Ratomir Jelić

Hydrolysis of [Pt(dien)H2O]2+ and [Pd(dien)H2O]2+ complexes in water

The hydrolysis of the [Pt(dien)H2O]2+ and [Pd(dien)H2O]2+ complexes has been investigated by potentiometry at 298 K, in 0.1 mol dm−3 aqueous NaClO4. Least-squares treatment of the data obtained indicates the formation of mononuclear and μ-hydroxo-bridged dinuclear complexes with stability constants: log β11 = −6.94 for [Pt(dien)OH]+, log β11 = −7.16 for [Pd(dien)OH]+, and also log β22 = −9.37 for [Pt2(dien)2(OH)2]2+ and log β22 = −10.56 for [Pd2(dien)2(OH)2]2+. At pH values > 5.5, formation of the dimer becomes significant for the PtII complex, and at pH > 6.5 for the PdII complex. These results have been analyzed in relation to the antitumor activity of PtII complexes.

Antiproliferative activity and QSAR studies of a series of new 4-aminomethylidene derivatives of some pyrazol-5-ones.

Twenty five 4-aminomethylidene derivatives obtained from 3-phenyl-2-pyrazolin-5-one and 1,3-diphenyl-2-pyrazolin-5-one were synthesized and tested for their antiproliferative activity against human breast cancer MDA-MB-361 and MDA-MB-453 cell lines. The compounds derived from 1,3-diphenyl-2-pyrazolin-5-one exhibited the most remarkable activity in the treatment of both cell lines. In vitro antiproliferative activities were accompanied by an important apoptotic fraction of both cell lines; also, compounds inhibited key endothelial cell functions implicated in invasion and angiogenesis. QSAR methods were performed in order to analyze the influence of structural features of the compounds investigated on the antiproliferative potential on MDA-MB-361 and MDA-MB-453 cancer cells. One-parameter heuristic analysis was performed and different whole molecule and fragmental descriptors were considered for rationalization of mechanism of interaction of these compounds with active place of hypothetical target included in tumorigenesis.

Solution equilibria in l-glutamic acid and l-serine + iron(III) systems

Complex formation equilibria in l-glutamic acid (H2Glu) and l-serine (HSer) +iron(III) ion systems have been studied by a combination of glass electrode potentiometric and visible spectrophotometric measurements in 0.5 mol dm–3 (Na)NO3 ionic medium at 25°C. In the concentration range 1.0≤[Fe3+]≤5.0; 3.0≤[Glu2−]≤30.0 mmol dm−3 ([Glu]/[Fe]=3:1 to 30:1) and pH between 1.5 and 4.5, iron(III) and glutamic acid form the Fe(Glu)−2, Fe(Glu)+, Fe(HGlu)2+, Fe(OH)Glu, Fe2(OH)2Glu2+, Fe(OH)Glu22− complexes: and several pure hydrolytic products. Iron(III) and l-serine, beside pure hydrolytic complexes of iron(III), form the Fe(HSer)3+, Fe(Ser)2+, Fe(OH)Ser+, Fe(OH)2- Ser0, Fe(OH)Ser2 and Fe2(OH)2(Ser)2+2 complexes, over a broad concentration range of serine to iron ([Ser]/[Fe]=5:1 to 500:1), from pH 1.5 to 4.0. The stability constants of the complexes are given and their formation mechanism is suggested. The possible structure of the complexes, in solution, is discussed.Complex formation equilibria in l-glutamic acid (H2Glu) and l-serine (HSer) +iron(III) ion systems have been studied by a combination of glass electrode potentiometric and visible spectrophotometric measurements in 0.5 mol dm–3 (Na)NO3 ionic medium at 25°C. In the concentration range 1.0≤[Fe3+]≤5.0; 3.0≤[Glu2−]≤30.0 mmol dm−3 ([Glu]/[Fe]=3:1 to 30:1) and pH between 1.5 and 4.5, iron(III) and glutamic acid form the Fe(Glu)−2, Fe(Glu)+, Fe(HGlu)2+, Fe(OH)Glu, Fe2(OH)2Glu2+, Fe(OH)Glu22− complexes: and several pure hydrolytic products. Iron(III) and l-serine, beside pure hydrolytic complexes of iron(III), form the Fe(HSer)3+, Fe(Ser)2+, Fe(OH)Ser+, Fe(OH)2- Ser0, Fe(OH)Ser2 and Fe2(OH)2(Ser)2+2 complexes, over a broad concentration range of serine to iron ([Ser]/[Fe]=5:1 to 500:1), from pH 1.5 to 4.0. The stability constants of the complexes are given and their formation mechanism is suggested. The possible structure of the complexes, in solution, is discussed.

Interaction between tigecycline and human serum albumin in aqueous solution

The interaction between tigecycline (TGC) and human serum albumin (HSA) in aqueous solution was investigated by fluorescence, UV–Vis spectroscopic and molecular docking methods under physiological conditions. Results of UV–Vis and fluorescence spectroscopy showed that the fluorescence quenching of HSA was a result of the formation of HSA–TGC complex. The binding constants (Ka), binding sites (n), and the corresponding thermodynamic parameters (∆H, ∆S, and ∆G) of the interaction system were calculated. Thermodynamic parameters revealed that the binding process is spontaneous and the hydrophobic interactions were the main force to stabilize the complex. The distance r between the donor (HSA) and acceptor (TGC) molecules was obtained according to Förster’s theory of non-radiation energy transfer. Furthermore, the effect of some metal ions (Ca2+, Cu2+, and Fe3+) on the binding constants between TGC and HSA was examined. Finally, the binding of tigecycline to HSA was modeled using the molecular docking method.Graphical abstract

Solution Equilibria between Aluminum(III) Ion and L-histidine or L-tyrosine.

Toxic effects due to high aluminum body loads were observed in a number of conditions following ingestion of Al-containing antacids. Bio-availability of aluminum depends not only on the solubility of the ingested salt but also on the physico-chemical properties of the soluble Al complexes formed in body fluids. Amino acids may, upon interaction with Al-salts, form absorbable Al-complexes. Hence, complex formation equilibria between Al3+ and either, L- histidine or L-tyrosine were studied by glass electrode potentiometric (0.1 mol/L LiCl ionic medium, 298 K), proton NMR and uv spectrophotometric measurements. Non linear least squares treatment of the potentiometric data indicates that in the concentration ranges: 0.5≤CA1≤2.0 ; 1.0≤CHis≤10.0; 2.5≤PH≤6.5, in Al3+ + His solutions, the following complexes (with log overall stability constants given in parenthesis) are formed: Al(HHis)3+(12.21±0.08); Al(His)2+, (7.25±0.08); and Al(HHis)His2+, (20.3±0.1). In Al3+ + Tyr solutions in the concentration range 1.0≤CTyr≤3.0 mmol/L and ligand to metal concentration ratio from 2:1 to 3:1, in the pH interval from 3.0 to 6.5 the formation of the following complexes was detected: Al(HTyr)2+, (12.72±0.09); Al(Tyr)2+, (10.16±0.03) and Al(OH)2Tyr , (2.70±0.05). Proton NMR data indicate that in Al(His)2+ complex histidine acts as a monodentate ligand but its bidentate coordination is possible with carboxylate oxygen and imidazole 1-nitrogen as donors. In Al(HTyr)3+ complex tyrosine is a monodentate ligand with carboxylate oxygen as donor. The mechanism of the formation of complexes in solution is discussed as well as their possible role in aluminum toxicity.

THE EFFECT OF SURFACE ACTIVE SUBSTANCES ON HYDROLYSIS OF ALUMINIUM(III) ION

The hydrolysis of aluminium(lll) ion has been studied in 0.01, 0.1 and 1.0 mol/L LiCI ionic medium, at 298 Κ by glass electrode Potentiometrie measurements. Measurements were made in absence and in the presence of either polyoxyethylene sorbitanmonolauerate (tween-20, 0.5%), polyethylene glycol tert—octylphenyl ether (triton-x 100, 0.5%), sodium n-dodecylsulphate (SDS, 10 mmol/L) or n-cetyl trimethylamonium bromide (CTAB, 1 mmol/L). The total concentrations of aluminium(lll) ion used were 0.5, 1.0, 2.5 and 5.0 mmol/dm. Measurements were made in the pH interval between 2.5 and 4.8. The model comprising the species (1,-1), (3,4) and (13,-32) constitutes the skeleton for all studied systems, in the pH interval 3.6 4.5. In addition to this model, to fit the data in 0.01 and 0.1 Μ LiCI medium it was necessary to include the soluble (1,-3) complex in a speciation scheme. This complex was also included in the presence of non-ionic surfactants. Re-dissolution of colloidal AI(OH)3 is hindered in the presence of SDS and CTAB but in considerably lesser extent in the presence of tween and triton X-100. All surfactants used mainly exert influence on higher molecular weight hydrolytic species of aluminium. Non-ionic surfactants (tween-20 and triton-x 100) influence the hydrolysis only slightly in terms of the stability constants of the hydrolytic complexes. The ionic surfactants (SDS and CTAB) influence the hydrolysis considerably in terms of both, the speciation and the stability of the formed hydrolytic complexes. The speciation is significantly changed i.e. (1,-3) complex was not detected, while much higher values for the stability constants of (3,-4) and (13, -32) hydrolytic species were obtained, than in the pure ionic medium. These effects were explained by the hydrophobic/hydrophilic properties of the surfactants as well as their solubilizing power. INTRODUCTION Aluminium(lll) ion in water solutions is very prone to hydrolysis [1]. The extent of hydrolysis, identity and stability of hydrolytic species formed in solution depend upon the nature and concentration of the supporting ionic medium, pH of the solution, the nature and concentration of the base used to force the hydrolysis, ageing time and the presence of other substances which may interact with aluminium(lll) ion and/or water molecules. Therefore, a wide variety of experimental protocols and methods for the data treatment have been used in studying the aluminium hydrolysis [2], As regards the Potentiometrie measurements of aluminium hydrolysis, two main approaches to the experimental protocol have been employed so far. First protocol is based on establishing of nearly true thermodynamic equilibrium in the solution while the other one is based on the measurements performed in metastable, steady state of the system. It is believed that thereby obtained speciation reflects one definite state of the system and that slow polymerization does not affect this state considerably. Titrations are performed either as continuous or batch. Taking into account slowness of the hydrolysis in the intermediate interval of pH (pH 4.0 4.5) batch titrations are advantageous, however, relatively small number of points and disturbance of standard electrode potential during the measurements limit the use of this method. Most frequently, continuous titrations were used. Their inherent drawbacks (diffusion, leak of reference electrode electrolyte, drift of potential) were mainly overcome by suitable experimental setup (use of Wilhelms bridge, anti-diffusion tips, etc). Main difficulty in spite of everything, remains stability of electrode readings over a prolonged period of time needed for hydrolysis to go to completeness. Usually, potential of electrode is monitored every 1 2 min after addition of the titrant and it is somewhat arbitrarily decided that if the potential does not change more than 0.1 0.05 mV during 5 1 0 min, to proceed with titration. When permanent drift of potential is encountered or turbidity was observed either visually or by turbidimetry, the titration is stopped. For the purpose of data analysis only points obtained in true solution are selected. There is no unique model for aluminium hydrolysis. The data accumulated so far indicate that at very low aluminium concentrations (micromolar) and in mildly acidic solutions (pH 3 5 ) mononuclear hydrolytic complexes, AI(OH) and AI(OH)2 are formed, rapidly and reversibly, by

Complex formation equilibria in iron(III)-L-alanine system

SummaryComplex formation in iron(III)-L-alanine solutions was studied by emf glass electrode and spectrophotometric measurements, in 0.5 mol dm −3 (Na)NO3 medium, at 25 ° C. In the concentration range 0.5 ⩽ [Fe]0 ⩽ 20.0, 5.0 ⩽ [Ala]0 ⩽ 1000.0 (mmol dm−3) and 1.0 ⩽ -log [H+] ⩽ 3.5; {[Ala]/[Fe] = 10:1-100:1| the equilibria in the title system were explained by the model including the species FeHL, FeL, Fe(OH)L, Fe2(OH)2L2 (where HL denotes L-alanine) and several hydrolytic products. The stability constants of complexes are given. The mechanism of formation and structure of complexes in solution is proposed.

Stereospecific ligands and their complexes. XXIV. Synthesis, characterization and some biological properties of Pd(II) and Pt(II) complexes with R2-S,S-eddtyr

Four new platinum(II) complexes of general formula [PtCl2(R2-S,S-eddtyr)] (R = ethyl, n-propyl, n-butyl and n-pentyl); S,S-eddtyr = ethylenediamine-N,N′-di-(2,2′-di(4-hydroxy)-benzyl-acetic acid) have been synthesized and characterized by microanalysis, and infrared, 1H NMR and 13C NMR spectroscopy. The in vitro antimicrobial activity of ligands L1–L4 [L = R2-S,S-eddtyr; R = ethyl (L1), n-propyl (L2), n-butyl (L3), n-pentyl (L4)], platinum(II) complexes C1–C4 [PtCl2(R2-S,S-eddtyr)] [R = ethyl (C1), n-propyl (C2), n-butyl (C3), n-pentyl (C4)] and palladium(II) complexes C5–C8 [PdCl2(R2-S,S-eddtyr)] [R = ethyl (C5), n-propyl (C6) or n-butyl (C7) or n-pentyl (C8)] was investigated. The cytotoxicity of ligands and platinum(II) complexes was investigated using MTT assay. The interaction of platinum and palladium complexes [MCl2(R2-S,S-eddtyr)] (M = Pt or Pd) with calf thymus DNA (CT-DNA) was investigated using UV-Vis absorption and fluorescence spectroscopy. The association constant (Kb) estimated from the absorption spectral study and the quenching constant (KSV) calculated from relevant fluorescence quenching data indicate a non-covalent interaction between the metal complex and DNA. Ethidium bromide (EB) competitive studies revealed that complexes C1–C8 could interact with CT-DNA through intercalation. Furthermore, the interactions between human serum albumin (HSA) and the platinum(II) and palladium(II) complexes were also investigated by UV-Vis absorption and fluorescence spectroscopy, showing that the new complexes could strongly bind with HSA.

Synthesis, structural analysis, solution equilibria and biological activity of rhodium(III) complexes with a quinquedentate polyaminopolycarboxylate

Two rhodium(III) complexes [Rh(ed3a)(OH2)]·H2O (1) and Na[Rh(ed3a)Cl]·H2O (2) with ethylenediamine-N,N,N′-triacetate (ed3a) have been synthesized and characterized by elemental, spectroscopic and structural analyses. The crystal structure of (1) and (2) and the spectroscopic analysis of the two rhodium(III)–ed3a complexes are discussed in detail. The protonation constants of H3ed3a and the conditional stability constants of its RhIII complexes have been determined in aqueous solution by pH potentiometry and UV-Vis spectrophotometry. Molecular mechanics (MM) and density functional theory (DFT) have been used to model all possible geometric isomers, determine the global energy minimum and compare the computed with the experimentally observed structures. The cytotoxic activity of the new RhIII complexes was evaluated by an MTT assay against four human cancer lines (MCF-7, A549, HT-29 and HeLa) and a normal human cell line (MRC-5). A549, HT-29 and HeLa cells were sensitive to all compounds tested, while the breast carcinoma cell line MCF-7 was only sensitive to the reference compounds (doxorubicin and cisplatin). Western blot (WB) analysis of the effects of the tested compounds indicates that both complexes increase the expression of caspase 3 and consequently the involvement of this enzyme in apoptotic processes of the treated cells. WB also demonstrates proteolytic cleavage of poly-(ADP-ribose)polymerase (PARP) in HeLa cells after treatment with both tested substances. Flow cytometry confirmed apoptotic cell death and showed the induction of cell cycle termination as a possible promoter of apoptosis.

The Effect of Tigecycline on the Binding of Fluoroquinolones to Human Serum Albumin

Abstract The co-administration of several drugs in multidrug therapy may alter the binding of each drug to human serum albumin (HSA) and, thus, their pharmacology effect. Therefore, in this study, the interaction mechanism between HSA and two fluoroquinolones (FQs), sparfloxacin (SPF) and levofloxacin (LVF), was investigated using fluorescence and absorption methods in the absence and presence of the competing drugtigecycline (TGC). The the UV-Vis and fluorescence spectroscopy results showed that the fluorescence quenching of HSA was a result of the formation of the HSA-SPF and HSA-LVF complexes. The fluorescence quenching of HSA-TGC revealed that tigecycline can regulate the binding sites, binding mode and binding affinity of fluoroquinolones. The binding constants (KA) and binding sites (n) of the interaction systems were calculated. The results confirmed that the KA values of the HSA-FQ system decreased in the presence of TGC, indicating that TGC can affect the binding ability of FQ for HSA. This interaction may increase the free plasma concentration of unbound FQ and enhance their pharmacology effect.