A Bisamide Derivative of [Mn(1,4‐DO2A)] – Solution Thermodynamic, Kinetic, and NMR Relaxometric Studies

Abstract

Abstract:A new 1,4-DO2A-bisamide [1, 1,4,7,

Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands

“…In the recent years, the research in the field of Mn(II) coordination chemistry has been intensified aiming to develop Mn(II) complexes suitable for in vivo application as magnetic resonance imaging (MRI) contrast agents (CA) (Drahos et al, 2012 ; Gale et al, 2015 ; Forgács et al, 2016 ; Garda et al, 2016 ). Gd(III) complexes are used as CAs in millions of doses.…”

“…Macrocyclic ligands have also been screened with the aim of finding a suitable macrocyclic platform for Mn(II) complexation. The investigated macrocyclic ligands were mostly the acetate, rarely the phosphonate and phosphinate derivatives of tacn (tacn = 1,4,7,-triazacyclononane), cyclen and pyclen; efforts were also devoted to the investigation of some rigid pyridine-based 15-membered and other macrocyclic complexes formed with 9-, 12-, 14-, and 15-membered macrocyclic ligands (Dees et al, 2007 ; Drahos et al, 2010 , 2011 , 2012 ; Molnar et al, 2014 ; Forgács et al, 2016 , 2017 ; Garda et al, 2016 ). The main goal of these studies was the development of a ligand platform that would allow a solvent molecule to be coordinated in the inner coordination sphere of the Mn(II) complexes, which is necessary to achieve appropriate relaxation enhancement.…”

“…The only structures that represented an acceptable compromise between the apparently contradictory requirements (thermodynamic and redox stability/inertness/relaxivity) were the Mn(II) chelates of the cis -DO2A and the 15-PyaneN 3 O 2 ligands (Dees et al, 2007 ; Drahos et al, 2010 ; Garda et al, 2016 ). The kinetic properties improved by the replacement of two carboxylate moieties with dimethylamide metal binding units (Forgács et al, 2016 ). The results obtained in our laboratory by studying monopicolinates of 9-, 12- and 14-membered macrocyclic ligands have also indicated that the best kinetic data were obtained for the Mn(II) complex of a 12-membered macrocyclic derivative, but further ligand optimization is required to identify the best candidates for in vivo applications (Molnar et al, 2014 ).…”

Nyíltláncú és makrociklusos aminokarboxilát ligandumok szintézise és fémkomplexeik vizsgálata: koordinációs kémia az orvosi képalkotás szolgálatában

“…39 Ezen információkat az elõzõekben bemutatott szisztematikus vizsgálatok eredményeivel "összefésülve" megterveztük, elõállítottuk és vizsgáltuk az oldalláncok alfa szénatomján metilcsoportot tartalmazó ciszDO2MA, ill. az amidszármazék ciszDO2AM Me2 , és a ciszDO2AM Pip ligandumokat. 40,41 A ciszDO2MA ligandummal kapott eredményeinket a [Mn(ciszDO2A)]-komplexre jellemzõ adatokkal összehasonlítva a ciszDO2MA komplex nagyobb termodinamikai, de kisebb redoxi stabilitását tapasztaltuk. A [Mn(ciszDO2MA)]-komplex savkatalizált disszociációjára jellemzõ sebességi állandó 1/6-a a ciszDO2A esetében tapasztalt állandónak, ami jó összhangban van a DOTA ® DOTMA 9 és a PCTA ® PCTMA 11 ligandumok Gd 3+ -komplexeire kapott eredményeinkkel.…”

“…Az acetátcsoportok amidcsoportra történõ cseréje ugyanakkor a stabilitási állandó csökkenését (log K MnL =12,64(5)), de a relaxivitás és a kinetikai inertség további javulását eredményezi. 40,41 …”