfruttando sintesi note a partire dalle opportune aldeidi aromatiche e verranno impiegati nella reazione di bridge-splitting del complesso dinucleare trans-[Pt(μ-Cl)Cl(PPh3)]2. La reazione verrà seguita spettroscopicamente e gli equilibri coinvolgenti la geometria delle specie formate saranno studiati in soluzione. Dei prodotti preparati sarà valutata la solubilità ed eventualmente la stabilità in mezzo idroalcolico o in dimetilsolfossido. Nei casi possibili, l’attività antiproliferativa in vitro verrà valutata su opportuni ceppi cellulari, in collaborazione con il gruppo di ricerca della Prof.sa Lisa Dalla Via, presso l’università di Padova. A lato di questo studio, verranno effettuate prove preliminari di reattività dei sistemi ottenuti, al fine di sfruttare a scopi sintetici l’acidità del raggruppamento ossidrilico del gruppo ossimico

Platinum(II) complexes bearing triphenylphosphine and chelating oximes: antiproliferative effect and biological profile in resistant cells

Platinum(II) complexes of the type [Pt(Cl)(PPh3){(\u3ba2-N,O)-(1{C(R)=N(OH)-2(O)C6H4})}] with R = Me, H, (1 and 2) were synthesized and characterized. Single crystal X-ray diffraction confirmed for 1 the proposed (SP4-3) configuration. The study of the antiproliferative activity, performed on a panel of human tumor cell lines and on mesothelial cells, highlighted complex 2 as the most effective. In particular, it showed a remarkable cytotoxicity on ovarian carcinoma cells (A2780) and interestingly, a significant antiproliferative effect on cisplatin resistant cells (A2780cis). The investigation on the intracellular mechanism of action demonstrated for 2 a lower ability to platinate DNA with respect to cisplatin, taken as reference, and a notably higher uptake in resistant cells. A significant accumulation in mitochondria, along with the ability to induce concentration-dependent mitochondrial membrane depolarization and intracellular reactive oxygen species production, allowed us to propose a mitochondria-mediated pathway as responsible for the interesting cytotoxic profile of complex 2

Platinum(II) Complexes Bearing Triphenylphosphine and Chelating Oximes: Antiproliferative Effect and Biological Profile in Resistant Cells

Platinum(II) complexes of the type [Pt(Cl)(PPh3){(κ2-N,O)-(1{C(R)=N(OH)-2(O)C6H4})}] with R = Me, H, (1 and 2) were synthesized and characterized. Single crystal X-ray diffraction confirmed for 1 the proposed (SP4-3) configuration. The study of the antiproliferative activity, performed on a panel of human tumor cell lines and on mesothelial cells, highlighted complex 2 as the most effective. In particular, it showed a remarkable cytotoxicity on ovarian carcinoma cells (A2780) and interestingly, a significant antiproliferative effect on cisplatin resistant cells (A2780cis). The investigation on the intracellular mechanism of action demonstrated for 2 a lower ability to platinate DNA with respect to cisplatin, taken as reference, and a notably higher uptake in resistant cells. A significant accumulation in mitochondria, along with the ability to induce concentration-dependent mitochondrial membrane depolarization and intracellular reactive oxygen species production, allowed us to propose a mitochondria-mediated pathway as responsible for the interesting cytotoxic profile of complex 2