Binding of Platinum(II) to Some Biologicaly Important Thiols

The reactions between [Pt(terpy)Cl+ and thiols, such as glutathione, L-cysteine, D-penicillamine and thioglycolic acid have been Studied by conventional UV-VIS spectrophotometry and H NMR spectroscopy. The second-ordero rate constants, K2, are similar for these four thiols, varying between 1.06 x 10-2 and 6.10 x 10+3 M-1 s-1 at 25°C. The activation entropies have large negative values between -100 and -200 J mol-1 which are compatible with an associative A mechanism. However, L-methionine, as thioether ligand, is unreactive under the same experimental conditions. The obtained results have been analyzed in relation to the antitumor activity and toxicity of platinum(II) complexes

Inhibitory effect of cisplatin and [Pt(dach)Cl2] on the activity of phospholipase A2

This work has been focused on testing the influence of two selected Pt(II) complexes cisplatin, Pt(NH3)(2) Cl-2, and [Pt(dach)Cl-2] on the activity of porcine pancreatic phospholipase A(2) (PLA(2)). It has been assumed that this enzyme plays a role in carcinogenesis and that it could be a target in the tumour therapy. The results of this study show that both Pt(II) complexes inhibit the activity of the enzyme, though they bind to it in a different manner. While cisplatin interacts with the enzyme in an acompetitive manner, the stable interaction of [Pt(dach)Cl-2] with PLA(2) could not be detected under our experimental conditions

Kinetics and mechanism of substitution reactions of the new bimetallic [{PdCl(bipy)}{mu-(NH2(CH2)(6)H2N)}{PtCl(biPY)}]Cl(ClO4) complex with important bio-molecules

The new dinuclear bimetallic complex, [{PdCl(bipy)}{mu-(NH2(CH2)(6)H2N)}{PtCl(biPY)}]Cl(ClO4) (bipy is 2,2-bipyridine), has been prepared and characterized by elemental microanalysis, IR, H-1 NMR spectroscopy and MALDI-TOF mass spectrometry. Substitution reactions of the studied complex with selected biologically important ligands such as: thiourea (Tu), L-methionine (L-Met), L-cysteine (L-Cys), L-histidine (L-His) and guanosine-5-monophosphate (5-GMP), were studied under the pseudo-first order conditions as a function of concentration and temperature using stopped-flow and UV-Vis spectrophotometry. The reactions were monitored in 0.1 M NaClO4 at pH 5.0, in the presence of 40 mM NaCI. All fast reactions were monitored by stopped-flow at three temperatures (288 K, 298 K, 308 K) to determine the activation parameters, while the reactions studied by UV-Vis spectrophotometry were tested only at 298 K. Observed order of reactivity of the used ligands is: Tu GT L-Met GT L-Cys GT L-His GT 5-GMP. Substitution reactions of the investigated bimetallic complex with Tu, L-Cys and L-His were followed by degradation to the corresponding substituted mononuclear complexes of palladium (II) and platinum (II), [Pd(bipy)(Nu)(2)] and [Pt(bipy)(Nu)(2)] (where Nu = Tu, L-Cys, L-His), by releasing of the bridge ligand,1,6-diaminohexane. In contrast, during the substitution reactions with L-Met and 5-GMP, the structure of starting bimetallic complex was preserved and the process of degradation can be halted. The proposed pathways of the substitution reactions of [{PdCl(bipy)}{mu-(NH2(CH2)(6)H2N)}{PtCl(biPY)}]Cl(ClO4) complex with all selected ligands were confirmed by H-1 NMR spectroscopy at 295 K. Additionally, the two pK(a) values of studied diaqua complex, [(Pd(H2O)(bipy)}(mu-(NH2(CH2)(6)H2N)}(Pt(H2O)(biPY)}](4+), were determined by spectrophotometric pH titration. The large negative values for the entropy of activation, Delta S-not equal, support an associative substitution mechanism. (C) 2015 Elsevier Ltd. All rights reserved

Laser desorption and ionization time-of-flight versus matrix-assisted laser desorption and ionization time-of-flight mass spectrometry of Pt(II) and Ru(III) metal complexes

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been recently established as a powerful, soft ionization technique for the analysis of both transition metal complexes, which are used as metallo-drugs in the therapy of various types of tumors, and biomolecules. Since some metal complexes absorb light in the UV range, it should be possible to analyse them without additional matrices, i.e. using LDI-TOF MS. In this study, the matrix-free approach was tested for the analysis of [PtCl(2)(dach)] (dichloride(1,2-diamincyclohexane) platinum(II)), [RuCl(2)(en)(2)]Cl (dichloridobis(ethylenediamine) ruthenium(III) chloride) and [RuCl(2)(bipy)(2)]Cl (bis(bipyridine)dichloridoruthenium(III) chloride) and the detection limit for these compounds was determined. In summary, the LDI-TOF mass spectra of [PtCl(2)(dach)] and [RuCl(2)(en)(2)]Cl are rather simple, whereas in the presence of 2,5-DHB as a matrix, additional peaks are generated. On the other hand, the standard MALDI-TOF mass spectrum of [RuCl(2)(bipy)(2)]Cl exhibits only one peak arising from the complex, in contrast to six peaks detectable in the LDI-TOF mass spectrum. The detection limit in the MALDI-TOF MS analysis of [PtCl(2)(dach)] and [RuCl(2)(bipy)(2)]Cl complexes was lower than that determined in LDI-TOF MS. Taking all into account, in this paper, we have demonstrated some advantages and drawbacks of the matrix-free LDI-TOF mass spectrometric analysis of transition metal complexes

Classification of stacking interaction geometries of terpyridyl square-planar complexes in crystal structures

Stacking interactions of terpyridyl square-planar complexes in crystal structures were studied analyzing data from the Cambridge Structural Database. In most of the crystal structures, two terpyridyl complexes were oriented "head-to-tail" or "head-to-head", with "head-to-tail orientation" being most prevalent. The number of structures with other orientations was very small. Based on the analysis of interacting geometries, we classified overlaps of terpyridyl complexes into six types. The types were defined by values of several geometrical parameters and all interactions of the same type had very similar overlap patterns

Kinetics and mechanism of the reactions of Ru(II)-arene complex with some biologically relevant ligands

The reactions of ruthenium(II)-arene complex [Ru-II(eta(6)-p-cym)(pydc)Cl] (where p-cym = p-isopropyl toluene, pydc = 2,3-pyridinedicarboxylato) with biologically nitrogen-donor nucleophiles, such as guanosine-5'-monophosphate (5'-GMP), guanosine (Guo) and L-histidine (L-His) were studied by UV-Vis spectrophotometry and H-1 NMR spectroscopy. The reactions were studied at pH 2.5 and at 7.2. All reactions were followed under pseudo-first order conditions with large excess of the nucleophiles. The selected nucleophiles have a high affinity for Ru(II)-arene complex. The reactivity of the used ligands follow the same order at both pH values: Guo gt 5'-GMP gt L-His, while the reactions at pH 7.2 are always faster. The negative entropies of activation (Delta S-not equal) support an associative mode of activation. However, the rate constants obtained by H-1 NMR at 295 K in D2O follow the same order of the ligand reactivity. The hydrolysis of the [Ru-II(eta(6)-p-cym)(pydc)Cl] complex was very fast and completed by the time the first spectrum was measured. Addition of excess of NaCl to equilibrium solutions reversed the hydrolysis. (C) 2011 Elsevier Ltd. All rights reserved

Matrix-assisted laser desorption and ionisation time-of-flight mass spectrometry of Pt(II) and Pd(II) complexes

In this work, we have analysed matrix-assisted laser desorption and ionisation time-of-flight (MALDI-TOF) mass spectra of [PtCl(2)(en)], [PtCl(2)(dach)] and [PdCl(dien)]Cl acquired either with 2,5-dihydroxybenzoic acid (DHB) or alpha-cyano-hydroxycinnamic acid (CHCA) as matrices. For certain experiments, small amounts of trifluoro, acetic acid (TFA) or higher concentration of inorganic salts (NaCl or KCl) was added to the matrix solution. The majority of peaks arising from the Pt(II) and Pd(II) complexes could be identified, but certain ions detectable in the spectra were generated upon ligand loss. Additionally. the analysis of Pt(II) complexes was also possible in the presence of a higher salt content, which is a commonly used analysis condition for the samples of biological origin. While DHB appears to be the best suited for MALDI-TOF mass spectrometric analysis of Pt(II) complexes, CHCA seems to be a better matrix for Pd(II) complex used in this study. On the other hand, small amounts of TFA improve the spectra quality of Pt(II) complexes. but lead most probably to the degradation of Pd(II) complex. Taken together, we have demonstrated that the analysis of metallo-drugs using MALDI-TOF MS, though accompanied with certain identification problems, is easy and reliable. On the other hand, having in mind that some complexes (i.e. a combination of a particular transition metal/ligand) cannot be analysed under conditions usually applied for others, we deem it necessary to find out the best conditions for MALDI-TOF MS analysis of each metal complex. (C) 2009 Elsevier Ltd. All rights reserved

New bimetallic palladium(II) and platinum(II) complexes: studies of the nucleophilic substitution reactions, interactions with CT-DNA, bovine serum albumin and cytotoxic activity

Two new dinuclear bimetallic complexes, [{PdCl(bipy)}{mu-(pyrazine)}{PtCl(bipy)}]Cl(ClO4) (1) (bipy is 2,2-=bipyridine) and [{PdCl(en)}{mu-(pyrazine)}{PtCl(en)}]Cl(ClO4) (2) (en is ethylenediamine), have been synthesized and characterized by elemental microanalysis, IR, H-1 NMR spectroscopy and MALDI-TOF mass spectrometry. The pK(a) values of the coordinated water molecules of the diaqua species were determined as well. Substitution reactions of complexes (1) and (2) with thiourea (Tu), L-methionine (L-Met), L-cysteine (L-Cys), L-histidine (L-His) and guanosine-5-monophosphate (5-GMP) were studied under the pseudo-first order conditions as a function of nucleophile concentration and temperature. The order of reactivity of nucleophiles was: Tu GT L-Met GT L-Cys GT L-His GT 5-GMP. Substitution reactions with Tu, L-Cys and L-His were followed by decomposition of bimetallic complexes to the corresponding substituted mononuclear complexes [Pd(N-N)(Nu)(2)] and [Pt(N-N)(Nu)(2)] (N-N = bipy, en), releasing the bridging ligand. However, the structures of starting bimetallic complexes were preserved during the reactions with L-Met and 5-GMP. The absorption spectroscopic study of interactions of calf-thymus DNA (CT-DNA) with complexes (1), (2) and [{PdCl(bipy)}{mu-(NH2(CH2)(6)H2N)} {PtCl(bipy)}] Cl(ClO4) (3), has shown that all the complexes exhibit high intrinsic binding constants (K-b = 10(4)-10(5) M-1). DNA-ethidium bromide (DNA-EB) fluorescence was quenched after addition of complexes (1), (2) or (3), indicating displacement of intercalating EB by complexes. All complexes have shown good binding affinity to bovine serum albumin protein (BSA). Chemosensitivity of A375 (human melanoma) and HeLa (human cervical cancer) cell lines toward complexes (1), (2) and (3) was analyzed by SRB assay. Complex (1) displayed significant inhibitory effect on the growth of both cell lines

Factors that influence the antiproliferative activity of half sandwich RuII-[9]aneS3 coordination compounds: activation kinetics and interaction with guanine derivatives.

Half sandwich Ru(II) \u2013 [9]aneS3 complexes ([9]aneS3 = 1,4,7-trithiacyclononane) are being studied for their antiproliferative activity. We investigated here the activation kinetics of three such complexes, namely [Ru([9]aneS3)(en)Cl](PF6) (1), [Ru([9]aneS3)(bpy)Cl](PF 6 ) (2) and [Ru([9]aneS3)(pic)Cl] (3) (en = 1,2-diaminoethane, pic = picolinate), and their interaction with DNA model bases. The aim of the study was to assess how they are affected by the nature and charge of the chelating ligand. The model reactions of 1 \u2013 3 with the guanine derivatives 9-methylguanine (9MeG), guanosine (Guo), and guanosine 5 \u2032 -monophosphate (5 \u2032 -GMP) were studied by NMR spectroscopy. All reactions lead, although with different rates and to different extents, to the formation of monofunctional adducts with the guanine derivatives N7-bonded to the Ru center. Two products, the complexes [Ru([9]aneS3)(en)(9MeG-N7)](PF 6 ) 2 (4) and [Ru([9]aneS3)(pic)(9MeG-N7)](PF 6 ) (10), were structurally characterized also by X-ray crystallography. The structure of 4 is stabilized by strong intramolecular H-bonding between an NH of en and the carbonyl O6 of 9MeG. The kinetics of aquation and anation of complexes 2 and 3, as well as the kinetics and the mechanism of the reaction of complexes 1 \u2013 3 with the biologically more relevant 5 \u2032 -GMP ligand were studied by UV-Vis spectroscopy. The rate of the reaction of 1 \u2013 3 with 5 \u2032 -GMP depends on the nature of the chelating ligand rather than on the charge of the complex, decreasing in the order 3 48 2 > 1