Metal Complexes of Pentadentate Macrocyclic Ligands Containing Oxygen and Nitrogen as Donor Atoms

Four macrocyclic ligands have been synthesized: 1-oxa-4,7,10,13-tetraazacyclopentadecane ( 1 ), 1,4-dioxa-7,10,13-triazacyclopentadecane ( 2 ), 1,4-dioxa-7,11,14-triazacyclohexadecane ( 3 ), 1,4-dioxa-7,11,15-triazacycloheptadecane ( 4 ), one of them 3 , for the first time. The protonation constants of the ligands and the stability constants of the complexes formed by the four ligands with some divalent first-series transition-metal ions, Cd²⁺ and Pb²⁺, were determined by potentiometric methods, in aqueous solution, at 25° and I = 0.10M (KNO₃). The sequence of protonation of ligand 1 was studied by ¹H-NMR spectroscopy. The Irving-Williams' order of stability is obeyed for the complexes of all the ligands, and the metal complexes of 1 present the higher values of stability. A drop in the stability of all the metal complexes studied is observed when the metal complexes of 1 are compared with the corresponding complexes of 2 . The effect of the increase of the ring size of the macrocycle can be observed for metal complexes of the series of ligands 2 4 , where, in spite of the slight increase of the overall basicity of the ligands (20.28, 22.25, and 24.96 for 2, 3 , and 4 respectively), small differences in stability are found for the corresponding complexes of 2 and 3 , but a significant drop occurs for all the metal complexes formed with the 17-membered ligand, specially for the larger metal ions like Mn²⁺ and Pb²⁺.     

Synthesis,structure, spectral properties,and electrochemistry of bis(crown ether) containing 1,3-distyrylbenzenes

The reaction of tetraethyl [1,3-phenylenedi(methylene)]bis(phosphonate) with formyl derivatives of benzocrown-ethers or formyl derivatives of o-dimethoxybenzene lead to high yield formation of the respectful bis(crown ether) containing 1,3-distyrylbenzenes or tetramethoxy-substituted 1,3-distyrenebenzenes. NMR spectra and quantum-chemical calculations showed the prevalence of unsymmetrical syn/anti,(syn,anti),syn/anti-conformations in 1,3-distyrylbenzenes. 1,3-Distyrylbenzenes absorb in shorter wavelength spectral region and have a weaker fluorescence than 1,4-distyrylbenzenes. The difficulty in the electrochemical reduction of 1,3-distyrylbenzenes comparing with 1,4-distyrylbenzenes is due to a less effective conjugation system in the metaderivatives.     

Linear and Star-Shaped Extended Di- and Tristyrylbenzenes: Synthesis,Characterization and Optical Response to Acid and Metal Ions

Two linear 1,4-distyrylbenzenes and five star-shaped 1,3,5-tristyrylbenzene derivatives ( L_2a and L_2b , Y₀–Y₃ and Y_NBu ) were synthesized and spectroscopically characterized. The photophysical properties, optical response to acid and metal ions were investigated. Upon backbone extension of linear distyrylbenzenes or the introduction of dibutylanilines, the electronic spectra are redshifted. Incorporation of electron-deficient pyridyl units does not significantly affect the optical properties. Variation of the number of pyridine rings and substitution pattern tune the fluorescence response to acids and metal ions. The novel arenes discriminate Al³⁺, Mn²⁺, Fe³⁺, Fe²⁺, Cd²⁺, Ag⁺ and Hg²⁺.     

Complexing ability of dimeric zinc octaalkylporphyrinates with a poly(ethyleneoxy) bridge toward 1,4-diazabicyclo[2.2.2]octane and 1,4-diazine

The formation of “guest-host” complexes from dimeric zinc octaalkylporphyrinates with a poly(ethyleneoxy) bridge and various bidentate ligands containing two N atoms was studied by spectrophotometric titration and ¹H NMR spectroscopy in toluene-methanol (5: 1). The reactions of dimeric porphyrinates with 1,4-diazabicyclo[2.2.2]octane and 1,4-diazine gave 1: 1 or 1: 2 complexes, depending on the molar ratio of metal porphyrin and the ligand. The stability constants of the complexes obtained and the concentration ranges for their formation were determined.     

Effect of ionic strength on the stabilities of ciprofloxacin – Metal complexes

Proton–ligand dissociation constant of 1-cyclopropyl-1,4-dihydro-4-oxo-7-(1-piperazinyl) quinolone-3-carboxylic acid is ciprofloxacin and metal–ligand stability constants of its complexes with some metal ions have been determined potentiometrically in the presence of (0.01, 0.02 and 0.03 mol/dm³) NaClO₄. The order of the stability constants of the formed complexes increases in the sequence Cu²⁺, Fe³⁺, Ni²⁺ and Zn²⁺ and decreases with increase in the concentration of ionic strength.     

Synthesis and spectral characterization of macrocyclic Ni<Superscript>II</Superscript> complexes derived from various diamines,Ni<Superscript>II</Superscript> perchlorate and 1,4-bis(2-carboxyaldehydephenoxy)butane

Six new macrocyclic complexes were synthesized by reaction of 1,4-bis(2-carboxyaldehyde phenoxy)butane with various diamines. Then, their nickel(II) perchlorate complexes were synthesized by the template effect by reaction of 1,4-bis(2-carboxyaldehyde phenoxy)butane, Ni(ClO₄)₂ · 6H₂O and various diamines. The metal-to-ligand ratio of Ni^II metal complexes was found to be 1:1. The compounds are coordinated to the central metal as tetradentate O₂N₂ ligands The Ni^II complexes are proposed to exhibit tetrahedral geometry. Ni^II metal complexes are 1:2 electrolytes as shown by their molar conductivities (Λ_M) in DMF (dimethyl formamide) at 10⁻³ m. The structure of Ni^II metal complexes is proposed from elemental analysis, f.t.-i.r., u.v.-vis., magnetic susceptibility measurements, molar conductivity measurements and mass spectra.     

Ternary Cu2+ Complexes: Stability,Structure, and Reactivity

The driving forces leading to the formation of ternary Cu²⁺ complexes are outlined; they are (i) statistical reasons, (ii) neutralization of charge in the mixed-ligand complexes, (iii) steric factors (bulky groups, ring size of chelates), and (iv) formation of π bonds. The last point is important for achieving a large stability, as well as for the observation of discriminating qualities. An additional stability increase may possibly be achieved through a direct interaction between the two ligands bound to the same metal ion, i.e. Schiff base formation, hydrogen bonding or a charge-transfer relation. The latter leads to distinct structures, i.e. metal ion-bridged charge-transfer complexes. The relation between stability and structure on the reactivity of mixed-ligand complexes is emphasized. The relevance of the results for mixed-ligand complexes containing metal ions other than Cu²⁺ is briefly outlined.     

Rational Design,Synthesis, and Evaluation of Tetrahydroxamic Acid Chelators for Stable Complexation of Zirconium(IV)

Metals of interest for biomedical applications often need to be complexed and associated in a stable manner with a targeting agent before use. Whereas the fundamentals of most transition‐metal complexation processes have been thoroughly studied, the complexation of Zr^IV has been somewhat neglected. This metal has received growing attention in recent years, especially in nuclear medicine, with the use of ⁸⁹Zr, which a β⁺‐emitter with near ideal characteristics for cancer imaging. However, the best chelating agent known for this radionuclide is the trishydroxamate desferrioxamine B (DFB), the Zr^IV complex of which exhibits suboptimal stability, resulting in the progressive release of ⁸⁹Zr in vivo. Based on a recent report demonstrating the higher thermodynamic stability of the tetrahydroxamate complexes of Zr^IV compared with the trishydroxamate complexes analogues to DFB, we designed a series of tetrahydroxamic acids of varying geometries for improved complexation of this metal. Three macrocycles differing in their cavity size (28 to 36‐membered rings) were synthesized by using a ring‐closing metathesis strategy, as well as their acyclic analogues. A solution study with ⁸⁹Zr showed the complexation to be more effective with increasing cavity size. Evaluation of the kinetic inertness of these new complexes in ethylenediaminetetraacetic acid (EDTA) solution showed significantly improved stabilities of the larger chelates compared with ⁸⁹Zr‐DFB, whereas the smaller complexes suffered from insufficient stabilities. These results were rationalized by a quantum chemical study. The lower stability of the smaller chelates was attributed to ring strain, whereas the better stability of the larger cyclic complexes was explained by the macrocyclic effect and by the structural rigidity. Overall, these new chelating agents open new perspectives for the safe and efficient use of ⁸⁹Zr in nuclear imaging, with the best chelators providing dramatically improved stabilities compared with the reference DFB.     

Characterization of Hydrocarbon Soluble Metal Oxides. Precursors to Supported Catalysts

Abstract

The metal oxide carboxylate complexes described in the previous chapter have been characterized by infrared spectroscopy, x-ray diffraction, electron microscopy, and analytical ultracentrifugation. The molecular weights and solution particle diameters have been determined for a number of the hydrocarbon soluble particles by analytical ultracentrifugation methods, and the use of a spherical model consistent with the particulate shape observed by electron microscopy. The size of the soluble complexes has been studied as a function of: metal, metal/acid ratio, acid composition, and solvent. The molecular weights for the ultimate particles are reasonably independent of the metal employed in the synthesis and are relatively constant for materials with similar metal/acid equivalents ratios. The single particle molecular weights for the complexes studied ranged from approximately 5×10⁴ to 1.5×10⁶g mole^?1. The solution size distribution was polydisperse in all cases, with aggregates of the ultimate particles prevalent. Weight average molecular weights in excess of 10⁹g mole^?1 have been observed. The aggregation is dependent on the surface acid composition and on the solvent in which the soluble complex is dispersed. Solubility and stability of these materials have been examined in a number of solvents. The metal oxide particles are initially soluble in octane, isooctane, cyclohexane, mineral spirits, carbon tetrachloride, benzene, and tetrahydrofuran. However, most of the complexes eventually precipitate from dilute solutions in carbon tetrachloride, benzene, and tetrahydrofuran. The stability of the particles is decreased in the presence of oxygen, or when carboxylic acids, alcohols, or ketones are present even in small amounts, and is decreased even further at temperatures above 100°C. Heterogeneous catalysts have been prepared by deposition of several of the soluble metal oxides onto supports such as alumina, silica, or kieselguhr followed by oxidation to yield supported metal oxides or reduction to yield supported metal. The application of few supported metals and metal oxides in hydrogenations of olefins, benzene, and naphthalene is described.     

Conditional Stability Constant Determination of Metal-Fulvic Acid Complexes

Abstract

Conditional stability constants for metal complexes of a terrestrial fulvic acid were determined using an ion-exchange chromatography—atomic absorbance spectroscopy method. Employing the Scatchard model, conditional stability constants were determined for the metal (II) fulvic acid complexes of cadminum, copper, lead, nickel, manganese, and zinc. The order of metal binding by the fulvic acid was determined to be: Cu > Ni > Pb > Zn > Cd > Mn. Complexes of weakly bound metal ions were determined with an added metal ion concentration of 2 × 10^–5 M to 1 × 10^–4 M while complexes of strongly bound metal ions were determined with an added metal ion concentration of 1 × 10^–5 M to 8 × 10^–4 M. The fulvic acid concentration was kept constant at 4 × 10^–4 M. The effect of pH and ionic strength on the copper-fulvic acid complex also was investigated.     

Coordination Complexes of a Neutral 1,2,4‐Benzotriazinyl Radical Ligand: Synthesis,Molecular and Electronic Structures,and Magnetic Properties

A series of d‐block metal complexes of the recently reported coordinating neutral radical ligand 1‐phenyl‐3‐(pyrid‐2‐yl)‐1,4‐dihydro‐1,2,4‐benzotriazin‐4‐yl ( 1 ) was synthesized. The investigated systems contain the benzotriazinyl radical 1 coordinated to a divalent metal cation, Mn^II, Fe^II, Co^II, or Ni^II, with 1,1,1,5,5,5‐hexafluoroacetylacetonato (hfac) as the auxiliary ligand of choice. The synthesized complexes were fully characterized by single‐crystal X‐ray diffraction, magnetic susceptibility measurements, and electronic structure calculations. The complexes [Mn( 1 )(hfac)₂] and [Fe( 1 )(hfac)₂] displayed antiferromagnetic coupling between the unpaired electrons of the ligand and the metal cation, whereas the interaction was found to be ferromagnetic in the analogous Ni^II complex [Ni( 1 )(hfac)₂]. The magnetic properties of the complex [Co( 1 )(hfac)₂] were difficult to interpret owing to significant spin–orbit coupling inherent to octahedral high‐spin Co^II metal ion. As a whole, the reported data clearly demonstrated the favorable coordinating properties of the radical 1 , which, together with its stability and structural tunability, make it an excellent new building block for establishing more complex metal–radical architectures with interesting magnetic properties.     

Monosaccharides and the VO(IV) metal ion: Equilibrium,thermal studies and hypoglycemic effect

Protonation and complexation equilibriums of monosaccharides and the VO(IV) metal ion in aqueous solution were studied as well as their effect on the hyperglycemia of diabetic rats. The complexes formed were characterized by potentiometric titrations, paramagnetic resonance spectroscopy (EPR) and thermogravimetric–differential scanning calorimetry (TGA–DSC). The system involving d-gluconic acid (HGlu) and oxovanadium(IV) (VO²⁺) was chosen to study the serum glucose levels in alloxan-induced diabetic rats. A binuclear species was detected in small quantities, which was formed by coordination of two HGlu molecules and two VO²⁺ ions through a hydroxide bridge. The mononuclear species formed by HGlu and VO²⁺ were confirmed by EPR. The anisotropic spectra obtained from aqueous frozen solutions (77 K) are characteristic of mononuclear VO-hexoses. The cyclic sugars d-ribone-1,4-lactone (Riblac), d-galactone-1,4-lactone (Galac) and 2-deoxy-d-glucopyranose (dGlu) showed weak interactions with the metal ion and they are not able to hold the metal in solution above pH 4.6 resulting in hydrolysis of the metal ion. Also, the acute treatment with sugar complexes of HGlu–VO led to a significant hypoglycemic effect (23% and 18% by intraperitoneal or oral gavage treatment, respectively) in diabetic rats. These results show the potential effectiveness of VO–HGlu complexes as anti-hyperglycemic agents through intraperitoneal injection in alloxan-induced diabetic rats.     

Coordination chemistry of a new tetranucleating 26-membered polyaza macropolycyclic ligand and a novel phenolate/phthalazine-bridged copper(II) and zinc(II) complexes

The novel phenol and phthalazine-based symmetric compartmental 26-membered polyaza macropolycyclic ligand LH₂, was synthesised, incorporating 2,6-diformyl-p-cresol and 1,4-dihydrazinophthalazine via 1:1 condensation. Its coordination behaviour with Cu^II and Zn^II ions was investigated. The tetranuclear complexes [M₄μ(Cl₂)(L)Cl₄]·2H₂O exhibited aremarkably high stability, suggesting that, along with the large number of nitrogen donors available for metal binding, deprotonated phenolic functions were also involved in binding the metal ion. Incorporation of the bridging units into the macrocyclic cavity influenced electronic communications between the metal ions.     

Diarylamino groups as photostable auxofluors in 2-benzoxazolylfluorene, 2,5-diphenyloxazoles, 1,3,5-hexatrienes, 1,4-distyrylbenzenes,and 2,7-distyrylfluorenes

The relationship of structure to optical spectral properties was determined for five types of fluors in a search for an optimum-wavelength shifter to be used as part of the detection systems for high-energy particles from accelerators. In a search for photostable fluors to serve as waveshifters in plastic fibers it was found that the wavelengths of interest, absorption max 410 +/- 10 nm and fluorescence emission max 480 +/- 20 nm, along with other properties, such as high solubility and short fluorescence decay time, could be obtained from fluorophors composed of aromatic rings and vinyl groups only by using amino groups as auxochromes to give bathochromic shifts of wavelengths. Since primary, monoalkyl, and dialkylamino groups were not sufficiently photostable, a number of fluorophores bearing diarylamino groups were investigated. Syntheses of the fluors made use of the Buchwald amination, an improved version of the Emmons-Horner reaction, and other common reactions. The fluor types were the following: a 2-benzoxazolyl-7-(4-diarylamino)fluorene 7, 2-(4-cyanophenyl)-5-(4-aminophenyl)oxazoles 14 and 20, 1,3,5-hexatrienes 24a-d and 26a-c, 1,4-distyrylbenzenes 31d-g and 32a-e, and 2,7-distyrylfluorenes 40a,d-e. The unsymmetrical fluors 7, 14, and 20 were not as bright as the best hexatrienes, distyrylbenzenes, and distyrylfluorenes, which were all symmetrical. Where the 1,6-diaryl-1,3,5-hexatrienes 24a-d had high fluorescence quantum yield (Phi(f)), the 1,1,6,6-tetraryl-1,3,5-hexatrienes 26a-c had both lower epsilon and Phi(f). Where the 1,4-distyrylbenzenes 31d-g had high Phi(f), the 1,4-bis(2-phenylstyryl)benzenes 32a-e had Phi(f) = 0. Diarylamino groups as auxofluors conferred higher photochemical stability than dialkylamino groups on similar fluorophores. The 1,4-distyrylbenzenes 31d,e and the 2,7-distyrylfluorenes 40d,ehad the most desirable properties overall, which included fast decay times of 2 ns. Computer simulations predicted absorption and emission wavelengths fairly well, but were of little help for the prediction of brightness, stability, Phi(f), or decay time.     

Conformational equilibria in 7-membered ring metal chelate complexes

Bis(diphosphine)metal and (diphosphine)(diene)metal (M = Rh, Ir) cationic complexes containing 7-membered chelate rings have been studied by low temperature ³¹P and ¹H NMR spectroscopy. For cyclooctadiene-1,4-bis(diphenylphosphino)butane- and -DIOP-rhodium, and cyclooctadiene-1,4-bis(diphenylphosphino)butane-iridium complexes, boat and chair conformations may be distinguished at low temperature. ¹H NMR spectra of these and analogous complexes suggest that both boat and chair conformers are significantly populated at room temperature. Bis(diphosphine) complexes of rhodium and iridium show very complex dynamic behaviour.     

Spectral,thermal, electrochemical,biological and DFT studies on nanocrystalline Co(II), Ni(II), Cu(II) and Zn(II) complexes with a tridentate ONO donor Schiff base ligand

Co(II), Ni(II), Cu(II) and Zn(II) Schiff base complexes derived from 3-hydrazinoquionoxaline-2-one and 1,2-diphenylethane-1,2-dione were synthesized. The compounds were characterized by elemental analyses, molar conductance, magnetic susceptibility measurements, FTIR, UV–vis, ¹H NMR, ¹³C NMR, ESR, and mass spectral studies. Thermal studies of the ligand and its metal complexes were also carried out to determine their thermal stability. Octahedral geometry has been assigned for Co(II), Ni(II), and Zn(II) complexes, while Cu(II) complex has distorted octahedral geometry. Powder XRD study was carried out to determine the grain size of ligand and its metal complexes. The electrochemical behavior of the synthesized compounds was investigated by cyclic voltammetry. For all complexes, a 2 : 1 ligand-to-metal ratio is observed. The ligand and its metal complexes were screened for their activity against bacterial species such as E. coli, P. aeruginosa, and S. aureus and fungal species such as A. niger, C. albicans, and A. flavus by disk diffusion method. The DNA-binding of the ligand and its metal complexes were investigated by electronic absorption titration and viscosity measurement studies. Agarose gel electrophoresis was employed to determine the DNA-cleavage activity of the synthesized compounds. Density functional theory was used to optimize the structure of the ligand and its Zn(II) complex.     

Coordination properties of N,O-carboxymethyl chitosan (NOCC). Synthesis and equilibrium studies of some metal ion complexes. Ternary complexes involving Cu(II) with (NOCC) and some biorelevant ligand

In the present study, the acid-base equilibria of N,O-carboxymethy chitosan abbreviated as (NOCC), is investigated. The complex formation equilibria with the metal ions Cu^(II), Ni^(II), Co^(II), Mn^(II), and Zn^(II) are investigated potentiometrically. The stability constant values of the binary and ternary complexes formed in solution were determined and the binding centers of the ligands were assigned. The relationships between the properties of the studied central metal ions as ionic radius, electronegativity, atomic number, and ionization potential, and the stability constants of the formed complexes were investigated in an effort to give information about the nature of chemical bonding in complexes and make possible the calculation of unknown stability constants. Cu^(II), Ni^(II), and U^(VI) complexes with NOCC are isolated as solid complexes and characterized by conventional chemical and physical methods. The structures of the isolated solid complexes are proposed on the basis of the spectral and magnetic studies. The ternary copper(II) complexes involving NOCC and various biologically relevant ligands containing different functional groups, as amino acids and DNA constituents are investigated. The stability constants of the complexes are determined and the concentration distribution diagrams of the complexes are evaluated.     

Determination of Relative Stabilities of Metal-Peptide Bonds in the Gas Phase

Understanding binding site preferences in biological systems as well as affinities to binding partners is a crucial aspect in metallodrug development. We here present a mass spectrometry-based method to compare relative stabilities of metal-peptide adducts in the gas phase. Angiotensin 1 and substance P were used as model peptides. Incubation with isostructural N-heterocyclic carbene (NHC) complexes of Ru^II, Os^II, Rh^III, and Ir^III led to the formation of various adducts, which were subsequently studied by energy-resolved fragmentation experiments. The gas-phase stability of the metal-peptide bonds depended on the metal and the binding partner. Of the four complexes used, the Os^II derivative bound strongest to Met, while Ru^II formed the most stable coordination bond with His. Rh^III was identified as the weakest peptide binder and Ir^III formed peptide adducts with intermediate stability. Probing these intrinsic gas-phase properties can help in the interpretation of biological activities and the design of site-specific protein binding metal complexes.     

Theoretical study of interaction of 2,6-dithiopurine with Li+, Na+, K+, Be2+, Mg2+, and Ca2+ metal cations

The geometries of the complexes of Li⁺, Na⁺, K⁺, Be²⁺, Mg²⁺, and Ca²⁺ metal cations with different possible 2,6-dithiopurine anions (DTP) were studied. The complexes were optimized at the B3LYP level and the 6-311++G(d, p) basis set. The interactions of the metal cations at different nucleophilic sites of various possible 2,6-dithiopurine anions were considered. It was revealed that metal cations would interact with 2,6-dithiopurine anions in a bicoordinate manner. In the gas phase, the most preferred position for the interaction of Li⁺, Na⁺, and K⁺ cations is between the N₃ and S₂ sites, while all divalent cations Be²⁺, Mg²⁺, and Ca²⁺ prefer binding between the N₇ and S₆ sites of the corresponding 2,6-dithiopurine. The influence of aqueous solvent on the relative stability of different complexes has been examined using the Tomasi’s polarized continuum model. The basis set superposition error (BSSE) corrected interaction energy was also computed for complexes. The AIM theory has been applied to analyze the properties of the bond critical points (electron densities and their Laplacians) involved in the coordination between 2,6-dithiopurine anions and the metal cations. It was revealed that aqueous solution would have significant effect on the relative stability of complexes obtained by the interaction of 2,6-dithiopurine anions with Mg²⁺ and Ca²⁺ cations. The effect of metal cations on different NH and CS stretching vibrational modes of 2,6-dithiopurine has also been discussed.     

The Use of Bridging Ligand Substituents to Bias the Population of Localized and Delocalized Mixed-Valence Conformers in Solution

The electronic structure and associated spectroscopic properties of ligand-bridged, bimetallic ‘mixed-valence’ complexes of the general form {M}(μ-B){M⁺} are dictated by the electronic couplings, and hence orbital overlaps, between the metal centers mediated by the bridge. In the case of complexes such as [{Cp*(dppe)Ru}(μ-C≡CC₆H₄C≡C){Ru(dppe)Cp*}]⁺, the low barrier to rotation of the half-sandwich metal fragments and the arylene bridge around the acetylene moieties results in population of many energy minima across the conformational energy landscape. Since orbital overlap is also sensitive to the particular mutual orientations of the metal fragment(s) and arylene bridge through a Karplus-like relationship, the different members of the population range exemplify electronic structures ranging from strongly localized (weakly coupled Robin-Day Class II) to completely delocalized (Robin-Day Class III). Here, we use electronic structure calculations with the hybrid density functional BLYP35-D3 and a continuum solvent model in combination with UV-vis-NIR and IR spectroelectrochemical studies to show that the conformational population in complexes [{Cp*(dppe)Ru}(μ-C≡CArC≡C){Ru(dppe)Cp*]⁺, and hence the dominant electronic structure, can be biased through the steric and electronic properties of the diethynylarylene (Ar) moiety (Ar=1,4-C₆H₄, 1,4-C₆F₄, 1,4-C₆H₂-2,5-Me₂, 1,4-C₆H₂-2,5-(CF₃)₂, 1,4-C₆H₂-2,5-ⁱPr₂).