Tetraamide Ligands Research Articles

Investigating the Potential of Flexible and Pre-Organized Tetraamide Ligands to Encapsulate Anions in One-Dimensional Coordination Polymers: Synthesis, Spectroscopic Studies and Crystal Structures

The synthesis of amide-based molecules, possessing pre-organized structures, has received significant attention due to their potential applications as molecular receptors and as components of nanomaterials. In this study, four extended tetraamide ligands incorporating ethylene and propylene spacers, namely 1,2-bis[N,N′-6-(3-pyridylmethylamido)pyridyl-2-carboxyamido]ethane (L1), 1,2-bis[N,N′-6-(4-pyridylmethylamido)pyridyl-2-carboxyamido]ethane (L2), 1,2-bis[N,N′-6-(3-pyridylmethylamido)pyridyl-2-carboxyamido]propane (L3) and 1,2-bis[N,N′-6-(4-pyridylmethylamido)pyridyl-2-carboxyamido]propane (L4), were successfully synthesized. Further, reaction of L2 and L4, incorporating pendant 4-pyridyl donors as the metal coordinating sites, with cadmium salts, produced two close-packed one-dimensional coordination polymers, {[Cd3(L2)4(H2O)10](NO3)6·12H2O·CH3OH}n and {[Cd(SO4)(L4)(H2O)2]·4H2O·CH3OH}n. X-ray crystallography reveals that the flexible tetraamide ligands fold upon themselves in the coordination polymer structure. As a consequence, the anion pocket in {[Cd(SO4)(L4)(H2O)2]·4H2O·CH3OH}n incorporating the ligand with the propylene spacer was blocked from encapsulating charge-balancing anions, which were involved in bridging the di-cadmium units. Interestingly, a strong interaction between the 2,6-pyridine dicarboxamide moiety with the nitrate anions was found in {[Cd3(L2)4(H2O)10](NO3)6·12H2O·CH3OH}n, showing potential for materials made from these ligands to serve as anion receptors.

Alkaline-earth metallacyclic complexes bearing a diborane-bridged tetraamide ligand: synthesis, structure and fluorescence property.

A series of alkaline-earth (Mg, Ca, and Sr) metallacyclic complexes bearing a diborane-bridged tetraamide ligand were achieved for the first time through a clean one-step approach. All of these metallacycles were characterized by single-crystal X-ray diffraction analyses. UV-Vis absorption/emission spectroscopy showed deep blue fluorescence of these complexes.

Characterization of a Dinuclear Copper(II) Complex and Its Fleeting Mixed-Valent Copper(II)/Copper(III) Counterpart.

The synthesis of a dinuclear copper(II) complex, supported by a 1,3-diamino-2-propanol-based tetraamide ligand, is reported. Structural properties in the solid state and in solution, by means of XRD analysis and NMR spectroscopy, respectively, provide evidence of a highly flexible complex that can display several conformations, leading to the image of the wings of a butterfly. The complex was fully characterized and the redox properties were investigated. Room-temperature spectro-electrochemistry was used to monitor the formation of a metastable mono-oxidized product that displayed an absorption band centered at λ=463 nm. EPR investigation of the low-temperature, chemically generated, mono-oxidized product reveals the presence of an intermediate described as a mixed-valent CuII CuIII species, which is a model of the possible highly oxidizing intermediate in particulate methane monooxygenase.

Nickel and copper complexes of a pyridyl-appended tetra-amide ligand : Syntheses and characterization

Nickel and copper complexes of a pyridyl-appended tetra-amide ligand : Syntheses and characterization

Multifunctional Polymeric Scaffolds for Enhancement of PARACEST Contrast Sensitivity and Performance: Effects of Random Copolymer Variations

A DOTA (1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid) tetraamide ligand having a single acrylamide side-chain (M1) was copolymerized with either 2-methylacrylic acid (MAA), 2-(acryloylamino)-2-methyl-1-propanesulfonic acid (AMPS) or N-isopropylacrylamide (NIPAM) to create a series of linear random copolymers using classical free radical chain polymerization chemistry. The metal ion binding properties of hydrolyzed M1 were investigated by pH potentiometry and the europium (III) complexes of the resulting heteropolymers were evaluated as PARACEST imaging agents. All polymeric agents were found to possess similar intermediate-to-slow water exchange and CEST characteristics as the parent EuDOTA-tetraamide monomer. Consistent with basic multiplexing principles, the highest molecular weight polymer, Eu-DMAA 3.1, also showed the highest CEST sensitivity with a detection limit of 20 ± 2 μM. The second arylamide component gave polymers with widely different chemical characteristics and CEST properties. In particular, the Eu-DNIPAM 4.0 and Eu-DMAA 4.1 polymers displayed different solubility characteristics as a function of pH or temperature which, in turn, affected the water exchange and CEST properties of the corresponding agents. It was concluded that introduction of hydrophobic groups into the polymer backbone reduces solvent accessibility to the Eu(3+) component, effectively slowing water exchange between the inner-sphere water coordination position at each Eu(3+) center with bulk water. The CEST properties of the heteropolymers when dissolved in plasma suggest that the more hydrophobic characteristics of these polymers could be advantageous for in vivo applications.

Improved synthesis of DOTA tetraamide ligands for lanthanide(III) ions: A tool for increasing the repertoire of potential PARACEST contrast agents for MRI and/or fluorescent sensors

The synthesis of new DOTA tetraamide (DOTAMR(4)) compounds is of great interest given their application in the formation of Ln(III) complexes as potential PARACEST contrast agents in MRI or fluorescent molecular probes. In this context amino acid and peptide DOTAMR(4) derivatives are particularly attractive since the amino-acid and/or peptide moiety can show responsive properties dependent on a given stimuli which might translate to changes in water exchange rates of the corresponding Ln(III) complex. Current synthesis of DOTAMR(4) derivatives is typically carried out by reacting haloacetamide intermediates with cyclen. However, this method fails to generate the tetra-substituted products when bulky substituents are present in the haloacetamide and in some cases this intermediate cannot be prepared by conventional acylation procedures limiting the number of DOTAMR(4) compounds available for study. As a solution to these limitations, an improved methodology for the synthesis of DOTAMR(4) by coupling DOTA to an appropriate amine containing reagent (i.e. protected amino-acids with the alpha-amino group free) is presented in this work. Several DOTAMR(4) derivatives which are difficult or impossible to prepare with the traditional methodologies were easily obtained starting with DOTA. A new protocol was derived using this methodology for the solution-phase synthesis of DOTA peptide derivatives. With this methodology, many other DOTAMR(4) peptide and non-peptide derivatives have been prepared in our laboratories with several of these new compounds showing interesting properties for molecular imaging.

Synthesis and Characterization of DOTA‐(amide)4 Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes

Lanthanide complexes of tetraamide derivatives of DOTA are of interest today because of their application as chemical exchange saturation transfer (CEST) agents for magnetic resonance imaging (MRI). The protonation constants of some simple tetraamide derivatives of DOTA and the stability constants of the complexes formed with some endogenous metal ions, namely Mg(2+), Ca(2+), Cu(2+), Zn(2+), and lanthanide(III) ions, have been studied. These complexes were found to be considerably less stable than the corresponding [M(DOTA)](2-) complexes, largely due to the lower basicity of the tetraamide ligands. The Mg(2+) and Ca(2+) complexes are well described by formation of only ML species at equilibrium while the Zn(2+) and Cu(2+) complexes exhibit one and two additional deprotonation steps above a pH of around 6, respectively. The extra deprotonation that occurs at high pH for the [Zn{DOTA-(amide)(4)}](2+) complexes has been assigned to an amide deprotonation by (1)H NMR spectroscopy. The first deprotonation step for the Cu(2+) complexes was traced to formation of the ternary hydroxo complexes ML(OH) (by UV/Vis spectrophotometry) while the second step corresponds to deprotonation of an amide group to form ML(OH)H(-1)-type complexes. The trends in the stability constants of the [Ln{DOTA-(amide)(4)}](3+) complexes follow similar trends with respect to ion size as those reported previously for the corresponding [Ln(DOTA)](-) complexes, but again, the stability constants are about 10-11 orders of magnitude lower. A kinetic analysis of complex formation has shown that complexes are directly formed between a Ln(3+) cation and fully deprotonated L without formation of a protonated intermediate. [Ln{DOTA-(MeAm)(4)}](3+) complex formation occurs at a rate that is two to three orders of magnitude slower than those of the corresponding [Ln(DOTA)](-) complexes, while the variation in complex formation rates with Ln(3+) ion size is opposite to that observed for the corresponding [Ln(DOTA)](-) complexes. The Ce(3+) and Eu(3+) complexes of DOTA-(MeAm)(4) are kinetically inert with respect to acid-catalyzed dissociation, which suggests that these complexes may potentially be safe for use in vivo.

Chemical and Spectroscopic Evidence for an Fe V -Oxo Complex

Iron(V)-oxo species have been proposed as key reactive intermediates in the catalysis of oxygen-activating enzymes and synthetic catalysts. Here, we report the synthesis of [Fe(TAML)(O)]- in nearly quantitative yield, where TAML is a macrocyclic tetraamide ligand. Mass spectrometry, Mössbauer, electron paramagnetic resonance, and x-ray absorption spectroscopies, as well as reactivity studies and density functional theory calculations show that this long-lived (hours at -60 degrees C) intermediate is a spin S = 1/2 iron(V)-oxo complex. Iron-TAML systems have proven to be efficient catalysts in the decomposition of numerous pollutants by hydrogen peroxide, and the species we characterized is a likely reactive intermediate in these reactions.

Speciation, stability constants and structures of complexes of copper(II), nickel(II), silver(I) and mercury(II) with PAMAM dendrimer and related tetraamide ligands

The acid–base properties and Cu(II), Ni(II), Ag(I) and Hg(II) binding abilities of PAMAM dendrimer, L, and of the simple model compounds, the tetraamides of EDTA and PDTA, L 1, were studied in solution by pH-metric methods and by 1H NMR and UV–Vis spectroscopy. PAMAM is hexabasic and six p K a values have been determined and assigned. PAMAM forms five identifiable complexes with copper(II), [Cu LH 4] 6+, [Cu LH 2] 4+, [Cu LH] 3+, [Cu L] 2+ and [Cu LH -1] + in the pH range 2–11 and three with nickel(II), [Ni LH] 3+, [Ni L] 2+ and [Ni LH -1] + in the pH range 7–11. The complex [Cu LH 4] 6+, which contains two tertiary nitrogen and three amide oxygen atoms coordinated to the metal ion, is less stable than the analogous EDTA and PDTA tetraamide complexes [Cu L 1] 2+, which contain two tertiary nitrogen and four amide oxygen atoms, due to ring size and charge effects. With increasing pH, [Cu LH 4] 6+ undergoes deprotonation of two coordinated amide groups to give [Cu LH 2] 4+ with a concomitant change from O-amide to N-amidate coordination. Surprisingly and in contrast to the tetraamide complexes [Cu L 1] 2+, these two deprotonation steps could not be separated. As expected the nickel(II) complexes are less stable than their copper(II) analogues. The tetra- N-methylamides of EDTA, L 1( b), and PDTA form mononuclear and binuclear complexes with Hg(II). In the case of L 1 ( b) these have stoichiometries Hg L 1 ( b)Cl 2, [Hg L 1 ( b)H −2Cl 2] 2−, [Hg 2 L 1 ( b)Cl 2] 2+, Hg 2 L 1 ( b)H −2Cl 2 and [Hg 2 L 1 ( b)H −5Cl 2] 3−. Based on 1H NMR and pH-metric data the proposed structure for Hg L 1 ( b)Cl 2, the main tetraamide ligand containing species in the pH range <3–6.5, contains L 1 ( b) coordinated to the metal ion through the two tertiary nitrogens and two amide oxygens while the structure of [Hg L 1 ( b)H −2Cl 2] 2−, the main tetraamide ligand species at pH 7.5–9.0, contains the ligand similarly coordinated but through two amidate nitrogen atoms instead of amide oxygens. The proposed structure of [Hg 2 L 1 ( b)Cl 2] 2+, a minor species at pH 3–6.5, also based on 1H NMR and pH-metric data, contains each Hg(II) coordinated to a tertiary amino nitrogen, two amide oxygens and a chloride ligand while that of [Hg 2 L 1 ( b)H −5Cl 2] 3−, contains each Hg(II) coordinated to a tertiary amino nitrogen, two amidate nitrogens, a chloride and a hydroxo ligand in the case of one of the Hg(II) ions. The parent EDTA and PDTA amides only form mononuclear complexes. PAMAM also forms dinuclear as well as mononuclear complexes with mercury(II) and silver(I). In the pH range 3–11 six complexes with Hg(II) i.e. [Hg LH 4Cl 2] 4+, [Hg LH 3Cl 2] 3+, [Hg 2 LCl 2] 2+, [Hg 2 LH −1Cl 2] +, [Hg LH −1Cl 2] − and [Hg LH −2Cl 2] 2− were identified and only two with Ag(I), [Ag LH 3] 4+ and [Ag 2 L] 2+. Based on stoichiometries, stability constant comparisons and 1H NMR data, structures are proposed for these species. Hence [Hg LH 4Cl 2] 4+ is proposed to have a similar structure to [Cu LH 4] 6+ while [Hg 2 LCl 2] 2 +has a similar structure to [Hg 2 L 1 ( b)H −5Cl 2] 3−.

Structural analysis of nine-coordinate lanthanide complexes: steric control of the metal-water distance across the series.

The structures of 10 isomorphous lanthanide (Ln) complexes of a chiral DOTA tetra-amide ligand (L(1)), [LnL(1)(H(2)O)](CF(3)SO(3))(3).3H(2)O, crystallizing in space group P2(1), have been studied by single-crystal X-ray diffraction. The Ln coordination is a O(4)N(4) square antiprism, the O(4) base of which is capped by an aqua ligand. The sterically demanding position of the latter results in the lengthening of the Ln-OH(2) distance along the Pr to Lu series by 0.06 A (after allowing for the lanthanide contraction). In parallel, the distance between the bound water oxygen and the second-sphere water oxygen is reduced from 3.17 A (Pr) to 3.04 A (Lu), consistent with the enhanced hydrogen bond acceptor ability of the coordinated water oxygen across the series. A Cambridge Structural Database survey of [Ln(H(2)O)(9)](CF(3)SO(3))(3) salts (space group P6(3)/m) and of six reported isostructural complexes of DOTA [L(2)] revealed a similar trend. The implications of the resultant destabilization of the ground state structure for the water interchange process are discussed.

Unusually sharp dependence of water exchange rate versus lanthanide ionic radii for a series of tetraamide complexes.

The tetraamide ligand, DOTA-tetra(glycine ethyl ester), forms complexes with the lanthanide(III) cations that exist in solution predominantly as the square antiprism structure with single, slowly exchanging inner-sphere water molecule. Variable-temperature 1H and 17O NMR studies revealed that the bound water lifetimes in these complexes were sharply dependent upon the ionic radius of Ln3+ cation. A novel lanthanide-induced shift technique was used to unmask the bound water 17O resonance of SmL3+ and YL3+ complexes from the bulk water resonance. The bound water lifetime (tauM298) was approximately 800 mus in the EuL3+ complex but became much shorter (several microseconds) for Ln3+ cations with larger and smaller ionic radii. This demonstrates that water exchange is exquisitely fine-tuned in this macrocyclic tetraamide system and that a variety of Ln3+ complexes meet with the exchange requirement, Deltaomega*tauM >/= 1, necessary for an efficient MT agent.

Effect of Axial Ligation on the Magnetic and Electronic Properties of Lanthanide Complexes of Octadentate Ligands

A detailed investigation of the solution structure of two Yb(III) complexes of C4 symmetric chiral tetraamide ligands based on cyclen is performed in different solvents with the combined use of 1H NMR, NIR-CD, and luminescence techniques. Pseudocontact chemical shifts and NOE measurements allow one to assess the relative positions of the ring and the side chains; NIR-CD spectra provide a description of the local stereochemistry around the metal ion; and finally, the axial exchange dynamics can be quantitatively characterized by means of the luminescence emission data. The two complexes can be described by a Λ(δδδδ) (i.e., square antiprismatic) coordination polyhedra, capped by a ninth axial solvent molecule. On changing the solvent composition (water, methanol, acetonitrile, dimethylsulfoxide), equilibria involving the ring or the sidearms are not detected, and the macrocycle conformation stays the same: the relevant changes in the observed spectra can thus be related to different axial coordinations. Th...

Synthesis and crystal structure of [U(η-C 8H 8)] 2[μ-η 4:η 4-HN(CH 2) 3N(CH 2) 2N(CH 2) 3NH], a dinuclear compound with a bridging tetra-amide ligand

The title compound was prepared by the transamination reaction of [U(COT)(N{SiMe 3} 2) 2] and H 2N(CH 2) 3NH(CH 2) 2NH(CH 2) 3NH 2. The X-ray crystal structure reveals the shortest UU distance [3.3057(9) Å] ever observed in a molecular compound.

A Convenient New Route to Tetradentate and Pentadentate Macrocyclic Tetraamide Ligands

A crucial diamide diamine intermediate in the synthesis of tetradentate macrocyclic tetraamide ligands protected against oxidative decomposition has been synthesized without the use of potentially hazardous organic azide intermediates. This intermediate has also been used to synthesize a new class of pentadentate macrocyclic tetraamide ligands.

Restoration of Catalytic Activity by Replacement of a Coordinated Amide Group: Synthesis and Laser-Induced Luminescence Studies of the Phosphate Diester Transesterification Catalyst [Eu(NBAC)]3+

The europium(III) complex of the octadentate tetraamide ligand is inactive as a catalyst for phosphate diester transesterification or for RNA cleavage. Replacement of one of the amide coordinating groups to form a new heptadentate ligand yields a europium(III) complex ([Eu(NBAC)]3+) that is a very active catalyst for phosphate diester transesterification at 37 °C, pH 7.40. Laser-induced luminescence is used to study the number of bound water molecules and self-association of the [Eu(NBAC)]3+ complex as well as the dissociation of the complex in the presence of competing ligands.

Spectroscopic properties of iron(III) and iron(IV) coordinated by tetraamide ligands.

Spectroscopic properties of iron(III) and iron(IV) coordinated by tetraamide ligands.

ChemInform Abstract: A Water‐Stable Manganese(V)‐Oxo Complex: Definitive Assignment of a νMn(V)O Infrared Vibration.

AbstractThe manganese(V)‐monooxo complex (IVb) of a new macrocyclic tetraamide ligand, which is water‐stable, crystallizes in the space group P21/c with Z=4.

Synthetic and solution studies on metal complexes of N,N,N′,N′-tetrakis(2-carbamoylethyl)ethylenediamine

The preparation of the tetra-amide ligand N,N,N′,N′-tetrakis(2-carbamoylethyl)ethylenediamine (H2L) by Michael addition of ethylenediamine to acrylamide is described. The ligand forms complexes with CuII, NiII, CoII, FeII, MnII, BaII, ZnII, CdII, HgII, and LaIII, which have been characterised in the solid state. With CuII, NiII, and PdII, deprotonated complexes [ML] can be prepared in solution and the solid state. For the other metal ions the complexes can be formulated as Mn+(H2L)Cln·xH2O. The stepwise protonation of the ligand has been studied by potentiometric titration, giving log K1= 7.20(1) and log K2= 3.25(2) at 25 °C and I= 0.1 mol dm–3(NaClO4). Titration data for the molar ratio H2L/MII= 1 : 1 (MII= CuII, NiII, or PdII) can be fitted to the stepwise equilibria (i)–(iii) and the corresponding log β values are reported. M2++ H2L [graphic omitted] [M(H2L)]2+(i), M2++ H2L [graphic omitted] [M(HL)]++ H+(ii), M2++ H2L [graphic omitted] [ML]+ 2H+(iii)