Determination of Stability Constants of Metal Complexes by Capillary Electrophoresis

The stability constants of several divalent first row transition and trivalent lanthanide metal complexes were determined by capillary electrophoresis (CE) methods. Four different approaches, i.e. direct formation, ligand exchange, metal exchange and metal-ligand double exchange were developed. To verify if these CE methods are indeed applicable, the stability constant of CuHEDTA was re-determined to be 17.47 ± 0.20 (consistent with the published 17.50) using the CuEDTA and ZnHEDTA metal-ligand double exchange approach. The stability constants of lanthanide (Ce³⁺ and Eu³⁺) and transition metal (Ni²⁺ and Zn²⁺) complexes of an aminopolycarboxylate ligand, DO2A (1,7-dicarboxymethyl-1,4,7,10-tetraazacyclododecane) were measured under the direct complex formation condition. The stability constant of the NiDO2A complex was determined by the ligand exchange method using 1,4,8,11-tetraazaundecane (2,3,2-tet) as the competing ligand. The stability constant of CuDO2A complex was determined by the metal exchange method using Zn²⁺ ion as the competing metal ion, and complex formation competitions of Ni²⁺ and Cu²⁺ between DO2A and 2,3,2-tet were studied by the metal-ligand double exchange method. Effects of experimental conditions and the advantages and limitations of these CE methods are discussed.     

Thermochemical study of the stepwise protonation of 1,10-diaza-4,7-dithiadecane,and its complex formation with copper(II) and nickel(II) ions in aqueous solution

The behaviour of 1,10-diaza-4,7-dithiadecane (2,2,2-NSSN) in aqueous solution in equilibria with protons, Cu²⁺ or Ni²⁺ ions has been investigated potentiometrically and calorimetrically. The protonation constants for the ligand, and the stability constants for its complexes at 25°C in 0.5 mole dm^?3 (K)NO₃ are reported, together with the corresponding thermodynamic parameters ΔG, ΔH and ΔS. The results are compared with those for 1-aza-4-thiapentane and 1,7-diaza-4-thiaheptane. The ligand 2,2,2-NSSN forms complexes of formula ML²⁺ and MHL³⁺ with both Cu²⁺ and Ni²⁺. It is found that in the non-protonated 1:1 complexes the ligand acts as a tetradentate. In the CuHL³⁺ complex, the ligand is bound through one nitrogen and two sulphur donors, whereas in the NiHL³⁺ complex the ligand is probably bound through only one nitrogen and one sulphur donor. Explanations are suggested.     

Stability Constants of Complexes of Divalent and Rare Earth Metals with Substituted Salicynals

 5-Chloro-4-6-dimethyl-salicylaldehyde was synthesized from 4-chloro-3,5-dimethyl-phenol. A series of substituted salicynals were obtained by condensation of 5-chloro-4,6-dimethyl-salicylaldehyde with several amines. The amines were chosen such as to vary the basicity of salicynals by changing the substituents at one of the coordination sites. The stability constants of complexes of bivalent (Mg²⁺, Ca²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺) and trivalent (Y³⁺, La³⁺, Pr³⁺, Nd³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Er³⁺, Yb³⁺) metal ions with these salicynals and the pK values corresponding to the dissociation of the phenolic proton and the association of a proton to the azomethine nitrogen were determined potentiometrically using the Calvin-Bjerrum technique as adopted by Irving and Rossotti at 303 K and a constant ionic strength of 0.1 M in a 75:25 (v/v) dioxan-water mixture in an inert atmosphere. The influence of substituents on the proton affinity of the ligands was examined on the basis of inductive and mesomeric effects. It is also shown that some of the complexes possess antibacterial, antitubercular, antifungal, and anticoagulant activity.     

Stability Constants of Complexes of Divalent and Rare Earth Metals with Substituted Salicynals

Summary.  5-Chloro-4-6-dimethyl-salicylaldehyde was synthesized from 4-chloro-3,5-dimethyl-phenol. A series of substituted salicynals were obtained by condensation of 5-chloro-4,6-dimethyl-salicylaldehyde with several amines. The amines were chosen such as to vary the basicity of salicynals by changing the substituents at one of the coordination sites. The stability constants of complexes of bivalent (Mg²⁺, Ca²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺) and trivalent (Y³⁺, La³⁺, Pr³⁺, Nd³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Er³⁺, Yb³⁺) metal ions with these salicynals and the pK values corresponding to the dissociation of the phenolic proton and the association of a proton to the azomethine nitrogen were determined potentiometrically using the Calvin-Bjerrum technique as adopted by Irving and Rossotti at 303 K and a constant ionic strength of 0.1 M in a 75:25 (v/v) dioxan-water mixture in an inert atmosphere. The influence of substituents on the proton affinity of the ligands was examined on the basis of inductive and mesomeric effects. It is also shown that some of the complexes possess antibacterial, antitubercular, antifungal, and anticoagulant activity. Received August 5, 1999./Accepted November 11, 1999     

Spectrophotometric determination of the formation constants of some transition metal cations with a new synthetic Schiff base in dichloromethane and chloroform using rank annihilation factor analysis

The complex formation between a new synthesized Schiff base and the cations Ni²⁺, Co²⁺, Cu²⁺, Zn²⁺ in dichloromethane (DCM) and chloroform solutions was investigated spectrophotometrically using rank annihilation factor analysis (RAFA). The results of mole ratio plots and continuous variation data show the stoichiometry of complexation were found to be 1:1, and 2:1 metal ion to ligand. The stoichiometry was obtained as 1:1 metal ion to ligand ratio for Co²⁺, Ni²⁺ and Zn²⁺ in chloroform and 2:1 for Cu²⁺. In DCM the stoichiometry was obtained as 1:1 for Co²⁺ and 2:1 for Ni²⁺ and Zn²⁺ and a consecutive 2:1 metal ion to ligand ratio was obtained for Cu²⁺. Formation constants of these complexes were estimated by application of RAFA on spectrophotometric data. In this process the contribution of ligand was removed from the absorbance data matrix when the complex stability constant acts as an optimizing object and simply combined with the pure spectrum of the ligand, the rank of the original data matrix can be reduced by one by annihilating the information of the ligand from the original data matrix.     

Complexation of di-benzyloxy ether derivatives of calix[4]arene with alkali earth metal cations

The synthesis and complexing abilities of 26,28-bis-benzyloxy-25,27-dihydroxy-5,11,17,23-tetra-tertbutyl-calix[4]arene towards alkali earth metal ions Mg²⁺, Ca²⁺, Sr²⁺, and Ba²⁺ in a methanol-chloroform mixture have been evaluated at 25°C, using UV-Vis spectrophotometric techniques. The results showed that the ligand is capable to complex all alkali earth cations by 1:1 metal to ligand ratios. The selectivity presented considering the calculated stability constants are in the order Mg²⁺ > Ca²⁺ > Sr²⁺ > Ba²⁺ towards the ligand.     

Syntheses,Characterization, and DNA Binding Studies of a Series of Copper(II), Nickel(II), Platinum(II) and Zinc(II) Complexes Derived from Schiff Base Ligands

Three series of metal salophen complexes derived from Zn²⁺, Cu²⁺, Pt²⁺ and Ni²⁺ have been synthesized and their interaction with quadruplex DNA has been evaluated. The compounds differ on the number of ethyl piperidine substituents. They have been characterized by ¹H NMR, IR and UV-visible spectroscopies and by HR-mass spectrometry. Their luminescent properties have been also evaluated and we can observe that, as expected, Zn²⁺ and Pt²⁺ complexes are those displaying more interesting luminescence with an emission band red-shifted with respect to the corresponding uncoordinated ligand. DNA interactions with G4 and duplex DNA were evaluated by FRET melting assays (for the Zn²⁺, Cu²⁺ and Ni²⁺ complexes) and by emission titrations (for one Pt²⁺ complex) which indicated that the disubstituted compounds 2-Ni and 2-Pt are the only ones that display good affinity for G4 DNA structures.     

A Study of Formation Equilibria of the Complexes of Some Metal Cations with Polyoxa Macrocyclic Ligands

Abstract

The complexes formed by the Na⁺, K⁺, Rb⁺, Ca²⁺, UO²⁺ ₂, and Ag⁺ cations with the macrocyclic polyethers 18-crown-6, benzo-15-crown-5, and dicyclohexy1-18-crown-6 are investigated. The stability constants of these complexes have been determined potentiometrically in (90% vol.) ethanol-water solutions at 25[ddot]C and an ionic strength μ= 0.1 (achieved with tetrabuty lammonium perchlorate). The stablity of the investigated complexes was interpreted in terms of “caging” the metal cation into the cavity of the macrocyclic ligand, an effect which depends on the ratio of the diameter of the complexed cation over the diameter of the cavity of the complexing ligand.     

Determination and comparison of the stability constants of some bivalent ion complexes of 5,7-dichloro-, 5,7-dibromo-, and 5,7-dinitro-8-Hydroxyquinoline and their N-oxides

The stability constants of complexes of Mn⁺⁺, Fe⁺⁺, Co⁺⁺, Ni⁺⁺, Cu⁺⁺, Zn⁺⁺, Cd⁺⁺ and UO with 5,7-dichloro-, 5,7-dibromo- and 5,7-dinitro-8-hydroxyquinoline and their corresponding N-oxides have been determined in 75 + 25 v/v dioxan + water medium at 35°C in presence of 0.20 M sodium perchlorate by pH-titration technique as given by IRVING and Rossotti. A possible explanation for the observed orders of the stability constants of the metal complex with the different ligands, and of the complexes of a particular ligand with different metal ions is also proposed.     

Challenges in Modelling and Optimization of Stability Constants in the Study of Metal Complexes with Monoprotonated Ligands. Part II

The influence of 2‐hydroxy‐3‐[(2‐hydroxy‐1,1‐dimethylethyl)amino]propane‐1‐sulfonic acid (AMPSO=HL) on systems containing copper(II) was studied by glass‐electrode potentiometry (GEP) and direct‐current polarography (DCP), at fixed total‐ligand‐to‐total‐metal‐concentration ratios and various pH values (25°, 0.1M KNO₃ medium). The predicted model ([CuL]⁺, [CuL(OH)], [CuL₂], [CuL₂(OH)]^?, [CuL₂(OH)₂]^2?, and [CuL₃]^?) and the overall stability constants for species found were obtained by combining results from both electrochemical techniques. The last five complexes are reported for the first time. For the species [CuL]⁺, [CuL₂], [CuL₃]^?, and [CuL₂(OH)₂]^2?, it was possible to determine stability constants with reasonable certainty and their values, as log β, were found to be 4.62±0.04, 9.5±0.1, 13.4±0.1, and 21.2±0.1, respectively. For the species [CuL(OH)] and [CuL₂(OH)]^?, stability constants 11.7±0.2 and 15.6±0.2, respectively, are presented as indicative values. It was demonstrated that AMPSO buffer may decrease the Cu²⁺ concentration by ten orders of magnitude by forming complexes with Cu²⁺. For the first time, the correction in DCP waves for the adsorption of the ligand and quasi‐reversibility of the metal allowed to determine stability‐constant values that are in good agreement with the values obtained by GEP. The importance of graphic analysis of data and significance of employing two analytical techniques was demonstrated; neither GEP nor DCP would be able to provide the correct M/L/OH^? model and reliable stability constants when used independently.     

Construction of template ligand sites in polymeric matrices with dithizone

Metal ion specific template ligand sites were developed by physically immobilizing dithizone molecules oriented according to a particular complex geometry in various polymeric films. Four polymeric systems, polystyrene, poly(methyl methacrylate), poly(vinyl chloride), and polycarbonate, were used for making template sites for Cu²⁺, Ni²⁺, Zn²⁺, and Co²⁺ ions. A high degree of specificity could be achieved independent of stability constants, though about half of the ligand sites were unavailable to the metal ions. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 3729–3734, 1997     

Tandem mass spectroscopy as a tool for investigation of complexes of PNP‐lariat ether derivative with metal ions

The novel PNP‐lariat ether L with cyclotriphosphazene ring incorporated in the macrocyclic structure was synthesized and checked by the electrospray mass spectrometry (ESI‐MS) method for the ability to bind different types of ions Ag⁺, Ca²⁺, Cd²⁺, Cu²⁺, and Pb²⁺. Furthermore, the stability constants of the abovementioned ion complexes with the investigated ligand have been determined by direct and competitive potentiometric methods. To evaluate the stability of various complex types and to confirm the way of metal cation binding, the tandem mass spectra of the investigated ligand and its complexes were taken. As a result, we obtained quite a good relationship between the number and main types of complex species observed in ESI‐MS experiments and the forms of complexes for which the stabilization constants were determined by potentiometric methods. Moreover, we also concluded that in case of big discrepancies of stability constants, ESI‐MS experiments could provide information about the most stable form of the complexes, but they fail when the differences between the strength of the coordination binding are slightly different.     

Calculation of the equilibrium constants and binding cooperativity parameters of ammonia with Group II metal cations in solution

The matrix model was used to analyze the distribution diagrams and formation functions of ammonia complexes [M(NH₃) _n ]²⁺ (n = 0−4) of Group II metal ions (Mg²⁺, Ca²⁺, Zn²⁺, Cd²⁺, and Hg²⁺) in solution. Intrinsic binding constants of the ligand (K _in) and mutual influence corrections (ω) for complex formation with aqua ions in solution were calculated. The equilibrium constants were calculated by the matrix method. The coordination sphere of Mg²⁺, Ca²⁺, and Zn²⁺ by ammonia in a cooperative manner; with Cd²⁺ and Hg²⁺, both cooperative and anticooperative binding occur concurrently. Possibilities for differentiation between tetrahedral and square planar coordination polyhedra on the basis of the characteristic features of ligand binding, determined by the matrix model, are discussed.     

Complexation of Cd2+, Ni2+, and Ag+ metal ions with 4,13-didecyl-l,7,10,16-tetraoxa-4,13-diazacyclooctadecane in acetonitrile-ethylacetate binary mixtures

Conductometric titrations have been performed in acetonitrile-ethylacetate (AN-EtOAc) binary solutions at 288, 298, 308, and 318 K to obtain the stoichiometry, the complex stability constants and the standard thermodynamic parameters for the complexation of Cd²⁺, Ni²⁺, and Ag⁺ cations with 4,13-didecyl-1,7,10,16-tetraoxa-4,13-diazacyclooctadecane (cryptand 22DD). The stability constants of the resulting 1: 1 complexes formed between the metal cations and the ligand were determined by computer fitting of the conductance-mole ratio data. There is a non-linear relationship between the logK _f values of complexes and the mole fraction of ethylacetate in the mixed solvent system. In addition, the conductometric data show that the stoichiometry of the complexes formed between the Cd²⁺, Ni²⁺, and Ag⁺ cations with the ligand changes with the nature of the solvent. The standard enthalpy and entropy values for the 1: 1 [ML] complexation reactions were evaluated from the temperature dependence of the formation constants. Thermodynamically, the complexation processes of the metal cations with the C22DD, is mainly entropy governed and the values of thermodynamic parameters are influenced by the nature and composition of the binary mixed solvent solutions.     

Potentiometric and Thermodynamic Studies of 4-Sulfamethazineazo-3-methyl-1-phenyl-2- pyrazolin-5-one and Its Metal Complexes

Proton–ligand dissociation constants of 4-sulfamethazineazo-3-methyl-1-phenyl-2- pyrazolin-5-one (SMP) and metal–ligand stability constants of its complexes with bivalent metal ions (Mn²⁺, Co²⁺, Ni²⁺ , Cu²⁺, and Zn²⁺) have been determined potentiometrically in 0.1 M KCl, and a 40% (v/v) ethanol–water mixture. The order of the stability constants of the complexes was found to be Mn²⁺ < Co < Ni < Cu < Zn. The dissociation constants, pK ^H, of SMP and the stability constants, log K, of its complexes were determined at different temperatures and the corresponding thermodynamic parameters ( G, H, and S) were derived and discussed. The dissociation process is nonspontaneous, endothermic, and entropically unfavorable. The formation of the complexes were found to be spontaneous, endothermic, and entropically favorable.     

Facile Synthesis of Nitrogen Tetradentate Ligands and Their Applications in CuI‐Catalyzed N‐Arylation and Azide–Alkyne Cycloaddition

Five new tetradentate ligands [NNNN] with benzimidazolyl‐imine or amine nitrogen donors have been synthesized in good yields under mild conditions from easily available substrates. trans‐N,N′‐bis(1‐Ethyl‐2‐benzimidazolylmethylene)cyclohexane‐1,2‐diimine is the best accelerating ligand in this series that supports the Cu^I‐catalyzed Ullmann N‐arylation and the direct three‐component azide–alkyne cycloaddition reaction to give the corresponding substituted imidazole, pyrazole, and triazole in high yields. Single‐crystal X‐ray diffraction analysis of its complex with CuI reveals a novel one‐dimensional coordination polymer of the metal chain bridged alternately by the [NNNN] ligand and diiodides.     

Reactions of 2-pyrrole-[N-(o-hydroxyphenyl)aldimine] with metal ions

The Schiff-base 2-pyrrole-[N-(o-hydroxyphenyl)aldimine] has been synthesized by the condensation of 2-pyrrolecarboxaldehyde and o-aminophenol. Its reactions with several metal ions have been investigated. The Schiff-base behaved either as a bidentate monoaionic ligand with the pyrrole nitrogen intact and uninvolved in bonding to the metal, or as a tridentate dianion using the pyrrolate deprotonated nitrogen, the azomethine nitrogen and the phenolate oxygen in bonding. Thus complexes of Zn²⁺, Pb²⁺, Pd²⁺ and Pt²⁺ were synthesized with the ligand as a tridentate dianion; and complexes of Cu²⁺, Fe³⁺ and Co³⁺ were obtained with the Schiff-base behaving as a bidentate monoanion.     

Synthesis,characterization, speciation and biological studies on metal chelates of 1-benzoyl(1,2,4-triazol-3-yl)thiourea

Proton-ligand association constants of 1-benzoyl(1,2,4-triazol-3-yl)thiourea (BTTU) and its complex formation constants with some bivalent metal ions Ni(II), Co(II), Mn(II), Zn(II), and Cu(II), have been determined potentiometrically in 50% EtOH–H₂O and 0.1 M NaNO₃. The complexes formed in solution have a stoichiometry of 1:1 and 1:2 [M:L], where M represents the metal ion and L the BTTU ligand. The corresponding thermodynamic parameters are derived and discussed. The complexes are stabilized by enthalpy changes and the results suggest that complexation is an enthalpy-driven process. The effects of metal ion, ionic radius, electronegativity, and nature of ligand on the formation constants are discussed. The formation constants of the complexes with 3d transition metals follow the order Mn²⁺ < Co²⁺ < Ni²⁺ < Cu²⁺ > Zn²⁺. The metal complexes were synthesized and characterized by elemental analyses, conductance, IR, ¹H NMR, and magnetic measurements. The low magnetic moment of 0.11 BM for the Cu(II) complex is suggestive of dimerization through Cu–Cu interaction. The concentration distribution diagrams of the complexes were evaluated. The ligands and their metal complexes have been screened in vitro against some bacteria and fungi.     

Synthesis and Applications of a New Polysiloxane-Immobilized Macrocyclic Ligand System

Abstract

Insoluble porous solid, macrocyclic 22-membered ring, 1-oxa-6,9,12,15,18-pentaaza-2,22-disilacyclododocosane polysiloxane ligand system has been prepared by the reaction of a macro-silane agent with tetraethylorthosilicate. The macro-silane agent was prepared by the reaction of imino-bis(N-2-aminoethylacetamide) ligand with 3-iodopropyltrimethoxysilane in 1:3 molar ratio. The new prepared polysiloxane system exhibits variable potentials for the extraction of metal ions (Fe³⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Ag⁺, Cd²⁺, Hg²⁺, and Pb²⁺) from aqueous solutions. The ligand system shows high capacity to extract silver, lead, and mercury. Chemisorption of the metal ions by the ligand system at the optimum conditions was found in the order Ag ⁺ > Pb²⁺ > Hg²⁺ > Cu²⁺ > Ni²⁺ > Fe³⁺ > Co²⁺ > Cd²⁺ > Zn²⁺.     

Cytotoxic urea Schiff base complexes for multidrug discovery as anticancer activity and low in vivo oral assessing toxicity

Novel mononuclear complexes 2–8 derived from hybrid Urea Schiff base HL were synthesized using various metal Ni²⁺, Fe³⁺, Cu²⁺, Co²⁺, Mn²⁺, Zn²⁺, and Cr³⁺. The results revealed the ligand HL reacts with metal ions as monobasic or neutral monodentate chelator it via the nitrogen of azomethine and deprotonated/protonated phenolic oxygen atom adopting octahedral geometry. The elemental analysis of the complexes showed the bonding of the ligand with the metal ions in a ratio of 1: 1 in all-metal complexes. XRD analysis of the ligand and its complexes indicate a monoclinic, tetragonal, orthorhombic corresponding to urea Shiff base (1) and zinc complex (7), nickel complex (2), and cobalt complexes (5), respectively. The bioactivity of synthesized compounds was tested and screened against three cancer cell lines PC3 (prostate), SK-OV-3 (ovarian), and HeLa (cervical). The results revealed a weak activity for the ligand, whereas nickel and iron complexes present moderate activities against three cancer cells. The best results were mentioned with copper and proved the best results against three cancer cells PC3, SKOV3, and HeLa displaying an excellent activity with IC₅₀ values of 0.71 ± 0.06, 0.12 ± 0.06, and 0.79 ± 0.23 μg/mL respectively. Moreover, the urea Schiff base complexes showed good safety in vivo toxicity test. The present study demonstrates that all urea Schiff base complexes is inactive against saint tissue and five metal complexes investigated herein can be effective and promising chemotherapeutic drugs for ovarian cancer cell SKOV3, emphasizing the copper-urea Schiff base complex.