Quantitative structure activity relationships for some antitumor platinum(II) complexes

The INDO–SCF method is used to provide electronic indices which are used as independent variables. These attempt to account for the variation in the antitumor activity and toxicity observed within a series of analogs of cis-diamino dichloro platinum(II).     

Two copper(II) complexes of curcumin derivatives: synthesis,crystal structure and in vitro antitumor activity

Two Cu(II) complexes of curcumin derivatives, formulated as CuL ₂ ^a (1) and CuL ₂ ^b (2) [HL^a = 1,7-bis(4-ethyloxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione and HL^b = 1,7-bis(4-butyloxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione], have been synthesized and characterized by single-crystal X-ray diffraction, along with physicochemical and spectroscopic methods. In both complexes, each Cu(II) center is surrounded by four oxygen atoms from two β-diketone ligands in a square planar geometry. Complex 1 forms a 2D layer structure through intermolecular π–π stacking interactions, as well as weak coordination interactions between the Cu and O atoms of the solvent 1,4-dioxane molecules. Complex 2 displays a 1D column structure stabilized by intermolecular π–π stacking interactions. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays were used to evaluate the cytotoxicities of these complexes against three human cancer cell lines. The results show that the Cu(II) complexes exhibit more potent inhibition tumor growth in comparison with the free ligands.     

Triamine-type complexes of platinum(II) and their antitumor properties

Triamines of platinum(II) (Pt(NH₃)₂LCl]Cl with a cis-structure (L represents cytosine, cytidine, isocytosine, theobromine, theophylline) and cis- and trans-isomers with theophylline and inosine were synthesized. The coordination formulas were demonstrated by methods of conductometry and long-wave spectroscopy. The coordination of pyrimidines through the N(3) atoms and purines through the N(7) atoms was established by PMR methods. An intensification of the acidic properties of the NH group of the ligands upon coordination with platinum was demonstrated. Cis-triamines have an antitumor effect on solid tumors and leukemias, which permits them to be assigned to a new class of water-soluble cationic monofunctional antitumor complexes of platinum(II).Leningrad Chemicopharmacological Institute. Translated from Teoreticheskaya i Éksperimental'naya Khimiya, No. 3, pp. 354–361, May–June, 1991. Original article submitted March 11, 1991.     

The first acetimino complexes of Rh(III). 4-imino-2-methylpentan-2-amino-Rh(III) complexes through metal-assisted intramolecular aldol-type condensation of two acetimino ligands

[Rh(Cp)Cl(mu-Cl)](2) (Cp = pentamethylcyclopentadienyl) reacts (i) with [Au(NH=CMe(2))(PPh(3))]ClO(4) (1:2) to give [Rh(Cp)(mu-Cl)(NH=CMe(2))](2)(ClO(4))(2) (1), which in turn reacts with PPh(3) (1:2) to give [Rh(Cp)Cl(NH=CMe(2))(PPh(3))]ClO(4) (2), and (ii) with [Ag(NH=CMe(2))(2)]ClO(4) (1:2 or 1:4) to give [Rh(Cp)Cl(NH=CMe(2))(2)]ClO(4) (3) or [Rh(Cp)(NH=CMe(2))(3)](ClO(4))(2).H(2)O (4.H(2)O), respectively. Complex 3 reacts (i) with XyNC (1:1, Xy = 2,6-dimethylphenyl) to give [Rh(Cp)Cl(NH=CMe(2))(CNXy)]ClO(4) (5), (ii) with Tl(acac) (1:1, acacH = acetylacetone) or with [Au(acac)(PPh(3))] (1:1) to give [Rh(Cp)(acac)(NH=CMe(2))]ClO(4) (6), (iii) with [Ag(NH=CMe(2))(2)]ClO(4) (1:1) to give 4, and (iv) with (PPN)Cl (1:1, PPN = Ph(3)P=N=PPh(3)) to give [Rh(Cp)Cl(imam)]Cl (7.Cl), which contains the imam ligand (N,N-NH=C(Me)CH(2)C(Me)(2)NH(2) = 4-imino-2-methylpentan-2-amino) that results from the intramolecular aldol-type condensation of the two acetimino ligands. The homologous perchlorate salt (7.ClO(4)) can be prepared from 7.Cl and AgClO(4) (1:1), by treating 3 with a catalytic amount of Ph(2)C=NH, in an atmosphere of CO, or by reacting 4with (PPN)Cl (1:1). The reactions of 7.ClO(4) with AgClO(4) and PTo(3) (1:1:1, To = C(6)H(4)Me-4) or XyNC (1:1:1) give [Rh(Cp)(imam)(PTo(3))](ClO(4))(2).H(2)O (8) or [Rh(Cp)(imam)(CNXy)](ClO(4))(2) (9), respectively. The crystal structures of 3 and 7.Cl have been determined.     

New palladium(II) and platinum(II) complexes with the model nucleobase 1-methylcytosine: antitumor activity and interactions with DNA

Palladium and platinum complexes with the model nucleobase 1-methylcytosine (1-Mecyt) of the types [Pd(N-N)(C6F5)(1-Mecyt)]ClO4 [N-N = bis(3,5-dimethylpyrazol-1-yl)methane (bpzm), bis(pyrazol-1-yl)methane (bpzm), N,N,N',N'-tetramethylethylenediamine (tmeda), or 2,2'-bipyridine (bpy)] and [M(dmba)(L')(1-Mecyt)]ClO4 [dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl; L' = PPh(3) (M = Pd or Pt), DMSO (M = Pt)] have been obtained. Palladium and platinum complexes of the types cis-[M(C6F5)2(1-Mecyt)2] (M = Pd or Pt) and cis-[Pd(L')(C6F5)(1-Mecyt)2]ClO4 (L' = PPh(3) or t-BuNC) have also been prepared. The crystal structures of [Pd(bpzm)(C6F5)(1-Mecyt)]ClO4, [Pt(dmba)(DMSO)(1-Mecyt)]ClO4, cis-[Pd(C6F5)2(1-Mecyt)2], and cis-[Pd(t-BuNC)(C6F5)(1-Mecyt)2]ClO4 have been established by X-ray diffraction. There is extensive hydrogen bonding (N-H...O, C-H...F or C-H...O) in all the compounds. There are also intermolecular pi-pi interactions between pyrimidine rings of adjacent chains in [Pd(C6F5)2(1-Mecyt)2]. DNA adduct formation of the new complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pBR322 were also obtained. Values of IC(50) were also calculated for the new complexes against the tumor cell line HL-60. At a short incubation time (24 h) almost all new complexes were more active than cisplatin.     

Traceable platinum(II) complexes with alkylene diamine-derived ligands: synthesis,characterization and in vitro studies

Diiodido- (6a/6b) and dichloridoplatinum(II) complexes (7a/7b) with fluorescent ligands 2-[(2-aminoethyl)amino]ethyl-2-(methylamino)benzoate (5a) and 2-amino-1-(aminoethyl)ethyl-2-(methylamino)benzoate (5b) were prepared and characterized by elemental analysis, ESI-MS analysis, fluorescence spectrometry, as well as ¹H, ¹³C, and ¹⁹⁵Pt NMR spectroscopy. All compounds have been tested against A2780 ovarian cancer, A549 lung carcinoma, and HT-29 colon cancer cell lines using sulforhodamine-B assay. The activity increased from ligand precursors, diiodido- to dichloridoplatinum(II) complexes, except against HT-29 cell line where diiodido and dichlorido expressed similar activity. These compounds enter the tumor cells and emit a bright fluorescence at ca. 470 nm, mainly targeting nuclei.     

X-ray structures of the first platinum complexes with Z configuration iminoether ligands: trans-dichlorobis(1-imino-1-methoxy-2,2'-dimethylpropane)platinum(II) and trans-tetrachlorobis(1-imino-1-methoxy-2,2'-dimethylpropane)platinum(IV)

Platinum complexes with Z configuration iminoether ligands (trans-[PtCl(2)(HN=C(OMe)Bu(t))(2)], 1, and trans-[PtCl(4)(HN=C(OMe)Bu(t))(2)], 2) have been structurally characterized for the first time. The nearly planar Pt-N-C-O-C chain, all atoms being in gauche conformation, brings the terminal Pt and C atoms very close to one another. The steric clash is released by considerably increasing the Pt-N-C, N-C-O, and C-O-C bond angles (133, 124, and 121 degrees for 1, respectively; 147, 129, and 127 degrees for 2, respectively), which are well above the expected values (120 degrees for Pt-N-C and N-C-O; less than 120 degrees for C-O-C owing to the repulsive effect exerted by the lone pair of electrons on the oxygen atom). In the platinum(II) case the smaller increase of bond angles is accompanied by a greater value of the Pt-N-C-O torsion angle (27.3 and 15.6 degrees for 1 and 2, respectively). The stabilization of the Z configuration, notwithstanding the steric clashes described above, has been achieved by a careful choice of the R substituent in the iminoether moiety (a bulky tert-butyl group). The reactions of the platinum(IV) species (2) in basic and acidic conditions and with triphenylphosphine have been investigated. Bases and acids both interact with the coordinated ligand in such a way to weaken the coordinative bond and promote the release of the iminoether ligands. The phosphine promotes a ready and complete reduction of the platinum(IV) complex to the corresponding platinum(II) species (1). Compound 1 reacts with a stoichiometric amount of phosphine (1:1 molar ratio) to form cis-[PtCl(2)(PPh(3))(Z-HN=C(OMe)Bu(t))] and with excess phosphine to form [PtCl(2)(PPh(3))(2)] and free iminoether. The latter two reactions leading to formation of a mixed phosphine/iminoether platinum species and to free iminoether, which can be used as a synthon for further organic transformations, can be of synthetic utility.     

New palladium(II) and platinum(II) complexes with 9-aminoacridine: structures, luminiscence, theoretical calculations, and antitumor activity

The new complexes [Pd(dmba)( N10-9AA)(PPh 3)]ClO 4 ( 1), [Pt(dmba)( N9-9AA)(PPh 3)]ClO 4 ( 2), [Pd(dmba)( N10-9AA)Cl] ( 3), and [Pd(C 6F 5)( N10-9AA)(PPh 3)Cl] ( 4) (9-AA = 9-aminoacridine; dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl) have been prepared. The crystal structures have been established by X-ray diffraction. In complex 2, an anagostic C-H...Pt interaction is observed. All complexes are luminescent in the solid state at room temperature, showing important differences between the palladium and platinum complexes. Complex 2 shows two structured emission bands at high and low energies in the solid state, and the lifetimes are in agreement with excited states of triplet parentage. Density functional theory and time-dependent density functional theory calculations for complex 2 have been done. Values of IC 50 were also calculated for the new complexes 1- 4 against the tumor cell line HL-60. All of the new complexes were more active than cisplatin (up to 30-fold in some cases). The DNA adduct formation of the new complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pB R322 were also obtained.     

Tetrakis(thione)platinum(II) complexes: synthesis,spectroscopic characterization,crystal structures,and in vitro cytotoxicity

A new series of platinum(II) complexes based on thione ligands with general formula [Pt(thione)₄]X₂ (X^??=?Cl^?, NO₃^?) has been synthesized and characterized using CHNS elemental analysis, infrared, ¹H and ¹³C solution-state NMR as well as ¹³C and ¹⁵N solid-state NMR spectroscopy, and X-ray crystallography. The spectroscopic methods confirm the coordination of Pt(II) with thiocarbonyl groups via sulfur of the thione ligands. The X-ray structures showed a distorted square planar geometry for 1, [Pt(MeImt)₄]Cl₂ (MeImt = N-Methylimidazolidine-2-thione) while the hydrogen bonding interactions in 7, [Pt(iPrImt)₄](NO₃)₂·0.6(H₂O) induce a bent see-saw distortion relative to the ideal square planar geometry. The in vitro cytotoxicity studies showed that 2, [Pt(EtImt)₄]Cl₂ is generally the most effective, a two-fold better cytotoxic agent than cisplatin and carboplatin against MCF7 (human breast cancer).     

Synthesis,structure and in vitro anticancer activity of ruthenium(II) and platinum(II) complexes with chiral aminophosphine ligands

Transition Metal Chemistry - (R)-[Ru(η6-p-MeC6H4iPr)Cl2{Ph2PNHCH(CH3)(C6H4-4-F)}] (1) and cis-(R,R)-[PtCl2{Ph2PNHCH(CH3)(C6H4-4-F)}2] (2) have been obtained by the reaction of the chiral...     

Platinum(II) and platinum(IV) complexes of 2-amino-4, 6-dimethylpyrimidine

Summary Platinum(II) and platinum(IV) complexes of 2-amino-4, 6-dimethylpyrimidine, ADMPY, have been prepared. Solids of formula Pt(ADMPYH⁺)Cl₃, Pt(ADMPY)₂Cl₄ and Pt(ADMPY)₂Cl₄·2HCl have been isolated and characterized by elemental analyses in conjuction with i.r. and n.m.r. spectra. A paramagnetic tan to reddishbrown complex has been reproducibly prepared from the direct reaction of K₂PtCl₄ and ADMPY at pH 6.     

Cobalt(II) complexes bearing 2-imino-1,10-phenanthroline ligands: synthesis, characterization and ethylene oligomerization

A series of cobalt(II) complexes containing 2-imino-1,10-phenanthrolines have been synthesized and characterized by elemental and spectroscopic analysis. The molecular structures of complexes 2, 3, 8 and 14 were confirmed by X-ray diffraction analysis. On treatment with methylaluminoxane (MAO) or modified methylaluminoxane (MMAO), these cobalt(II) complexes show moderate to high catalytic activities for ethylene oligomerization and butene predominates among the oligomers produced. The parameters of the reaction conditions and the effects of the ligands environment were investigated. To cite this article: S. Jie et al. C. R. Chimie 9 (2006).     

Preparation,spectral characterization,in vitro antitumor and thermal studies of new platinum(IV) and palladium(II) thiohydrazone complexes

Pt^IV and Pd^II complexes [Pt(L)₂Cl₂] and [Pd(HL)Cl₂] [HL = salicyclaldehyde morpholine N-thiohydrazone (HL¹), benzaldehyde morpholine N-thiohydrazone (HL²), acetophenone morpholine N-thiohydrazone (HL³), p-methylacetophenone morpholine N-thiohydrazone (HL⁴), cinnamaldehyde morpholine N-thiohydrazone (HL⁵), cyclohexanone morpholine N-thiohydrazone (HL⁶), benzaldehyde aniline N-thiohydrazone (HL⁷), benzaldehyde N-(methyl, cyclohexyl)-thiohydrazone (HL⁸) and benzaldehyde N-(ethyl, cyclohexyl)-thiohydrazone (HL⁹)] were prepared in MeOH and characterized by elemental analysis, i.r., electronic, ¹H-n.m.r. and ¹³C-n.m.r. spectral data. For some of the complexes cyclic voltammetric and thermal studies were carried out. The in vitro antitumor activity of some complexes was measured.     

Palladium(II) and platinum(II) halide complexes with 2,6-dimethyl-4H-pyran-4-thione

Summary 2,6-Dimethyl-4H-pyran-4-thione (DMTP) acts as a sulphur donor towards Pt^II and Pd^II halides yielding adducts of general formula [M(DMTP)₂X₂] (M=Pd or Pt; X=Cl, Br or I). When complex syntheses are performed in benzene, the solvated species [M(DMTP)₂X₂]·C₆H₆ (M=Pd or Pt; X=Cl or Br) are obtained. The compounds have been characterized by i.r. and n.m.r. (¹H and¹³C) spectroscopy and by thermogravimetric data. The adduct geometry and the influence of benzene are discussed.     

Perfluoroalkylphosphine coordination chemistry of platinum: synthesis of (C2F5)2PPh and (C2F5)PPh2 complexes of platinum(II)

A 1:1 addition of Ph2PCl to an ethereal solution of C2F5Li (formed from the reaction of BuLi with C2F5Cl) yields Ph2P(C2F5)(abbreviated pfepp) (1). The introduction of a fluoroethyl group results in a phosphine with electronic characteristics that approximate phosphites, bridging the electronic gap between traditional donor phosphine ligands and more electrophilic phosphine ligands like PhP(C2F5)2 (2). The pfepp ligand 1 is isolated as a high boiling liquid, which crystallizes upon standing at room temperature in an inert atmosphere. A series of Pt(II) complexes of the type trans-L2PtCl2 (L = pfepp 3; PhP(C2F5)2 4) have been prepared and structurally characterized by multinuclear NMR, IR and X-ray crystallography. The crystal structure of is the first example of a structurally characterized monodentate phosphine with a pentafluoroethyl pendant group.     

Heterobimetallic complexes of platinum(II) with diferrocenylphenylphosphine and their in vitro activity against P388 leukaemia

Four platinum(II) complexes of the general formula cis‐[Pt{(Ferr)₂PhP}(DMSO)X₂], where X₂ = Cl₂, C₂O₄, O₂(CO)₂(C₆H₁₁)₂ and O₂(CO)₂CCH₂CH₂CH₂, have been synthesized and­characterized physicochemically and spec‐­troscopically as the first heterobimetallic platinum(II) complexes with the ligand diferrocenylphenylphosphine (Ferr = ferrocenyl). These complexes were tested in vitro against leukaemia cell line P388 using the MTT assay. The results obtained were compared with those of cisplatin, carboplatin, oxaliplatin and 5‐fluorouracil. Copyright © 1999 John Wiley & Sons, Ltd.     

Metallomesogens based on platinum(II) complexes: synthesis, luminescence and polarized emission

Two series of heteroleptic cyclometalated platinum(II) complexes [(C(n)Oppy)Pt(acac) and (C(n)OFppy)Pt(acac)] have been prepared. Their liquid-crystal and optophysical properties were studied, in which C(n)Oppy is 2-(4-alkoxyphenyl)-5-(alkoxymethyl)pyridine and C(n)OFppy is 2-(3-fluoro-4-alkoxyphenyl)-5-(alkoxymethyl)pyridine. Only the heteroleptic cyclometalated platinum(II) complexes (n = 12 and 16) exhibited enantiotropic mesophase transitions with smectic (S(m)) structure. Intense polarized luminescence with a maximum peak at 532 nm and a polarization ratio as high as 10.5 were obtained in an aligned polyimide film under opto-excitation at room temperature. This research work provides a simple approach to realize high-efficiency polarized emission by heteroleptic cyclometalated platinum(II) complexes.     

Synthesis,characterization, and antitumor activity of novel tumor-targeted platinum(IV) complexes

Four tumor-targeted platinum(IV) complexes with ammonia and cyclohexylamine as the carrier groups and biotin as the axial group were designed, synthesized, and characterized. In vitro evaluation of the antitumor activity of complexes C1–C4 against lung cancer cells (A549), liver cancer cells (SMMC-7721), breast cancer cells (MCF-7), and colon cancer cells (SW480) was carried out. Complex C3 had the best cellular activity. Compared with cisplatin, complex C3 showed good anticancer activity against A549 cell line,complex C3 (6.34±0.44) is 3 times more cytotoxic than cisplatin (19.40±0.71),and against MCF-7 cell line complex C3 (4.22±0.11) is 5.4 times more cytotoxic than cisplatin (22.96±0.58), and against SW480 cell line complex C3 (6.65±0.60) is 3.4 times more cytotoxic than cisplatin (23.15±0.22). (Table 1) Axial chloride increased the redox power of complex C3 to increase the intercellular accumulation and the introduction of mixed amine had the ability to overcome cisplatin resistance. Complex C3 works best on MCF-7, then SW480, A549, and SMMC-7721. Thus, complex C3 is targeted by the axial introduction of biotin.