Spectrophotometric Study of Mithramycin Complexes with Cu(II), Fe(III) and Tb(III)

Abstract

The coordination of the anticancer drug mithramycin to Tb(III), Fe(III) and Cu(II) was studied in aqueous solution using absorption measurements. The stability constants were calculated from equilibrium competition experiments by means of the SQUAD program. For both first ions, the competitor was oxalic acid and for the latter the competitor was the Cu(II) ions. Cu(II) at pH 7.5, Fe(III) at pH 3.5 and Tb(III) at pH 5.5 formed respectively 1:2, 1:3 and 1:4 metal-to-ligand species.     

Spectrophotometric and polarographic investigation of the Ofloxacin-Cu(II) complexes

By means of spectrophotometric methods it was found that ofloxacin reacts with copper(II) ions to form complexes with molar ratios of ofloxacin: Cu(II) of 1:1 at pH 4.00, 2:1 at pH 7.02 and 3:1 at pH 8.30. The stability constants of the complexes were determined. The formation of ofloxacin:Cu(II) 1:1 and 3:1 complexes was confirmed by a polarographic method and the corresponding overall stability constant was evaluated.     

A study of polyamine complex formation with H+, Cu(II), Zn(II), Pb(II), and Mg(II) in aqueous solution

Summary The composition and stability of the following biogenic amine complexes have been investigated: 1,4-diaminobutane(Put), 4-azaoctane-1,8-diamine(Spd), 4,9-diazadodecan-1, 12-diamine(Spm) as well as homologues such as 1,3-diaminopropane(Put3), 4-azaheptane-1, 7-diamine(Spd3,3) and 4,8-diazaundecan-1,11-diamine(Spm3,3,3) with H⁺, Cu(II), Zn(II), Pb(II) and Mg(II). A potentiometric method was used. The VIS technique enabled the determination of coordination mode in copper/amine systems. It was found that Mg(II) does not form coordination compounds with any of the studied polyamines in solution. An increase in the concentration of ligand and metal was found to result in a stronger tendency towards the formation of protonated compounds accompanied by a decrease in the concentration of hydroxocomplexes. At physiologicalpH (7.4) an increase in the concentration of protonated compounds by approximately 15% was observed within the ligand concentration range from 0.001 mol dm^–3 to 0.0001 mol dm^–3 at a Cu(II) concentration of 0.000177 mol dm^–3.

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Untersuchungen zur Komplexbildung von Polyaminen mit H⁺, Cu(II), Zn(II), Pb(II) und Mg(II) in wäßriger Lösung

Zusammenfassung Anhand einer Analyse von potentiometrischen Daten wurden Zusammensetzung und Beständigkeit folgender biogener Aminkomplexe untersucht: 1,4-Diaminobutan(Put), 4-Azaoktan-1,8-diamin(Spd), 4,9-Diazadodekan-1,12-diamin(Spm), sowie auch deren Homologen 1,3-Diaminopropan(Put3), 4-Azaheptan-1,7-diamin(Spd3,3) und 4,8-Diazaundekan-1,11-diamin(Spm3,3,3) mit H⁺, Cu(II), Zn(II), Pb(II) und Mg(II). Mit Hilfe der VIS-Technik wurde die Koordinationsweise in Kupfer/Amin-Systemen bestimmt. Es wurde festgestellt, daß Mg(II) keine Koordinationsverbindungen mit den untersuchten Polyaminen bildet. Eine höhere Konzentration von Ligand und Metall führte zu stärkerer Tendenz der Bildung protonierter Verbindungen, wobei die Konzentration von Hydroxokomplexen kleiner wurde. Bei physiologischempH (7.4) wurde im Bereich der Ligand-Konzentration von 0.001 mol dm^–3 bis 0.0001 mol dm^–3 bei einer Cu(II)-Konzentration von 0.000177 mol dm^–3 ein Anstieg der Konzentration protonierter Verbindungen um etwa 15% beobachtet.

     

The complex formation of calcium with aliphatic dipeptides

Dissociation constants for complexes of calcium with a series of dipeptides consisting of glycine, alanine, leucine and proline have been determined bypH-titrations. Two of these dissociation constants were checked by means of titration using a calcium sensitive electrode. The influence of the side chains on the stability of the complexes is discussed. Calcium forms only 1:1 complexes of the type CaLH⁺ (LH₂ = H₃ -CHR-CO-NH-CHR-COO^–) and probably also of the type CaLH ₂ ²⁺ . The two PMR signals of the non-equivalent methylene protons of glycylglycine were measured with and without the addition of calcium chloride at variouspH. On the basis of these results, possible structures of the complexes CaLH⁺ are postulated.

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Komplexbildung von Calcium mit aliphatischen Dipeptiden

Zusammenfassung Für eine Reihe Reihe von Dipeptiden, bestehend aus den Aminosäuren Glycin, Alanin, Leucin und Prolin, wurden Dissoziationskonstanten für deren Calcium-Komplexe mit Hilfe vonpH-Titrationen bestimmt. Zwei dieser Dissoziationskonstanten wurden durch Messung mit einer Ca-sensitiven Elektrode überprüft. Der Einfluß der Seitenketten auf die Stabilität der Komplexe wird diskutiert. Calcium bildet nur 1:1 Komplexe der Form CaLH⁺ (LH₂=H₃ -CHR-CO-NH-CHR-COO^–) und vielleicht auch der Form CaLH ₂ ²⁺ . In einer H¹-NMR Untersuchung wurden die Signale der beiden nicht äquivalenten Methylengruppen von Glycylglycin gemessen, und zwar mit und ohne Zugabe von Calciumchlorid bei verschiedenstenpH-Werten. Auf Grund dieser Ergebnisse werden mögliche Strukturen für die Komplexe vorgeschlagen.

     

Stability constants of phthalate complexes of copper (II), nickel (II), zinc (II), cobalt (II), uranyl (II) and throium (IV) by paper electrophoresis

Summary Stoichiometric stability constants of Cu(II), Ni(II), Zn(II), Co(II), UO₂(II) and Th(VI) phthalate have been determined by paper electrophoresis. Phthalic acid (0.005 mol dm⁻³) was added to the background electrolyte: 0.1 mol dm⁻³ HClO₄. The proportions of C₆H₅C₂O ₄ ⁻ and C₆H₄C₂O ₄ ⁼ were varied by changing the pH of the electrolyte. These anions yielded the complexes, Cu C₆H₅C₂O ₄ ⁺ , Cu C₆H₄C₂O₄, Zn C₆H₅C₂O ₄ ⁺ , Co C₆H₅C₂O ₄ ⁺ , Ni C₆H₅C₂O ₄ ⁺ , UO₂ C₆H₅C₂O ₄ ⁺ , UO₂ (C₆H₄C₂O₄) ₂ ⁼ and Th (C₆H₄C₂O₄)₂ whose stability constants are found to be 10^3.0, 10^4.7, 10^2.6, 10^2.5, 10^2.3, 10^3.5, 10^12.6 and 10^13.4 respectively (μ=0.1, temp 40°C).     

Stability of Copper(II), Nickel(II) and Zinc(II) Binary and Ternary Complexes of Histidine,Histamine and Glycine in Aqueous Solution

The binary and mixed-ligand complexes formed between ligands (histidine (His), histamine (Him) and glycine (Gly)) and some transition metals (Cu(II), Ni(II) and Zn(II)) were studied potentiometrically in aqueous solution at (25.0 ± 0.1) C and I = 0.10 M KCl in order to determine the protonation constants of the free ligands and stability constants of binary and ternary complexes. The complexation model for each system has been established by the software program BEST from the potentiometric data. The most probable binding mode for each binary species of histidine and for all mixed species was also discussed based upon derived equilibrium constants and stability constants related to the binary species. The ambidentate nature of the histidine ligand, i.e. the ability to coordinate histamine-like, imidazolepropionic acid-like and glycine-like modes was indicated from the results obtained. The stability of ternary complexes was quantitatively compared with their corresponding binary complexes in terms of the parameters, log K, log X and ₁₁₁₀. The concentration distributions of various species formed in solution were also evaluated. In terms of the nature of metal ion, the complex stability follows the trend Cu(II) > Ni(II) > Zn(II), which is in agreement with the Irving-Williams order of metal ions. Thus, the results obtained were compared and evaluated with those in the literature.     

Synthesis,complex formation kinetics and thermodynamic study of some acyclic polyamine and N2O2 ligands with copper(II)

The polydentate ligands, 3-(2-aminocyclohexylamino)-2-(2-aminocyclohexyl aminomethyl) propionic acid (L¹ ), 4,7,10-triazatridecanedinitrile trihydrochloride (L² ), and 2,2′-(ethane-1,2-diyl) bis(methylazanediyl) diethanol (L³ ) were prepared and their structures investigated by FT-IR, NMR, and MS. The kinetics of complex formation between Cu(II) and L¹, L², and L³ were investigated in acidic aqueous solutions using the stopped-flow method. The stability constants of the complexes were determined by spectrophotometric titration (T?=?293?K, μ?=?0.1?mol?L^?1 NaClO₄), using a diode array UV-Vis spectrophotometer equipped with peristaltic pump and pH meter. The stability constants for the complexes were CuL^1?>?CuL^2?>?CuL³. Activation enthalpies (ΔH#) of these complexes were 55?kJ?mol^?1 for CuL¹, 61?kJ?mol^?1 for CuL², and 36?kJ?mol^?1 for CuL³, respectively.     

SOLVERSTAT: a new utility for multipurpose analysis. An application to the investigation of dioxygenated Co(II) complex formation in dimethylsulfoxide solution

A new utility for multipurpose analysis, SOLVERSTAT, taking advantage of the versatility of spreadsheets is here described. By means of this tool advanced statistical tests have introduced in Microsoft Excel Solver thus allowing regression diagnostic and discrimination between different models. The utility is here applied to the determination, by UV-Vis spectroscopy, of the stability constant for the uptake of molecular dioxygen by the 1:2 complex of Co(II) with N,N′-dimethylethylenediamine (dmen) in the aprotic solvent dimethylsulfoxide (dmso) at 298 K and in a medium adjusted to 0.1 mol dm⁻³ with Et₄NClO₄. The reliability of the model and parameters obtained are discussed and the results compared with those obtained by Dynafit, a different software package, and by independent voltammetric measurements. The validity of SOLVERSTAT has been also examined applying it to the discrimination between different models already discussed in the literature.     

Spectrophotometric study of uranium(VI) complex equilibria with N,N-dimethylformamide

Spectrophotometric study of solvation equilibria of uranium(VI) with N,N-dimethyl formamide (DMF) in solutions with ionic strength I = 3.0 mol^.dm^-3 (Na, H)ClO₄ shows that DMF forms with UO₂ ²⁺ several relatively stable solvates absorbing in VIS range (350-490 nm). The absorbance of UO₂ ²⁺ bands increases and their absorption maxima shift to longer wavelengths while uranyl solvates are formed stepwise with increasing concentration of DMF. Areas of prevailing existence of individual solvates with stoichiometry 1 : n (n = 1, 2, 4, 6) have been found and their stability constants and molar absorption coefficients estimated using both graphical methods and computer minimization programs.     

Spectrophotometric study of the complex formation of 3-(2-hydroxyphenyl)-2-mercaptopropenoic acid with Ni(II) and Zn(II)

The dissociation and complex formation equilibria between Ni(II) and Zn(II) with 3-(2-hydroxyphenyl)-2-mercaptopropenoic acid, at 25 degrees in aqueous 0.1 and 1.0M sodium perchlorate solutions, containing about 1% ethanol, have been studied spectrophotometrically. The data were connected directly from the spectrophotometer to an IBM-PC via a serial interface, using the DUMOD program (written in BASIC), described in the paper. The obtained spectra were treated by the factor analysis program NIPALS in order to determine the number of absorbing species and the experimental error. Dissociation constants of ligand (H(3)L), and formation constants for the complexes Ni(HL), Ni(HL)(2), Zn(HL) and Zn(HL)(2) at 0.1 and 1.0M ionic strengths, refined by the SQUAD program, are reported.     

Synthesis,characterization, equilibria and biological activity of dimethyltin(IV) complex with 1,4-piperazine

The interaction of dimethyltin(IV) dichloride (DMT) with 1,4-piperazine (PIP) was investigated. The complex formation equilibria of the complexes formed in solution were investigated. The stoichiometry and stability constants of the complexes formed in solution phase were determined at different temperatures and in solutions of dioxane–water mixtures of different dielectric constants. The equilibrium constant for the displacement of piperazine coordinated to dimethyltin(IV) by inosine as a representative of DNA was calculated. (DMT)(PIP)·3H₂O was synthesized and characterized by elemental analysis, spectral, and thermal techniques. The antitumor activity of the complex was screened.     

Potentiometric study of complex formation equilibria of alpha-oxooximes with copper(II) and nickel(II) and ions

Complex formation equilibria between copper(II) and nickel(II) with phenylglyoxal 2-oxime (HPGO) and 1-phenyl-1,2-propanedione 2-oxime (HPPO) have been studied in 50% (v/v) ethanol-water solution containing 0.5M sodium nitrate as constant ionic medium at 25 degrees , using glass electrode potentiometry. The emf data obtained have been analysed with MINIGLASS and SUPERQUAD programs. Formation constants for the Cu(PGO)(+), Cu(2)(PGO)(OH)(2+), Cu(2)(PGO)(2)(OH)(+), Ni(PGO)(+), Ni(2)(PGO)(3)(+), Ni(2)(PGO)(4), Ni(2)(PGO)(2)(OH)(2), Cu(2)(PPO)(OH)(+) and Cu(2)(PPO)(2)(OH)(+) complexes are reported.     

The Interaction of Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) with Mixed Donor Macrocycles Containing Pendant Carboxylic Acid Functions

The syntheses of mixed oxygen-nitrogen donor macrocycles incorporating two or three pendant carboxylic acid groups are described. Potentiometric titrations in water (I = 0.1; KNO₃) at 25°C have been used to determine the stability constants for the 1: 1 (metal:ligand) complexes of Co(II). Ni(II), Cu(II), Zn(II), and Cd(II). The constants obtained are compared with the previously determined values for the corresponding complexes of the unsubstituted macrocyclic precursors. The results of these studies indicate that each carboxylate function participates in binding to the central metal. For some metal-ion/ligand systems there is evidence that ring size effects influence the overall stability patterns and that, in such cases, both the ether oxygens as well as the tertiary amines of the macrocyclic rings appear to bind to the metal.     

Mode of coordination and stability of Cu(II) and Zn(II) complexes with adenosine,deoxyadenosine, cytidine and deoxycytidine

Summary Stability constants of Cu(II) and Zn(II) complexes with nucleosides have been determined from a computer analysis of potentiometric titration results. Spectral investigations prove that in acidic solution adenosine coordinates to Cu(II)via its N1 or N7 atoms, while atpH>7 only N7 is involved. Similar interactions are observed for dAdo complexes. Spectral and potentiometric studies suggest that Zn does not form stable complexes with dAdo. In the case of cytidine and deoxycytidine, the preferred site of coordination is the N3 atom of the nucleoside. Oxygen atoms from the carbonyl groups are not involved in Cu(II) or Zn(II) coordination. The results of the spectral investigation have excluded the ribose and deoxyribose moieties of all studied ligands from participation in the interactions. In general, the mode of coordination of nucleosides and deoxynucleosides with Cu(II) and Zn(II) has been found analogous.

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Art der Koordination und Stabilität von Cu(II)- und Zn(II)-Komplexen mit Adenosin, Deoxyadenosin, Cytidin und Deoxycytidin

Zusammenfassung Mittels einer Computeranalyse von Ergebnissen aus potentiometrischen Titrationen wurden Stabilitätskonstanten für Komplexe aus Cu(II) bzw. Zn(II) und Nucleosiden bestimmt. Spektroskopische Untersuchungen zeigen, daß Adenosin in saurer Lösung über N1 oder N7 an Cu(II) koordinieren kann, während beipH>7 nur N7 reagiert. Analoges wird für die Komplexe mit dAdo beobachtet. Aus spektroskopischen und potentiometrischen Untersuchungen geht hervor, daß Zn mit dAdo keine stabilen Komplexe bildet. Im Fall von Cytidin und Deoxycytidin ist N3 die bevorzugte Koordinationsstelle des Nucleosids. Die Sauerstoffatome der Carbonylgruppen sind an der Bindung an Cu(II) und Zn(II) nicht beteiligt. Die spektroskopischen Ergebnisse schließen eine Beteiligung der Ribose- und Deoxyriboseeinheiten an den Wechselwirkungen aus. Allgemein wurde für Nucleoside und Deoxynucleoside ein analoger Koordinationsmodus gefunden.

     

Polarographic study of composition and stability constants of Pb(II) N-(2-acetamido) imino diacetate complexes

Summary The complexation of Pb(II) by N-(2-acetamido) imino diacetate (ADA) has been studied polarographically (dc and ac polarographic techniques). Ac polarographic studies have been particularly helpful in deciding the reversibility of the reduction of both simple and complexed metal ions and for confirmation of the overall stability constants. A weighted least squares numerical technique has been applied for the calculation of the overall stability constants using both dc and ac techniques. The reduction of Pb(II) in N-(2-acetamido) iminodiacetate solutions has been found to be reversible and diffusion controlled, involving a two electron transfer process. Potential vs. concentration data at =0.1 mol dm^–3 (KNO₃) are interpreted on the basis of the formation of two complex species PbADA and Pb(ADA)^2– in thepH range 6.85–8.50. The logarithms of the stability constants (calculated from ac measurements) of these complexes are 8.73±0.12, 10.86±0.18 at 25°C, 8.31±0.28, 10.31±0.09 at 35°C and 7.61±0.20, 10.10±0.11 at 45°C, respectively. The thermodynamic parameters G, H and S have been calculated at 35°C.

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Polarographische Untersuchung von Zusammensetzung und Stabilitätskonstanten von Pb(II) N-(2-Acetamido)iminodiacetat-Komplexen

Zusammenfassung Es wurde die Komplexierung von Pb(II) mit N-(2-Acetamido)iminodiacetat (ADA) polarographisch mittels DC- und AC-Techniken untersucht. Insbesonders AC-Polarographie ergab eine klare Entscheidung bezüglich der Reversibilität der Reduktion von einfachen und komplexierten Metallionen und für die Bestätigung der Stabilitätskonstanten. Zur Bestimmung der Gesamtstabilitätskonstanten wurde eine gewichtete mittlere Fehlerquadrat-Methode auf Basis von DC- und AC-Messungen herangezogen. Die Reduktion von Pb(II) in N-(2-Acetamido)iminodiacetat-Lösung stellte sich als ein reversibler und diffusionskontrollierter Zweielektronen-Transferprozess heraus. Die Abhängigkeit des Potentials von der Konzentration bei =0.1 mol dm^–3 (KNO₃) läßt sich mit der Bildung von zwei Komplex-Spezies PbADA und Pb(ADA)^2– impH-Bereich 6.85–8.50 erklären. Die Logarithmen der Stabilitätskonstanten dieser Komplexe (aus AC-Messungen) sind 8.73±0.12 und 10.86±0.18 bei 25°C, 8.3 ±0.28 und 10.31±0.09 bei 35°C bzw. 7.61±0.20 und 10.10±0.11 bei 45°C. Die thermodynamischen Parameter G, H und S wurden für eine Temperatur von 35°C berechnet.

     

Unexpected formation of the copper(II) dinuclear mixed-ligand species in the ternary system of N,N,N′,N″,N″-pentamethyldiethylenetriamine with methionine- or histidinehydroxamic acids in aqueous solution

Equilibrium studies of the mixed-ligand complexes of the copper(II) ion with pentamethyldiethylenetriamine (N,N,N′,N″,N″-pentamethyl-[bis(2-aminoethyl)amine], Me₅dien) as a primary ligand and methioninehydroxamic acid (2-amino-4-(methylthio)butanehydroxamic acid, Metha) or histidinehydroxamic acid (2-amino-3-(4′-imidazolyl)propanehydroxamicacid, Hisha) as a secondary ligand L were performed by potentiometric titration, UV–Vis and EPR spectroscopy. The results show that in these ternary systems the dinuclear [Cu₂(Me₅dien)L₂H₋₁]⁺ mixed-ligand species is formed as a predominant one in the basic solution. The monouclear [Cu(Me₅dien)L]⁺ species is formed in low concentration. Our spectroscopic results indicate that the geometry of these mixed-ligand five-coordinate complexes is strongly distorted towards trigonal-bipyramidal.