Three novel Gd chelates containing on their external surface pendant phosphonate and carboxylate groups, which promote the interaction with the positively charged groups of polyornithine and polyarginine, have been synthesized. Their solution structures have been assessed on the basis of 1H- and 31P-NMR spectra of the Eu and Yb analogues. A thorough investigation of the relaxometric (1H and 17O) properties of the Gd chelates has been carried out and the observed relaxivities have been accounted for the sum of three contributions arising from water molecules in the first, second, and outer coordination layers, respectively. It has been found that the occurrence of a tight second coordination coating renders the dissociation of the water molecule directly coordinated to the Gd ion more difficult. The binding interactions between the negatively charged Gd chelates and the positively charged groups of polyornithine (ca. 140 residues) and polyarginine (ca. 204 residues) have been evaluated by means of the proton relaxation enhancement (PRE) method. Although the binding interaction decreases markedly in the presence of competitive anions in the solution medium, the affinity is strong enough that in blood serum it is possible to meet the conditions where most of the chelate is bound to the polyamino acid substrate. On this basis one may envisage a novel route for a MRI location of tumors as it is known that positively charged polyamino acids selectively bind to tumors having a greater negative charge than non-tumor cells.
Macromolecular Gd(III) complexes may find useful application as contrast agents for magnetic resonance angiography (MRA). Herein two novel systems are reported, namely Gd(DO3ASQ)3-lys16 and Gd(DO3ASQ)30-orn114. Their syntheses are based on the ability of the squaric acid moiety to act as a linker between the DO3A (1,4,7, 10-tetraazacyclododecane-1,4,7-triacetic acid) chelate moiety and the polyamino acidic chain. Moreover, the squaric acid participates in the coordination cage of the Gd(III) ion. The investigation of 1H and 17O NMR relaxation processes of solvent water nuclei allowed a detailed characterization of the systems under study. Gd(DO3ASQ)30-orn114 displays a remarkable ability to enhance the water proton relaxation rate of its solutions, and it may be considered as potential contrast agent for MRA applications.
This study proposes a novel route to improved contrast agents for magnetic resonance imaging (MRI) applications based on the formation of a non-covalent adduct between a paramagnetic complex and an exogeneous macromolecule. For this purpose a 12-membered pyridine-containing triacetate macrocyclic ligand with a p-bromobenzyloxy substituent on the pyridine moiety was synthesized.
Spalte das Amin! Für die Ugi‐Vierkomponentenreaktion (Ugi‐4CR) ist eine Komponente mit einer primären Aminogruppe notwendig. Dieses Protokoll wurde durch „Spalten“ des primären Amins in zwei sekundäre Amine modifiziert. Die daraus resultierende Variante der Ugi‐4CR verläuft mit guten bis ausgezeichneten Ausbeuten und ermöglicht Variationen des Molekülgerüsts, was die Nützlichkeit der ursprünglichen Mehrkomponentenreaktion erhöht.
Prompted by the favourable relaxometric, thermodynamic and kinetic properties of the bis‐hydrated Gd(OBETA) (OBETA=2,2′‐oxybis(ethylamine)‐N,N,N′,N′‐tetraacetic acid) complex, a novel derivative tailored with an n‐hexadecyl chain was synthesised. The amphiphilic gadolinium complex was designed and prepared with the aim of obtaining high relaxivity supramolecular aggregates by self‐assembly in micelles and liposomes. Thus, lipidic nanoparticles were prepared and characterised by dynamic light scattering and 1H NMR relaxometry. Relaxivity values of up to 48.3 mm−1 s−1 (20 MHz and 298 K) were registered in liposomal aggregates. The binding to human serum albumin (HSA), evaluated both in terms of affinity and relaxometric properties of the supramolecular adduct, yielded exceptionally high relaxivity values (71.4 mm−1 s−1 at 30 MHz and 298 K).
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