Abstract The kinetics of the metal exchange reactions between open‐chain Gd(DTPA) 2− and Gd(DTPA‐BMA), macrocyclic Gd(DOTA) − Gd(HP‐DO3A) complexes, Cu 2+ ions were investigated in presence endogenous citrate, phosphate, carbonate histidinate ligands pH range 6–8 NaCl (0.15 M ) at 25 °C. rates Gd(DTPA‐BMA) are independent concentration citrate occur via dissociation Gd 3+ complexes catalyzed by ions. HCO 3 /CO H 2 PO 4 also catalyze complexes. ligands, about two orders magnitude higher than...

The heptadentate ligand 1,4-bis(hydroxycarbonylmethyl)-6-[bis(hydroxycarbonylmethyl)]amino-6-methylperhydro-1,4-diazepine (AAZTA) and its derivatives were recently reported to give stable complexes with Gd(3+) superior efficiency as MRI contrast agents. Nevertheless, only preliminary data are available on the coordination behavior of this interesting ligand. In work, thermodynamic kinetic stability determined for formation AAZTA lanthanoid metal ions, other divalent ions interest...

Radiometals play an important role in the diagnosis of physiological processes vivo by means imaging technologies, but also increasingly contribute to treatment diseases. The far dominant way apply advantages nuclear transformations radiometals is use radiometal‐ligand complexes. In this context, it turns out that DOTA (and its derivatives) currently most potent chelator. This article reviews physico‐chemical properties and [*M(DOTA)] – complexes, which made moiety chelator for theranostics...

An integrated 1 H and 17 O NMR relaxometric study on model systems allowed to highlight that the Fe(III) complexes might represent best alternative Gd-based MRI contrast agents at magnetic fields of current future clinical scanners.

The Gd3+-DO3A–arylsulphonamide (DO3A–SA) complex is a promising pH-sensitive MRI agent. stability constants of the DO3A–SA and DO3A complexes formed with Mg2+, Ca2+, Mn2+, Zn2+, Cu2+ ions are similar, whereas logKLnL values Ln(DO3A–SA) 2 orders magnitude higher than those Ln(DO3A) complexes. protonation constant (log KMHL) sulphonamide nitrogen in very similar to that free ligand, logKLnHL lower by about 4 logK units, indicating strong interaction between Ln3+ N atom. Ln(HDO3A–SA) via...

Abstract Unprecedented fast and efficient complexation of Sc III was demonstrated with the chelating agent AAZTA (AAZTA=1,4‐bis(carboxymethyl)‐6‐[bis(carboxymethyl)]amino‐6‐methylperhydro‐1,4‐diazepine) under mild experimental conditions. The robustness 44 Sc(AAZTA) − chelate conjugated biomolecules thereof is further shown by in vivo PET imaging healthy tumor mice models. new results pave way towards development Sc‐based radiopharmaceuticals using chelator.

Human hepatocytes are the gold standard for toxicological studies but they have several drawbacks, like scarce availability, high inter-individual variability, a short lifetime, which limits their applicability. The aim of our investigations was to determine, whether HepaRG cells could replace human in uptake experiments toxicity studies. is hepatoma cell line with most hepatic functions, including considerable expression transporters contrast other immortalized lines. We compared effect...

During the past few years increasing attention has been devoted to Mn(II) complexes as possible substitutes for Gd(III) contrast agents in MRI. Equilibrium (log KMnL or pMn value), kinetic parameters (rates and half-lives of dissociation) relaxivity formed with 12-membered macrocyclic ligands were studied. The selected a way gain information on how ligand rigidity, nature donor atoms macrocycle (pyridine N, amine, etheric oxygen atom), pendant arms (carboxylates, phosphonates, primary,...

The kinetic inertness profile of Cu(<sc>ii</sc>) complexes TRAP-conjugates enables simple removal after click functionalisation and confirms their suitability for Cu-64-PET.

Abstract Magnetic Resonance Imaging (MRI) plays a vital role in the accurate diagnosis of numerous human diseases and disorders, with Gd(III)‐based contrast agents (GBCAs) being used ≈30%–40% procedures, resulting ≈30 million doses administered annually worldwide. The careful design rigid macrocyclic chelator featuring highly hydrophilic periphery leads to development gadopiclenol, first bis‐hydrated MRI agent, recently approved for clinical use by both FDA EMA. stereochemistry coordinating...

A cyclen-based ligand containing trans-acetate and trans-methylenephosphonate pendant groups, H6DO2A2P, was synthesized its protonation constants (12.6, 11.43, 5.95, 6.15, 2.88, 2.77) were determined by pH-potentiometry 1H NMR spectroscopy. The first two protonations shown to occur at the macrocyclic ring N–CH2–PO32– nitrogens while third fourth phosphonate groups. In parallel with of −PO32– protons from NH+−CH2−PO32– are transferred N−CH2−COO– nitrogens. stability Ca2+, Cu2+, Zn2+ (ML, MHL,...

The conformational properties of lanthanide(III) complexes with the mono- and biphosphonate analogues 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) are investigated by means density functional theory (DFT) calculations NMR spectroscopy. Geometry optimizations performed at B3LYP/6-31G(d) level using a 46 + 4f(n) effective core potential for lanthanides provide two energy minima corresponding to square-antiprismatic (SAP) twisted (TSAP) geometries. Our give relative free energies...

Abstract A detailed study of the structures, thermodynamic stabilities and kinetics dissociation Ga 3+ , In Cu 2+ complexes formed with heptadentate ligand AAZTA is reported. The stability constants (log K ML ) are 22.18, 29.58 22.27, respectively, which suggests that seven‐membered‐ring skeleton suited to accommodation these metal ions. solid‐state structure [Cu(H 2 AAZTA)] · H O shows a distorted octahedral coordination. equatorial coordination sites occupied by one ring N atoms, water...

Abstract [Gd(DTPA‐BMA)] is the principal constituent of Omniscan, a magnetic resonance imaging (MRI) contrast agent. In body fluids, endogenous ions (Zn 2+ , Cu and Ca ) may displace Gd 3+ . To assess extent displacement at equilibrium, stability constants DTPA‐BMA 3− complexes Zn have been determined 37 °C in 0.15 M NaCl. The order these as follows: GdL≈CuL&gt;ZnL≫CaL. Applying simplified blood plasma model, dissociation Omniscan (0.35 m [Gd(DTPA‐BMA)]) was found to be 17 % by formation...

Abstract Tissue hypoxia occurs in pathologic conditions, such as cancer, ischemic heart disease and stroke when oxygen demand is greater than supply. An imaging method that can differentiate hypoxic versus normoxic tissue could have an immediate impact on therapy choices. In this work, the gadolinium(III) complex of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) with a 2‐nitroimidazole attached to one carboxyl group via amide linkage was prepared, characterized tested...

GdDOTA propionamide derivatives preserve a good thermodynamic stability and kinetic inertness while possessing rate of water exchange two orders magnitude greater than acetamide.

OBETA, you bet: Thermodynamic and kinetic measurements show an apparent paradox. The stability of complexes lanthanide trivalent ions is higher with the heptadentate ligand OBETA (ethylene glycol-bis(2-aminoethyl ether)-N,N,N′,N′-tetraacetic acid) than its octadentate homologue EGTA (2,2′-oxybis(ethylamine)-N,N,N′,N′-tetraacetic acid). unusual properties Gd(OBETA)− (see structure), combined presence two fast exchanging coordinated water molecules, candidates this complex as MRI contrast...

The Mn²⁺ complexes of two differently benzyl-substituted 1,4-DO2AM ligands show a strong increase in relaxivity upon human serum albumin binding.

Abstract A new 1,4‐DO2A‐bisamide [1,4‐DO2AM; 1,4‐DO2A = 2,2′‐(1,4,7,10‐tetraazacyclododecane‐1,4‐diyl)diacetic acid] ligand was synthesized, and its Mn II complex prepared investigated in detail by solution thermodynamic, kinetic, 1 H 17 O NMR relaxometric measurements. Although the stability constant of [Mn(1,4‐DO2AM)] 2+ (log K MnL 12.64) is 2.5 log units lower than that [Mn(1,4‐DO2A)], kinetic inertness, through transmetallation reactions with Zn ions, much higher. In particular,...

The heptadentate ligand OBETA (2,2′-oxybis(ethylamine)-N,N,N′,N′-tetraacetic acid) was reported to form complexes with Ln3+ ions more stable than those formed by the octadentate and popular congener EGTA (ethylene glycol O,O′-bis(ethylamine)-N,N,N′,N′-tetraacetic acid). structural features leading this puzzling coordination paradox were investigated X-ray diffraction, solution state NMR, molecular modeling, relaxometric studies. stability constant of Gd(OBETA) (log KGdL = 19.37, 0.1 M KCl)...

Kinetic inertness is a key property for Gd-based contrast agent. The Gd(III) complex of cyclohexyl-fused AAZTA derivative shows the highest kinetic non-macrocyclic bis hydrated (q = 2) Gd(III)-complexes with dissociation half-life 91 years under physiological conditions, very close to that macrocyclic clinically approved agents. It also optimal relaxometric performance (r1 8.3 mM(-1) s(-1) at 20 MHz and 25 °C) due presence two inner sphere water molecules in fast exchange bulk not displaced...