14096-51-6Relevant articles and documents
The Influence of the Axial Ligands of a Series of Platinum(IV) Anti-Cancer Complexes on their Reduction to Platinum(II) and Reaction with DNA
Ellis, Leanne T.,Er, Hui Meng,Hambley, Trevor W.
, p. 793 - 806 (1995)
The electrochemical reduction and DNA binding have been studied for a series of platinum(IV) complexes with Cl(-), OH(-), and carboxylate anions as the axial ligands; , , and , R = CH3, CH2CH3, CH2CH2CH3.Cathodic reduction potentials vary by more than 650 mV with the tetrachloro complex reduced most readily and the dihydroxo least readily.The binding of the complexes correlates with the reduction potentials with the more readily reduced complexes binding more readily to DNA.The influence of the reducing agent glutathione on platinum binding to DNA was found to depend on whether it was added before or after Pt/DNA incubation.The results are consistent with octahedral platinum(IV) binding monofunctionally to DNA, and molecular modelling studies have been used to confirm that this is sterically feasible.The crystal structure of has been determined by X-ray diffraction methods and refined to R = 0.028 (977 F).The crystals are monoclinic, space group C 2/c, a 15.569(6), b 8.104(1), c 13.188(1) Angstroem, β 136.38(2) deg.
Trend in cytotoxic activity of a series of cis-[APtCl2] (A = ethylenediamine methylated at different positions) complexes
Milanesio, Marco,Monti, Elena,Gariboldi, Marzia Bruna,Gabano, Elisabetta,Ravera, Mauro,Osella, Domenico
, p. 2803 - 2814 (2008)
The study of a series of cis-[APtCl2] complexes (A = ethylenediamine, en, methylated at different positions) was carried out to evaluate the effect of different methyl substitutions on the cytotoxic properties of the resulting derivatives. As expected, differentially methylated complexes were found to differ widely in their cytotoxic effects on human cultured ovarian carcinoma cells (A2780). Molecular mechanics (MM) calculations have been performed to assess the relationship between differential diamine methylation and the repulsive energy of the corresponding complexes when interacting with DNA. Compounds that bind DNA at high energetic cost relative to cisplatin, due to the steric hindrance of additional methyl groups, have shown high values for IC50 (concentration inhibiting tumour cell growth by 50%). Semi-quantitative analyses with a DNA electrochemical biosensor confirm that the interaction between cis-[APtCl2] complexes and ds-DNA deposed onto the electrode is stronger for the non-methylated derivative with respect to the fully methylated congener. In addition, MM calculations were used to investigate the interactions between DNA and cis-[(P-L-A)PtCl2] complexes [A = en group linked to an antiestrogen-like pharmacophore, P, via a -(CH2)n- spacer (n = 2, 4, 6, 8 and 10), L].
Selective Co-Encapsulation Inside an M6L4Cage
Leenders, Stefan H. A. M.,Becker, René,Kumpulainen, Tatu,de Bruin, Bas,Sawada, Tomohisa,Kato, Taito,Fujita, Makoto,Reek, Joost N. H.
, p. 15468 - 15474 (2016)
There is broad interest in molecular encapsulation as such systems can be utilized to stabilize guests, facilitate reactions inside a cavity, or give rise to energy-transfer processes in a confined space. Detailed understanding of encapsulation events is required to facilitate functional molecular encapsulation. In this contribution, it is demonstrated that Ir and Rh-Cp-type metal complexes can be encapsulated inside a self-assembled M6L4metallocage only in the presence of an aromatic compound as a second guest. The individual guests are not encapsulated, suggesting that only the pair of guests can fill the void of the cage. Hence, selective co-encapsulation is observed. This principle is demonstrated by co-encapsulation of a variety of combinations of metal complexes and aromatic guests, leading to several ternary complexes. These experiments demonstrate that the efficiency of formation of the ternary complexes depends on the individual components. Moreover, selective exchange of the components is possible, leading to formation of the most favorable complex. Besides the obvious size effect, a charge-transfer interaction may also contribute to this effect. Charge-transfer bands are clearly observed by UV/Vis spectrophotometry. A change in the oxidation potential of the encapsulated electron donor also leads to a shift in the charge-transfer energy bands. As expected, metal complexes with a higher oxidation potential give rise to a higher charge-transfer energy and a larger hypsochromic shift in the UV/Vis spectrum. These subtle energy differences may potentially be used to control the binding and reactivity of the complexes bound in a confined space.
Synthesis, characterization, cytotoxic activity, and 19F NMR spectroscopic investigations of (OC-6-33)-diacetato(ethane-1,2-diamine)bis(3,3,3-trifluoropropanoato)platinum(IV) and its platinum(II) counterpart
H?fer, Doris,Cseh, Klaudia,Hejl, Michaela,Roller, Alexander,Jakupec, Michael A.,Galanski, Markus,Keppler, Bernhard K.
, p. 190 - 199 (2019)
Tetracarboxylatoplatinum(IV) complexes are interesting representatives of potential anticancer active platinum(IV) drugs. Revealing higher kinetic inertness in comparison to their cytotoxic platinum(II) counterparts, they offer an opportunity to reduce toxic and deactivating side reactions. Platinum(IV) complexes are generally considered as prodrugs, which have to be reduced in order to exert their anticancer activity. Two model complexes, a platinum(II) and platinum(IV) complex featuring two equatorial 3,3,3-trifluoropropanoato (tfpa) and in the case of the latter two axial acetato ligands, were synthesized and characterized in detail by multinuclear (1H, 13C, 15N, 19F, 195Pt) one- and two-dimensional NMR spectroscopy, high-resolution electrospray ionization mass spectrometry, elemental analysis and X-ray diffraction analysis. Cytotoxicity was evaluated in three human cancer cell lines (A549, SW480 and CH1/PA-1) by the MTT colorimetric assay, exhibiting IC50 values down to the low micromolar range. The fluorinated ligands in equatorial positions allowed detailed and highly sensitive 19F NMR spectroscopic investigations. Besides reaction studies in the presence of small molecules, e.g. ascorbic acid and 5′-GMP, the reduction of the platinum(IV) complex was additionally investigated in two cancer cell extracts deriving from the cell lines SW480 and CH1/PA-1 in order to estimate the intracellular reduction behavior. A significant increase in the rate of reduction in cell extracts (depending on the chosen cell line) compared to the reduction with ascorbic acid could be demonstrated.
Bekaroglu, Oe.,Breer, H.,Endres, H.,Keller, H. J.,Gung, H. Nam
, p. 183 - 186 (1977)
Distribution of Halogen Atoms in Mixed-Valence Linear-Chain Complexes of Platinum: A Solid-State (15)N NMR Study
Austin, Elliot J. W.,Barrie, Patrick J.,Clark, Robin J. H.
, p. 3859 - 3863 (1995)
High-resolution solid-state (15)N NMR spectroscopy is used to demonstrate unambiguously the presence of Cl-Pt(IV)-Br units in [Pt(en)2][Pt(en)2Cl(2-2x)Br2x](ClO4)4 complexes (0 a measure of the bromine concentration in the chain to be made.It is demonstrated that the halogen distribution is fairly close, but not identical, to random about this site. This suggests that the overall distribution of halogen atoms throughout the mixed-valence chain can be treated as being virtually random.
Thermodynamic and kinetic studies on reactions of Pt(II) complexes with biologically relevant nucleophiles
Summa, Nadine,Schiessl, Wolfgang,Puchta, Ralph,Van Eikema Hommes, Nico,Van Eldik, Rudi
, p. 2948 - 2959 (2006)
The effect of different N-N spectator ligands on the reactivity of platinum(II) complexes was investigated by studying the water lability of [Pt(diaminocyclohexane)(H2O)2]2+ (Pt(dach)), [Pt(ethylenediamine)(H2O)2]2+(Pt(en)), [Pt-(aminomethylpyridine)(H2O)2]2+(Pt(amp)), and [Pt(N,N′-bipyridine)(H2O)2]2+(Pt(bpy)). Some of the selected N-N chelates form part of the coordination sphere of Pt(II) drugs in clinical use, as in Pt(dach) (oxaliplatin), or are models, regarding the nature of the amines, with higher stability in terms of substitution and hydrolysis of the diamine moiety, as in Pt(en) (cisplatin) and Pt(amp) (AMD473). The effect of π-acceptors on the reactivity was investigated by introducing one (Pt(amp)) or two pyridine rings (Pt(bpy)) in the system. The pKa values for the two water molecules (viz., Pt(dach) (pKa1 = 6.01, pKa2 = 7.69), Pt(en) (pKa1 = 5.97, pKa2 = 7.47), Pt(amp) (pKa1 = 5.82, pKa2 = 6.83), Pt(bpy) (pKa1 = 4.80, pKa2 = 6.32) show a decrease in the order Pt(dach) > Pt(en) > Pt(amp) > Pt(bpy). The substitution of both coordinated water molecules by a series of nucleophiles (viz., thiourea (tu), L-methionine (L-Met), and guanosine-5′-monophosphate (5′GMP-)) was investigated under pseudo-first-order conditions as a function of concentration, temperature, and pressure using UV-vis spectrophotometric and stopped-flow techniques and was found to occur in two subsequent reaction steps. The following K1 values for Pt(dach), Pt(en), Pt(amp), and Pt(bpy) were found: tu (25°C, M-1 s-1) 21 ± 1, 34.0 ± 0.4, 233 ± 5, 5081 ± 275; L-Met (25°C) 0.85 ± 0.01, 0.70 ± 0.03, 2.15 ± 0.05, 21.8 ± 0.6; 5′GMP- (40°C) 5.8 ± 0.2, 3.9 ′ 0.1, 12.5 ± 0.5, 24.4 ± 0.3. The results for k2 for Pt(dach), Pt(en), Pt(amp), and Pt(bpy) are as follows: tu (25°C, M-1 s-1) 11.5 ± 0.5, 10.2 ± 0.2, 38 ± 1, 1119 ± 22; L-Met (25°C, s-1) 2.5 ± 0.1, 2.0 ± 0.2, 1.2 ± 0.3, 290 ± 4; 5′GMP- (40°C, M-1 s-1) 0.21 ± 0.02, 0.38 ± 0.02, 0.97 ± 0.02, 24 ± 1. The activation parameters for all reactions suggest an associative substitution mechanism. The pKa values and substitution rates of the complexes studied can be tuned through the nature of the N-N chelate, which is important in the development of new active compounds for cancer therapy.
The first examples of platinum amine hydroxamate complexes: Structures and biological activity
Failes, Timothy W.,Hall, Matthew D.,Hambley, Trevor W.
, p. 1596 - 1600 (2003)
Two novel benzohydroxamate complexes of anticancer active Pt(II)-diamine moieties have been synthesised in which Pt-C bonds are present in the dinuclear structures. The complexes, [{Pt(en)}2(μ-bha)]ClO 4·H2O (en = ethane-1,2-diamine) and [{Pt(R,R-chxn)}2(μ-bha)]NO3·2H2O (chxn = cyclohexane-1,2-diamine), have two platinum centres that are bridged through the bha ligand via (O,O) and (C,N) coordination modes, the latter mode occurring through deprotonation of the ortho carbon of the phenyl ring. The cytotoxicities of the complexes were tested against a panel of cell lines based on the A2780 ovarian cancer cell line and revealed that both dinuclear complexes were less active than their corresponding dichloro parent complexes. It is likely that they act in a similar manner to the parent complexes, but with the cytotoxicity mediated by factors influencing cellular uptake, such as the charge and lipophilicity of the compounds. The Royal Society of Chemistry 2003.
Hydrolysis of the amide bond in N-acetylated l-methionylglycine catalyzed by various platinum(II) complexes under physiologically relevant conditions
?ivkovi?, Marija D.,A?anin, Darko P.,Rajkovi?, Sne?ana,Djuran, Milo? I.
, p. 947 - 952 (2011)
The hydrolytic reactions between various Pt(II) complexes of the type [Pt(L)Cl2] and [Pt(L)(CBDCA-O,O′] (L is ethylenediamine, en; (±)-trans-1,2-diaminocyclohexane, dach; (±)-1,2-propylenediamine, 1,2-pn and CBDCA is the 1,1-cyclobutanedicarboxylic anion) and the N-acetylated l-methionylglycine dipeptide (MeCOMet-Gly) were studied by 1H NMR spectroscopy. All reactions were realized at 37 °C with equimolar amounts of the Pt(II) complex and the dipeptide at pH 7.40 in 50 mM phosphate buffer in D2O. Under these experimental conditions, a very slow cleavage of the Met-Gly amide bond was observed and this hydrolytic reaction proceeds through the intermediate [Pt(L)(H2O)(MeCOMet-Gly-S)]+ complex. In general, it can be concluded that faster hydrolytic cleavage of the MeCOMet-Gly dipeptide was observed in the reaction with the chloride complex than with corresponding CBDCA Pt(II) complexes. The steric effects of the Pt(II) complex on the hydrolytic cleavage of the amide bond in the MeCOMet-Gly dipeptide were also investigated by 1H NMR spectroscopy. It was found that the rate of hydrolysis decreases as the steric bulk of the CBDCA and chlorido Pt(II) complexes increase (en > 1,2-pn > dach). These results contribute to a better understanding of the toxic side effects of Pt(II) antitumor drugs and should be taken into consideration when designing new potential Pt(II) antitumor drugs with preferably low toxic side effects.
High-water-solubility platinum catalyst precursor and synthesis method thereof
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Paragraph 0022-0026; 0031-0034; 0039-0042, (2021/07/21)
The invention discloses a synthesis method of a high-water-solubility platinum catalyst precursor in order to solve the problems that in the prior art, a platinum catalyst precursor compound used as an impregnation method contains chlorine or is insufficient in water solubility and chemical stability. The preparation method comprises the following steps: synthesizing dichloro(ethylenediamine)platinum by taking acidified chloroplatinous acid or chloroplatinite solution and acidified ethylenediamine solution as raw materials, adding excessive ethylenediamine for dissolving, and conducting reacting with silver acetate to obtain a platinum catalyst precursor. The invention also discloses a high-water-solubility platinum catalyst precursor. The invention provides the method for synthesizing a high-water-solubility platinum catalyst precursor, the pH value of a reaction system is regulated and controlled, the adding speed of an acidic ethylenediamine mixture solution is adjusted, and the release of an ethylenediamine ligand is controlled by utilizing the hydrolysis balance of ethylenediamine acid salt, so that the purity of a dichloroethylenediamine platinum product is improved, and further, the purity of the platinum diethylenediamine acetate is ensured. The invention further provides the high-water-solubility platinum catalyst precursor which is very high in water solubility.
