Macrocyclic Nitrogen Research Articles

Study of Structural Elucidation, Degradation Kinetics and Antimicrobial Analysis of Copper (II) Sesame-Soap Complexes with Urea and Thiourea Ligand in Non-aqueous Solvents

Abstract: Surfactants have great importance in biological and drug industries and the complexes of metallic soaps with various ligands are used in approximately every region of national economy. Therefore, our keen interest to study of degradation kinetics and biological importance of Cu (II) surfactants in non-aqueous and non-polar solvent benzene. Present research work has been initiated with synthesis, systematic study of structural elucidation, thermal degradation, kinetics and biocidal activities of copper (II) sesame-soap complexes with macrocyclic nitrogen and sulphur containing donar ligands like urea and thiourea. The thermal degradation of copper (II) sesame-soap complexes were carried out for analysis of degradation kinetics and estimation of kinetic and thermodynamic parameters using different methods at heating rate 10oC min-1. Copper (II) sesame-soap complexes of such ligands have also been analysed against Staphylococus aureus. This research work consolidates the synthesis of copper (II) sesame soap-urea and thiourea complexes by conventional methods and the structure of these complexes were assigned according to elemental analysis and molecular weight determinations. IR, NMR and ESR spectral studies have also been done to understand structural aspects. The anti-microbial activities of copper (II) sesame-soap urea and thiourea complexes have been evaluated by testing against Staphylococus aureus. The present research work includes information of thermal analysis using TGA technique to find out their kinetic and thermodynamic parameters by using diverse equations such as Coats-Redfern equation, Horowitz-Metzger equation, Broido equation, Piloyan–Novikova equation. Moreover, the results obtained from anti-microbial screening have been used to analyze the anti-microbial activities of copper (II) sesame-soap urea and thiourea complexes against gram-positive bacteria Staphylococus aureus. These results show that complexes of copper ion co-ordinated with different nitrogen, oxygen and sulphur containing ligands, are very important in the field of pharmaceutical chemistry due to its significant role in the inhibition activity. The study of these complexes concludes that the synthesized complexes were found to possess appreciable bactericidal properties at different concentrations because chelation increases the anti-microbial potency.

Synthesis and Characterization of Copper (II) Soap Complexes Derived from Natural Edible Oils with Substituted Benzothiazoles

The aim of this research work is to present the fundamental chemical properties and new investigations of coordination compounds of some transition metal ions with an overview of medicinal applications. The primary purpose of this study is to understand the characteristic nature and biocidal properties of copper (II) soap complexes with nitrogen and sulphur donor ligands. Wide varieties of geometries and reactivity of transition metal complexes have been reported to possess several biocidal activities. Copper (II) soaps derived from natural edible oils like sesame and groundnut have a tendency of complexation with nitrogen and sulphur containing ligands. Synthesized copper (II) soap complexes may play a significant role in biological activities and have sufficient pharmaceutical, industrial and analytical applications. During last few decades, the use of macrocyclic nitrogen and sulphur containing six-membered heterocyclic ligands with transition metal complexes has been an interesting and fascinating area of research activity in scientific community all over the world due to its various applications.

Structural Variations in Carboxylated Bispidine Ligands: Influence of Positional Isomerism and Rigidity on the Conformation, Stability, Inertness and Relaxivity of their Mn2+ Complexes.

Mn2+ complexes of 2,4-pyridyl-disubstituted bispidine ligands have emerged as more biocompatible alternatives to Gd3+-based MRI probes. They display relaxivities comparable to that of commercial contrast agents and high kinetic inertness, unprecedented for Mn2+ complexes. The chemical structure, in particular the substituents on the two macrocyclic nitrogens N3 and N7, are decisive for the conformation of the Mn2+ complexes, and this will in turn determine their thermodynamic, kinetic and relaxation properties. We describe the synthesis of four ligands with acetate substituents in positions N3, N7 or both. We evidence that the bispidine conformation is dependent on N3 substitution, with direct impact on the thermodynamic stability, kinetic inertness, hydration state and relaxivity of the Mn2+ complexes. These results unambiguously show that (i) solely a chair-chair conformation allows for favorable inertness and relaxivity, and (ii) in this family such chair-chair conformation is accessible only for ligands without N3-appended carboxylates.

Biological importance of copper (II) sesame soap-urea complex

The study of transition metal complexes containing macrocyclic nitrogen and sulphur donor ligands has been an attractive and fascinating area of modern research activity during last few decades, because of their synthetic investigations and for their usefulness. These ligands and their metal complexes are good complexing agents. The present research work reports fundamental chemical properties and new investigations of coordination compounds of some transition metal ions with an overview of medicinal applications. Transition metals appear in almost every facet of our day-to-day life, from industrial uses such as the manufacture of construction and building materials, tools, vehicles, up to cosmetics, paints and fertilizers. The present work deals with the study of synthesis and characterization of biological properties of novel copper (II) soap urea complex.

Electronic Structure and Magnetic Properties of o-Benzoquinone Iron Complexes with Tetraazamacrocyclic Ligands

Structure, energy characteristics, and magnetic properties of o-benzoquinone iron complexes with tetradentate macrocyclic nitrogen containing bases (pyridinophane and tris(2-pyridylmethyl)amine) are studied with a DFT (UTPSSh/6-311++G(d,p)) quantum chemical method. Electron withdrawing substituents in the redox-active ligand stabilize its dianionic form but do not significantly affect the energy difference between the electromers. Strong ferromagnetic exchange interactions are predicted in the isomers of complexes containing a high-spin divalent iron ion and the semiquinone form of o-benzoquinone. According to the calculations, all studied compounds can undergo thermally induced spin crossover transitions.

First step in preparation of multifunctional spin crossover material based on Fe(II) complex of cyclam-based ligand. Magnetism and DFT studies

With the aim to make the first step in preparation of magnetic multifunctional material combining spin crossover (SCO) together with single-molecule magnet (SMM) properties in one molecule (polynuclear complex), a specially designed ligand L-NH2 (1,8-bis(4-aminobenzyl)-4,11-bis(pyridin-2-ylmethyl)-1,4,8,11-tetraazacyclotetradecane) was synthesized. It contains (i) macrocyclic cyclam core substituted with two 2-pyridylmethyl pendant arms suitable for complexation of Fe(II), because such system was previously proven to provide SCO, and (ii) two p-aminobenzyl pendant arms introducing NH2 groups suitable for consequent attachment of SMM molecule (e.g. transformation to functional groups for selective complexation of other metals). Furthermore, Fe(II) complex [Fe(L-NH2)]Cl2·2.5H2O was prepared and characterized. Unfortunately, according to the magnetic measurements, SCO behavior was not observed and the complex remained in high-spin state with relatively high magnetic anisotropy (D = –17.7 cm−1, E/D = 0.31). This magnetic behavior was rationalized by the DFT computational study, which identified high-spin state as preferential for prepared complex in contrast to other structurally similar SCO systems with low-spin state preference. The most probable reason behind this difference appeared to be the electron-withdrawing effect of benzyl groups providing weaker ligand field of macrocyclic nitrogen donor atoms.

Structural Modulation of Chromic Response: Effects of Binding-Site Blocking in a Conjugated Calix[4]pyrrole Chromophore.

Herein, we modulate the chromic response of a highly colored tetrapyrrole macrocycle, namely, tetrakis(3,5‐di‐tert‐butyl‐4‐oxocyclohexadien‐2,5‐yl)porphyrinogen (OxP) by structural modification. N‐Benzylation at the macrocyclic nitrogen atoms leads to stepwise elimination of the two calix[4]pyrrole‐type binding sites of OxP and serial variation of the chromic properties of the products, double N‐benzylated Bz2OxP and tetra N‐benzylated Bz4OxP. The halochromic (response to acidity) and solvatochromic (response to solvent polarity) properties were studied by using UV/Vis spectroscopy and NMR spectroscopy in nonpolar organic solvents. Titration experiments were used to generate binding isotherms to elucidate their binding properties with difluoroacetic acid. Differences in the halochromic properties of the compounds allowed construction of a colorimetric scale of acidity in nonpolar solvents, as the compounds in the series OxP, Bz2OxP, and Bz4OxP are increasingly difficult to protonate but maintain their propensity to change color upon protonation. The concurrent effects of binding‐site blocking and modulation of acidity sensitivity are important new aspects for the development of colorimetric indicators.

Spectroscopic, DFT, optical band gap, powder X-ray diffraction and bleomycin-dependant DNA studies of Co(II), Ni(II) and Cu(II) complexes derived from macrocyclic Schiff base

Macrocyclic nitrogen ligand, (2E)-3,6,10,13-tetramethyl-2,7,9,14-tetraaza-1,8 (1,4)-dibenzena cyclotetradecaphane-2,6,9,13-tetraene (PDHDH) as well as its Co(II), Ni(II) and Cu(II) complexes were isolated and characterized by conventional methods. The morphology of the Cu(II) complex was further studied by X-ray powder diffraction. The complexes assigned the general formulae: [M(PDHDH)Cl2]Cl.mH2O (m = 5.5 for Co(II), 3 for Ni(II) and 8 for Cu(II), respectively adopting a distorted octahedral structure on the basis of magnetic and electronic spectral data with N4 tetradentate donor sites and two Cl atoms occupying the other two sites. ESR spectrum was displayed and the Hamiltonian parameters were evaluated. The geometry, HOMO, LUMO, polarizability and other energetic parameters were evaluated by DFT theory on Material Studio package. The thermal decomposition of the compounds and associated kinetic parameters employing Coats-Redfern and Horowitz-Metzger methods were determined. Optical band gap (Eg) has been estimated as well; revealing that Cu complex has the largest energy gap and considered as a highly efficient photovoltaic material. Further, the compounds were screened for in vitro against pathogenic bacteria and Bleomycin-dependant DNA assay was indicating the good inhibition of the title compounds against Gram-positive strains than the Gram-negative bacteria and they hold some protective effect on DNA by a particular mechanism.

Mononuclear iron(ii) complexes containing a tripodal and macrocyclic nitrogen ligand: synthesis, reactivity and application in cyclohexane oxidation catalysis.

Two novel tripodal ligands L1 and L2 based on a tris(methylpyridyl)amine (TPA) motif have been prepared and reacted with two different iron(ii) salts. The ligand L1 contains a bis(amino-phenyl)-TPA group whereas the macrocyclic ligand L2 displays two different coordinating cores, namely TPA and pyridine-dicarboxamide. The resulting mononuclear complexes 1-4 have been characterized in the solid state and in solution by spectroscopic and electrochemical methods. All complexes are high spin and mainly pentacoordinated. X-ray diffraction analyses of the crystals of complexes 2 and 3 demonstrate that the coordination sphere of the iron(ii) centre adopts either a distorted bipyramidal-trigonal or square pyramidal geometry. In the absence of an exogenous substrate, oxidation of complex 2 by H2O2 induces an intramolecular aromatic hydroxylation, as shown by the X-ray structure of the resulting dinuclear complex 2'. Catalytic studies in the presence of a substrate (cyclohexane) show that the reaction process is strongly impacted by the macrocyclic topology of the ligand and the nature of the counter-ion.

Macrocyclic Cu(II) and Pd(II) complexes with new 16-membered tetradentate [N4] ligand: synthesis, characterization, 3D molecular modeling and in vitro anticancer and antimicrobial activities

New Cu(II) and Pd(II) complexes of tetradentate macrocyclic nitrogen ligand i.e. (10E,13E)-11,13-dimethyl-4H-dibenzo[g,n]naphtho[1,8-bc][1,5,9,13]tetraazacyclohexa-decine 5,19(12H,20H)-dione have been synthesized. The compounds have been characterized by elemental analyses, spectral (IR, UV–Vis, 1H NMR, MS and ESR), 3D molecular modeling, molar conductivity, magnetic as well as thermal analysis measurements. On the basis of above studies, tetragonally distorted octahedral or square planar geometry has been proposed for the complexes. Also, the in vitro antitumor activity of the synthesized ligand and most complexes against human breast and human hepatocarcinoma cell lines (MCF-7 and HepG2, respectively) has been studied. Furthermore, the current compounds have been screened for their possible antimicrobial activity against Staphylococcus aureus as Gram-positive bacteria, Escherichia coli as Gram-negative bacteria Aspergillus flavus and Candida albicans as antifungal agents.

Selective octabromination of tetraarylporphyrins based on meso-substituent identity: Structural and electrochemical studies

Synthesis and isolation of selectively brominated tetraarylporphyrin derivatives is reported. Treatment with bromine of meso-5,10,15,20-tetrakis(3,4,5-trimethoxyphenyl)porphyrin (1) or meso-5,10,15,20-tetrakis(3,5-di-[Formula: see text]-butyl-4-hydroxyphenyl)porphinatocopper(II) (2-Cu) yields products octabrominated at the 2,6-positions of meso-aryl substituents [5,10,15,20-tetrakis(2,6-dibromo-3,4,5-trimethoxyphenyl)porphyrin, [Formula: see text]Br81] or macrocyclic [Formula: see text]-positions. The latter of these ([Formula: see text]-brominated) was identified as the oxoporphyrinogen 2,3,7,8,12,13,17,18-octabromo-5,10,15,20- tetrakis(3,5-di-[Formula: see text]-butyl-4-oxo-cyclohexa-2,5-dienylidene)porphyrinogen 3 obtained due to the adventitious oxidation and demetalation of 2-Cu, which could be alkylated at its macrocyclic nitrogen atoms yielding N[Formula: see text],N[Formula: see text],N[Formula: see text],N[Formula: see text]-tetrakis(4-bromobenzyl)-2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(3,5-di-[Formula: see text]-butyl-4-oxo-cyclo hexa-2,5-dienylidene)porphyrinogen 4. The former compound [Formula: see text]Br81 was complexed with Zn(II) ([Formula: see text]Br81-Zn) or Cu(II) ([Formula: see text]Br81-Cu) and could also be subjected to further bromination yielding 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(2,6-dibromo-3,4,5-trimethoxyphenyl)porphyrin, Br[Formula: see text]1. The effect on the electrochemical properties of the 2,6-bromophenyl-substituted porphyrin compounds over the more highly brominated products was assessed.

Six, Seven or Eight Coordinate Fe(II) , Co(II) or Ni(II) Complexes of Amide-Appended Tetraazamacrocycles for ParaCEST Thermometry.

Fe(II) , Co(II) and Ni(II) complexes of two tetraazamacrocycles (1,4,8,11-tetrakis(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradecane (L1) and 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (L2) show promise as paraCEST agents for registration of temperature (paraCEST=paramagnetic chemical exchange saturation transfer). The Fe(II) , Co(II) and Ni(II) complexes of L1 show up to four CEST peaks shifted ≤112 ppm, whereas analogous complexes of L2 show only a single CEST peak at ≤69 ppm. Comparison of the temperature coefficients (CT ) of the CEST peaks of [Co(L2)](2+) , [Fe(L2)](2+) , [Ni(L1)](2+) and [Co(L1)](2+) showed that a CEST peak of [Co(L1)](2+) gave the largest CT (-0.66 ppm (o) C(-1) at 4.7 T). NMR spectral and CEST properties of these complexes correspond to coordination complex symmetry as shown by structural data. The [Ni(L1)](2+) and [Co(L1)](2+) complexes have a six-coordinate metal ion bound to the 1-, 4-amide oxygen atoms and four nitrogen atoms of the tetraazamacrocycle. The [Fe(L2)](2+) complex has an unusual eight-coordinate Fe(II) bound to four amide oxygen atoms and four macrocyclic nitrogen atoms. For [Co(L2)](2+) , one structure has seven-coordinate Co(II) with three bound amide pendents and a second structure has a six-coordinate Co(II) with two bound amide pendents.

Photoinduced Charge Separation in a Donor–Spacer–Acceptor Dyad with N‐Annulated Perylene Donor and Methylviologen Acceptor

The first donor-acceptor species in which a strongly emissive N-annulated perylene dye is connected to a methylviologen electron acceptor unit via its macrocyclic nitrogen atom, is prepared by a stepwise, modular procedure. The absorption spectra, redox behavior, spectroelectrochemistry and photophysical properties of this dyad and of its model species are investigated, also by pump-probe fs transient absorption spectroscopy. Photoinduced oxidative electron transfer from the excited state of the dyad, centered on the N-annulated perylene subunit, to the appended methyviologen electron acceptor takes place in a few ps. The charge-separated species recombines in 19 ps. Our results indicate that N-annulated perylene can be connected to functional units by taking advantage of the macrocyclic nitrogen, an option never used until now, without losing their properties, so opening the way to new designing approaches.

Tetrabenzoporphyrin and -mono-, -cis-di- and Tetrabenzotriazaporphyrin Derivatives: Electrochemical and Spectroscopic Implications of meso CH Group Replacement with Nitrogen.

Nonperipherally hexyl-substituted metal-free tetrabenzoporphyrin (2H-TBP, 1a) tetrabenzomonoazaporphyrin (2H-TBMAP, 2a), tetrabenzo-cis-diazaporphyrin (2H-TBDAP, 3a), tetrabenzotriazaporphyrin (2H-TBTAP, 4a), and phthalocyanine (2H-Pc, 5a), as well as their copper complexes (1b-5b), were synthesized. As the number of meso nitrogen atoms increases from zero to four, λmax of the Q-band absorption peak becomes red-shifted by almost 100 nm, and extinction coefficients increased at least threefold. Simultaneously the blue-shifted Soret (UV) band substantially decreased in intensity. These changes were related to the relative electron-density of each macrocycle expressed as the group electronegativity sum of all meso N and CH atom groups, ∑χR. X-ray photoelectron spectroscopy differentiated between the three different types of macrocyclic nitrogen atoms (the Ninner, (NH)inner, and Nmeso) in the metal-free complexes. Binding energies of the Nmeso and Ninner,Cu atoms in copper chelates could not be resolved. Copper insertion lowered especially the cathodic redox potentials, while all four observed redox processes occurred at larger potentials as the number of meso nitrogens increased. Computational chemical methods using density functional theory confirmed 1b to exhibit a Cu(II) reduction prior to ring-based reductions, while for 2b, Cu(II) reduction is the first reductive step only if the nonperipheral substituents are hydrogen. When they are methyl groups, it is the second reduction process; when they are ethyl, propyl, or hexyl, it becomes the third reductive process. Spectro-electrochemical measurements showed redox processes were associated with a substantial change in intensity of at least two main absorbances (the Q and Soret bands) in the UV spectra of these compounds.

Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals.

Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Analysis of our database of U.S. FDA approved drugs reveals that 59% of unique small-molecule drugs contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our analysis is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures.

Synthesis, characterization and in vitro antimicrobial studies of Co(II), Ni(II) and Cu(II) complexes derived from macrocyclic compartmental ligand

New Co(II), Ni(II) and Cu(II) complexes derived from tetradentate macrocyclic nitrogen ligand, (1E,4E,8E,12E)-5,8,13,16-tetramethyl-1,4,9,12-tetrazacyclohexadeca-4,8,12,16-tetraene (EDHDH) have been synthesized. The complexes have been characterized by elemental analysis, spectral (IR, UV–Vis, 1H NMR and ESR (for Cu(II) complex)) mass, and magnetic as well as thermal analysis measurements. The complexes afforded the formulae: [Cu(EDHDH)Cl2]·2EtOH and [M(EDHDH)X2]·nH2O where M=Co(II) and Ni(II), X=Cl− or OH−, n=1,0, respectively. The data revealed an octahedral arrangement with N4 tetradentate donor sites in addition to two Cl atoms occupying the other two sites. ESR spectrum of Cu2+ complex confirmed the suggested geometry with values of a α2and β2 indicating that the in-plane σ-bonding and in-plane π-bonding are appreciably covalent, and are consistent with very strong σ-in-plane bonding in the complexes. The molecular modeling is drawn and showed the bond length, bond angle, chemical reactivity, energy components (kcal/mol) and binding energy (kcal/mol) for all the title compounds using DFT method. Also, the thermal behavior and the kinetic parameters of degradation were determined using Coats–Redfern and Horowitz–Metzger methods. Moreover, the in vitro antibacterial studies of all compounds screened against pathogenic bacteria (two Gram +ve and two Gram −ve) to assess their inhibiting potential. The assay indicated that the inhibition potential is metal ion dependent. The ligand, EDHDH, Co(II) and Cu(II) complexes exhibited a remarkable antibacterial activity against Streptococcus Pyogenes as Gram +ve and Proteus vulgaris as Gram −ve bacterial strains. On the other hand, Ni(II) complex revealed a moderate antibacterial activity against both Gram +ve organisms and no activity against Gram −ve bacterial strain.

New Bifunctional Chelator for 64Cu-Immuno-Positron Emission Tomography

A new tetraazamacrocyclic bifunctional chelator, TE2A-Bn-NCS, was synthesized in high overall yield from cyclam. An extra functional group (NCS) was introduced to the N-atom of TE2A for specific conjugation with antibody. The Cu complex of TE2A-Bn-NCS showed high kinetic stability in acidic decomplexation and cyclic voltammetry studies. X-ray structure determination of the Cu-TE2A-Bn-NH2 complex confirmed octahedral geometry, in which copper atom is strongly coordinated by four macrocyclic nitrogens in equatorial positions and two carboxylate oxygen atoms occupy the elongated axial positions. Trastuzumab was conjugated with TE2A-Bn-NCS and then radiolabeled with 64Cu quantitatively at room temperature within 10 min. Biodistribution studies showed that the 64Cu-labeled TE2A-Bn-NCS-trastuzumab conjugates maintain high stability in physiological conditions, and NIH3T6.7 tumors were clearly visualized up to 3 days by 64Cu-immuno-positron emission tomography imaging in animal models.

Simulated annealing and density functional theoretical prediction of macrocyclic ligand conformations, protonation sites and complex metal–ligand exchange reaction directions

The prediction of conformations and protonation sites for the macrocyclic ligands H2DO2A (1,4,7,10-tetraazacyclododecane-1,7-diacetic acid) and H2ODO2A (1-oxa-4,7,10-triazacyclododecane-4,10-diacetic acid) has been performed employing the simulated annealing (SA) method and density functional theory (DFT) calculations using the B3LYP/6-31G* method in a vacuum and aqueous solution. These SA method/DFT calculations reveal that, in contrast to the H2ODO2A ligand system, the H2DO2A ligand system is (i) pre-organized for trivalent lanthanide (Ln) and other metal ion complexation, (ii) structurally more symmetrical and slightly more compact in aqueous solution (i.e. more and/or shorter intra-molecular hydrogen bonds), and (iii) with a greater degree of partial positive charge accumulation on the hydrogen atoms bonded to macrocyclic ring nitrogen atoms when protonated. The H2ODO2A ligand system is not pre-organized. These observations are in accord with the experimental findings that the LnODO2A(+) complexes are less thermodynamically stable and kinetically more labile as compared to those of the corresponding LnDO2A(+) complexes. The results on the prediction of the ligand protonation sites are consistent with those experimentally obtained via NMR spectroscopy. The calculations of the first and second protonation constants are, however, not as accurate as compared to those experimentally determined using either the thermodynamic cycle (TC) or the isodesmic reaction (IRn) methodology, although the latter gave relatively better results. The lowest energy structures of the LnL(+) and ZnL (Ln = Eu, Y; L = DO2A, ODO2A) complexes are also calculated using the same method. The Gibb's free energies (ΔGaq) for a number of ligand and/or metal ion exchange reactions such as LnDO2A(+) + HnODO2A((2-n)-) -->/<-- LnODO2A(+) + HnDO2A((2-n)-) (Ln = Eu, Y; n = 0, 1, 2), LnDO2A(+) + Ln'ODO2A(+) -->/<-- LnODO2A(+) + Ln'DO2A(+) (Ln = Eu, Ln' = Y), LnDO2A(+) + Ln'(3+) -->/<-- Ln'ODO2A(+) + Ln(3+) (Ln = Eu, Ln' = Y) and LnDO2A(+) + ZnODO2A -->/<-- LnODO2A(+) + ZnDO2A (Ln = Eu, Y) have been calculated in aqueous phase and the reaction directions in some cases could be predicted to be consistent with experimental or expected results. The errors between the calculated and experimental Gibb's free energy data are in the range ΔG(aq,calc) - ΔG(aq,exp) = -1.89 to +7.00 kcal mol(-1) in seven selected cases involving LnDO2A(+), LnODO2A(+) (Ln = Eu, Y), ZnDO2A and ZnODO2A complexes. The predicted reaction directions with the small core effective core potential (ECP) data are not necessarily better than those using large core ECP. However, the former takes much longer computer time to obtain the energy data.

Mn2+ complexes of 1-oxa-4,7-diazacyclononane based ligands with acetic, phosphonic and phosphinic acid pendant arms: Stability and relaxation studies

A new class of macrocyclic ligands based on 1-oxa-4,7-diazacyclononane was synthesized and their Mn(2+) complexes were investigated with respect to stability and relaxation properties. Each ligand has two pendant arms involving carboxylic (H(2)L(1)--1-oxa-4,7-diazacyclononane-4,7-diacetic acid), phosphonic (H(4)L(2)--1-oxa-4,7-diazacyclononane-4,7-bis(methylenephosphonic acid)), phosphinic (H(2)L(3)--1-oxa-4,7-diazacyclononane-4,7-bis(methylenephosphinic acid)) or phenylphosphinic (H(2)L(4)--1-oxa-4,7-diazacyclononane-4,7-bis[methylene(phenyl)phosphinic acid]) acid moieties. H(2)L(3) and H(2)L(4) were synthesized for the first time. The crystal structure of the Mn(2+) complex with H(2)L(4) confirmed a coordination number of 6 for Mn(2+). The protonation constants of all ligands and the stability constants of their complexes with Mn(2+) and some biologically or biomedically relevant metal ions were determined by potentiometry. The protonation sequence of H(2)L(3) was followed by (1)H and (31)P NMR titration and the second protonation step was attributed to the second macrocyclic nitrogen atom. The potentiometric data revealed a relatively low thermodynamic stability of the Mn(2+) complexes with all ligands investigated. For H(2)L(3) and H(2)L(4), full Mn(2+) complexation cannot be achieved even with 100% ligand excess. The transmetallation of MnL(1) and MnL(2) with Zn(2+) was too fast to be followed at pH 6. Variable temperature (1)H NMRD and (17)O NMR measurements have been performed on MnL(1) and MnL(2) to provide information on water exchange and rotational dynamics. The (17)O chemical shifts indicate hydration equilibrium between mono- and bishydrated species for MnL(1), while MnL(2) is monohydrated. The water exchange is considerably faster on MnL(1) (k(ex)(298) = 1.2 × 10(9) s(-1)) than on MnL(2) (k(ex)(298) = 1.2 × 10(7) s(-1)). Small endogenous anions (phosphate, carbonate, citrate) do not replace the coordinated water in either of the complexes, but they induce their slow decomposition. All Mn(2+) complexes are stable toward air-oxidation.

Two macrocyclic pentaaza compounds containing pyridine evaluated as novel chelating agents in copper(II) and nickel(II) overload

Two pentaaza macrocycles containing pyridine in the backbone, namely 3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene ([15]pyN 5), and 3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19),15,17-triene ([16]pyN 5), were synthesized in good yields. The acid–base behaviour of these compounds was studied by potentiometry at 298.2 K in aqueous solution and ionic strength 0.10 M in KNO 3. The protonation sequence of [15]pyN 5 was investigated by 1H NMR titration that also allowed the determination of protonation constants in D 2O. Binding studies of the two ligands with Ca 2+, Ni 2+, Cu 2+, Zn 2+, Cd 2+, and Pb 2+ metal ions were performed under the same experimental conditions. The results showed that all the complexes formed with the 15-membered ligand, particularly those of Cu 2+ and especially Ni 2+, are thermodynamically more stable than with the larger macrocycle. Cyclic voltammetric data showed that the copper(II) complexes of the two macrocycles exhibited analogous behaviour, with a single quasi-reversible one-electron transfer reduction process assigned to the Cu(II)/Cu(I) couple. The UV–visible-near IR spectroscopic and magnetic moment data of the nickel(II) complexes in solution indicated a tetragonal distorted coordination geometry for the metal centre. X-band EPR spectra of the copper(II) complexes are consistent with distorted square pyramidal geometries. The crystal structure of [Cu([15]pyN 5)] 2+ determined by X-ray diffraction showed the copper(II) centre coordinated to all five macrocyclic nitrogen donors in a distorted square pyramidal environment.