α-Diimine homologues of cisplatin: synthesis, speciation in DMSO/water and cytotoxicity

The Pt( ii ) α-diimine complexes [PtCl 2 {κ 2 N -(HCNR) 2 }] (R = C 6 H 11 , 1 ; 4-C 6 H 10 OH, 2 ; 4-C 6 H 4 CH 3 , 3 ; 4-C 6 H 4 OH, 4 ) and [PtCl 2 {κ 2 N -(CH 3 CNOH) 2 }] ( 5 ) were prepared in 60–81% yields from the 1 : 1 molar reactions of cis -[PtCl 2 (DMSO) 2 ] with the appropriate α-diimin...

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Bibliographic Details
Published in:New journal of chemistry 2018, Vol.42 (21), p.17453-17463
Main Authors: Biancalana, Lorenzo, Batchelor, Lucinda K., Dyson, Paul J., Zacchini, Stefano, Schoch, Silvia, Pampaloni, Guido, Marchetti, Fabio
Format: Article
Language:English
Subjects:
Acetone
Admixtures
Aspirin
Crystal structure
Crystallography
Cytotoxicity
Esterification
Homology
Hydroxyl groups
Infrared spectroscopy
Kidneys
NMR spectroscopy
Single crystals
Sodium chloride
Speciation
Spectrum analysis
Synthesis
Toxicity
X-ray diffraction
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Summary:The Pt( ii ) α-diimine complexes [PtCl 2 {κ 2 N -(HCNR) 2 }] (R = C 6 H 11 , 1 ; 4-C 6 H 10 OH, 2 ; 4-C 6 H 4 CH 3 , 3 ; 4-C 6 H 4 OH, 4 ) and [PtCl 2 {κ 2 N -(CH 3 CNOH) 2 }] ( 5 ) were prepared in 60–81% yields from the 1 : 1 molar reactions of cis -[PtCl 2 (DMSO) 2 ] with the appropriate α-diimine, [HCN(R)] 2 (R = C 6 H 11 , L1 ; 4-C 6 H 10 OH, L2 ; 4-C 6 H 4 Me, L3 ; 4-C 6 H 4 OH, L4 ), or dimethylglyoxime (dmgH 2 ), in acetone at reflux. The reaction of cis -[PtCl 2 (DMSO) 2 ] with two molar equivalents of dmgH 2 and NEt 3 in methanol at reflux afforded the bis-dimethylglyoximato compound [Pt{κ 2 N , N ′-(ONC(CH 3 )C(CH 3 )NOH)} 2 ], [Pt(dmgH) 2 ], as an insoluble material, in 97% yield. The oxalato derivative [Pt(κ 2 O -C 2 O 4 ){κ 2 N -(HCN(C 6 H 11 )) 2 }], 6 , was obtained from the sequential treatment of 1 with AgNO 3 and Na 2 C 2 O 4 , in 61% yield. Attempts to functionalize 4 via esterification of the hydroxyl groups with aspirin (aspCO 2 H) led to [PtCl 2 {κ 2 N -(HCN(4-C 6 H 4 OCO-asp)) 2 }], 7 , in an admixture with 4 . All the products were characterized by elemental analysis, and IR and multinuclear NMR spectroscopy, and the molecular structures of 4·THF and 5 were elucidated by single crystal X-ray diffraction. NMR spectroscopic studies in DMSO or DMSO/water/NaCl evidenced the substantial stability of 1–2 at 37 °C over 72 hours, whereas 3–5 released their N , N -ligand. The cytotoxic activity of 1 , 2 and 6 was assessed on cisplatin sensitive and cisplatin resistant human ovarian carcinomas (A2780 and A2780cisR) and non-tumorigenic human embryonic kidney (HEK-293) cells. Compound 1 is moderately cytotoxic, whereas 2 and 6 did not display appreciable antiproliferative activity.
ISSN:1144-0546
1369-9261
DOI:10.1039/C8NJ04195D