The effects of intramolecular H‐bond formation on the stability constant and water exchange rate of the Gd(III)‐diethylenetriamine‐N′‐(3‐amino‐1,1‐propylenephosphonic)‐N, N,N″,N″‐tetraacetate complex

Abstract

The binding interaction of metal chelates to biological macromolecules, though driven by properly devoted recognition synthons, may cause dramatic changes in some property associated with the coordination cage such as the thermodynamic stability or the exchange rate of the metal coordinated water. Such changes are due to electrostatic and H-bonding interactions involving atoms of the coordination cage and atoms of the biological molecule at the binding site. To mimic this type of H-bonding interactions, lanthanide(III) complexes with a DTPA-monophosphonate ligand bearing a propylamino moiety (H6NP-DTPA) were synthesized. Their thermodynamic stabilities and the exchange lifetime of the coordinated water molecule (for the Gd-complex) were compared with those of the analog complexes with DTPA and the parent DTPA-monophosphonate derivative (H6P-DTPA). It was found that the intramolecular H-bond between the epsilon-amino group and the phosphonate moiety in NP-DTPA complexes causes displacements of electric charges in their coordination cage that are markedly pH dependent. In turn, this affects the characteristic properties of the coordination cage. In particular it results in a marked elongation of the exchange lifetime of the coordinated water molecule.

Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes

“…Its reaction with diethylphosphite and paraformaldehyde in refluxing EtOH/toluene mixture [13] tris(t-butyl)phosphite and N-benzyloxycarbonyl-3-aminopropanal in acetonitrile at 80 • C [119] led to the corresponding phosphonate ester derivatives. Hydrazinolysis of phthaloyl protecting groups and further amine alkylation by bromoacetic acid derivatives afforded, after hydrolysis, the required H 5 DTPA phosphonic acid analogs.…”

Release of Toxic Gd3+ Ions to Tumour Cells by Vitamin B12 Bioconjugates

“…Upon binding to receptors, 1 lies on the cellular membrane and likely is establishing hydrogen-bonding interactions between oxygen atoms of the co-ordination cage and surrounding hydrogen donor groups. These hydrogen-bonding interactions remove the negative charge from the donor atoms [31] of the ligand, thus decreasing the co-ordination ability and favouring the dissociation of the metal ion. The high toxicity observed for K562 cells treated with 1 appears as a further indication of the massive uptake of Gd 3 + ions.…”

“…Hydrolysis of the Eu analogue of 1 (Eu-1) was investigated by collecting 31 P NMR spectra of a solution (7 mm) of the Eu-1 in HEPES buffer at pH 7.2 and 298 K over time. The reaction was followed by monitoring the decrease of intensity of the Eu-1 31 P resonance at d = 0.76 ppm (from H 3 PO 4 85 %) and the concomitant increase of intensity of the resonance of CNCbl at d = 0.025 ppm.…”

Synthesis of phosphonic analogues of AAZTA†AAZTA=6-Amino-6-methylperhydro-1,4-diazepine-N,N′,N″,N″-tetraacetic acid.† and relaxometric evaluation of the corresponding Gd(III) complexes as potential MRI contrast agents

“…On the other hand, The s M values of the monophosphonic derivatives of Gd(DTPA) complexes are strongly influenced by the protonation state of the phosphonic group due to the formation of intramolecular H-bond with the neighboring donor groups. 27 Since the 17 O-VT NMR and NMRD studies of the Gd(III)-complexes were performed at pH 7.0, it can be assumed that the phosphonic group(s) of Gd(III)-complexes are partially protonated which can be responsible for the elongation of the exchange lifetime of the coordinated water molecule.In conclusion, the synthetic approach to mixed phosphoniccarboxylic AAZTA analogues was demonstrated, leading to the preparation of three novel chelating agents. Relaxometric studies on the corresponding Gd(III) complexes showed an active participation of the phosphonic groups in the coordination of the paramagnetic lanthanide ion.…”

“…On the other hand, The s M values of the monophosphonic derivatives of Gd(DTPA) complexes are strongly influenced by the protonation state of the phosphonic group due to the formation of intramolecular H-bond with the neighboring donor groups. 27 Since the 17 O-VT NMR and NMRD studies of the Gd(III)-complexes were performed at pH 7.0, it can be assumed that the phosphonic group(s) of Gd(III)-complexes are partially protonated which can be responsible for the elongation of the exchange lifetime of the coordinated water molecule.…”