Synthesis, structure and spectroscopy of new thiopyrone and hydroxypyridinethione transition-metal complexes

The coordination chemistry of several O,S mixed donor ligands, namely thiopyrone and hydroxypyridinethione chelators, with a variety of middle and late first-row transition-metal ions is described. Complexes of 3-hydroxy-2-methyl-4-thiopyrone (thiomaltol) with cobalt(II), copper(II) and zinc(II); 3-hydroxy-1,2-dimethyl-4(1H)-pyridinethione (3,4-HOPTO) with iron(III), nickel(II), copper(II) and zinc(II); and 3-hydroxy-1-methyl-2(1H)-pyridinethione (3,2-HOPTO) with iron(III), nickel(II), copper(II) and zinc(II) have been synthesized and characterized. The structures, absorbance spectroscopy, cyclic voltammetry and superconducting quantum interferometer device (SQUID) measurements of selected metal complexes, as well as ligand protonation constants, are reported. Most of the metal complexes show coordination geometries indicative of a strong trans influence by the O,S chelators. The data presented herein provide the most detailed study of the transition-metal coordination chemistry of both thiopyrone and hydroxypyridinethione O,S donor ligands to date, and provide the basis for the investigation of these ligands in realm of biological inorganic chemistry.     

Synthesis, Cu(II) complexation, 64Cu-labeling and biological evaluation of cross-bridged cyclam chelators with phosphonate pendant arms

A new class of cross-bridged cyclam-based macrocycles featuring phosphonate pendant groups has been developed. 1,4,8,11-tetraazacyclotetradecane-1,8-di(methanephosphonic acid) (CB-TE2P, 1) and 1,4,8,11-tetraazacyclotetradecane-1-(methanephosphonic acid)-8-(methanecarboxylic acid) (CB-TE1A1P, 2) have been synthesized and have been shown to readily form neutral copper(II) complexes at room temperature as the corresponding dianions. Both complexes showed high kinetic inertness to demetallation and crystal structures confirmed complete encapsulation of copper(II) ion within each macrocycle's cleft-like structure. Unprecedented for cross-bridged cyclam derivatives, both CB-TE2P (1) and CB-TE1A1P (2) can be radiolabeled with (64)Cu at room temperature in less than 1 h with specific activities >1 mCi μg(-1). The in vivo behavior of both (64)Cu-CB-TE2P and (64)Cu-CB-TE1A1P were investigated through biodistribution studies using healthy male Lewis rats. Both new compounds showed rapid clearance with similar or lower accumulation in non-target organs/tissues when compared to other copper chelators including CB-TE2A, NOTA and Diamsar.     

Adsorption of lead(II) and copper(II) on activated carbon by complexation with surface functional groups

The adsorption of lead(II) and copper(II) on an activated carbon (Filtrasorb 300, Chemviron) was characterized assuming that it takes place by formation of complexes with functional groups, present in the activated carbon. Their concentration and conditional adsorption coefficients were determined for each metal by titration of the carbon in suspension in aqueous phase, at constant acidity, with the metal itself. For each titration point, the concentration of the metal in the solution phase after equilibration was determined, and the data were processed by the Ruzic linearization method, to obtain the concentration of the active sites involved in the sorption, and the conditional constant. The effect of the pH was also examined, in the range 4-6, obtaining that the adsorption increases at increasing pH. The protonation and adsorption constants were determined from the conditional adsorption coefficients obtained at the different acidities. The concentration of the active sites is 0.023 and 0.042 mmol g⁻¹, and the protonation constants are 1.0×10⁶ and 4.6×10⁴ M⁻¹ for Pb(II) and Cu(II). The corresponding adsorption constants are respectively 1.4×10⁵ and 6.3×10³ M⁻¹. All the parameters are affected by a large uncertainty, probably due to the heterogeneity of the active groups in the activated carbon. Even if so, these parameters make it possible a good prediction of the adsorption in a wide range of conditions. Other sorption mechanism can be set up at different conditions, in particular at different pH, as it has been demonstrated in the case of copper(II).     

Thermodynamics of complexation of lead(II) and cobalt(II) with N-(carboxymethyl)aspartic acid in aqueous solutions

The enthalpies of complexation of lead(II) and cobalt(II) with N-(carboxymethyl)aspartic acid (H₃Y) were determined calorimetrically at 298.15 K within a wide ionic strength range (KNO₃). The thermodynamic characteristics of formation of the CoY₂- and PbY_2? complexes were calculated at non-zero and zero ionic strengthes. The explanation of the obtained values is given.     

Crystal structure of tris[(2.2.2-cryptand)× (nitrato-O,O′)lead(II)] pentakis(nitrato-O,O′)lead(II)

A novel coordination compound tris[(2.2.2-cryptand)(nitrato-O,O′)lead(II)] pentakis(nitrato-O, O′)lead(II), 3[Pb(NO₃)(Crypt-222)]⁺·[Pb(NO₃)₅]^3? (I) has been prepared and studied by the single crystal X-ray diffraction technique. The crystals of I are monoclinic: space group Pc, a = 25.944 Å, b = 18.389 Å, c = 17.145 Å, β = 93.33°, Z = 4. The structure of I has been solved by the direct and heavy atom methods and refined in a full-matrix anisotropic-isotropic approximation to R = 0.122 for the total of 11145 measured reflections (automated diffractometer CAD-4, λMoK _α). The structure of I includes six independent host-guest complex cations [Pb(NO₃)(Crypt-222)]⁺ and two independent complex anions [Pb(NO₃)₅]^3?. Coordination number of the cation Pb²⁺ equals ten in all these complex ions, and its coordination polyhedron in the first of them is a strongly distorted “hexagonal bipyramid” with two forked vertices, while for the latter ones it is a strongly distorted “square pyramid” with all five vertices forked.     

Aqueous complexation studies of lead(II) and cadmium(II) with 1,3-bis(tris(hydroxymethyl)methylamino)propane pH buffer

Hydrogen buffers are important in biological studies, as a steady hydrogen concentration is of great importance in most scientific studies. One of these buffers is 1,3-bis(tris(hydroxymethyl)methylamino)propane (BTP), which, considering its structure, has complexing capabilities, as previously shown for other metals. In order to know the stability constants for Cd(II) or Pb(II) with BTP, glass electrode potentiometry and direct current polarography studies were carried out. Our results show that both metals form metal complexes, with Pb(II) forming stronger complexes with BTP as evidenced by its higher stability constants. In the Pb-BTP system, five species were described; PbHL, PbL, PbL₂, PbL₂(OH), and PbL₂(OH)₂, and their stability constants were determined to be 11.4 ± 0.3, 4.7 ± 0.3, 8.8 ± 0.2, 14.4 ± 0.3, and 18.4 ± 0.3, respectively. For the Cd-BTP system, four complexes were detected; CdHL, CdL, CdL(OH), and CdL(OH)₂, and their stability constants were also determined as 10.9 ± 0.4, 4.10 ± 0.07, 8.2 ± 0.2, and 10.9 ± 0.2, respectively. These complexes decrease considerably the amount of free metal in solution within the buffering pH range. This fact should be considered when planning experiments were BTP and Pb(II) and/or Cd(II) ions are present.     

Copper(II) complexation with ampicillin,amoxicillin, and cephalexin

The interaction of Cu²⁺ ions with ampicillin, amoxicillin, and cephalexin (L) anions in an aqueous solution at 20°C with 0.1 M KNO₃ as a background electrolyte was studied by pH-potentiometry. Formation of CuL⁺ and Cu(OH)L complexes was revealed, and their stability constants were determined.     

A photometric study of the complexation reaction between Alizarin complexan and zinc(II), nickel(II), lead(II), cobalt(II) and copper(II)

The complexation reaction between Alizarin complexan ([3-N,N-di(carboxymethyl)aminomethyl]-1,2-dihydroxyanthraquinone; H(4)L) and zinc(II), nickel(II), lead(II), cobalt(II) and copper(II) has been studied by a spectrophotometric method. All these metal ions form 1:1 complexes with HL; 2:1 metal:ligand complex were found only for Pb(II) and Cu(II). The stability constants are (ionic strength I = 0.1, 20 degrees C): Zn(2+) + HL(3-) right harpoon over left harpoon ZnHL(-) log K +/- 3sigma(log K) = 12.19 +/- 0.09 (I = 0.5) Ni(2+) + HL(3-) right harpoon over left harpoon NiHL(-) log K +/- 3sigma(log K) = 12.23 +/- 0.21 Pb(2+) + HL(3-) right harpoon over left harpoon PbHL(-) log K +/- 3sigma(log K) = 11.69 +/- 0.06 PbHL(-) + Pb(2+) right harpoon over left harpoon Pb(2)L + H(+) log K approximately -0.8 Co(2+) + HL(3-) right harpoon over left harpoon CoHL(-) log K 3sigma(log K) = 12.25 + 0.13 Cu(2+) + HL(3-) right harpoon over left harpoon CuHL(-) log K 3sigma(log K) = 14.75 +/- 0.07 Cu(2+) + CuHL(-) right harpoon over left harpoon Cu(2)L + H(+) log K approximately 3.5 The solubility and stability of both the reagent and the complexes and the closenes of the values of the stability constants make this reagent suitable for the photometric detection of several metal ions in the eluate from an ion-exchange column.     

Potentiometric stripping analysis and anodic stripping voltammetry for measurement of copper(II) and lead(II) complexation by fulvic acid: A comparative study

The utility of potentiometric stripping analysis (PSA) for studying the interaction of fulvic acid with Cu^II and Pb^II at pH 1.8 and 4.8 was assessed. The impact of fulvic acid on both the deposition and stripping steps was considered. In contrast to results obtained by anodic stripping voltammetry, fulvic acid influenced both these steps in PSA, and to different degrees. Surface active substances have been claimed to have self-compensatory effects in PSA; this work shows that this is not valid for heterogenous natural complexants such as fulvic acid.     

Oligosaccharide-modified poly(propyleneimine) dendrimers: synthesis, structure determination, and Cu(II) complexation

The multiple application of reductive amination on primary amino groups of first and second generation poly(propyleneimine) dendrimers is used as a one-pot approach to introduce twice the amount of the oligosaccharide units as surface groups, compared to initially present amino groups in the first and second generation dendrimers. This was proven by (1)H NMR, MALDI-TOF-MS, and LILBID-MS analysis. The size of these dendrimers was determined by the hydrodynamic radius using pulsed field gradient NMR and dynamic light scattering. Molecular modeling confirmed the presence of dense-shell dendrimers. These dendrimers exhibit a generation dependent Cu(II)/dendrimer ratio in an aqueous environment, highlighting these materials as possible metal-carrier systems with a well-defined oligosaccharide protection shell for application in a biological environment.     

Dissociation and complexation ofN-m-tolyl-p-methoxybenzohydroxamic acid with manganese(II), nickel(II), copper(II) and zinc(II)

Summary The thermodynamic ionisation and formation constant at different ionic strengths of some divalent metal ions ofN-m-tolyl-p-methoxybenzohydroxamic acid at 25 and 35° were determined in several dioxanwater media. The solid complexes of Cu^II, Ni^II and Mn^II withN-m-tolylbenzo-,N-m-tolyl-p-methylbenzo- andN-m-tolyl-p-methoxybenzohydroxamic acids were prepared and their magnetic susceptibilities measured at room temperature.     

Experimental study and computer modeling of Ni(II) and Cu(II) complexation with ceftazidime

The protonation constants of the anion of the cephalosporin antibiotic ceftazidime Ctzd^– and formation constants of its complexes with Ni²⁺ and Cu²⁺ have been determined by pH metric titration at 25°С and ionic strength 0.1 (KNO₃): logβ(HCtzd) = 4.82 ± 0.04, logβ(H₂Ctzd⁺) = 7.62 ± 0.06, logβ(H₃Ctzd²⁺) = 9.23 ± 0.09, logβ(NiCtzd⁺) = 4.04 ± 0.03, logβ(Ni(Ctzd)₂) = 6.41 ± 0.06, and logβ(CuCtzd⁺) = 5.03 ± 0.06. The potentiometric method has failed to reveal the complexation of Ctzd^– with Co²⁺, Zn²⁺, and Cd²⁺. The composition of the [Ni(Ctzd)₂] and [CuCtzd]⁺ complexes has been confirmed by spectrophotometry. The computer models of the [NiCtzd]⁺ and [CuCtzd]⁺ complexes have been calculated by the DFT method with the use of the B3LYP hybrid functional and the LACV3P**++ basis set.     

Pt(II) complexes with bidentate and tridentate pyrazolyl-containing chelators: synthesis, structural characterization and biological studies

A series of four Pt(II) complexes anchored by bidentate or tridentate pyrazolyl-alkylamine chelators bearing different substituents at the azolyl rings has been prepared with the aim to assess their interest in the design of novel anticancer drugs. All complexes have been fully characterized by classical analytical methods and three of them were characterized also by X-ray diffraction analysis. Their solution behavior, together with lipophilicity measurements, cell uptake, antiproliferative properties, DNA interaction have been evaluated. Albeit all the complexes were less active than cisplatin on ovarian carcinoma A2780 cell line, greatly retained their activity in the cisplatin-resistant A2780cisR cell line and presented a lower resistance factor compared to cisplatin. Moreover, the Pt(II) complexes under investigation were less prone to undergo deactivation by glutathione, believed to be the major cellular target of cisplatin that inactivates the drug by binding to it irreversibly.     

Kinetics of the complexation of manganese(II), cobalt(II) and zinc(II) with DL-isocitric acid

The kinetics of complexation of Mn^II, Co^II and Zn^II by isocitric acid have been studied by the stopped flow method at 15,25 and 35°C, ionic strength 0.20 M (NaClO₄) and pH range 4.50–6.35. Under these experimental conditions, one process is observed for each system within a few seconds. A mechanism is proposed to account for the observed behaviour, which is associated with participation of the OH group in complex formation. Activation energies are also reported. TMC 2593     

Nickel(II), copper(II) and zinc(II) binding properties and cytotoxicity of tripodal, hexadentate tris(ethylenediamine)--analogue chelators

Three tripodal hexamine chelators based on cis,cis-1,3,5-triaminocyclohexane (tach) have been synthesized and their aqueous coordination chemistry with Ni(II), Cu(II) and Zn(II) is reported. The chelators have a 2-aminoethyl pendant arm attached to each nitrogen of tach, specifically 'tachen'(N,N',N'-tris(2-aminoethyl)cyclohexane-cis,cis-1,3,5-triamine), and two with S,S,S-chiral pendant arms, 'tachpn'(N,N',N'-tris(2-aminopropyl)cyclohexane-cis,cis-1,3,5-triamine) and 'tachbn'(N,N',N'-tris(2-amino-3-phenylpropyl)cyclohexane-cis,cis-1,3,5-triamine. These chelators complex Ni(II), Cu(II) and Zn(II) in aqueous or aqueous/methanolic medium. The crystalline products [M(II)L](X)2 are isolated, where M = Ni(II), Cu(II) or Zn(II), L = tachen, tachpn or tachbn, and X = ClO4-. Crystallographic study of selected tachpn and tachbn complexes shows the chelate arms are constrained in a Lambda(deltadeltadelta) configuration about M(II), which is attributed to their chirality. Solution UV-vis spectroscopy of the Ni(II) and Cu(II) complexes indicates six-coordination and little effect of the pendant arm substitution on ligand-field strength. The single exception is [Cu(tachbn)]2+, whose spectrum is consistent with five-coordination in solution. The cytotoxicities of tachen, tachpn and tachbn toward cultured cancer cells is in the order tachen < tachpn < tachbn < tachpyr, where tachpyr is the aminopyridyl chelator N,N',N'-tris(2-pyridylmethyl)cyclohexane-cis,cis-1,3,5-triamine. The cytotoxicity difference is attributed to an order of increasing lipophilicity, tachen < tachpn < tachbn.     

1,6-Bis(hydrazidomethylsulfinyl)hexane: the solution state and complexation with copper(II)

Russian Chemical Bulletin - The solution state of a new antituberculosis drug 1,6-bis(hydrazidomethylsulflnyl)hexane (L) and its complexation with copper(II) were investigated by spectrophotometry,...