Cross-bridged Cyclam Ligand Research Articles

Homogeneous activation of peroxymonosulfate using a low-dosage cross-bridged cyclam manganese(II) complex for organic pollutant degradation via a nonradical pathway

The high dosage of catalyst requirement and weak anti-interference ability limit current heterogeneous manganese (Mn) catalyst/peroxymonosulfate (PMS) systems to remediate the organic polluted wastewater in complicated environment. Inspired by the concept of atom economy, herein, a homogenous manganese complex bearing a cross-bridged cyclam ligand Mn(cbc)Cl2 (MnL, L = cbc = 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane)) is capable of activating PMS for reactive brilliant red K-2BP (RBR K-2BP) degradation. The dosage of MnL for PMS activation was low, in a range of 0.38∼3.8 mg/L. The quenching experiments demonstrated that the degradation was a nonradical-controlled process. Using methyl phenyl sulfoxide (PMSO) as a probe, the dominated degradation process of substrate was via an oxygen transfer pathway. Moreover, a high-valent Mn-oxo [(O)MnVLCl2]+ was directly detected using electrospray ionization mass spectrometry (ESI/MS). This system showed excellent anti-interference ability to both anions and humic acid, a typical natural organic matter. The atom economy, represented by an index ((mg pollutant)/h/(g catalyst)), showed that MnL 22737 in PMS activation was much higher than those of Mn-based heterogeneous catalytic systems 67∼960 and was only behind that of iron-tetraamidomacrocyclic ligand Fe-TAML 59139. This work provides insights into designing an atom-economic Mn-based PMS activator for efficient treatments for organic pollutants in a complicated environment.

Selective degradation of estrogens by a robust iron(III) complex bearing a cross-bridged cyclam ligand via iron(V)-oxo species

Selective degradation by enzyme-like iron complex is a potential way to remove the micropollutant estrogens in wastewater. However, the poor stability of complex always limits its applications. Herein, a robust iron complex bearing a cross-bridge cyclam ligand, cis-[Fe(cbc)Cl2]+ (Fe(L1), cbc = 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane), is effective to catalyze selective degradation of estrogens. This complex was able to remove higher than 90% of 17β-estradiol in three cyclic experiments, showing better stability than the reported iron complexes. No hydroxyl or superoxide radicals was detected and the high valent iron(V)-oxo species formation was observed by electron paramagnetic resonance spectroscopy, proving the degradation of estrogens by Fe(L1)/H2O2 is a non-radical control process. The estrogenic activity of substrate was greatly reduced by approximately 95% after Fe(L1)/H2O2 treatment. This work provides insights to the removal of micropollutants in complicate environment and helps widen the application of homogeneous catalysts in environment remediation.

Synthesis, structural studies, and oxidation catalysis of the late-first-row-transition-metal complexes of a 2-pyridylmethyl pendant-armed ethylene cross-bridged cyclam.

The first 2-pyridylmethyl pendant-armed ethylene cross-bridged cyclam ligand has been synthesized and successfully complexed to Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+) cations. X-ray crystal structures were obtained for all six complexes and demonstrate pentadentate binding of the ligand with the requisite cis-V configuration of the cross-bridged cyclam ring in all cases, leaving a potential labile binding site cis to the pyridine donor for interaction of the complex with oxidants and/or substrates. The electronic properties of the complexes were evaluated using solid-state magnetic moment determination and acetonitrile solution electronic spectroscopy, which both agree with the crystal structure determination of high-spin divalent metal complexes in all cases. Cyclic voltammetry in acetonitrile revealed reversible redox processes in all but the Ni(2+) complex, suggesting that catalytic reactivity involving electron-transfer processes is possible for complexes of this ligand. Kinetic studies of the dissociation of the ligand from the copper(II) complex under strongly acidic conditions and elevated temperatures revealed that the pyridine pendant arm actually destabilizes the complex compared to the parent cross-bridged cyclam complex. Screening for oxidation catalysis using hydrogen peroxide as the terminal oxidant for the most biologically relevant Mn(2+), Fe(2+), and Cu(2+) complexes identified the Mn(2+) complex as a potential mild oxidation catalyst worthy of continued development.

Catalytic oxidation of water and alcohols by a robust iron(iii) complex bearing a cross-bridged cyclam ligand

An iron(iii) complex bearing a cross-bridged cyclam ligand (4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) is an efficient catalyst for the oxidation of both water and alcohols using sodium periodate as the oxidant. In catalytic water oxidation a maximum turnover number (TON) of 1030 is achieved, while in catalytic alcohol oxidation >95% conversions and yields can be obtained.

Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands

Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn2+ complex of this ligand was the most potent with IC50s of 0.127 and 0.157μM against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better anti-malarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn2+. Few of the Cu2+ and Fe2+ complexes also showed improvement in activity but Ni2+, Co2+ and Zn2+ complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development.

Lewis-Acid-Promoted Stoichiometric and Catalytic Oxidations by Manganese Complexes Having Cross-Bridged Cyclam Ligand: A Comprehensive Study

Redox-inactive metal ions have been recognized to be able to participate in redox metal-ion-mediated biological and chemical oxidative events; however, their roles are still elusive. This work presents how the redox-inactive metal ions affect the oxidative reactivity of a well-investigated manganese(II) with its corresponding manganese(IV) complexes having cross-bridged cyclam ligand. In dry acetone, the presence of these metal ions can greatly accelerate stoichiometric oxidations of triphenylphosphine and sulfides by the manganese(IV) complexes through electron transfer or catalytic sulfoxidations by the corresponding manganese(II) complexes with PhIO. Significantly, the rate enhancements are highly Lewis-acid strength dependent on added metal ions. These metal ions like Al(3+) can also promote the thermodynamic driving force of the Mn(IV)-OH moiety to facilitate its hydrogen abstraction from ethylbenzene having a BDE(CH) value of 85 kcal/mol, while it is experimentally limited to 80 kcal/mol for Mn(IV)-OH alone. Adding Al(3+) may also improve the manganese(II)-catalyzed olefin epoxidation with PhIO. However, compared with those in electron transfer, improvements in hydrogen abstraction and electron transfer are minor. The existence of the interaction between Lewis acid and the manganese(IV) species was evidenced by the blue shift of the characteristic absorbance of the manganese(IV) species from 554 to 537 nm and by converting its EPR signal at g = 2.01 into a hyperfine 6-line signal upon adding Al(3+) (I = 5/2). Cyclic voltammograms of the manganese(IV) complexes reveal that adding Lewis acid would substantially shift its potential to the positive direction, thus enhancing its oxidizing capability.

Manganese complexes with a lengthy o -xylylene cross-bridged cyclam ligand: synthesis, characterization and catalytic hydrogen abstraction by dioxygen activation

Two ultra rigid, o-xylylene cross-bridged macrobicyclic ligands, 1,10,13,19-tetraazatricyclo[8.6.6.03,8]docosa-3,5,7-triene (H2XBC), and 13,19-dimethyl-1,10,13,19-tetraazatricyclo[8.6.6.03,8]docosa-3,5,7-triene (Me2XBC), have been synthesized and the manganese complexes have been synthesized and characterized, including an X-ray structure determination. Mn(Me2XBC)Cl2 displays a relatively high redox potential for the Mn2+/Mn3+ couple (+0.947V vs SHE, measured in CH3CN), suggesting that the manganese(III) complex may be capable of hydrogen abstraction from moderately active substrates. Direct reaction of the freshly synthesized manganese(III) complex, [Mn(Me2XBC)Cl2]PF6, with 1,4-cyclohexadiene confirmed its hydrogen abstracting ability. The manganese(II)/Me2XBC complex is activated by dioxygen in buffered basic aqueous solutions and catalyzes hydrogen abstraction from selected substrates. A possible mechanism for this manganese complex catalyzed dioxygen activation and hydrogen abstraction is proposed.

Olefin Epoxidation by Alkyl Hydroperoxide with a Novel Cross-Bridged Cyclam Manganese Complex: Demonstration of Oxygenation by Two Distinct Reactive Intermediates

Olefin epoxidation provides an operative protocol to investigate the oxygen transfer process in nature. A novel manganese complex with a cross-bridged cyclam ligand, MnIV(Me2EBC)(OH)2(2+) (Me2EBC = 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane), was used to study the epoxidation mechanism with biologically important oxidants, alkyl hydroperoxides. Results from direct reaction of the freshly synthesized manganese(IV) complex, [Mn(Me2EBC)(OH)2](PF6)2, with various olefins in neutral or basic solution, and from catalytic epoxidation with oxygen-labeled solvent, H2 18O, eliminate the manganese oxo moiety, Mn(IV)=O, as the reactive intermediate and obviate an oxygen rebound mechanism. Epoxidations of norbornylene under different conditions indicate multiple mechanisms for epoxidation, and cis-stilbene epoxidation under atmospheric 18O2 reveals a product distribution indicating at least two distinctive intermediates serving as the reactive species for epoxidation. In addition to alkyl peroxide radicals as dominant intermediates, an alkyl hydroperoxide adduct of high oxidation state manganese(IV) is suggested as the third kind of active intermediate responsible for epoxidation. This third intermediate functions by the Lewis acid pathway, a process best known for hydrogen peroxide adducts. Furthermore, the tert-butyl peroxide adduct of this manganese(IV) complex was detected by mass spectroscopy under catalytic oxidation conditions.

The long and short of it: the influence of N-carboxyethyl versusN-carboxymethyl pendant arms on in vitro and in vivo behavior of copper complexes of cross-bridged tetraamine macrocycles

A cross-bridged cyclam ligand bearing two N-carboxymethyl pendant arms (1) has been found to form a copper(II) complex that exhibits significantly improved biological behavior in recent research towards (64)Cu-based radiopharmaceuticals. Both the kinetic inertness and resistance to reduction of Cu-1 are believed to be relevant to its enhanced performance. To explore the influence of pendant arm length on these properties, new cross-bridged cyclam and cyclen ligands with longer N-carboxyethyl pendant arms, 2 and 4, and their respective copper(II) complexes have been synthesized. Both mono- as well as di-O-protonated forms of Cu-2 have also been isolated and structurally characterized. The spectral and structural properties of Cu-2 and Cu-4, their kinetic inertness in 5 M HCl, and electrochemical behavior have been obtained and compared to those of their N-carboxymethyl-armed homologs, Cu-1 and Cu-3. Only the cyclam-based Cu-1 and Cu-2 showed unusually high kinetic inertness towards acid decomplexation. While both of these complexes also exhibited quasi-reversible Cu(II)/Cu(I) reductions, Cu-2 is easier to reduce by a substantial margin of +400 mV, bringing it within the realm of physiological reductants. Similarly, of the cyclen-based complexes, Cu-4 is also easier to reduce than Cu-3 though both reductions are irreversible. Biodistribution studies of (64)Cu-labeled 2 and 4 were performed in Sprague Dawley rats. Despite comparable acid inertness to their shorter-armed congeners, both longer-armed ligand complexes have poorer bio-clearance properties. This inferior in vivo behavior may be a consequence of their higher reduction potentials.

Synthesis, Characterization, and Solution Properties of a Novel Cross-Bridged Cyclam Manganese(IV) Complex Having Two Terminal Hydroxo Ligands

A novel monomeric tetravalent manganese complex with the cross-bridged cyclam ligand 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (Me2EBC), [Mn(IV)(Me2EBC)(OH)2](PF6)2, was synthesized by oxidation of Mn(II)(Me2EBC)Cl2 with H2O2 in the presence of NH4PF6)in aqueous solution. The X-ray crystal structure determination of this manganese(IV) compound revealed that it contains two rare terminal hydroxo ligands. EPR studies in dry acetonitrile at 77 K show two broad resonances at g = 1.96 and 3.41, indicating that the manganese(IV) exists as a high-spin d3 species. Resonance Raman (rR) spectra of this manganese(IV) species reveal that the dihydroxy moiety, Mn(IV)(OH)2, is also the dominant species in aqueous solution (pH < 7). pH titration provides two pK(a) values, 6.86(4) and 10.0(1), associated with stepwise removal of the last two oxygen-bound protons from [Mn(IV)(Me2EBC)(OH)2](2+). The cyclic voltammetry of this manganese(IV) complex in dry acetonitrile at 298 K demonstrates two reversible redox processes at +0.756 and -0.696 V (versus SHE) for the Mn4+/Mn3+ and Mn3+/Mn2+ couples, respectively. This manganese(IV) complex is relatively stable in weak acidic aqueous solution but easily degrades in basic solution to manganese(III) derivatives with an 88 +/- 1% yield.

Lanthanide complexes of a cross-bridged cyclam ligand: Isolation and structural characterization of unusual trinuclear μ 3-imido Yb(III) cluster cations and a mixed valence Yb(II/III) salt containing an Yb(II) anion

The reaction of the cross-bridged cyclam ligand H 2CBC with divalent ytterbium precursors, Yb[N(SiMe 3) 2] 2[L] 2 (L = THF or Et 2O) or Yb(C 5Me 5) 2(OEt 2) afforded polymeric [Yb(CBC)] n ( 1), as the primary product. In addition, the Yb[N(SiMe 3) 2] 2[L] 2 reactions also afforded a small amount of an unusual mixed valence salt containing a trinuclear Yb(III) cluster cation featuring a triply bridging NH group and a mononuclear Yb(II) anion, {[Yb(CBC)] 3[μ 3-NH]} + {Yb[N(SiMe 3) 2] 3} − ( 2). A related cluster containing an iodide counterion, {[Yb(CBC)] 3[μ 3-NH]} + I − ( 3), was also isolated in one case. The structures of salts 2 and 3 were determined by X-ray crystallography. Reaction of [Yb(CBC)] n with p-tolyldisulfide, (C 6H 4MeS) 2, produced burgundy crystals of [Yb(CBC)(S-p-C 6H 4Me)] n ( 4). The 1H NMR spectra of 2 suggests that the trinuclear cation remains intact in THF-d 8 solution.

Inside or outside a ligand cleft? Synthetic, structural, and kinetic inertness studies of zinc, cadmium, and mercury complexes of cross-bridged cyclam and cyclen

Ethylene cross-bridging of the popular tetraazamacrocyclic ligand cyclam has led to metal complexes with enhanced kinetic inertness. The synthesis and spectral characterization of zinc(II), cadmium(II), and mercury(II) complexes of cross-bridged cyclam (L1) as well as cross-bridged cyclen (L2) are reported along with the details of our synthetic route to L2. X-ray structural studies revealed that all Zn(II) and Cd(II) cations are fully kappa(4)N-coordinated inside the respective ligand's molecular cleft with L1 providing the better fit for Zn(II). While Hg(II) is similarly coordinated to L2, it has been found to complex L1 outside the ligand cleft in a novel exo-kappa(2)N-mode. Solution NMR data of the kappa(4)N complexes are consistent with the presence of only a single cis-folded isomer in each case. Ligand (1)H and (13)C coupling to both (111,113)Cd and (199)Hg in their complexes can be clearly discerned. The relative kinetic inertness of representative cross-bridged complexes in acidic aqueous solution has been assessed and found to be in the following order: Zn(II) > Cd(II)[dbl greater-than] Hg(II). The data also reaffirm that cross-bridged cyclam ligand L1 forms a substantially more inert complex with zinc(II) than either the smaller cyclen analogue L2 or the unbridged 1,4,8,11-tetramethyl-cyclam L3.

Two novel zinc(II) complexes of the 1,8-cross-bridged cyclam ligand and their structures

Without special precautions to exclude moisture or protic solvents, cross-bridged cyclam ligand 1 was found to readily complex zinc dichloride and yield two types of cis-folded complexes in the solid-state; one a chloride-bridged dimer and the other an aqua complex featuring a coordinated [ZnCl 4] 2− counterion.