Tetradentate Macrocyclic Ligand Research Articles

Synthesis, spectroscopic elucidation, density functional theory calculation, and molecular docking studies of a novel series of tetradentate macrocyclic Schiff base ligands and their Zn(II) complexes and investigations of their antimicrobial, anti‐inflammatory, and anticancer activities

In the present work, novel Schiff base macrocyclic Zn(II) complexes [Zn(N8O4MacL1)Cl2–Zn(N8O4MacL3)Cl2] were synthesized by the reaction of ZnCl2 and macrocyclic ligands (N8O4MacL1–N8O4MacL3) derived from the condensation of ligand (L) and dicarboxylic acids [HOOC‐(CH2)n‐COOH]. The structural confirmation of the newly synthesized compounds was accomplished through various analytical techniques, including elemental analysis, infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), UV–visible spectroscopy, and powder X‐ray diffraction (XRD) studies. The spectral data provided evidence that the macrocyclic ligands acted as tetradentate ligands, forming coordination bonds with Zn(II) ions through the nitrogen atom of the imine (>C=N) group. The coordination complexes exhibited an octahedral geometry around the zinc ion, with two chloro groups covalently attached. Density functional theory (DFT) studies of the synthesized Schiff base macrocyclic compounds were carried out to determine their structural and electronic properties. The antimicrobial potential of the macrocyclic compounds was examined against a panel of pathogenic microbes, including four bacterial strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Xanthomonas campestris) and two fungal strains (Fusarium oxysporum and Candida albicans). Then, the newly synthesized Schiff based macrocyclic compounds were evaluated for their anti‐inflammatory activity using an egg albumin method. The synthesized compounds were subjected to further evaluation to assess their potential as anticancer agents against MCF‐7 (human breast adenocarcinoma cell line), HCT‐116 (human colon cancer cell line), and A549 (human alveolar adenocarcinoma epithelial cell line). In addition, molecular docking studies were conducted to explore the potential interactions between the synthesized compounds and the target proteins VEGFR2 (PDB ID 1YWN), EGFR (PDB ID 1M17), and DNA gyrase B (PDB ID 4URO). It was found that there was a high correlation between the experimental results and the docking calculations.

Palladium K-edge X-ray Absorption Spectroscopy Studies on Controlled Ligand Systems.

X-ray absorption spectroscopy (XAS) is widely used across the life and physical sciences to identify the electronic properties and structure surrounding a specific element. XAS is less often used for the characterization of organometallic compounds, especially for sensitive and highly reactive species. In this study, we used solid- and solution-phase XAS to compare a series of 25 palladium complexes in controlled ligand environments. The compounds include palladium centers in the formal I, II, III, and IV oxidation states, supported by tridentate and tetradentate macrocyclic ligands, with different halide and methyl ligand combinations. The Pd K-edge energies increased not only upon oxidizing the metal center but also upon increasing the denticity of the ligand framework, substituting sigma-donating methyl groups with chlorides, and increasing the charge of the overall metal complex by replacing charged ligands with neutral ligands. These trends were then applied to characterize compounds whose oxidation states were otherwise unconfirmed.

Synthesis, DFT calculation, molecular docking studies and biological evaluation of a novel series of Schiff base tetradentate macrocyclic ligands and their Zn(II) complexes as antimicrobial, anti-inflammatory and anticancer agents

Synthesis, DFT calculation, molecular docking studies and biological evaluation of a novel series of Schiff base tetradentate macrocyclic ligands and their Zn(II) complexes as antimicrobial, anti-inflammatory and anticancer agents

Mechanochemical Synthesis and Reactivity of a Stable Nickel Borohydride

AbstractWe report the solvent‐assisted mechanochemically synthesised mononuclear Ni(II) borohydride complex supported by a macrocyclic tetradentate ligand. It was characterised as stable high‐spin [(LMe)Ni(η2‐BH4)]+ cation in solid‐state and in solution by various physicochemical methods and capable of transferring hydride. The stoichiometric reactivity of [(LMe)Ni(η2‐BH4)]+ cation was examined with trityl cation, alkyl halide, disulphide, thiol, carboxylic acid and enol at room temperature.

One-pot synthesis, characterization, photocatalytic activity and biological studies of Co(II), Ni(II) and Cu(II) complexes of a tetraazamacrocyclic Schiff base

Template condensation between pentane-1,5-dial and triethylenetetramine in the presence of divalent metal salts in methanolic solution resulted in mononuclear 15-membered tetraazamacrocyclic Schiff base metal complexes, [M(C11H22N4)X2], where M = Co(II), Ni(II) and Cu(II), X = Cl− and C11H22N4 is the tetradentate macrocyclic ligand. The bonding and overall geometry of the complexes are inferred through elemental analysis, FT-IR, UV–vis, 1H/13C NMR, ESI-mass, molar conductance, magnetic susceptibility and TG measurements. On the basis of the absorption bands in UV–vis spectra and magnetic moment analyses, a six-coordinate octahedral geometry is proposed for all the metal complexes. The formulation of the metal chelates is compatible with the thermal decomposition profiles. Photocatalytic efficiency of the macrocyclic Ni(II) complex was studied using solar water-splitting. The in vitro antimicrobial activity of metal complexes has been tested against certain bacterial and fungal species. The scavenging ability of DPPH free radicals was used to test the antioxidant activity of the complexes. In addition, MTT assay was used to assess the cytotoxicity of Cu(II) chloro complex against L929 mouse fibroblast cell lines.

Spectroscopic and antimicrobial studies of Cr(III), Mn(II) and Co(II) complexes with a tetradentate macrocyclic ligand

Complexes of Cr(III), Mn(II) and Co(II) with a tetradentate macrocyclic ligand i.e. 2,6,12,16,21,22-hexaaza;3,5,13,15-tetraphenyltricyclo[15,3,1,17–11]docosa;1(21),2,5, 7,9,11(22),12,15,17,19-decaene (L). These complexes were characterized by elemental analysis, molar conductance measurements, magnetic susceptibitity measurements, mass, 1H NMR, IR, electronic and EPR spectral studies. These spectral studies suggest an octahedral geometry for Cr(III), Mn(II) and Co(II) complexes. The ligand and its complexes have been screened in vitro against some species of bacteria and plant pathogenic fungi.

Tuning of spin crossover properties in a series of mononuclear cobalt(II) complexes based on a macrocyclic tetradentate ligand and pseudohalide coligands.

The three mononuclear cobalt(II) complexes, [Co(L)(NCX)2] (L = N,N'-di-tert-butyl-2,11-diaza[3,3](2,6)pyridinophane, and X = S (1), Se (2), and [C(CN)2] (3)), have been synthesized and characterized using variable temperature single-crystal X-ray crystallography, and spectroscopic, magnetic, and electrochemical studies. All three complexes have a similar distorted octahedral CoN6 coordination geometry produced by the macrocyclic tetradentate ligand L and two NCX- co-ligands in the cis position. Complexes 1 and 2 crystallized in the monoclinic P21/n (Z = 4) space group, while complex 3 was isolated in the monoclinic P21/c (Z = 4) space group. Interestingly, complexes 1 and 2 exhibit a reversible and gradual spin-crossover behavior between the high-spin (S = 3/2) and low-spin (S = 1/2) states at ca. 168 K and 255 K, respectively. However, for complex 3, a low-spin configuration persists up to 260 K and it exhibits an incomplete and reversible spin crossover even at 400 K. In addition, complex 1 displays a reversible redox behavior indicating the paramagnetic cobalt(II) to diamagnetic cobalt(III) conversion.

Graphene oxide modified H4L‐ion imprinting electrochemical sensor for the detection of uranyl ions

AbstractThe rapid development of the nuclear industry has gradually aroused people′s attention to the problem of nuclear pollution. Due to the biological toxicity of uranium and its aqueous solution, simple and rapid detection of uranium in the water environment is quite important. An ion imprinted carbon nanomaterial (graphene oxide) electrochemical sensor for the detection of trace uranyl ions was prepared by using the synthesized bipolar tetradentate macrocyclic uranyl ligand cyclo‐bis‐phenylenediamine‐bis‐(phenylmethyl‐diphyrrolecarbaldehyde) (H4L) as functional monomer. The sol‐gel polymer was prepared by hydrolysis and polymerization of H4L ligand, 3‐aminopropyltrimethoxysilane and tetraethoxysilane. H4L‐ion imprinted polymer (U‐IIP) was prepared by adding 1 mM uranyl ion as template ions. Then the polymer was bonded to graphene oxide modified carbon paste electrode, and the template ions were eluted to obtain H4L‐ion imprinted‐graphene oxide modified carbon paste electrode (U‐IIP/GO/CPE). Differential pulse voltammetry was used to detect trace uranyl ions. The results showed that the U‐IIP/GO/CPE sensor system can detect uranyl ions with high sensitivity and specificity, and the peak current appeared around −0.26v. In the range of 0.01 μM∼3.0 μM, the detection current had a good linear relationship with the molar concentration of uranyl ions, and the method detection limit was 1.32 nM (S/N=3). Through the detection of actual samples, it had a good acceptable recovery rate (95.45 %∼106.25 %), and the relative standard deviation was less than 3.25 %.

Controlled Regulation of the Nitrile Activation of a Peroxocobalt(III) Complex with Redox-Inactive Lewis Acidic Metals.

Redox-inactive metal ions play vital roles in biological O2 activation and oxidation reactions of various substrates. Recently, we showed a distinct reactivity of a peroxocobalt(III) complex bearing a tetradentate macrocyclic ligand, [CoIII(TBDAP)(O2)]+ (1) (TBDAP = N,N'-di-tert-butyl-2,11-diaza[3.3](2,6)pyridinophane), toward nitriles that afforded a series of hydroximatocobalt(III) complexes, [CoIII(TBDAP)(R-C(═NO)O)]+ (R = Me (3), Et, and Ph). In this study, we report the effects of redox-inactive metal ions on nitrile activation of 1. In the presence of redox-inactive metal ions such as Zn2+, La3+, Lu3+, and Y3+, the reaction does not form the hydroximatocobalt(III) complex but instead gives peroxyimidatocobalt(III) complexes, [CoIII(TBDAP)(R-C(═NH)O2)]2+ (R = Me (2) and Ph (2Ph)). These new intermediates were characterized by various physicochemical methods including X-ray diffraction analysis. The rates of the formation of 2 are found to correlate with the Lewis acidity of the additive metal ions. Moreover, complex 2 was readily converted to 3 by the addition of a base. In the presence of Al3+, Sc3+, or H+, 1 is converted to [CoIII(TBDAP)(O2H)(MeCN)]2+ (4), and further reaction with nitriles did not occur. These results reveal that the reactivity of the peroxocobalt(III) complex 1 in nitrile activation can be regulated by the redox-inactive metal ions and their Lewis acidity. DFT calculations show that the redox-inactive metal ions stabilize the peroxo character of end-on Co-η1-O2 intermediate through the charge reorganization from a CoII-superoxo to a CoIII-peroxo intermediate. A complete mechanistic model explaining the role of the Lewis acid is presented.

(H,H)-Isomerism of cis- and trans-di[benzo]porphyrazines: Quantum chemical modeling within the framework of the DFT method

Quantum-chemical calculation of the molecular structures of potential isomeric (NNNN)- donoratomic macrocyclic tetradentate ligands, cis- and trans-di[benzo]porphyrazines, was carried out using the density functional theory (DFT) B3PW91/TZVP. It is noted that the first of these compounds can exist in four forms [so-called ([Formula: see text]-isomers], differing from each other by the mutual orientation of hydrogen atoms bonded to the nitrogen atoms, while the second compounds take the form of two similar isomers. The values of the most important bond lengths, bond and non-bond angles in each of these ([Formula: see text] -isomeric compounds, as well as the values of their relative energy, standard enthalpy, entropy, and Gibbs energy of formation are presented. It was found that the most stable among both cis- and trans-di[benzo]porphyrazines is the ([Formula: see text]-isomer with the trans-orientation of hydrogen atoms bonded to nitrogen atoms, while the ([Formula: see text] -isomers with cis-oriented hydrogen atoms for both of these compounds had significantly higher relative energies.

Synthesis and Spectral Characterization of Mn(II) and Co(II) Complexes with Tetradentate Macrocyclic Ligand

Manganese(II) and cobalt(II) complexes were synthesized with [N4] tetradentate macrocyclic ligand using different metal salts i.e. MnCl2, Mn(NO3)2, CoCl2 and Co(NCS)2. The ligand was prepared by condensation of glyoxal and carbahydrazide. All these were characterized by elemental analysis, molar conductance measurements, magnetic moment, IR, mass, electronic and EPR spectral studies. Elemental analysis indicates that the complexes have composition MLX2 where (X = Cl–, NO3 –,NCS–). All the complexes were found to be non-electrolytic in nature so can be formulated as [MLX2]. Infrared spectra of metal complexes suggest that the ligand behaves as tetradentate. On the basis of magnetic moment, electronic and EPR spectral data, all the metal complexes were found to be high spin with octahedral geometry.

Reversible Spin-State Switching and Tuning of Nuclearity and Dimensionality via Nonlinear Pseudohalides in Cobalt(II) Complexes.

The self-assembly of a macrocyclic tetradentate ligand, cobalt(II) tetrafluoroborate, and nonlinear pseudohalides (dicyanamide and tricyanomethanide) has led to two cobalt(II) complexes, {[Co(L)(μ1,5-dca)](BF4)·MeOH}n (1) and [Co2(L)2(μ1,5-tcm)2](BF4)2 (2) (L = N,N'-di-tert-butyl-2,11-diaza[3,3](2,6)pyridinophane; dca- = dicyanamido; tcm- = tricyanomethanido). Both complexes were characterized by single-crystal X-ray diffraction, spectroscopic, magnetic, and electrochemical studies. Structural analyses revealed that 1 displays a one-dimensional (1D) coordination polymer containing [Co(L)]2+ repeating units bridged by μ1,5-dicyanamido groups in cis positions, while 2 represents a discreate dinuclear cobalt(II) molecule bridged by two μ1,5-tricyanomethanido groups in a cis conformation. Both complexes have a CoN6 coordination environment around each cobalt center offered by the tetradentate ligand and cis coordinating bridging ligands. Complex 1 exhibits a high-spin (S = 3/2) state of cobalt(II) in the temperature range of 2-300 K with a weak ferromagnetic coupling between two dicyanamido-bridged cobalt(II) centers. Interestingly, complex 2 exhibits reversible spin-state switching associated with spin-spin coupling. Complexes 1 and 2 also exhibit interesting redox-stimuli-based reversible paramagnetic high-spin cobalt(II) to diamagnetic low-spin cobalt(III) conversion, offering an additional way to switch magnetic properties. A detailed theoretical calculation was consistent with the stated results.

Mechanistic insight into hydroxamate transfer reaction mimicking the inhibition of zinc-containing enzymes.

A hydroxamate transfer reaction between metal complexes has been investigated by a combination of experimental and theoretical studies. A hydroxamate-bound cobalt(ii) complex bearing a tetradentate macrocyclic ligand, [CoII(TBDAP)(CH3C(–NHO)O)]+ (1), is prepared by the reduction of a hydroximatocobalt(iii) complex with a biological reductant. Alternatively, 1 is accessible via a synthetic route for the reaction between the cobalt(ii) complex and acetohydroxamic acid in the presence of a base. 1 was isolated and characterized by various physicochemical methods, including UV-vis, IR, ESI-MS, and X-ray crystallography. The hydroxamate transfer reactivity of 1 was examined with a zinc complex, which was followed by UV-vis and ESI-MS. Kinetic and activation parameter data suggest that the hydroxamate transfer reaction occurs via a bimolecular mechanism, which is also supported by DFT calculations. Moreover, 1 is able to inhibit the activity against a zinc enzyme, i.e., matrix metalloproteinase-9. Our overall investigations of the hydroxamate transfer using the synthetic model system provide considerable insight into the final step involved in the inhibition of zinc-containing enzymes.

Structure and Reactivity of a Mononuclear Nonheme Manganese(III)-Iodosylarene Complex.

Transition metal-iodosylarene complexes have been proposed to be key intermediates in the catalytic cycles of metal catalysts with iodosylarene. We report the first X-ray crystal structure and spectroscopic characterization of a mononuclear nonheme manganese(III)-iodosylarene complex with a tetradentate macrocyclic ligand, [MnIII(TBDAP)(OIPh)(OH)]2+ (2). The manganese(III)-iodosylarene complex is capable of conducting various oxidation reactions with organic substrates, such as C-H bond activation, sulfoxidation and epoxidation. Kinetic studies including isotope labeling experiments and Hammett correlation demonstrate the electrophilic character on the Mn-iodosylarene adduct. This novel intermediate would be prominently valuable for expanding the chemistry of transition metal catalysts.

Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.

Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis. On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species. The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core. The proposed structure was supported by DFT (B3LYP) calculations. Furthermore, a π-laminated dimer architecture linked through the inner carbons was obtained from the one-electron oxidation of CuNCC4. We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.

Selective Synthesis of Ni(II) and Pd(II) Complexes with either ‘Normal’ or ‘Abnormal’ N‐Heterocyclic Carbene Coordination Modes

AbstractA family of Ni(II) and Pd(II) complexes of one bidentate and three tetradentate, N‐heterocyclic carbene (NHC) / amidate ligands have been prepared. The imidazolium salt pro‐ligands used in the synthesis of these complexes were designed to facilitate the ‘abnormal’ NHC coordination mode, through the introduction of either (1) methyl blocking group at the C2 position of the imidazolium units or (2) sterically demanding tert‐butyl imidazolium wingtip substituents or (3) the ligand was macrocyclic in nature. In all cases, the desired complexes were uncharged, with square‐planar coordination geometries about the metal centres. These studies showed that in the case of Ni(II), abnormal NHC complexes could be formed for the C2‐blocked tetradentate ligands only. In contrast for Pd(II), ‘abnormal’ NHC complexes could be prepared from C2‐blocked bidentate and tetradentate ligands with sterically demanding tert‐butyl NHC wingtip substituents. For the macrocyclic tetradentate ligand, Ni(II) and Pd(II) complexes displaying the ‘normal’ NHC coordination mode were obtained.

Synthesis, structural characterization and NMR studies of group 10 metal complexes with macrocyclic amine N-heterocyclic carbene ligands.

A series of Ni(ii), Pd(ii) and Pt(ii) complexes [ML][PF6]2 [L = L1, M = Ni (1), Pd (2), Pt (3); L = L2, M = Ni (4), Pd (5), Pt (6)] and [Pt(L2)(acac)] (7) have been prepared by the reactions of two tetradentate macrocyclic amine-NHC ligand precursors, [H2L1][PF6]2 and [H2L2][PF6]2, with Ni(OAc)2·4H2O, Pd(OAc)2 and Pt(acac)2 in the presence of NaOAc. Complex 7 is isolated along with 6 from the same reaction between [H2L2][PF6]2 and Pt(acac)2. There are two atropisomers in 1-3 and two achiral conformers in 4-6. The crystal structures of 1-3 and one conformer of 4-6 (4a-6a) have been determined by single-crystal X-ray diffraction studies. The metal ion is found to reside in the cavity of the macrocyclic ring and adopts a square-planar configuration. Detailed NMR studies including variable-temperature NMR spectroscopy reveal a dynamic interconverting process between two atropisomers of 1-3 in the solutions via a ring twisting mechanism. Two conformers in the equilibrated solution of 4-6, probably arising from the orientation of two amine N-H bonds with respect to the coordination plane, exchange slowly. Time-dependent 1H NMR spectra show that one conformer (4a-6a) in solution converts into the other (4b-6b) via the inversion of the nitrogen atom.

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.

Distinct Reactivity of a Mononuclear Peroxocobalt(III) Species toward Activation of Nitriles.

A mononuclear side-on peroxocobalt(III) complex with a tetradentate macrocyclic ligand, [CoIII(TBDAP)(O2)]+ (1), shows a novel and facile mode of dioxygenase-like reactivity with nitriles (R-C≡N; R = Me, Et, and Ph) to produce the corresponding mononuclear hydroximatocobalt(III) complexes, [CoIII(TBDAP)(R-C(═NO)O)]+, in which the nitrile moiety is oxidized by two oxygen atoms of the peroxo group. The overall reaction proceeds in one-pot under ambient conditions (ca. 1 h, 40 °C). 18O-Labeling experiments confirm that both oxygen atoms are derived from the peroxo ligand. The structures of all products, hydroximatocobalt(III) complexes, were confirmed by X-ray crystallography and various spectroscopic techniques. Kinetic studies including the Hammett analysis and isotope labeling experiments suggest that the mechanistic mode of 1 for activation of nitriles occurs via a concerted mechanism. This novel reaction would be significantly valuable for expanding the chemistry for nitrile activation and utilization.

Synthesis, crystal structure and magnetism of [Cu(cyclam)Ni(NCS)4(H2O)2

Abstract[Cu(cyclam)Ni(NCS)4(H2O)2]n(1) (cyclam = 1,4,8,11-tetraazacyclodecane) exhibits bent 1D crystal structure in which paramagnetic Cu(II) and Ni(II) atoms are linked by bridging μ2-NCS- ligands. The Cu(II) atom exhibit tetragonally elongated hexacoordination in the 4+2 form with one tetradentate macrocyclic cyclam ligands placed in the equatorial plane while the axial positions are occupied by S atoms from bridging NCS- ligands. The Ni(II) atom in NiN4O2donor set is deformed octahedrally coordinated by four isothiocyanato ligands among which two in trans positions are bridging in nature; additional aqua ligands occupy the remaining two positions in trans arrangement. Weak hydrogen bonding interactions of the O-H···S type links the formed chains into 3D supramolecular structure. The magnetism of 1 is dominated by a sizable single-ion anisotropy DNi/hc = +7.49 cm-1along with a weak exchange interaction of the ferromagnetic nature.