Kálmán, Ferenc KrisztiánEstifanos Debretsion, Abraham2025-06-262025-06-262025https://hdl.handle.net/2437/394585For the last three decades, intensive research has been conducted to synthesize rigidified ligands for Gd(III) complexation to produce MRI contrast agent candidates with high thermodynamic stability and inertness. In this work, we report the macrocyclic ligand H4OPDMA, whose Gd(III) complex has high thermodynamic stability and inertness as well as exhibits a relaxation enhancement effect similar to that of the frequently used MRI contrast agents [Gd(DTPA)]²⁻ and [Gd(DOTA)]⁻ complexes. Our results show that the conditional stability of the [Gd(OPDMA)]⁻ (pGd = 14.8) calculated under physiological conditions, is comparable to that of [Gd(DTPA)]²⁻ (pGd = 15.6) and higher than those were reported for [Gd(AAZTA)]⁻ and [Gd(PCTA)] chelates (pGdAAZTA = 13.4 and pGdPCTA = 13.1). The [Gd(OPDMA)]⁻ complex is exceptionally inert, with a dissociation half-life of 3.2 years at 37 °C and pH = 7.4. The complex, which contain one water molecule (q = 1) bears a high water exchange rate (kex298 = 73(12) × 10⁶ s⁻¹). The fast exchange rate is attributed to the high steric compression around the water binding site. DFT calculations also revealed that the Gd(III) ion is coordinated in this complex, while one carboxylate group remains uncoordinated. The mono-malonate derivative of the o-pyclen ligand, designed as [Mn(OPMMA)], was synthesized following promising results with the analogous Gd complex, [Gd(OPDMA)]⁻. However, the stability of [Mn(OPMMA)] is significantly lower, with its logKMnL value being 3 and 7 orders of magnitude less than those of [Mn(OPC2A)] and [Mn(3,9-PC2A)], respectively, and its pMn value also over two orders of magnitude lower. Inertness studies using Cu²⁺ as a scavenger showed that [Mn(OPMMA)] dissociates too quickly, prompting the use of the stopped-flow method; results confirmed that its kinetic stability is much lower than the reference complexes. Despite this, [Mn(OPMMA)] shows slightly higher relaxivity, attributed to its asymmetric and more open structure.125 oldalenmagnetic resonance imaging, contrast agent, manganese, gadolinium, inertness; mágneses rezonanciás képalkotás, kontrasztanyag, mangán, gadolínium, inertségPhD, doktori értekezésKémiai tudományokTermészettudományok