Search

International audience; The preparation of two cyclens both possessing two triethoxysilyl groups through click chemistry is described. These two cyclens were incorporated into bis(triethoxysilyl)ethenylene‐based periodic mesoporous organosilica nanoparticles (PMO NPs) at different proportions of bis(triethoxysilyl)ethenylene/cyclens (90/10, 75/25). The obtained nanorods were analyzed with different techniques and showed high specific surface areas at low proportion of cyclens. The nanorods containing free amino groups of cyclen were then used for Ni(II) and Co(II) removal from model solutions. The kinetics and isotherms of adsorption of Ni(II) and Co(II) were determined, and the materials showed high uptake of metals (up to 3.9 mmol ⋅ g−1). They demonstrated pronounced selectivity in separation of rare earth elements from late transition metals, e. g. Ni(II) and Co(II) by adsorption and even more so by controlled desorption..

Recent advances in the use of radiometals for both imaging and therapy has spurred on the development of an original chemistry that endows radionuclide-chelating molecular cages with ever sharper physicochemical properties. Macrocyclic polyamines (MPAs) such as cyclen and DOTA are among the most frequently encountered cages for the design of new radiotracers, owing to their versatile chemistry that makes them customizable molecular tools. The idea of using MPAs for alternative purposes has recently emerged, with an eye towards benefiting from their unique topology, versatility, symmetry and water-solubility. This review summarizes strategies that have been recently implemented in which MPAs are used as multivalent molecular platforms for constructing sophisticated suprastructures that found applications in various fields, from material chemistry to chemical biology. These original approaches are invaluable in that they successfully expand the scope of applications of MPAs far beyond their restricted roles of metal chelating appendages.

We present two novel octadentate cyclen-based ligands bearing one (L1 ) or two (L2 ) phenylacetamide pendants with two CF3 groups either at positions 3 and 5 (L1 ) or 4 (L2 ). The corresponding Gd3+ complexes possess one coordinated water molecule, as confirmed by luminescence lifetime measurements on the EuIII and TbIII analogues. A detailed 1 H and 17 O relaxometric characterization has revealed the parameters that govern the relaxivities of these complexes. The water-exchange rate of the mono-amide derivative GdL1 (kex298 =1.52×106 s-1 ) is faster than that determined for the bis-amide complex GdL2 (kex298 =0.73×106 s-1 ). 1 H and 19 F NMR studies have indicated that the complexes are present in solution almost exclusively as the square-antiprismatic (SAP) isomers. 19 F NMR relaxation studies indicated Gd⋅⋅⋅F distances of 7.4±0.1 and 9.1±0.1 A for GdL1 and GdL2 , respectively. Phantom MRI studies revealed the favorable properties of GdL2 as a dual 1 H/19 F magnetic resonance imaging (MRI) probe, whereas the shorter Gd⋅⋅⋅F distance of GdL1 reduces the signal-to-noise ratio due to the very short transverse relaxation time of the 19 F NMR signal.

A cyclen-based hybrid supermolecule crystal, [(FeCl2 )(cyclen)]Cl (1), where cyclen=1,4,7,10-tetraazacyclododecane, was prepared using a liquid-liquid diffusion approach. The variable crystal structures exhibit that compound 1 belongs to an orthorhombic crystal system, Pna21 space group (point group C2V ) in the temperature range of 150-400 K. This hybrid supermolecule shows a dielectric relaxation behavior around room temperature, and the ferroelectric nature of 1 has been directly verified by hysteresis measurements. In addition, the AC (alternating current) conductivity study reveals that the 1 displays a beyond limiting behavior. These interesting findings are for the first time reported in the field of supermolecular ferroelectrics. This study may open a new way to construct supermolecular ferroelectrics and give insights into their conductor behavior.

WOS: 000496596200001, Novel ruthenium(II)bpy complexes of the phenanthrimidazole-pendant cyclen and cyclam macrocyclic ligands were synthesized as inorganic host molecules. Inorganic host design was planned as a "complex ligand" form because of its tetraaza macrocyclic unit, which has the ability to coordinate to the metals. Photophysical properties and metal selectivity of inorganic hosts RuL1A and RuL2 complex ligands were investigated by UV-vis and fluorescence spectroscopy in aqueous medium. Among Ag(I), Li(I), Na(I), K(I), Cd(II), Cr(II), Fe(II), Hg(II), Ni(II), Pb(II), Zn(II), Cu(II), Mn(III), and Co(III) metal ions, Fe(II) addition causes spectral changes for both RuL1A and RuL2 complex ligands. Electrochemical studies were performed for RuL1B and also for cis-[Ru(bpy)(2)Cl-2]. Bimetallic complexes [[Ru(bpy)(2)([Ni(2-(4-((1,4,8,11-tetraazacyclotetradecan-1-yl)methyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline])](ClO4)(4), RuL1-NiA and [Ru(bpy)(2)([Ni(2-(4-((1,4,8,11-tetraazacyclotetradecan-1-yl)methyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline])]Cl-4, RuL1-NiB solid complexes were also obtained by the reaction of the RuL1B and Nickel(II)., Selcuk University (Konya/TURKEY)Selcuk University [18401062], Selcuk University (Konya/TURKEY), Grant/Award Number: 18401062

The Eu3+/2+ redox couple provides a convenient design platform for responsive pO2 sensors for magnetic resonance imaging (MRI). Specifically the Eu2+ ion provides T1w contrast enhancement under hypoxic conditions in tissues, whereas, under normoxia, the Eu3+ ion can produce contrast from chemical exchange saturation transfer in MRI. The oxidative stability of the Eu3+/2+ redox couple for a series of tetraaza macrocyclic complexes was investigated in this work using cyclic voltammetry. A series of Eu-containing cyclen-based macrocyclic complexes revealed positive shifts in the Eu3+/2+ redox potentials with each replacement of a carboxylate coordinating arm of the ligand scaffold with glycinamide pendant arms. The data obtained reveal that the complex containing four glycinamide coordinating pendant arms has the highest oxidative stability of the series investigated.

A stable cyclen-based Eu(III) complex precursor is synthesized as a fast-screening tool and template to select suitable chromophores for sensitizing Eu(III) luminescence by a one-step coupling reaction. A library of chromophores has been synthesized and screened by either Sonogashira or Suzuki reaction to confirm proof of concept and the ease of this methodology. The photophysical properties of these corresponding complexes as well as their potential properties for biological applications has been assessed.

Invited for the cover of this issue are the groups of Y. Ye from Zhengzhou University, China, A. Angerhofer from the University of Florida, USA, Y. Zhao from Xiamen University, China, and L.-J. Ming from the University of South Florida, USA. The cover image shows the pathways for dinuclear catechol oxidation by CuII complexes of cyclotriphosphazene derivatives with up to six metal-binding sites.

Double-arm cyclen-based Gd3+ tags are shown to produce accurate nanometer scale Gd3+-Gd3+ distance measurements in double electron-electron resonance (DEER) experiments by confining the space accessible to the metal ion. The results show excellent agreement with predictions both for the maximum and width of the measured distance distributions. For distance measurements in proteins, the tags can be attached to two cysteine residues located in positions i and i+4, or i and i+8, of an α-helix. In the latter case, an additional mutation introducing an aspartic acid at position i+4 achieves particularly narrow distribution widths. The concept is demonstrated with cysteine mutants of T4 lysozyme and maltose binding protein. We report the narrowest Gd3+-Gd3+ distance distributions observed to date for a protein. By limiting the contribution of tag mobility to the distances measured, double-arm Gd3+ tags open new opportunities to study the conformational landscape of proteins in solution with high sensitivity.

The development of in material-supported molecular logic gate mimics (MLGMs) for contained application and device fabrication has become of increasing interest. Herein, we present the application of ~ 5 nm gold nanoparticles (AuNPs) that have been surface-modified (via a thiol linkage) with heptadentate cyclen-based complexes of europium and terbium for sensing applications using delayed lanthanide luminescence and as integrated logic gate mimics within competitive media

The facile redox-assisted assembly of a water-soluble, extremely robust, cyanide-bridged mixed-valence [{CoIII{(Me)2(μ-ET)cyclen}}2{(μ-NC)2FeII(CN)4}2]2− square is reported. The preparation process involved the use of the enhanced lability of inert CoIII synthons triggered by outer-sphere redox processes. Characterization of the final compounds has been carried out by NMR, UV/Vis, electrochemistry, and ICP analyses. DFT calculations have been conducted to optimize a structure that has the same hydrodynamic radius as that obtained from DOSY experiments. The new compound is extremely robust, surviving in aqueous solution within the 0–12 pH range for months. The species shows a high affinity for both protons and hydroxo ions in aqueous medium.

New and highly stable Eu(III) and Tb(III) complexes based on two triarylborane functionalized cyclen derivative ligands L1 and L2, have been achieved. The Eu(III) and Tb(III) lanthanide compounds have been found to display highly distinct and contrasting temperature-dependent dual emission and decay lifetimes, rendering them as potential sensitive temperature probes. The emission colors of the new lanthanide complexes can be tuned by controlling the ratio of the Eu(III) and Tb(III) complexes in a binary composite and the temperature. Bright white light emission based on the new binary Eu(III) and Tb(III) complexes has been achieved. Furthermore, the triarylborane functionality of the new complexes enables their use as effective probes for anions such as fluoride ions, allowing the further tuning of the lanthanide emission.

Two coordination complexes EuII2EuIII4(OH)4(bza)4L2 (1) and EuIII5(H2O)(OH)4(NO3)3(bza)4L (2) have been assembled with the tetrasubstituted cyclen ligand N,N′,N′′,N′′′-tetrakis(2-hydroxy-3-methoxy-5-methylbenzyl)-1,4,7,10-tetraazacyclododecane (H4L) and the auxiliary ligand benzoic acid (Hbza). Complex 2 is a pentanuclear EuIII cluster whereas complex 1 is a huge heterovalent 2EuII/4EuIII cluster in which two divalent europium ions are trapped within the macrocyclic cavities of the designed ligands L and are further isolated from the environment by peripheral phenyl rings and the tetrahedral 4EuIII cluster, which results in the enhanced oxidative stability of Eu2+. The luminescence of complex 1 was investigated and is discussed in comparison with the luminescence of ligand H4L and complex 2. Owing to the protection of Eu2+ by the macrocyclic ligands L, the heterovalent complex exhibits a strong broad emission band with a maximum at 533 nm as well as the characteristic sharp emissions of Eu3+. The broad emission is redshifted compared with that of ligand H4L and has been attributed to the Laporte-allowed 4f65d1 → 4f7 transition of Eu2+.

Lanthanide complexes of tetrapicolyl cyclen displayed remarkably high affinities for fluoride (log K≈5) in water, and were shown to form 1:1 complexes. The behaviour of these systems can be rationalised by changes to the magnitude of the crystal-field parameter, B20 . However, such changes are not invariably accompanied by a change in sign of this parameter: for early lanthanides, the N8 donor set with a coordinated axial water molecule ensures that the magnetic anisotropy has the opposite sense to that observed in the analogous dehydrated lanthanide complexes.

The development of noninvasive methodologies for the detection of d-block metal ions such as copper (Cu2+), zinc (Zn2+), and manganese (Mn2+) is important for understanding their biological roles and relationship with diseases. We have been interested in the use of 11B NMR probes for the detection of d-block metal ions, because 11B is an ultratrace element in living systems. o-Carboranes, which consist of ten boron and two carbon atoms, have been applied to numerous drugs and biological active agents. In this work, we found that the o-carborane-pendant cyclens (L3–L5) (cyclen = 1,4,7,10-tetraazacyclododecane) are decomposed in the presence of Mn2+ or Cu2+ in aqueous solution at neutral pH, accompanied by the release of 4–9 equiv. of B(OH)3. Furthermore, it was found that o-carborane derivatives that contain hydroxyl groups instead of a cyclen unit also undergo decomposition in the presence of Cu2+ and the corresponding complexes such as Cu(bpy) to afford 10 equiv. of B(OH)3, as confirmed by 11B NMR spectroscopic analysis and an azomethine-H assay. These reactions are applied to 11B MRI (magnetic resonance imaging) probes for Cu2+.

Can cyclen (1,4,7,10-tetraazacyclododecane) bind alkali metal azides? This question is addressed by studying the geometric and electronic structures of the alkali metal azide-cyclen [M(cyclen)N3] complexes using density functional theory (DFT). The effects of adding a second cyclen ring to form the sandwich alkali metal azide-cyclen [M(cyclen)2N3] complexes are also investigated. N3(-) is found to bind to a M(+) (cyclen) template to give both end-on and side-on structures. In the end-on structures, the terminal nitrogen atom of the azide group (N1) bonds to the metal as well as to a hydrogen atom of the cyclen ring through a hydrogen bond in an end-on configuration to the cyclen ring. In the side-on structures, the N3 unit is bonded (in a side-on configuration to the cyclen ring) to the metal through the terminal nitrogen atom of the azide group (N1), and through the other terminal nitrogen atom (N3) of the azide group by a hydrogen bond to a hydrogen atom of the cyclen ring. For all the alkali metals, the N3-side-on structure is lowest in energy. Addition of a second cyclen unit to [M(cyclen)N3] to form the sandwich compounds [M(cyclen)2N3] causes the bond strength between the metal and the N3 unit to decrease. It is hoped that this computational study will be a precursor to the synthesis and experimental study of these new macrocyclic compounds; structural parameters and infrared spectra were computed, which will assist future experimental work.

Four novel chelators (L1-L4) and their 89zirconium complexes were prepared and compared with the 89zirconium desferrioxamine B (DFO) complex. The new chelates are based on 1,4,7,10-tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) scaffolds and present either three or four hydroxamate arms for coordination with Zr4+ ions with coordination numbers between six and eight. The 89Zr-L4 complex showed similar stability to that of 89Zr-DFO when incubated in either rat blood plasma or ethylenediaminetetraacetic acid challenge experiments. Positron imaging and biodistribution studies in mice showed that 89Zr-L4 had similar pharmacokinetic behavior to that of 89Zr-DFO, with rapid renal elimination and low residual activity in background tissues. A bifunctional version of L4 (L5) was synthesized and conjugated to trastuzumab; an anti-HER2/neu antibody. Immunopositron emission tomography imaging and biodistribution with 89Zr-L5-trastuzumab revealed high tumor to background ratios (tumor/blood ratio: 14.2 ± 2.25) and a high tumor specificity that was comparable to the performance of 89Zr-DFO-trastuzumab.

Recent advances in nanomaterials have identified nanogels as an excellent matrix for novel biomimetic catalysts using the molecular imprinting approach. Polymerisable Co‐cyclen complexes with phosphonate and carbonate templates have been prepared, fully characterised and used to obtain nanogels that show high activity and turnover with low catalytic load, compared to the free complex, in the hydrolysis of 4‐nitrophenyl phosphate, a nerve agent simulant. This work demonstrates that the chemical structure of the template has an impact on the coordination geometry and oxidation state of the metal centre in the polymerisable complex resulting in very significant changes in the catalytic properties of the polymeric matrix. Both pseudo‐octahedral cobalt(III) and trigonal‐bipyramidal cobalt(II) structures have been used for the synthesis of imprinted nanogels, and the catalytic data demonstrate that: i) the imprinted nanogels can be used in 15 % load and show turnover; ii) the structural differences in the polymeric matrices resulting from the imprinting approach with different templates are responsible for the molecular recognition capabilities and the catalytic activity. Nanogel P1, imprinted with the carbonate template, shows >50 % higher catalytic activity than P2 imprinted with the phosphonate.

A quinone methide precursor featuring a bis-cyclen anchoring moiety has been synthesized and its capacity to alkylate oligonucleotide targets quantified in the presence and absence of divalent metal ions (Zn(2+) , Ni(2+) and Cd(2+) ). The oligonucleotides were designed for testing the sequence and secondary structure specificity of the reaction. Gel electrophoretic analysis revealed predominant alkylation of C-rich bulges, regardless of the presence of divalent metal ions or even the bis-cyclen anchor. This C-selectivity appears to be an intrinsic property of the quinone methide electrophile as reflected by its reaction with an equimolar mixture of the 2'-deoxynucleosides. Only dA-N1 and dC-N3 alkylation products were detected initially and only the dC adduct persisted for detection under conditions of the gel electrophoretic analysis.

The synthesis, crystal structures, and magnetic properties of three cyano-bridged heterodimetallic compounds prepared from the paramagnetic RuIII building block mer-[RuIII(CN-sap)(CN)3]2– (1) are described. Complex 1 reacts with [MnII(LN5)(Cl)(H2O)]Cl and [MnII(bipy)2(Cl)2] (bipy = bipyridine) to produce the 1D zigzag chain {[RuIII(CN-sap)(CN)](μ-CN)2[MnII(LN5)]·3MeOH}n {2; LN5 = 2,13-dimethyl-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene, CN-sapH2 = 2-hydroxy-N-(2-hydroxyphenyl)benzimidoyl cyanide} and the octanuclear compound {[RuIII(CN-sap)(CN)](μ-CN)2[MnII(bipy)(MeOH)][RuIII(CN-sap)](μ-CN)3[MnII(bipy)2]}2·8MeOH (3), respectively. The MnII centers have a pentagonal-bipyramidal environment in 2 and a distorted octahedral environment in 3. Complex 1 reacts with [NiII(cyclen)(Cl)2] (cyclen = 1,4,7,10-tetraazacyclododecane) in MeOH to produce the molecular square {[RuIII(CN-sap)(CN)](μ-CN)2[NiII(cyclen)]}2·8MeOH (4). Compounds 2 and 3 exhibit antiferromagnetic coupling between the RuIII and MnII centers, whereas 4 exhibits ferromagnetic coupling between the RuIII and NiII centers through the cyano bridges.

[Abstract] A series of mono‐, di‐, and trinuclear complexes of Eu and Tb was designed to study the influence of the number of Ln emitting centers on the luminescence properties of discrete polynuclear complexes. The complexes are based on a cyclen scaffold, functionalized by two picolinic acid pendant arms. These coordinating units are separated by a 1,3‐dimethylbenzene spacer for the dinuclear complex and a 1,3,5‐trimethylbenzene bridge in the case of the trinuclear complex. The synthesis and characterization of the ligands are presented, together with the preparation and spectroscopic characterization of the complexes. The luminescence properties of the complexes were determined by UV/Vis absorption spectroscopy and steady‐state and time‐resolved luminescence spectroscopy in buffered aqueous solutions. Comparison of the electronic absorption spectra showed that the absorption properties can almost be considered as extensive parameters within experimental error, as expected for electronically non‐conjugated systems. A small drop of both the excited state luminescence lifetimes and the luminescence quantum yields was observed for the trinuclear complexes in the case of Tb. To understand this behavior, theoretical HF (Hartree–Fock) calculations were performed for the three complexes. Models indicate that the average intermetallic distance in the dinuclear complex is almost the same as in the trinuclear one, disfavoring a possible distance dependence of the observed phenomena. Francia. Agence Nationale de la Recherche; ANR P2N 2012

The stability constants of complexes of the macrocyclic ligand do3a-pic4– (H4do3a-pic = 2,2′,2″-{10-[(6-carboxypyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triyl}triacetic acid) with several divalent metal ions (Pb2+, Cd2+, Zn2+, Cu2+, Ca2+, and Mg2+) have been determined by using pH-potentiometric titrations (I = 0.1 M KCl, 25 °C). The stability of these complexes follows the trend Cu2+ > Cd2+ ≈ Pb2+ ≈ Zn2+ >> Ca2+ >> Mg2+. A particularly high stability constant has been determined for the Cu2+ complex [log KCuL = 23.20(4)]. Analysis of the titration curves indicate the presence of protonated forms of the complexes in solution, with protonation constants of log KM(HxL) = 6.9–2.0 (x = 1, 2, or 3). The structure of the complexes in solution has been investigated by using 1H and 13C NMR spectroscopy and DFT calculations performed in aqueous solution at the TPSSh/6-31G(d) level. In the case of the Pb2+ and Cd2+ complexes, relativistic effects were considered with the use of relativistic effective core potentials. Calculations show that the complexes with the largest metal ions (Pb2+ and Ca2+) are nine-coordinate, with their coordination polyhedra being best described as capped twisted square antiprisms. The Cd2+ and Mg2+ complexes are seven-coordinate, with the metal ions being bound to the four nitrogen atoms of the cyclen unit and the three acetate pendant arms. Finally, in the Cu2+ and Zn2+ complexes, the metal ions are six-coordinated, with the metal ions being asymmetrically placed inside the macrocyclic cavity of the ligand, and the coordination polyhedra can be described as an octahedron and a trigonal prism, respectively.

A transition-metal-free method for the synthesis of N-substituted unsymmetrical sulforhodamine fluorophores from an unusual monobrominated sulfoxanthene dye and primary or secondary amines by direct SNAr-type reactions is presented. The simplicity and effectiveness of this “postamination” procedure were demonstrated through the rapid preparation of a library of multifunctional red-emitting rhodamine analogues. Some of these analogues are equipped with a reactive handle and retain the two water-solubilizing sulfonic acid moieties of the starting halogenated derivative; this makes them ideal candidates for biolabeling applications. The potential utility of this expeditious strategy to finely tune the photophysical (Stokes shift) and physicochemical properties (amphiphilic character and water solubility) of the sulforhodamine scaffold was also demonstrated through the appendage of a fluorescent amine to create a fluorescence resonance energy transfer (FRET) pair, a long-chain amine, and tetraazamacrocycles derived from cyclen.

Two macrotricyclic ligands composed of two face-to-face octadentate metal chelates were synthesized. These cage-shaped disodium complexes had special recognition ability for various counter anions. Specific chiral dicarboxylates bound to the complexes within the cavity and exhibited chirality induction properties. For instance, N-Boc-Asp dianion strongly induced circular dichroism (CD) signals, but N-Boc-Glu dianion, which is one carbon longer, did not.

In our previous paper, we reported that a dimeric Zn(2+) complex with a 2,2'-bipyridyl linker (Zn2L(1)), cyanuric acid (CA), and a Cu(2+) ion automatically assemble in aqueous solution to form 4:4:4 complex 3, which selectively catalyzes the hydrolysis of mono(4-nitrophenyl)phosphate (MNP) at neutral pH. Herein, we report that the use of barbital (Bar) instead of CA for the self-assembly with Zn2L(1) and Cu(2+) induces 2:2:2 complexation of these components, and not the 4:4:4 complex, to form supramolecular complex 6 a, the structure and equilibrium characteristics of which were studied by analytical and physical measurements. The finding show that 6 a also accelerates the hydrolysis of MNP, similarly to 3. Moreover, inspired by the crystal structure of 6 a, we prepared barbital units that contain functional groups on their side chains in an attempt to produce supramolecular phosphatases that possess functional groups near the Cu2(μ-OH)2 catalytic core so as to mimic the catalytic center of alkaline phosphatase (AP).

An efficient copper-catalyzed N-arylation reactions of imidazole, indole, and triazole with aryl or heteroaryl halides using cyclen derivatives as efficient organic base and ligand at moderate temperature have been investigated. The cross-couplings proceed smoothly with good to excellent yields.

International audience; Lanthanide complexes (Ln=Eu, Tb, and Yb) that are based on a C2-symmetric cyclen scaffold were prepared and characterized. The addition of fluoride anions to aqueous solutions of the complexes resulted in the formation of dinuclear supramolecular compounds in which the anion is confined into the cavity that is formed by the two complexes. The supramolecular assembly process was monitored by UV/Vis absorption, luminescence, and NMR spectroscopy and high-resolution mass spectrometry. The X-ray crystal structure of the europium dimer revealed that the architecture of the scaffold is stabilized by synergistic effects of the Eu[BOND]F[BOND]Eu bridging motive, π stacking interactions, and a four-component hydrogen-bonding network, which control the assembly of the two [EuL] entities around the fluoride ion. The strong association in water allowed for the luminescence sensing of fluoride down to a detection limit of 24 nM.

A simple and efficient method based on magnetic-bead technology has been developed for the enrichment of thiol-containing biomolecules, such as l-glutathione and cysteine-containing peptides. The thiol-binding site on the bead is a mononuclear complex of zinc(II) with 1,4,7,10-tetraazacyclododecane (cyclen); this is linked to a hydrophilic cross-linked agarose coating on a particle that has a magnetic core. All steps for the thiol-affinity separation are conducted in aqueous buffers with 0.10 mL of the magnetic beads in a 1.5 mL microtube. The entire separation protocol for thiol-containing compounds, from addition to elution, requires less than one hour per sample, provided the buffers and the zinc(II)-cyclen-functionalized magnetic beads have been prepared in advance. The thiol-affinity magnetic beads are reusable at least 15 times without a decrease in their thiol-binding ability, and they are stable for six months at room temperature.

RATIONALE Differentiation and structural characterization of Asp/cyclen conjugates by electrospray ionization tandem mass spectrometry (ESI-MSn) are significantly important for their biomedical application. Hence, the present study is conducted. METHODS The fragmentations of Asp/cyclen conjugates generated by positive ion mode electrospray ionization were examined here by low-energy collision-induced dissociation (CID). ESI-MSn spectra of cyclen were acquired to confirm cyclen contraction products derived from the studied compounds. The fragments derived from the Asp/cyclen conjugates were proved by deuterium-exchange experiments. RESULTS Asp/cyclen conjugates displayed characteristic dissociation pathways, including cleavages of amide bonds, loss of NH3 and cyclen contraction pathways. It was observed that cleavages of C-terminal amide bonds generated b2 and b2 + H2O ions from the protonated CyclenAspAspAsp and a b1 + H2O ion from the protonated CyclenAspAsp. In addition, various cyclen contraction products were also observed. CONCLUSIONS In ESI-MSn spectra of studied compounds, fragments of bn-1 + H2O or cyclic anhydride were generated due to facile mobilization of C-terminal or side-chain COOH protons. In addition, the cyclen contraction products were detected. These results might provide sufficient information for the identification of Asp/cyclen conjugates by mass spectrometry. Copyright © 2014 John Wiley & Sons, Ltd.

A series of 1, 4, 7, 10-tetraazacyclododecane (cyclen)-based cationic lipids, namely 5a-c bearing a biotin moiety and a variety of end groups (cholesterol, diosgenin, and α-tocopherol) via biodegradable carbamate bond linkage were prepared and applied as non-viral gene delivery vectors. The liposomes formed from 5 and dioleoylphosphatidylethanolamine could bind and condense plasmid DNA into nanoparticles with appropriate size and zeta potentials. All biotinylated cyclen cationic lipids showed higher cell viability than commercially available lipofectamine 2000 even at high N/P ratios, while their transfection efficiency was relatively lower. Further, results indicate that among the three lipids, α-tocopherol-containing compound 5c has higher DNA-binding ability, lower cytotoxicity, and higher transfection efficiency. Transfection in two different cell lines revealed that these lipoplexes have higher gene delivery efficiency toward tumor cells.

The synthesis and characterization of a series of BODIPY derivatives substituted with acyclic and cyclic polyamines, in particular, cyclen and homocyclen, are reported. The 19F NMR, UV/Vis, and fluorescence spectroscopic data of these compounds are discussed. One compound was found to be very selective for CuII ions, which makes it a very promising system for CuII detection.

One of the big challenges in the organic chemistry of functionalized carbon nanotubes (CNTs) is the characterization of their structure together with their physicochemical properties. In this work, we report the utilization of an acridine-derived ZnII-cyclen complex as a multidentate ligand for recognizing thymidine-derived multiwalled carbon nanotube derivatives (Td-MWCNTs). The effectiveness of the ZnII-cyclen recognition has been confirmed through a combination of analytical techniques such as the Kaiser test, TGA-MS, IR, X-ray photoemission spectroscopy, TEM, UV/Vis absorption, and fluorescence spectroscopy. Taken together, the different characterization techniques have unambiguously shown the 1:1 recognition of the nucleoside by a ZnII-cyclen complex, allowing an accurate estimation of the Td moieties present on the CNTs surface.

We reported the synthesis process and the proteolytic ability of a novel crosslinked chitosan resin modified by azamacrocycle copper complex (CMCR). Characterization of CMCR showed that the Cu(II)Cyclen complex had successfully bound to the resin matrix covalently. Its proteolytic activity toward peptide bonds was evaluated by investigating the hydrolysis of bovine serum albumin in heterogeneous media. The maximum-observed pseudo-first-order rate constant (kobs) was achieved under 60°C, pH 6.0, where protein was hydrolyzed into smaller peptides and amino acids confirmed by SDS–PAGE and ninhydrin reaction. The results indicated that the hydrolyzing efficiency delivered by CMCR was 4 × 105 times higher than that of spontaneous hydrolysis. CMCR also featured a desirable stability for chelating Cu2+ ions, which paved the way for its feasible recovery process and good reusability. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci, 2013

A synthetic methodology was developed for the preparation of metal-chelating ligands that possess arginine pendant groups relying on the alkylation of 1,4,7,10-tetraazacyclododecane (cyclen) with arginine-containing electrophiles. Conditions for the selective trialkylation or peralkylation of cyclen are described, the outcome being dependent on the nature of the arginine-derived electrophile and the solvent used for the reaction. Lanthanide metal complexes of the ligands prepared by the described route were evaluated for their suitability as PARACEST contrast agents for use in magnetic resonance imaging. The Dy3+ and Tm3+ complexes display CEST effects that are associated with the amide protons proximate to the metal center. These signals exhibit pH dependence in the range of 6.0–8.0 and thus may have the potential for pH measurement in physiological range. Copyright © 2012 John Wiley & Sons, Ltd.

Two novel cationic lipids based on protonated cyclen and steroid (cholesterol or diosgenin) moieties with carbamate linkage have been designed and synthesized for gene delivery. Cationic liposomes were easily prepared from each of these lipids individually or from the mixtures of each cationic lipid and dioleoylphosphatidyl ethanolamine (DOPE). Several studies including dynamic light scattering, gel retardation assay, ethidium bromide intercalation assay, and transmission electron microscopy (TEM) imaging demonstrate that these amphiphilic molecules are able to bind and compact DNA into nanoparticles which may act as nonviral gene delivery agents. Results from in vitro transfection show that in association with (DOPE), two cationic lipids can induce effective gene transfection in HEK 293, A549, and H460 cells. Especially, in tumor cells (A549 and H460), the gene transfection efficiency of two cationic lipids were found to be higher than that of commercially available Lipofectamine 2000. The lipoplexes formed from both cationic lipids were found to have low cytotoxicity in three cell lines even at high N/P ratios.

International audience; The lanthanide (Ln3+) complexes of three cyclen-based ligands containing three methylphosphonate pendant arms were studied, the ligands being 1,4,7,10-tetraazacyclododecane-1,4,7-triyltris(methylphosphonic acid) (H6do3p), 3-[4,7,10-tris(phosphonomethyl)-1,4,7,10-tetraazacyclododec-1-yl]propanoic acid (H7do3p1pr), and 10-(3-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyltris(methylphosphonic acid) (H6do3p1ol). The three macrocyclic ligands form complexes of very high thermodynamic stability with all studied Ln3+ ions. Kinetic studies showed that the acid-assisted dissociation of Ce3+ complexes of these ligands is much faster than for the complex of the related ligand H8dotp [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayltetrakis(methylphosphonic acid)]. The number of water molecules coordinated to the Eu3+ and Gd3+ complexes was estimated to be < 1 for the do3p1ol ligand but ca. 1 for the other two ligands, as obtained by time-resolved luminescence spectroscopy and by 1H and 17O relaxometric measurements. The NMR spectroscopic data indicate the existence of a considerable contribution from second-sphere water molecules to the relaxivity of all the Gd3+ complexes studied. The 1H and 31P NMR spectra of the Eu3+, Yb3+ and Lu3+ complexes showed that the propionate arm in the [Ln(do3p1pr)]4- complexes and the propanol arm in the [Ln(do3p1ol)]3- complexes are not bound to the Ln3+ ion. The [Ln(do3p)]3- and [Ln(do3p1pr)]4- complexes have a clear preference for the TSAP (twisted square antiprismatic) isomer, while both SAP (square antiprismatic) and TSAP isomers are present in solutions of the [Ln(do3p1ol)]3- complexes.

Three compounds that are based on cyclen and contain three methylphosphonate pendant arms ? (1,4,7,10-tetraazacyclododecane-1,4,7-triyl)tris(methylene)trip hosphonic acid (H6do3p), 3-{4,7,10-tris[(dihydroxyphosphoryl)methyl]-1,4,7,10-tetraazacy clododecan-1-yl}propanoic acid (H7do3p1pr) and [10-(3-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triy l]tris(methylene)triphosphonic acid (H6do3p1ol) ? were synthesized and characterized. X-ray crystal structures were determined for H6do3p and for the complex [Cu(H2O)6]2+[Cu(H2O)(H4dotp)]2 of a related ligand H8dotp [H8dotp = (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(methy lene)tetraphosphonic acid]. They show the copper(II) centre coordinated only to the four amines of the macrocycle and one water molecule in the apical position. The acidbase properties of the three compounds were studied in aqueous solution by potentiometry and 31P NMR spectroscopy. All ligands exhibit very high basicity and their protonation schemes are dominated by proton relocations between the basic sites and intramolecular hydrogen bonding. The thermodynamic stability constants for complexes of the three ligands with Cu2+ and Zn2+ metal ions were determined by potentiometry and exhibit very high values for the complexes of Cu2+. UV/Vis spectroscopy was used to assess the acid-assisted dissociation of the Cu2+ complexes and showed that the dissociation rates are faster than for the corresponding complex of H8dotp, whereas the [Cu(do3p1ol)]4 complex is the most inert one in this series.

In this study, two novel cationic lipids containing protonated cyclen and quaternary ammonium moieties were designed and synthesized as non-viral gene delivery vectors. The structures of the two lipids differ in their hydrophobic region (cholesterol or diosgenin). Cationic liposomes were easily prepared from the lipids individually or from the mixtures of each cationic lipid and dioleoylphosphatidylethanolamine. Several studies including DLS, gel retardation assay, and ethidium bromide intercalation assay suggest that these amphiphilic molecules are able to bind and compact DNA into nanometer particles which can be used as non-viral gene delivery agents. Our results from in vitro transfection show that in association with dioleoylphosphatidylethanolamine, two cationic lipids can induce effective gene transfection in human embryonic kidney 293 cells, although the gene transfection efficiencies of two cationic lipids were found to be lower than that of lipofectamine 2000TM. Besides, different cytotoxicity was found for two lipoplexes. This study demonstrates that the title cationic lipids have large potential to be efficient non-viral gene vectors.

Paramagnetic lanthanide(III) complexes stable in aqueous solutions have gained increasing interest in the recent years due to their importance as contrast agents in magnetic resonance imaging (MRI). Lanthanide(III) complexes with macrocyclic ligands derived from 1,4,7,10-tetraazacyclododecane (cyclen) are widely used for the design of MRI probes because of their high thermodynamic stability and kinetic inertness. The rational design of more efficient contrast agents requires a better understanding of the structure and dynamics of these systems in solution. This contribution reviews the work of the author and his collaborators on the solution structure and dynamics of lanthanide(III) complexes with different cyclen-based ligands and closely related systems. DFT calculations provide molecular geometries and relative energies of the different stereoisomers of these complexes in good agreement with the experimental data. The conformational analysis performed with the aid of density functional theory (DFT) calculations was validated with the investigation of the YbIII-induced 1H NMR paramagnetic shifts, which encode information on the position of the observed NMR nuclei with respect to the LnIII ion. Additionally, DFT calculations provide a better understanding of the dynamic processes responsible for the interconversion between the square-antiprismatic (SAP) and twisted-square-antiprismatic (TSAP) isomers of these complexes in solution, which might proceed through the inversion of the cyclen unit or the rotation of the pendant arms. The activation barriers obtained from theoretical calculations show a good agreement with the experimental values obtained from variable-temperature NMR spectroscopy. The work presented in this paper shows that DFT calculations in combination with NMR spectroscopy provide detailed information on the structure and dynamics of lanthanide(III) complexes at the molecular level and represent a powerful tool for the characterization of lanthanide(III) complexes relevant to the field of MRI contrast agents.

π-Stacked naphthalenediimide (NDI) arrays are of interest as charge-transport materials. We have designed and synthesized an NDI derivative with two Zn(II)-cyclens that act as receptors for the thymine base in DNA. UV/Vis and CD spectroscopy, gel filtration, and molecular-modeling studies have shown that the bis(Zn(II)-cyclen)-NDI can be assembled in the presence of oligo-dT to form π-stacked NDI arrays. The assembly of the NDI arrays was found to be dependent on the length of the oligo-dT and the temperature. The NDI-oligo-dT assembly on a gold substrate exhibits photocurrent responses due to electron transfer through the π-stacked array.

The Cu+-catalyzed Huisgen [3+2] cycloaddition has been used to elaborate analogues of a candidate PARACEST MRI contrast agent, which is a complex of Eu3+ with DOTAM–Gly–Phe–OH. Analogues possessing either one L-tyrosine in place of an L-phenylalanine, or with all four phenylalanine units replaced, were transformed into Tyr(O-propargyl) substrates for “click” chemistry. Conjugation of the Eu3+–DOTAM derivatives with a spectrum of azides, including simple hydrophilic, hydrophobic, and aromatic groups, propyl glucoside, and a nucleoside were successful. The magnetic resonance properties of the resultant conjugates were examined, and their chemical exchange saturation transfer (CEST) properties are reported.

A novel coumarin-appended PNA binding cyclen derivative ligand, C1, and its copper(II) complex, C2, have been synthesized and characterized. The interaction of these compounds with DNA was systematically investigated by absorption, fluorescence, and viscometric titration, and DNA-melting and gel-electrophoresis experiments. DNA Melting and viscometric titration experiments indicate that the binding mode of C1 is a groove binding, and C2 is a multiple binding mode that involves groove binding and electrostatic binding. From the absorption-titration data, we can state that the primary interaction between CT DNA and the two compounds may be H-bonds between nucleobases. Fluorescence studies indicate that the binding ability of C1 to d(A)(9) is as twice or thrice as that of other oligodeoxynucleotides. Agarose gel-electrophoresis experiments demonstrate that C2 is an excellent chemical nuclease, which can cleave plasmid DNA completely within 24 h.

A series of water-soluble bis- and tetrakis-ZnII–cyclen complexes with rigid structures was prepared to enhance the carboxylate and phosphate ion binding response in contrast to analogues with less-confined molecular structures. Boc-protected 6-chloro-1,3,5-triazine–bis-cyclen was coupled to different aryl and alkyl moieties in moderate to high yields and subsequently converted into the corresponding bis- or tetrakis-ZnII–cyclen complexes. The bis-ZnII–cyclen moiety is known for its affinity to anions. Depending on the arene substituent some of the synthesized synthetic receptors are luminescent. They were studied by absorption and emission spectroscopy for their response to the presence of phosphate anions of biological relevance in buffered aqueous solution at neutral pH and for their affinity to the genetically encodable oligoaspartate and glutamate sequences (D4 and E4 tag) recently introduced. The rigid structures of the compounds enhance the electronic coupling between the metal complex binding site and the reporter dye. This leads to an increased anion binding response in homogeneous aqueous solution.