605670-01-7

Upstream product

• 85317-52-8 methyl 2-amino-3-(4-nitrophenyl)propionate 
• 109-76-2 Trimethylenediamine 
• 1991-83-9 4-nitrophenylalanine 
• 17193-40-7 (+)-Methyl 2-amino-3-(4-nitrophenyl)propionate hydrochloride 

Downstream Products

• 605670-03-9 {[2-{[3-(bis-tert-butoxycarbonylmethyl-amino)-propyl]-tert-butoxycarbonylmethyl-amino}-1-(4-nitro-benzyl)-ethyl]-tert-butoxycarbonylmethyl-amino}-acetic acid tert-butyl ester 
• 605670-02-8 N¹-(3-amino-propyl)-3-(4-nitro-phenyl)-propane-1,2-diamine 

Relevant academic research and scientific papers

Ligand and metal complex

A ligand of Formula (I) is provided: wherein A4 represents a hydrogen atom, a nitro group, an amino group, a thiocyanato group, or —Z—Y, in which Z is a divalent linking group and Y is a group derived from a biocompatible molecule, with the proviso that when X is methylene, A4 cannot be a hydrogen atom or a nitro group. A metal complex having the ligand is also provided and is useful as a blood pool contrast agent or a targeting contrast agent.

GdIII complexes with fast water exchange and high thermodynamic stability: potential building blocks for high-relaxivity MRI contrast agents.

On the basis of structural considerations in the inner sphere of nine-coordinate, monohydrated Gd(III) poly(aminocarboxylate) complexes, we succeeded in accelerating the water exchange by inducing steric compression around the water binding site. We modified the common DTPA(5-) ligand (DTPA=(diethylenetriamine-N,N,N',N",N"-pentaacetic acid) by replacing one (EPTPA(5-)) or two (DPTPA(5-)) ethylene bridges of the backbone by propylene bridges, or one coordinating acetate by a propionate arm (DTTA-prop(5-)). The ligand EPTPA(5-) was additionally functionalized with a nitrobenzyl linker group (EPTPA-bz-NO(2) (5-)) to allow for coupling of the chelate to macromolecules. The water exchange rate, determined from a combined variable-temperature (17)O NMR and EPR study, is two orders of magnitude higher on [Gd(eptpa-bz-NO(2))(H(2)O)](2-) and [Gd(eptpa)(H(2)O)](2-) than on [Gd(dtpa)(H(2)O)](2-) (k(ex)298=150x10(6), 330x10(6), and 3.3x10(6) s(-1), respectively). This is optimal for attaining maximum proton relaxivities for Gd(III)-based, macrocyclic MRI contrast agents. The activation volume of the water exchange, measured by variable-pressure (17)O NMR spectroscopy, evidences a dissociative interchange mechanism for [Gd(eptpa)(H(2)O)](2-) (DeltaV(not equal sign)=(+6.6+/-1.0) cm(3) mol(-1)). In contrast to [Gd(eptpa)(H(2)O)](2-), an interchange mechanism is proved for the macrocyclic [Gd(trita)(H(2)O)](-) (DeltaV (not equal sign)=(-1.5+/-1.0) cm(3) mol(-1)), which has one more CH(2) group in the macrocycle than the commercial MRI contrast agent [Gd(dota)(H(2)O)](-), and for which the elongation of the amine backbone also resulted in a remarkably fast water exchange. When one acetate of DTPA(5-) is substituted by a propionate, the water exchange rate on the Gd(III) complex increases by a factor of 10 (k(ex)298=31x10(6) s(-1)). The [Gd(dptpa)](2-) chelate has no inner-sphere water molecule. The protonation constants of the EPTPA-bz-NO(2) (5-) and DPTPA(5-) ligands and the stability constants of their complexes with Gd(III), Zn(II), Cu(II) and Ca(II) were determined by pH potentiometry. Although the thermodynamic stability of [Gd(eptpa-bz-NO(2))(H(2)O)](2-) is reduced to a slight extent in comparison with [Gd(dtpa)(H(2)O)](2-), it is stable enough to be used in medical diagnostics as an MRI contrast agent. Therefore both this chelate and [Gd(trita)(H(2)O)](-) are potential building blocks for the development of high-relaxivity macromolecular agents.