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1.
Summary Peripheral blood lymphocytes of patients with Fanconi's anemia (FA) were tested for their susceptibility to chromosome breakage by cis-platinum(II)-diamminedichloride [cis-Pt(II)], cis-platinum(IV)diamminetetrachloride [cis-Pt(IV)], and trans-platinum(IV)diamminetetrachloride [trans-Pt(IV)]. Low doses (0.1 g/ml) of the DNA-DNA cross-linking agents cis-Pt(II) and cis-Pt(IV) dramatically increased the chromosome breakage level in FA cultures without affecting the controls. The predominantly DNA-protein cross-linking compound trans-Pt(IV), however, was much less effective in producing chromosomal damage in FA. The differential response of FA cells to cis-Pt(IV) and trans-Pt(IV) suggests that the high susceptibility of FA to bifunctional cross-linking agents is due to an impairment of the cells to tolerate DNA-DNA cross-links, rather than DNA-protein cross-links. 相似文献
2.
Elena Pantoja Steven van Zutphen Anthony L. Spek Jan Reedijk 《Inorganica chimica acta》2006,359(13):4335-4342
Asymmetric cis-platinum(II) complexes with isopropylamine and two different azole ligands were synthesized and characterized with different techniques. In addition, for one of the complexes the X-ray structure was determined. Cytotoxicity tests using several human tumor cell lines, including the cisplatin-sensitive cell line A2780 and its cisplatin-resistant analogue. These results were compared with the results obtained for the trans isomers of the presented complexes and a relation between the structure and the activity was established. It was found that complexes with cis geometry are less active than their trans analogues, in particular in the resistant cell line A2780R. However, complex 1 can overcome cisplatin resistance to a certain extent. In the interaction with GMP, the asymmetric cis-Pt(II) complexes react with similar rates as their trans analogues and they behave as bifunctional species. 相似文献
3.
Christian Tessier 《Inorganica chimica acta》2010,363(11):2652-2660
Pt(II) and Pd(II) compounds containing the free radical 4-aminoTEMPO (4amTEMPO) were synthesized and characterised by X-ray diffraction methods. The disubstituted complexes cis- and trans-Pt(4amTEMPO)2I2 were studied. The trans isomer was prepared from the isomerisation of the cis analogue. The two Pd(II) compounds trans-Pd(4amTEMPO)2X2 (X = Cl and I) were also characterised by crystallographic methods. A mixed-ligand complex cis-Pt(DMSO)(4amTEMPO)Cl2 was synthesized from the isomerisation of the trans isomer in hot water. Its crystal structure was also determined. In all the complexes, the 4amTEMPO ligand is bonded to the metal through the -NH2 group, since the nitroxide O atom is not a good donor atom for the soft Pt(II) and Pd(II) metals. The conformation of the 4-aminoTEMPO ligand was compared to those of the few reported structures in the literature. 相似文献
4.
Moschos Polissiou Minh Tan Phan Viet Maurice St-Jacques Theophile Theophanides 《Inorganica chimica acta》1985,107(3):203-210
The molecular mode of action leading to the anticancer activity of the drug cis-diamminedichloroplatinum(II), cis-DDP or cis-platinum is still the subject of speculation. In the present high field (400 MHz) 1H NMR study the results on coupling constants for cis- and trans-diammine bis(guanosine- 5′-monophosphate) and (d-guanosine-5′-monophosphate)platinum(II) complexes are presented and discussed. The 1H and 13C NMR chemical shifts obtained are consistent with the drug binding to N7 of each guanine. It has been found that the drug induces different conformational changes in the nucleotide from the trans-DDP isomer. 相似文献
5.
《Inorganica chimica acta》1986,124(2):87-96
Complexes formed in aqueous solution between cisplatin or hydrolysis species and 5′ adenosine monophosphate (AMP) or 5′ adenosine triphosphate (ATP), the latter with and without chloride ions, have been determined using 195Pt, 31P, 13C and 1H NMR. The present results lead to the conclusion that the only monodentate complexes with AMP are cis-Pt(NH3)2(AMP-N7)Cl at acid pH and cis-Pt(NH3)2(AMP-N7)OH at neutral and basic pH. Other bidentate complexes were identified as cis-Pt(NH3)2(AMP-N7)2 and cis-Pt(NH3)2(AMP-N7)(AMP-PO). Also discussed herein are the binding of platinum to the phosphate group Pγ with ATP and at acid pH, and the formation of the [cis-Pt(NH3)2(ATP-N7)H2O]+ complex. In neutral and basic pH ranges, the phosphate moiety of ATP is the most reactive site. In the presence of an excess of chloride ions, the complexation rates between the ATP and the cisplatin are decreased. Furthermore, in the experimental conditions used neither the ATP nor the AMP have shown binding to N1. 相似文献
6.
E. coli chromosomal DNA wastreated with various Pt co-ordiantion compounds and then used as donor DNA in E. coli transformation. Genetic analysis of transformants obtained with Pt-treated DNA showed effects of cis-diamminedichloroplatinum(II) (cis-Pt(II)) and cis-dimethyl-1,3-diaminopropane CL4 (cis-Pt(IV) (DMDAP) on the processing of DNA. With trans-diamminedichloroplatinum(II) (trans-Pt(II)) appllied in similar concentrations no effects were found.The effects of cis-Pt(II) and cis-Pt(IV) (DMDAP) on the genetic processing were different. The effects of cis-Pt(II) could be explained by assuming intra-strand crosslinks as an important lesion. 相似文献
7.
《Inorganica chimica acta》1988,152(2):91-99
The reactions of PtCl2en or cis-Pt(NH3)2Cl2 and their aqua species with adenine and adenosine were studied by means of ion-pair HPLC. From the chromatograms, it was found that the first binding site of Pt(II) was the N(7) site of adenine under both acidic and neutral conditions. The rates of Pt(II) binding at the (N7) site of adenosine and deoxyadenosine were measured. The rate constants, k1, were obtained for the reactions of PtCl2en or cis-Pt(NH3)2Cl2 with adenosine and deoxyadenosine at pH 3 and 7 over the temperature range 9–25 °C. The k1 values were 6.8–7.7 × 10−4 dm3 mol−1 s−1 at 25 °C. For the aqua species, the rate of [cis-Pt(NH3)2ClH2O]+ with adenosine N(7) was measured. The rate constants, k2 which were found to be smaller than those of hydrolysis, kh, were calculated at pH 3 over the temperature range 25–40 °C. The k2 value obtained at 25 °C was 1.1 × 10−2 dm3 mol−1 s−1, 15 time larger than k1. The activation parameters were also calculated. 相似文献
8.
Complexes of the types cis- and trans-Pt(amine)2I2 were studied by spectroscopic methods, especially by multinuclear NMR spectroscopy. In 195Pt NMR, the cis diiodo compounds with primary amines were observed between −3342 and −3357 ppm in acetone, while the trans compounds were found between −3336 and −3372 ppm. For the secondary amines, the chemical shifts were observed at lower fields. In 1H NMR, the trans complexes were observed at higher fields than the cis compounds, while in 13C NMR, the reverse was observed. The 2J(195Pt-1H) and 3J(195Pt-1H) coupling constants are larger for the cis compounds (ave. 67 and 45 Hz, respectively) than for the trans isomers (ave. 59 and 38 Hz). In 13C NMR, the values of 2J(195Pt-13C) and 3J(195Pt-13C) were also found to be larger for the cis complexes (ave. 17 and 39 Hz versus 11 and 28 Hz). There seems to be a slight dependence of the pKa values of the protonated amines or the proton affinity in the gas phase with the δ(Pt) chemical shifts. The crystal structures of eight diiodo complexes were determined. These compounds are cis-Pt(CH3NH2)2I2, cis-Pt(n-C4H9NH2)2I2, cis-Pt(Et2NH)2I2, trans-Pt(n-C3H7NH2)2I2, trans-Pt(iso-C3H7NH2)2I2, trans-Pt(n-C4H9NH2)2I2, trans-Pt(t-C4H9NH2)2I2 and trans-Pt(Me2NH)2I2. The Pt-N bond distances located in trans position to the iodo ligands were compared to those located in trans position to the amines. The Pt-N bond in cis-Pt(Et2NH)2I2 are much longer than the others, probably caused by the steric hindrance of the two very bulky ligands located in cis positions. 相似文献
9.
Fernande D. Rochon Gassan Massarweh Catherine Bonnier 《Inorganica chimica acta》2008,361(5):1437-1446
Complexes of the types cis- and trans-Pt(amine)2(NO3)2 with amines containing a phenyl group were synthesized and studied mainly by IR and multinuclear magnetic resonance spectroscopies. The cis complexes could be synthesized pure only with the amines of the type Ph-R-NH2 (R = alkyl), while pure trans compounds were synthesized with all the studied amines. In 195Pt NMR spectroscopy, the dinitrato complexes of the amines Ph-R-NH2 were observed around −1700 ppm for the cis isomers and at about −1580 for the trans complexes. For the other amines, where a phenyl ring is directly attached to the amino group, the signals were observed at lower fields, −1528 ppm for cis-Pt(PhNH2)(NO3)2 and around −1450 ppm for all the trans isomers. There is a linear relationship between the δ(Pt) of the Pt(amine)2(NO3)2 complexes and the pKa of the protonated amines. The coupling constants 2J(195Pt-1HN) are larger in the cis compounds (ave. 76 Hz) than in the trans isomers (ave. 63 Hz). The complexes cis-Pt(amine)2(R(COO)2) with bidentate dicarboxylato ligands were also synthesized and characterized mainly by IR spectroscopy. The compounds apparently decompose in DMF and are too insoluble in other solvents for solution studies. 相似文献
10.
《Inorganica chimica acta》1988,152(3):151-157
Using the semi-empirical all-valence method (GRINDOL) (recently modified and extended to transition series elements), electronic structure and intermolecular interactions of the model antitumor Pt(II) compounds with guanine and thioguanine have been calculated. Several possible models of antitumor action of platinum compounds are discussed. It is concluded that cis-Pt(II) complexes with guanine form stable intrastrand N7N7 cross-links (but chelation to the O6 atom is also possible). The trans-isomers of platinum(II) exclusively form interstrand cross-links, but the cis-Pt(II) complexes with thioguanine form almost entirely the N7S five-membered chelates. 相似文献
11.
Synchronously growing HeLa cells demonstrated a different profile of DNA synthesis to that observed for Chinese hamster V79-379A cells after treatment with cis-Platinum(II) diamminedichloride (cis-Pt(II)) in the G1 phase of the cell cycle. The progression of G1 phase treated cells into the DNA synthetic phase was not affected. The peak rate of DNA synthesis in the first cycle was decreased in a dose dependent manner. However, no displacement in the time of appearance of this peak rate of DNA synthesis was observed in the first cycle as had been observed in Chinese hamster V79-379A cells. The timing of mitosis after the first cycle was delayed in a dose dependent manner and resulted in a concomitant delay in the appearance of the peak rate of DNA synthesis in the second cycle. The peak rate of DNA synthesis in the second cycle was reduced in a dose dependent manner. The ability of cells to divide after the first cycle was not related to their eventual ability to survive. Incubation of HeLa cells with caffeine after treatment with cis-Pt(II) did not increase the toxicity of cis-Pt(II). This was consistent with the lack of effect of caffeine posttreatment on the rate of DNA synthesis in cis-Pt(II) treated synchronously growing HeLa cells. HeLa cells did not show the characteristics of caffeine sensitive replication repair, nor did they show evidence for the presence of an inducible repair system. The rate of DNA synthesis, cell number and survival data were discussed in relation to a mechanism of cell death proposed for Chinese hamster cells. 相似文献
12.
The reaction products of adenosine with [Pt(NH3)3Cl]Cl or cis-Pt(NH3)2Cl2 have been studied using high performance liquid chromatography and uv spectroscopy. The reaction of [Pt(NH3)3Cl]Cl with adenosine (pH = 7.0, Pt/base = 0.5) gives four products. Two of them, mononuclear complexes in which platinum is bound to adenosine through N(7) or N(1), comprise more than 90% of all the products. The N(1) and N(7) sites on adenosine indicate almost equal binding affinity for [Pt(NH3)3Cl]Cl. The reaction of cis-Pt(NH3)2Cl2 with adenosine has been studied in the presence of a large excess of adenosine (Pt/base ? 0.05). The reaction gives four products. One is the monomeric 2:1 complex with cis-Pt(NH3)22+ bound to two adenosine molecules through the N(7) site and the N(1) site, and another is the monomeric 2:1 complex with cis-Pt(NH3)22+ bound to two adenosine molecules through the N(7) sites. cis-Pt(NH3)2Cl2 is stronger affinity to the N(7) site than of adenosine to the N(1) site. 相似文献
13.
Mixed-ligand complexes of the type cis- and trans-Pt(Ypy)(pm)Cl2 where Ypy = pyridine derivative and pm = pyrimidine were synthesized and characterized by IR spectroscopy and by multinuclear (195Pt, 1H and 13C) magnetic resonance spectroscopy. The cis compounds were prepared from the reaction of K[Pt(Ypy)Cl3] with pyrimidine (1:1 proportion) in water, while most of the trans isomers were synthesized from the isomerization of the cis compounds. The cis isomers could not be isolated with the Ypy ligands containing two -CH3 groups in ortho positions. When the aqueous reaction of K[Pt(Ypy)Cl3] with pyrimidine was performed in a Pt:pm ratio = 2:1, the pyrimidine-bridged dinuclear species were formed. Only the most stable trans-trans isomers could be isolated pure. In IR spectroscopy, the cis monomers showed two ν(Pt-Cl) bands, while the trans monomers and dimers showed only one ν(Pt-Cl) band. The 195Pt NMR signals of the cis monomers were found at slightly higher fields than those of the corresponding trans isomers. The δ(195Pt) of the dimers were found close to those of the trans monomers. The NMR results were interpreted in relation to the solvent effect, which seems important in these complexes. The coupling constants J(195Pt-1H) and J(195Pt-13C) are larger in the cis geometry. The crystal structures of the compounds cis-Pt(2,4-lut)(pm)Cl2, trans-Pt(2,6-lut)(pm)Cl2 and trans,trans-Cl2(2,6-lut)Pt(μ-pm)Pt(Ypy)Cl2 were studied by X-ray diffraction methods and the results have confirmed the configurations suggested by IR and NMR spectroscopies. 相似文献
14.
The survival of wild-type and repair-deficient Escherichia coli treated with cis-Pt(NH3)2Cl2, trans-Pt(NH3)2Cl2 and [Pt(dien)Cl]Cl (dien = H2NCH2CH2NHCH2CH2NH2) was inversely correlated with the ability of these compounds to inhibit DNA synthesis in different bacterial strains. The relative amounts of these 3 compounds covalently bound to DNA immediately after treatment with the same dose were, respectively, 1:?2:1, their relative abilities to inhibit DNA synthesis were 6:1:0 and their relative toxicities toward the wild-type and uvrA strains were 3–5:1:0. More repair synthesis, as measured by density-gradient centrifugation techniques, was observed in wild-type bacteria after treatment with the cis than with the trans isomer whereas no repair synthesis was detected after exposure to [Pt(dien)Cl]Cl.These results are consistent with the hypothesis that cis-Pt(NH3)Cl2 binds to DNA and inhibits DNA synthesis thereby killing the cell. The lower toxicity of this compound toward wild-type bacteria compared with repair-deficient strains is in part a consequence of DNA repair. trans-Pt(NH3)2Cl2 and [Pt(dien)Cl]Cl are less toxic than the cis isomer; this lesser toxicity is not a consequence of low levels of DNA binding or enhanced repair of the lesions but appears to reflect a weaker inhibition of DNA synthesis by these Pt-DNA adducts. 相似文献
15.
The interactions of cis- and trans-diammineplatinum compounds with 5′-GMP and 5′-dGMP in dilute aqueous solution at neutral pH were investigated by 1H nmr. In addition to the 1:2 Pt nucleotide complexes cis- and trans-Pt(NH3)2(GMP)2, it was possible to study the formation of the 1:1 Pt-nucleotide complexes with either one coordinated water or chloride ion. At 5°C GMP reacts with a stoichiometric amount of cis-diaquodiammine-platinum to yield cis-Pt(NH3)2(GMP) (H2O) as a sole reaction product. From the present results it is concluded that such a complex may play an important role as the initial reaction product between antitumor compounds like cis-Pt(NH3)2Cl2 and guanine in DNA in living organisms. The coupling constant 3J(H(1′)-H(2′)) of the H(1′) sugar proton in cis-Pt(NH3)2(GMP)2 is temperature dependent, indicating a conformational change in the sugar moiety. 相似文献
16.
Specific biological activity of platinum complexes. Contribution to the theory of molecular mechanism 总被引:1,自引:0,他引:1
The effect of various coordination complexes of Pt(II) on the renaturation of the DNA was studied with special attention to the degree of hydrolysis. We found that hydrolysed solutions of biologically active complexes (cis-dichlorodiammine-platinum(II) (cis-Pt(II)), dichloroethylenediamine platinum(II), oxalatodiammine-platinum(II), malonatodiammineplatinum(II) and malonatoethylenediaminepiatinum(II)) do stimulate the renaturation immediately after the mixing with DNA, whereas the inactive complexes (trans-dichlorodiammineplatinum(II), K2PtCl4 and K2PtCl6 have no effect, or have it only after a longer heating of the mixture. Higher concentration of chlorides shifts the optimal Pt/Pdna ratio to higher values. The interaction which is responsible for the stimulation of the renaturation cannot be removed by dialysis. All observations support the suggestion that hydrolysis is the first step in the interaction of biologically active complexes with the components of living systems. 相似文献
17.
The crystal structures of two Pt(cyclopentylamine)2I2 compounds were determined by X-ray diffraction methods. Both crystals contain disordered cyclopentylamine ligands. Crystal I contains two independent trans-Pt(cyclopentylamine)2I2 molecules and all the C atoms are disordered on two positions. The second crystal (II) is most interesting since it contains both cis- and trans-Pt(cyclopentylamine)2I2 isomers in the same unit cell. It was prepared from the recrystallization of the cis isomer in acetone. The C atoms of the trans molecule in crystal II are disordered on two positions, while only one position was determined in the cis molecule, although some of the C thermal factors are quite high. The reactions of cis-Pt(amine)2X2 and cis-Pt(NH3)(amine)X2 (amine = cyclobutylamine and cyclopentylamine) with guanosine in water were studied in different Pt:guanosine proportions by multinuclear (1H, 195Pt and 15N) magnetic resonance spectroscopy. The presence of several species in solution was observed. For the mixed-cyclobutylamine compound, 15N NMR has shown that some of the NH3 ligands have been displaced from the coordination sphere in the presence of an excess of guanosine. The reactions of the two mixed-ligand complexes cis-Pt(NH3)(amine)Cl2 with 9-methylguanine, inosine and 9-methylhypoxanthine were also studied in water and the results are discussed. 相似文献
18.
Lixin Zhou 《Inorganica chimica acta》2011,376(1):44-56
The monofunctional and bifunctional bindings of the potential anticancer drug trans-isopropylaminedimethylaminedichloroplatinum (trans-IPADMADP) and its cis isomer to purine base in DNA are explored by using density functional theory and IEF-PCM solvation models. The computed lowest free energy barrier in the aqueous solution is 14.0/11.6 kcal/mol (from trans-Pt-chloroaqua complex to trans-/cis-monoadduct) for guanine(G), and 11.7/13.3 kcal/mol (from trans-Pt-chloroaqua complex to trans-/cis-monoadduct) for adenine(A). Our calculations demonstrate that the trans reactant complexes (or isolated reactants) can generate trans- or cis-monoadducts via similar trigonal bipyramidal transition state structures, suggesting that the monoadducts can subsequently close to form the bifunctional intrastrand Pt-DNA adducts and simultaneously distort DNA in the similar way as cisplatin. Our calculations show that Pt(isopropylamine)(dimethylamine)G22+ head-to-head path has the lowest free energy of activation at 17.6 kcal/mol, closely followed by the Pt(isopropylamine)(dimethylamine)GA2+ head-to-head path at 19.6 kcal/mol when the monofunctional cis-Pt-G complex serves as the reactant; while the Pt(isopropylamine)(dimethylamine)G22+ head-to-tail adduct has the lowest barrier of 20.5 kcal/mol, closely followed by the Pt(isopropylamine)(dimethylamine)GA2+ head-to-tail adduct at 23.0 kcal/mol if the monofunctional trans-Pt-G complex is the reactant.The calculated relatively lower activation energy barrier than that of cisplatin theoretically confirm that trans-[PtCl2(isopropylamine)(dimethylamine)] is a potential anticancer drug as described by experiment. 相似文献
19.
New types of Pt(II) mixed-ligand complexes containing a pyridine derivative (Ypy) and pyrazine (pz) were synthesized. The compounds were characterized by infrared spectroscopy and by multinuclear (1H, 13C and 195Pt) magnetic resonance. The complexes cis-Pt(Ypy)(pz)Cl2 were synthesized from the reaction of K[Pt(Ypy)Cl3] with pyrazine (1:1 proportion) in water. When the reaction was carried on in a 2:1 ratio, a mixture of compounds was obtained, which was refluxed in CH2Cl2 for several days. The final product was found to be pure and it was identified as trans,trans-Cl2(Ypy)Pt(μ-pyrazine)Pt(Ypy)Cl2. The cis monomers isomerize to the trans isomers in organic solvents. Different methyl derivatives of pyridine were studied in order to determine the influence of substitution in ortho position on the pyridine ligand in the complexes. In IR spectroscopy, the cis monomers showed two ν(Pt-Cl) bands, while the trans monomers and dinuclear species showed only one ν(Pt-Cl) band. The NMR results were interpreted in relation to the solvent effect, which seems important in these complexes. The 195Pt NMR signals of the cis monomers were found at slightly higher fields than those of the corresponding trans isomers. The coupling constants J(195Pt-1H) and J(195Pt-13C) are larger in the cis geometry. The δ(195Pt) of the dinuclear species were found close to those of the trans monomers and the coupling constants are similar to those of the trans monomers, strongly suggesting a trans-trans configuration for the dinuclear compounds. The pyrazine-bridged complex K2[Cl3Pt(μ-pz)PtCl3] was also synthesized and spectroscopically studied. The crystal structures of the compounds cis-Pt(3,5-lut)(pz)Cl2 and trans-Pt(2,4,6-col)(pz)Cl2 were determined by X-ray diffraction methods. 相似文献
20.
The crystal and molecular structures of the N-rac-isomer of the nickel(II) complex of 14-membered amide-containing macrocycle [NiL1] · 4H2O (H2L1=5,12-dioxo-1,4,8,11-tetraazacyclotetradecane) have been determined. Two deprotonated amide and two amine donors co-ordinate to the nickel(II) in nearly square planar manner with Ni-Namine bonds longer than Ni-Namide ones (1.930 vs. 1.898 Å). Water molecules do not co-ordinate and form hydrogen bond bridges between macrocyclic units in the crystal lattice. The analysis of 1H NMR data confirmed that the solid-state conformation of the macrocycle in N-rac[NiL1] is retained in aqueous solution though equilibrated with some amount of N-meso isomer. The comparison of the spectroscopic characteristics of the M(II) and M(III) complexes and the redox potentials of M(III/II) couples (M=Ni and Cu) for ML1 with those for ML2(H2L2=5,7-dioxo-1,4,8,11-tetraazacyclotetradecane) revealed a rather small influence of the trans- vs. cis-arrangement of amide donors in co-ordination spheres of the metal ions. 相似文献