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A set of substituted 1,4,7-triazacyclononane ligands was synthesised, including a wide series of novel derivatives bearing a thiazole or thiophene side group, with the potential to incorporate these derivatives into a polymeric material; some previously known/studied ligands were also synthesised for comparative purposes. The corresponding copper(II) complexes were prepared, and their ability to mediate the hydrolysis of phosphate ester bonds was studied via UV-Vis spectrophotometry, using bis(p-nitrophenyl)phosphate as a model substrate. Some of the prepared complexes showed a considerable enhancement of the phosphate ester hydrolysis in comparison with previously studied systems, which makes them some of the most effective complexes ever tested for this purpose. Therefore, these novel, potentially bifunctional systems could provide the possibility of creating new coating materials for medicinal devices that could prevent biofilm formation.

The use of nanoscale sensors capable of detection of biological parameters is of great interest in diagnosis. Here, the authors use experimental and theoretical methods to develop a nanodiamond sensor with nitrogen vacancy defects for detection of pH and redox in a microfluidic device.

Three 1,4,7,10-tetraazacyclododecane-based ligands disubstituted in 1,4-positions with phosphonic acid, phosphonate monoethyl-ester, and H-phosphinic acid pendant arms, 1,4-H4do2p, 1,4-H2do2pOEt, and 1,4-H2Bn2do2pH, were synthesized and their coordination to selected metal ions, Mg(II), Ca(II), Mn(II), Zn(II), Cu(II), Eu(III), Gd(III), and Tb(III), was investigated. The solid-state structure of the phosphonate ligand, 1,4-H4do2p, was determined by single-crystal X-ray diffraction. Protonation constants of the ligands and stability constants of their complexes were obtained by potentiometry, and their values are comparable to those of previously studied analogous 1,7-disubstitued cyclen derivatives. The Gd(III) complex of 1,4-H4do2p is ~1 order of magnitude more stable than the Gd(III) complex of the 1,7-analogue, probably due to the disubstituted ethylenediamine-like structural motif in 1,4-H4do2p enabling more efficient wrapping of the metal ion. Stability of Gd(III)–1,4-H2do2pOEt and Gd(III)–H2Bn2do2pH complexes is low and the constants cannot be determined due to precipitation of the metal hydroxide. Protonations of the Cu(II), Zn(II), and Gd(III) complexes probably takes place on the coordinated phosphonate groups. Complexes of Mn(II) and alkali-earth metal ions are significantly less stable and are not formed in acidic solutions. Potential presence of water molecule(s) in the coordination spheres of the Mn(II) and Ln(III) complexes was studied by variable-temperature NMR experiments. The Mn(II) complexes of the ligands are not hydrated. The Gd(III)–1,4-H4do2p complex undergoes hydration equilibrium between mono- and bis-hydrated species. Presence of two-species equilibrium was confirmed by UV-Vis spectroscopy of the Eu(III)–1,4-H4do2p complex and hydration states were also determined by luminescence measurements of the Eu(III)/Tb(III)–1,4-H4do2p complexes.

The present study reveals the potential of magnetic nanoparticles based on the La0.75Sr0.25MnO3perovskite manganite for magnetic resonance imaging (MRI). Moreover, it describes the development of the dual imaging probe where the magnetic cores are combined with a fluorescent moiety while the improved colloidal stability is achieved by a two-ply silica shell. At first, the magnetic cores of La0.75Sr0.25MnO3are coated with a hybrid silica layer, comprising a covalently attached fluorescein moiety that is subsequently covered by a pure silica layer providing the enhanced stability. The detailed characterization of the intermediate and the final product reveals the importance of the complex two-ply shell. Viability tests show that the complete particles are suitable for biological studies. Internalization of the particles and their presence in intracellular vesicles are observed by fluorescence microscopy in different cell types. Further experiments prove no fatal interference with the vitality and insulin releasing ability of labeled pancreatic islets. Relaxometric measurements confirm high spin–spin relaxivities at magnetic fields of B0= 0.5–3 T, while visualisation of in vitrolabeled pancreatic islets by MRI is successfully tested. [ABSTRACT FROM AUTHOR]

New triphenylphosphines substituted with the gem-bis(phosphonate) moiety in the form of ethyl esters, tetraethyl [4-(diphenylphosphanyl)benzyl]methylene-bis(phosphonate) (2a) and octaethyl bis[4-(diphenylphosphanyl)benzyl]methylene-bis(phosphonate) (2b), and the corresponding free acids 3aand 3bwere prepared by a multi-step synthesis and characterized by multinuclear NMR spectroscopy and mass spectrometry. The ester ligands 2aand 2bwere conveniently purified through their borane adducts. The X-ray structure of 2b·2BH3·H2O was determined. Coordination properties of new ligands towards Rh(i), Pd(ii) and Pt(ii) ions were studied. 1H, 31P and 195Pt NMR spectroscopy showed that ligands 2aand 3aform the expected [RhCl(η2:η2-cod)(L)] (cod = cycloocta-1,5-diene) and [MCl2(L)2] (M = Pd, Pt) complexes. The compounds 2band 3bbehave as bridging bidentate ligands forming dinuclear complexes of the {[RhCl(η2:η2-cod)]2(μ-L-κ2P,P′)} and [M2Cl4(μ-L-κ2P,P′)2] (M = Pd, Pt) type. These findings are consistent with mass spectrometry and far-IR and Raman spectroscopy results. X-Ray structures of trans-[PdCl2(2a-κP)2] and cis,trans-[Pt2Cl4(μ-2b-κ2P,P′)2] were determined; the dinuclear complex exhibits a different arrangement on the Pt(ii) centres which was observed for the first time in the solid state. Salts of complexes of the free acid 3aare highly soluble in water. [ABSTRACT FROM AUTHOR]

A new phosphinic-acid DOTA-like ligand, DO3APBP, containing a geminal bis(phosphonic acid) moiety as a highly effective bone-seeking group, was synthesized in high yield. Its crystal structure was determined by X-ray analysis. Complexation with lanthanide(iii) ions occurs under mild conditions (pH = 8–9, 25 °C, 2–3 h). 1H, 31P, and 17O NMR spectroscopy show that DO3APBPforms nine-coordinated lanthanide(iii) complexes with one water molecule in the first coordination sphere except for Ln = Er–Lu, which have in addition a species without lanthanide(iii)-bound water. Selective formation of only two diastereomers (out of four possible) suggests that the coordinated phosphinate phosphorus atom occurs exclusively in one of the enantiomeric forms. The ratio of the twisted square antiprism (TSA) and square antiprism (SA) diastereomers changes along the lanthanide series; the gadolinium(iii) complex has about 35% of the TSA species. The bis(phosphonate) moiety remains free for anchoring to osseous tissue. The 1H longitudinal relaxivity of the Gd-DO3APBPcomplex (r1= 7.4 s−1mM−1, 20 MHz, 25 °C, pH = 7.5) is unexpectedly high compared to that of other monohydrated chelates of similar size thanks to a significant contribution from the second hydration sphere. The water residence time τM298is 198 ns. Further increase in the relaxivity was observed in the presence of Zn(ii), Mg(ii) or Ca(ii) ions, due to formation of coordination polymers. Slowing down of the tumbling rate of the Gd-DO3APBPcomplex upon adsorption on hydroxyapatite also leads to an increase of the relaxivity (r1= 17 s−1mM−1, 20 MHz, 25 °C, pH = 7.5). [ABSTRACT FROM AUTHOR]

A new efficient and easy method to anchor Gd(III) chelates onto a TiO2surface in order to prepare a nanoparticulate T1MRI contrast agent is reported. For this purpose, a new ligand, DOTAPP, a DOTA-monoamide derivative containing a phenylphosphonic acid function in the amide side chain, was synthesized. As expected, its Ln(III) complexes exhibit structure analogy to the Ln(III) complexes of DOTA with one water molecule bound in the apical position. The Gd(III)-DOTAPP complex shows similar relaxometric properties as Gd(III) complexes of other DOTA-monoamides. Gd(III)-DOTAPP was anchored onto the surface of nanocrystalline TiO2viaits phosphonate moiety. The oxide surface is completely covered by the complexes and a strong interaction between the TiO2surface and the phosphonate group results in stable chemisorption. The millimolar relaxivity (r1) of the Gd(III)-DOTAPP complex adsorbed on the surface is substantially higher than that of the free (non-anchored) complex. [ABSTRACT FROM AUTHOR]

The title ligand, 1,4,8,11-tetraazacyclotetradecane-1,4-diyl-bis(methylphosphonic acid) (H4te2p1,4, H4L), was prepared by an optimized synthetic approach and its complexing properties towards selected metal ions were studied by means of potentiometry. The ligand forms a very stable complex with copper(ii) (log β(CuL) = 27.21), with a high selectivity over binding of other metal ions (e.g. log β(ZnL) = 20.16, log β(NiL) = 21.92). The crystal structures of two intermediates in the ligand synthesis and two forms of the nickel(ii) complex (obtained by crystallization at different pH) were determined. From acid solution, the crystals of trans-O,O-[Ni(H3L)]Cl·H2O were isolated. In such complex species, one phosphonate pendant arm is double- and the second arm is monoprotonated. The isolation of such species demonstrates a high kinetic inertness of the complex. The central metal ion is surrounded by four in-plane nitrogen atoms (in the ring configuration III) and two oxygen atoms of pendant moieties in the apical positions of octahedral coordination sphere. From neutral solution, the crystals of {trans-O,O-[Ni(H2L)]}3·5H2O were isolated. The molecular structures of the complex units found in this structure are analogous to that found in trans-O,O-[Ni(H3L)]Cl·H2O. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging is a commonly used diagnostic method in medicinal practice as well as in biological and preclinical research. Contrast agents (CAs), which are often applied are mostly based on Gd(iii) complexes. In this paper, the ligand types and structures of their complexes on one side and a set of the physico-chemical parameters governing properties of the CAs on the other side are discussed. The solid-state structures of lanthanide(iii) complexes of open-chain and macrocyclic ligands and their structural features are compared. Examples of tuning of ligand structures to alter the relaxometric properties of gadolinium(iii) complexes as a number of coordinated water molecules, their residence time (exchange rate) or reorientation time of the complexes are given. Influence of the structural changes of the ligands on thermodynamic stability and kinetic inertness/lability of their lanthanide(iii) complexes is discussed. [ABSTRACT FROM AUTHOR]

A series of new compounds built up on the skeleton of 1,5,8,12-tetraazabicyclo[10.2.2]hexadecane (1,4-ethylene-bridged cyclam, 1,4-en-cyclam) were synthesized and characterized by means of NMR and MS spectroscopy and a single-crystal X-ray structure determination. The attempts to substitute the secondary amino group of the p-nitrobenzyl-1,4-en-cyclam 3, using acetic acid derivatives as the alkylating agents, led to unexpected substitution of one of the piperazine ring nitrogen atoms, yielding the monoquaternary derivatives 4Br and 5Br, respectively. In order to explain this reaction behaviour, the solution structure of the starting compound 3 was established using 2D-NMR techniques. The acid–base behaviour of the ligands and thermodynamic stability constants of their copper(ii) and zinc(ii) complexes were determined using potentiometric titrations. Stability constants of the investigated metal complexes are significantly lower than those of the cyclam complexes and comparable to those of the Me4cyclam complexes. A copper(ii) complex of amine 3 was prepared and characterized. In the solid state, this complex has the central copper atom surrounded by five donor atoms forming a coordination sphere with geometry between trigonal bipyramid and square pyramid. [ABSTRACT FROM AUTHOR]

New bifunctional H4dota-like ligands with three acetic acid and one phosphinic acid pendant arms and propionate (H5do3apPrA) or 4-aminobenzyl (H4do3apABn) reactive groups bound to the phosphorus atom were investigated. Potentiometric studies showed that the ligands have a similar basicity to the parent H4dota and the stability constants of their complexes with sodium(i) and selected lanthanide(iii) ions are also similar. Formation and acid-assisted decomplexation kinetics of yttrium(iii) complexes with a series of H4dota-like ligands (H4dota and its phosphinic/phosphonic acid analogues) were studied and the reactions are sensitive to a slight modification of the ligand structure. The (2-carboxyethyl)phosphinic acid derivative H5do3apPrA and the phosphonic acid ligand H5do3ap form complexes faster than H4dota. The most kinetically inert complex is that with H4do3apABn. Rates of complexation and decomplexation can depend on the ability to transfer proton(s) outside/inside the complex cavity and, therefore, on the hydrophobicity of the ligands. The results demonstrate that the new bifunctional ligands are suitable for labelling biomolecules with yttrium(iii) radioisotopes for utilization in nuclear medicine. [ABSTRACT FROM AUTHOR]

Two new macrocyclic DOTA-like chelates containing one phosphonate pendant arm were synthesised as potential contrast agents for MRI (magnetic resonance imaging). The chelates bind to the lanthanide(iii) in an octadentate manner, via four nitrogen atoms, three carboxylate and one phosphonate oxygen atoms. Solution structures of [Ln(do3apOEt2)(H2O)] and [Ln(do3apOEt)(H2O)]− were studied using 31P and 1H NMR spectroscopy and SAP (square-antiprismatic)/TSAP (twisted square-antiprismatic) isomerism was observed. Depending on the nature of the lanthanide(iii) ion, the lanthanide(iii) complexes of H4do3apOEt are present in solution as up to four different diastereoisomers observable with NMR. The TSAP isomer is the most abundant at the beginning of the lanthanide series and, with a decrease of the ionic radius of lanthanide(iii) ions, both TSAP and SAP forms were observed. A second interconversion (SAP↔TSAP′) becomes important at the end of the series (TSAP′ means the TSAP species without a coordinated water molecule). The remaining axial coordination site is occupied by one water molecule for the Gd3+-complex. The calculated fraction of the TSAP isomer in the gadolinium(iii) complexes increases in the order [Gd(DOTA)(H2O)]− < [Gd(do3apOEt2)(H2O)] < [Gd(do3apOEt)(H2O)]− < [Gd(do3ap)(H2O)]2−. Gadolinium(iii) complexes of phosphorus-containing chelates, generally, have the advantage of a relatively fast water exchange rate due to a greater sterical demand of the phosphorus acid moiety and of the presence of the second-sphere water shell, which also contributes to the overall relaxivity. The [Gd(do3apOEt2)(H2O)] and [Gd(do3apOEt)(H2O)]− complexes were studied by variable-temperature 17O NMR and 1H NMRD. The experimental data were evaluated simultaneously with commonly used equations based on Solomon–Bloembergen–Morgan approximation, extended by a contribution of the second coordination sphere. The water exchange rates were found to be strongly dependent on the TSAP/SAP isomeric ratio and the overall charge of the complex: the monoanionic [Gd(do3apOEt)(H2O)]− complex with TSAP molar fraction equal to 0.36 has the water exchange rate of 20 × 106 s−1 (τM = 50 ns) while neutral [Gd(do3apOEt2)(H2O)] complex with TSAP molar fraction 0.28 has an exchange rate equal to 4.4 × 106 s−1 (τM = 227 ns). [ABSTRACT FROM AUTHOR]

A new macrocyclic ligand, 1,4,8,11-tetraazacyclotetradecane-1,8-bis(methylphosphonic acid) (dipon), is selective complexing agent for copper(II) over other transition metal ions. The ligand was tested for analytical applications of copper(II) determination. Spectrophotometric determination under optimal experimental conditions (−log [H+] = 5.5, cL &ap; 5 × 10−4 mol L−1, &lgr; = 310 nm) is valid in dynamic range (5–200) × 10−6 mol L−1 with detection limit 2.2 × 10−6 mol L−1, i.e. 0.14 μg ml−1. Volumetric determination of copper(II) with standardized dipon solution was used for copper(II) determination at micromolar concentration level without any necessity to sequester interfering metal ions. A sharp end point of titration was detected by UV/VIS spectrophotometry. Both methods were tested on artificial and real samples (spiked mineral water, alloys) and gave satisfactory results without any systematic error. The advantage of both methods is their simplicity, rapidity and no sensitivity to the presence of other metal ions. [ABSTRACT FROM AUTHOR]