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We report a series of four cyclams and cross-bridged cyclams

Rigid derivatives of the acyclic ligand PDTA4- (H

We report a series of structurally related Gd(III) complexes designed to modulate the exchange of the coordinated water molecule, which is an important parameter to be controlled to achieve optimal performance of contrast agents for application in magnetic resonance imaging (MRI). The ligands contain a DO3A scafold functionalised with 2′-methoxyphenacyl or 4′-methoxyphenacyl groups (DO3A-oMAP and DO3A-pMAP), a 2′-aminophenacyl group (DO3A-oAnAP) or a 2′,4′-dihydroxyphenacyl moiety (DO3A-DiHAP). The results are compared with those obtained previously for the analogues containing 2′- or 4′-hydroxyphenacyl groups (DO3A-oHAP and DO3A-pHAP, respectively) and the parent system with an unsubstituted acetophenone pendant arm (DO3A-AP). 1H NMR studies performed on the Eu(III) complexes show that ligand functionalisation causes a very minor effect on the relative populations of the SAP and TSAP isomers present in solution, with the SAP isomer representing 70–80% of the overall population. The emission spectra of the Eu(III) complexes confirm the presence of a water molecule coordinated to the metal center and point to similar coordination environments around the metal ion. The analysis of the 1H NMRD profiles and 17O NMR data recorded for the Gd(III) complexes evidences that water exchange is modulated by the ability of peripherical substituents to establish hydrogen bonds with the coordinated and/or second sphere water molecules. DFT calculations were used to model the transition states responsible for the dissociative water exchange mechanism, providing support to the crucial role of hydrogen-bonds in accelerating water exchange.

The stability constants of Mn

[Abstract] The water exchange rates of water molecules coordinated to the metal ion in lanthanide complexes have been profusely investigated during the last 25 years, especially in the case of Gd3+ and Eu3+ complexes. This is mainly related to the important application of some Gd3+ complexes as contrast agents in magnetic resonance imaging (MRI), and the intensive investigation of Eu3+ complexes as contrast agent candidates providing contrast through the chemical exchange saturation transfer mechanism (CEST). Both applications require a fine tunning of the exchange rate of the coordinated water molecule to yield optimal response. Herein we review the progress made in this field to control water exchange in a rational way through ligand design, providing relationships between the observed trends, the structures of the complexes and the mechanisms responsible for the water exchange reaction. Ministerio de Economía y Competitividad; CTQ2016-76756-P Xunta de Galicia; ED431B 2017/59 Xunta de Galicia; ED431D 2017/01 Ministerio de Ciencia, Innovación y Universidades; PRX18/00201 Estados Unidos. U.S. National Institute of Biomedical Imaging and Bioengineering; R01EB009062 Estados Unidos; National Institute of Diabetes and Digestive and Kidney Diseases; U01DK104302

Three tacn (1,4,7-triazacyclononane)-based ligands substituted by methylthiazolylcarboxylate (tha) and/or methylthiazolyl (th) arms have been examined for copper complexation with the aim to study the impact of carboxylate groups on the complexation of Cu(ii), which can present an endo- or exo-cyclic coordination. Two new ligands have been synthesised: H

We report a series of pentadentate ligands based on a 1,4,7-triazacyclononane-1,4-diacetic acid (H2NO2A) containing different substituents attached to the third nitrogen atom of the macrocyclic unit. Detailed 1H Nuclear Magnetic Relaxation Dispersion (NMRD) characterisation of the corresponding Mn2+ complexes suggests the formation of six-coordinate species in solution containing an inner-sphere water molecule. This was confirmed by recording the transverse 17O relaxation time and chemical shift measurements. The water exchange rate of the coordinated water molecule was found to be strongly influenced by the nature of the substituent R at position 7 of the triazacyclononane unit (R = Me, k298ex = 62.6 × 107 s-1; R = Bz, k298ex = 4.4 × 107 s-1; R = 1-phenylethyl, k298ex = 2.6 × 107 s-1). The decreasing exchange rates are explained by the increasing bulkiness of the substituent, which hinders the approach of the entering water molecule in an associatively activated water exchange mechanism. This is supported by DFT calculations (M062X/TZVP), which confirm the associative nature of the water exchange reaction. A potentially decadentate ligand containing two NO2A units linked by a xylenyl spacer in the meta position was also synthesised. The corresponding binuclear Mn2+ complex contains two metal ions with different hydration numbers, as evidenced by 1H NMRD and 17O NMR measurements. DFT calculations show that this is related to the presence of a bridging bidentate μ-η1-carboxylate group connecting the two metal centers. The results reported in this work provide a straightforward strategy to control the exchange rate of the coordinated water molecule in this family of MRI contrast agent candidates.

We report a detailed study of the structure of the [Bi(DO3A)] complex both in the solid state and in solution. The X-ray crystal structure of [Bi(DO3A)] evidences the octa-coordination of the Bi(iii) ion, which is directly coordinated to the four nitrogen atoms of the cyclen unit and three oxygen atoms of the carboxylate groups. The octa-coordination is completed by an oxygen atom of a neighboring carboxylate group, which bridges Bi(iii) ions thanks to μ2-η1:η1 coordination, resulting in the formation of a coordination polymer. The Bi(iii) ion presents a twisted-square antiprismatic (TSAP) coordination geometry associated with the Δ(δδδδ)/Λ(λλλλ) enantiomeric pair. A computational DFT study indicates that the 6s2 lone pair of Bi(iii) is stereochemically active in [Bi(DO3A)] and most of the cyclen-based complexes reported in the literature. Depending on the spatial arrangement of the donor atoms of the ligand the lone pair points in different directions, so that Bi(iii) can easily accommodate different coordination environments. In solution the [Bi(DO3A)] complex exists as a monomeric complex, as demonstrated by DOSY measurements. The stability constant of the [Bi(DO3A)] complex, determined by using batch spectrophotometric titrations, was found to be rather high (log K = 26.85(5)). The complex presents characteristic absorption in the UV spectrum at 299 nm (ε = 8770 M-1 cm-1) that was attributed to the Bi(iii)-centered 6p ← 6s band on the basis of TDDFT calculations. Spectrophotometric titrations reveal weak binding of different anions to the [Bi(DO3A)] complex, with association constants of K11 = 3.55(8), 3.09(7), 6.2(1) and 2.19(5) for Cl-, Br-, I- and N3-, respectively.

We report two novel macrocyclic ligands based on the 1,4-DO2AM platform (1,4-DO2AM = 2,2'-(1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetamide) and containing two benzyl groups attached either to the nitrogen atoms of the macrocyclic unit (1,4-BzDO2AM) or to the amide pendant arms (1,4-DO2AMBz). The protonation constants of the ligands and the stability constants of their Mn

We have reported here a series of ligands containing pentadentate 6,6'-(azanediylbis(methylene))dipicolinic acid units that differ in the substituent present at the amine nitrogen atom (acetate: H

The syntheses of two new ligands based on a calix[4]arene scaffold in the cone conformation functionalized on the phenolic positions 1 and 3 by diethylthiophosphonates (L1) or tetra(tri)thioethyleneglycol (L2) crowns are described. Together with ligand L3, the parent calix[4]arene substituted by a penta(tetra)thioethyleneglycol crown, the spectroscopic properties of the ligands were determined by means of UV-Vis absorption spectroscopy and steady-state and time-resolved fluorescence spectroscopy, showing that the ligands display modest but non-negligible intrinsic fluorescence properties (ϕ

The synthesis of ligand L(1), based on the tetramethyl ester of [4'-ethynyl-(6,6''-bis(aminomethyl))-2,2':6',2''-terpyridine]tetrakisacetate, and its acidic form L(2), are described. Using a Cu-assisted coupling reaction, L(1) was connected to the Pt atom of a [(tpy)Pt] precursor (tpy = 2,2':6',2''-terpyridine) to afford the [(tpy)PtL(1)](BF(4)) metallosynthon, from which a hydrolysis reaction gave Na(3)[(tpy)PtL(2)]. The photophysical properties of the metallosynthons were studied by means of absorption and steady state emission spectroscopic techniques in various solvents, which revealed a dramatic impact of the solvent polarity. DFT and TDDFT calculations (B3LYP) were used to investigate the absorption and emission properties of the [(tpy)PtL(1)](+) system both in vacuo and in different solvents. Spectrophotometric titrations of [(tpy)PtL(1)](+) with EuCl(3) x 6 H(2)O in acetonitrile revealed the formation of complicated mixtures of complexes with different [(tpyPt(1))(x)Eu(y)] stoichiometries, all of which display the typical Eu(III) centred luminescence upon excitation into the Pt centred (1)MLCT absorption band. The energy transfer from the Pt subunit of [(tpy)PtL(2)](3-) to Eu(III) is inefficient in polar solvents, but it is restored in a TFA-CH(2)Cl(2) mixture, together with the observation of a new emission band at 684 nm, likely arising from a charge transfer process involving reduction of Eu(III).

The (17)O NMR shifts of aqueous samples of lanthanide triflates were measured and analysed. In these systems the triflate anion does not enter the first coordination sphere. The contact contribution to the shifts showed a break at Eu(III), which reflects a change in the number of water molecules in the first coordination sphere of the Ln(III) ion from 9 for La-Sm to 8 for the heavier lanthanides. This change in hydration number is accompanied by a change in the parameters governing the pseudo-contact shifts. Fitting of the data with tricapped trigonal prism and square antiprismatic geometries obtained by DFT (density function theory) calculations showed that the crystal field parameters for these geometries differ by an order of magnitude. The hyperfine coupling constant for both geometries was determined to be A/(Planck's constant)= -4.2 x 10(6) rad s(-1).