Platinum(IV) Metallacrown Ethers: Synthesis, Structures, Host Properties and Anticancer Evaluation

Abstract

Platinum(IV) metallacrown ethers [PtBr 2 Me 2 {im(CH 2 CH 2 O) x CH 2 CH 2 im}] (im ) imidazol-1-yl; x ) 2-5, 7; 3-7) and [PtBr 2 Me 2 {bim(CH 2 CH 2 O) x CH 2 CH 2 bim}] (bim ) benzimidazol-1-yl; x ) 1, 2, 5, 7; 9-12) were synthesized via the reaction of [(PtBr 2 Me 2 ) n ] with the appropriate R,ω-bis(imidazol-1-yl) or R,ω-bis(benzimidazol-1-yl) polyether. Reactions with 1,2-bis(imidazol-1-yl)ethane, bis(2-(imidazol-1-yl)ethyl) ether, or 1,2-bis(benzimidazol-1-yl)ethane yielded the dinuclear complexes [(PtBr 2 Me 2 ) 2 {µ-im(CH 2 CH 2 O) x CH 2 CH 2 im} 2 ] (x ) 0, 1; 1, 2) and [(PtBr 2 Me 2 ) 2 {µ-bimCH 2 CH 2 bim} 2 ] (8), respectively. In addition, the diiodo complex [PtI 2 Me 2 {im(CH 2 CH 2 O) 2 CH 2 CH 2 im}] (13) was prepared from the reaction of [PtMe 2 (cod)] with I 2 in the presence of im(CH 2 CH 2 O) 2 CH 2 CH 2 im. Characterization by microanalysis and NMR spectroscopy, as well as X-ray crystal structure analysis of several of the metallacrown ethers (3, 5, 9 and 10) and dinuclear complexes (2 and 8), is described. The ability of the larger metallacrown ethers (5-7, 11 and 12) to act as hosts to either dibenzyl-or di-n-butylammonium ions is investigated in solution (NMR and ESI-MS). Finally, several of these metallacrown ethers were found to possess in Vitro antitumor activity on three tumor cell lines (liposarcoma, A549 and 518A2). The activity of these complexes, all of which were found to induce apoptotic cell death, is discussed relative to their structure and the findings of platinum uptake studies.

Synthesis, characterization and X-ray crystal structures of polyether and ethylene bridged bis(azolyl) platinum(II) complexes

“…The interplanar angles between least squares planes of the [PtCl 2 N 2 ] atoms and the imidazolyl rings of 6 are 64.2(1) and 35.0(2)°. An unusual feature of this structure is the arrangement of the imidazolyl rings such that the N1-CH-N2 and N3-CH-N4 are directed to the same side of the macroring and are not inverted relative to one another, as is the case in solid state structures with similar ligands [8,24]. Cl1 and C14 are in relatively close proximity (3.177(4) Å ) indicating the possibility of a weak hydrogen bond (C-HÁÁÁCl), which may be a stabilizing factor for this arrangement.…”

“…Finely divided pale yellow powder precipitated from the reaction mixture after stirring for 72 h. (s, 4H, C 10 H 2 ), 3.67 ('t', 4H, C 9 H 2 ), 4.38 ('t', 4H, C 8 H 2 ), 7.38 (m, 4H, CH Ar ), 7.49 (m, 2H, CH Ar ), 8.34(m, 4H, CH Ar ). 13 C NMR (100 MHz, CD 3 CN): d 46.7 (s, C 8 H 2 ), 67.6 (s, C 9 H 2 ), 70.8 (s, C 10 H 2 ), 112.2 (s, C 7 H), 124.5 (s, CH Ar ), 125.6 (s, 2xCH Ar ); C 3a/7a , C 2 H not observed.…”

“…The interplanar angles of the least squares planes of the [PtCl 2 N 2 ] atoms and the imidazolyl rings in 5 are 58.3(3) and 47.4(3)°. L5 has been found to adopt a bridging coordination mode with the platinum(IV) PtBr 2 Me 2 moiety and yielded a dinuclear complex, [(PtBr 2 Me 2 ) 2 (l-imCH 2 CH 2 OCH 2 CH 2 im) 2 ] [8]. The reasons for this difference in coordination mode are not obvious.…”

“…6.8 Å ) or four (maximum distance ca. 8.8 Å ) ethyleneoxy groups connecting the imidazol-1-yl moieties [8]. It is also marginally larger than other metallacrown ether rings with three ethyleneoxy groups due to both the cis coordination of the polyether ligand and the ligating imidazolyl rings connecting the polyether backbone to the transition metal as oppose to a single atom [1,7,23].…”

“…We have synthesized a number of platinum(IV) metallacrown ether complexes bearing a,x-bis(imidazol-1-yl) polyether ligands [8]. However, bis(imidazol-1-yl) polyether compounds containing more than four ethyleneoxy groups on the ligand backbone did not react with K 2 [PtCl 4 ] to yield the corresponding platinum(II) metallacrown ether complexes and analogous reactions with bis(pyrazol-1-yl) polyether ligands gave inconsistent results.…”