Consuelo Vicente

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.

Novel bis-C,N-cyclometalated iridium(III) thiosemicarbazide antitumor complexes: interactions with human serum albumin and DNA, and inhibition of cathepsin B.

A series of new organoiridium(III) complexes [Ir(N-C)(2)(N-S)]Cl (HN-C = 2-phenylpyridine (Hppy), N-S = methyl thiosemicarbazide (1), phenyl thiosemicarbazide (2) and naphtyl thiosemicarbazide (3)) have been synthesized and characterized. The crystal structure of (1) has been established by X-ray diffraction, showing the thiosemicarbazide ligand bound to the iridium atom as N,S-chelate. The cytotoxicity studies show that they are more active than cisplatin (about 5-fold) in T47D (breast cancer) at 48 h incubation time. On the other hand, very low resistance factors (RF) of 1-3 in A2780cisR (cisplatin-resistant ovarian carcinoma) at 48 h were observed (RF ≈ 1). Ir accumulation in T47D cell line after 48 h continuous exposure for complexes 1-3 are higher than that corresponding to cisplatin (about 10 times). The complexes 1-3 bind strongly to HSA with binding constants of about 10(4) M(-1) at 296 K, binding occurring at the warfarin site I for 2. Complexes 2 and 3 are also capable of binding in the minor groove of DNA as shown by Hoechst 33258 displacement experiments. Furthermore, complex 2 is also a good cathepsin B inhibitor (an enzyme implicated in a number of cancer related events), being the enzyme reactivated by cysteine.

Synthesis and Antiproliferative Activity of a C,N-Cycloplatinated(II) Complex with a Potentially Intercalative Anthraquinone Pendant

The synthesis of the novel anthraquinone platinum derivate [Pt(ppy)Cl(1C3)] (2) [Hppy = N,C-chelating 2-phenylpyridine; 1C3 = 1-[(3-aminopropyl)amino]-anthracene-9,10-dione] and its values of IC(50) against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D) are reported. At 24 h incubation time, complex 2 was more active than cisplatin (about 9-fold) and the free ligand 1C3 (about 2-fold) in T47-D. The observation that the cisplatin IC(50) falls by about 10-fold from 24 to 72 h, whereas that for 2 changes little, suggests substantial differences in the mode of action. Complex 2 also showed high cytotoxicity against A2780 (about 3-fold greater than cisplatin at 24 h). On the other hand, very low resistance factors (RF) of 2 in A2780cisR at 24-72 h (RF = 1.3) were observed. The interaction of 2 with DNA was followed by electrophoretic mobility and UV-visible spectroscopy, and its reaction with the model nucleobase 9-EtG was studied by (1)H NMR and ESI-MS. Theoretical calculations at the B3LYP/def2-TZVPP//BP86/def2-TZVP level of theory on complex 2 show a labile Pt-Cl bond that allows easy replacement of Cl by N-nucleophiles such as 9-EtG, which forms a stronger Pt-N bond.

Synthesis and reactivity of hydroxo-bridged binuclear platinum complexes. Crystal structure of [NBu4]2[{Pt(C6F5)2(µ-OH)}2]

The reaction of [NBu4]2[{Pt(C6X5)2(µ-Cl)}2] with NBu4OH(aq) in acetone leads to the formation of the hydroxo-complexes [NBu4]2[{Pt(C6X5)2(µ-OH)}2](X = F 1 or Cl 2). These react with weak protic acids such as acetylacetone (Hacac), benzoylacetone (Hbzac) and 8-hydroxyquinoline (Hquin) yielding the mononuclear complexes [NBu4][Pt(C6X5)2(L–L)](X = F, L–L = acac 3, bzac 4, or quin 5; X = Cl, L–L = acac 6, bzac 7, or quin 8). Treatment of complexes 1 and 2 with PhCN in the presence of HBF4 gives the mononuclear compounds cis-[Pt(C6X5)2(PhCN)2](X = F 9 or Cl 10). When the benzonitrile complexes are treated with aniline the corresponding cis-[Pt(C6X5)(NH2Ph)2](X = F 11 or Cl 12) are formed. The benzamido derivatives [NBu4][Pt(C6X5)2(HNOCPh)(H2O)](X = F 13 or Cl 14) are formed when complexes 9 and 10 are treated with NBu4OH(aq) in acetone, and thermal treatment of 13 yields [NBu4]2[{Pt(C6F5)2(µ-HNOCPh)}2]15. Complexes 9 and 10 react with methanol in the presence of NBu4OH to give the corresponding imido ester derivatives [Pt(C6X5)2{HNC(OMe)Ph}2](X = F 16 or Cl 17). Spectroscopic (IR, 1H and 19F) data have been used for structural assignments, and an X-ray structure determination carried out for [NBu4]2[{Pt(C6F5)2(µ-OH)}2] has established the centrosymmetric binuclear nature of the anion [(C6F5)2Pt(µ-OH)2Pt(C6F5)2]2–. The structure has been solved and refined up to R= 0.049 and R′= 0.056 based on 2278 observed reflections. The Pt atoms are four-co-ordinated and show slight deviations from a square-planar arrangement.

Synthesis of palladium(II) and platinum(II) N,N-dialkyldithiocarbamates starting from hydroxo-halophenyl complexes

Abstract In dichloromethane, the hydroxo-complexes [NBu4]2[{M(C6X5)2(μ-OH)}2] [M = Pd (X = F or Cl) or Pt (X = F)] and [{Pd(C5X5)(PPh3)(μ-OH)}2] (X = F or Cl) react with amines in the presence of carbon disulfide to give the corresponding dithiocarbamate complexes [NBu4][M(C6X5)2(S2CNR2)] [M = Pd, X = F and R Me (I), Et (II), or C4H8 (III); M = Pd, X = Cl and R = Me (IV) or Et (V); M = Pt, X = F and R = Me (VI) or Et (VII)] and [Pd(C6X5)(PPh3)(S2CNR2)] [X = F and R = Me (VIII) or Et (IX); X = Cl and R = Me (X) or Et (XI)]. Conductance measurements and spectroscopic (IR, 1H and 19F NMR) methods have been used for structural assignments.

Synthesis and characterization of hydroxo, pyrazolato and carboxylato derivatives of the PdR(PPh3) moiety (R = C6F5 or C6Cl5)

Abstract The hydroxo-complexes [{PdR(PPh 3 )(μ-OH)} 2 ] (R  C 6 F 5 or C 6 Cl 5 ) have been obtained by reaction of the corresponding [{PdR(PPh 3 )(μ-Cl)}2] complexes with NBu 4 OH in acetone. In this solvent, the reaction of the hydroxo-bridged complexes with pyrazole (Hpz) and 3,5-dimethylpyrazole (Hdmpz) in 1:2 molar ratio leads to the formation of the new complexes [{Pd(C 5 F 5 )(PPh 3 )(μ-azolate)}2] and [{Pd(C 6 Cl 5 )(PPh 3 )} 2 (μ-OH)(μ-azolate)] (azolate = pz or dmpz). The reaction of the bis(μ-hydroxo) complexes with Hpz and Hdmpz in acetone in 1:1 molar ratio has also been studied, and the resulting product depends on the organic radical (C 6 F 5 or C 6 Cl 5 ) as well as the azolate (pz or dmpz). The identity of the isomer obtained has been established in every case by NMR ( 1 H, 19 F and 31 P) spectroscopy. The reaction of the bis(μ-hydroxo) complexes with oxalic (H 2 Ox) and acetic (HOAc) acids yields the binucle ar complexes [{PdR(PPh 3 )}2(μ-Ox)] (R  C 6 F 5 or C 6 Cl 5 ) and [{Pd(C 6 F 5 )(PPh 3 )(μ-OAc)}2], respectively. [{Pd(C 6 F 5 )(PPh 3 )(μ-OH)} 2 ] reacts with PPh 3 in acetone in 1:2 ratio giving the mononuclear complex trans -[Pd(C 6 F 5 ) (OH)(PPh 3 ) 2 ], whereas the pentachlorophenylhydroxo complex does not react with PPh 3 , even under forcing conditions.

New methoxo-, hydroxo- and pyrazolate-bridged platinum(II) complexes. Crystal structure of [NBu4]2[{Pt(C6F5)2}2(µ-OH)(µ-dmpz)](dmpz = 3,5-dimethylpyrazolate)

The hydroxo complex [{Pt(C6F5)2(µ-OH)}2]2– reacts with azoles (1 : 1 molar ratio) in benzene to give the double bridged complexes [{Pt(C6F5)2}2(µ-OH)(µ-L–L)]2–[L–L = pyrazolate (pz)1, 3,5-dimethyl-pyrazolate (dmpz)2, 3-methylpyrazolate (mpz)3 or indazolate(indz)4]. When the same reaction is carried out in methanol with the reactants in 1 : 2 molar ratio the corresponding di-µ-azolate derivatives [{Pt(C6F5)2(µ-L–L)}2]2–[L–L = pz 5, dmpz 6, mpz 7 or indz 8] are obtained. On treatment of [{Pt(C6F5)2(µ-OH)}2]2– with methanol the di-µ-methoxo complex [{Pt(C6F5)2(µ-OMe)}2]2–9 was obtained. The di-µ-azolate complexes 5–8 can be alternatively prepared by treatment of 9 with the respective azoles (1 : 2 molar ratio) in methanol. Reaction of complex 1 with methanol leads to the formation of [{Pt(C6F5)2}2(µ-OMe)(µ-pz)]2–10. All the complexes have been isolated as the [NBu4]+ salts. Spectroscopic (IR, 1H and 19F NMR) data have been used for structural assignments, and an X-ray structure determination carried out for [NBu4]2[{Pt(C6F5)2}2(µ-OH)(µ-dmpz)] has established the binuclear nature of the anion. The structure was solved and refined to R= 0.057 and R′= 0.089 based on 10 057 observed reflections. The Pt atoms are four-co-ordinated, Pt(1)–O 2.113(7), Pt(1)–N(1) 2.04(1), Pt(1)–C(10) 2.02(1), Pt(1)–C(20) 1.96(2), Pt(2)–O 2.077(9), Pt(2)–N(2) 2.075(9), Pt(2)–C(30) 1.97(2), Pt(2)–C(40) 2.00(1)A, and show deviations from a square-planar arrangement towards a tetrahedral disposition.

Synthesis of hydroxo-organo-complexes of the nickel group elements

The considerable nucleophilicity of the OH bridges in the new hydroxo complexes [(C6F5)2M(µ-OH)2M(C6F5)2]2–(M = Ni, Pd, Pt) is indicated by high field proton resonances and the formation of µ-pyrazolate derivatives from [(C6F5)Ni(µ-OH)2Ni(C6F5)2]2–.

New aliphatic and aromatic thiolato-bridged complexes of palladium(II) and platinum(II)

Abstract The hydroxo binuclear complexes [NBu 4 ] 2 [}M(C 6 F 5 ) 2 (μ-OH){ 2 ] (M = Pd or Pt) react with thiols in methanol at room temperature to give the binuclear di-μ-thiolato complexes [NBu 4 ] 2 [}M(C 6 F 5 ) 2 (μ-SR){ 2 ] (M = Pd, R = Et 1 , t-Bu 2 , C 6 H 5 , 3 , and p -MeC 6 H 4 4 ; M = Pt, R = Et 5 , t-Bu 6 , C 6 H 5 7 or p -MeC 6 H 4 8 ). The trinuclear palladium complexes [NBu 4 ] 2 [(C 6 F 5 ) 2 Pd(μ-SEt) 2 Pd(μ-SEt) 2 Pd(C 6 F 5 ) 2 ] 9 or [NBu 4 ] 2 [(C 6 5 ) 2 Pd(μ-1,2-S 2 C 6 H 4 )Pd(μ-1,2-S 2 C 6 H 4 )Pd(C 6 F 5 ) 2 ] 10 have been obtained by reaction of the binuclear hydroxo palladium complex [NBu 4 ] 2 [}Pd(C 6 F 5 ) 2 (μ-OH){ 2 ] with an excess of EtSH in refluxing methanol or with an excess of C 6 H 4 (SH) 2 -1,2, in methanol at room temperature, respectively. The mixed hydroxo-axolate bridged complexes [}M(C 6 F 5 ) 2 { 2 (μ-OH)(μ-L)] 2− M = Pd, L = pyrazolate (pz); M = Pt, L = pyrazolate (pz) or 3,5-dimethylpyrazolate (dmpz)]react with thiols (1 : 1 molar ratio) in methanol to give the corresponding mixed thiolato-azolate bridged palladium or platinum complexes [}M(C 6 F 5 ) 2 { 2 (μ-SR)(μ-L)] 2− (M = Pd, L = dmpz, R = C 6 H 5 , 11 , p -MeC 6 H 4 12 ; M = Pt, L = pz, R = C 6 H 5 13 , p -MeC 6 H 4 , 14 , Et 15 , t-Bu 16 ; L = dmpz, R = C 6 H 5 17 , R = p -MeC 6 H 4 18 , Et 19 ]. The complexes have been characterized by partial elemental analyses, conductance measurements and spectroscopic (IR and 1 H and 19 F NMR) methods.

Organometallic diaqua complexes of palladium(II)

Abstract The protonation of [(C6F5)LPd(μ-OH)2PdL(C6F5)] by triflic acid (CF3SO3H) results in the formation of the diaqua complexes [Pd(C6F5)L(H2O)2][CF3SO3] (L=PPh3 (1) or AsPh3 (2)). The crystal structure of 2 was elucidated by X-ray diffraction analysis revealing the presence of tetrameric units involving hydrogen bonds.