Macrocyclic Pyclen-Based Gd³⁺ Complex with High Relaxivity and pH Response

Abstract

We report the synthesis and characterization of the macrocyclic ligand 2,2′-((2-(3,9-bis­(carboxymethyl)-3,6,9-triaza-1­(2,6)-pyridinacyclodecaphane-6-yl)­ethyl)­azanediyl)­diacetic acid (H4L) and several of its complexes with lanthanide ions. The structure of the free ligand was determined using X-ray diffraction measurements. Two N atoms of the pyclen moiety in the trans position are protonated in the solid state, together with the exocyclic N atom and one of the carboxylate groups of the ligand. The relaxivity of the Gd3+ complex was found to increase from 6.7 mM–1 s–1 at pH 8.6 to 8.5 mM–1 s–1 below pH ≈ 6.0. Luminescence lifetime measurements recorded from H2O and D2O solutions of the Eu3+ complex evidence the presence of a single complex species in solution at low pH (∼5.0) that contains two inner-sphere water molecules. DFT calculations suggest that the coordination environment of the Ln3+ ion is fulfilled by the four N atoms of the pyclen unit, two oxygen atoms of the macrocyclic acetate groups, and an oxygen atom of an exocyclic carboxylate group. The two inner-sphere water molecules complete coordination number nine around the metal ion. At high pH (∼9.3), the lifetime of the excited 5D0 level of Eu3+ displays a biexponential behavior that can be attributed to the presence of two species in solution with hydration numbers of q = 0 and q = 1. The 1H NMR and DOSY spectra recorded from solutions of the Eu3+ and Y3+ complexes reveal a structural change triggered by pH and the formation of small aggregates at high pH values.

Assembly of Polyiodide Networks with Cu(II) Complexes of Pyridinol-Based Tetraaza Macrocycles

“…A noteworthy member of this class of macrocyclic ligands is 3,6,9-triaza-1-(2,6)-pyridinacyclodecaphane ( L1 , Figure ) which, in the three decades since its appearance, has given rise to a large family of derivatives that have been investigated for applications in many areas, including, among others, pharmaceutical and biomedical sectors, − catalysis, − and chemosensing − as well as in the preparation of polybromides and polyiodides , featuring iodine-dense three-dimensional networks that might open up new perspectives in crystal engineering and in the design of solid-state conductors as well as in the preparation of new chemicals with antimicrobial activity. − …”

Stabilisation of Exotic Tribromide (Br3−) Anions via Supramolecular Interaction with a Tosylated Macrocyclic Pyridinophane. A Serendipitous Case

“…It was later in the spotlight for its ability to form metal complexes [6][7][8], but its wider success was achieved thanks to its utilisation as a scaffold for the preparation of new materials that have proven effective in a variety of applications. Indeed, L derivatives decorated with different hanging functionalities have been studied for several biomedical (MRI contrast agents [9][10][11][12], antiproliferative treatments [13][14][15][16], radiotherapy [17,18], enzyme mimicking [19,20] and antioxidant activity [21][22][23]), chemosensing [24][25][26][27] and catalytic [28][29][30][31][32][33] applications. Very recently, (MRI contrast agents [9][10][11][12], antiproliferative treatments [13][14][15][16], radiotherapy [17,18], enzyme mimicking [19,20] and antioxidant activity [21][22][23]), chemosensing [24][25]…”

“…Anion-π interactions were also found to play an important role in the formation of highly organised polyiodide complexes [44,45] and iodide based permutable organised frameworks (POF) [46] with a pyridinium-based ligand such as Stoddart's blue box (BB, cyclobis(paraquat-p-phenylene)). (MRI contrast agents [9][10][11][12], antiproliferative treatments [13][14][15][16], radiotherapy [17,18], enzyme mimicking [19,20] and antioxidant activity [21][22][23]), chemosensing [24][25][26][27] and catalytic [28][29][30][31][32][33] applications. Very recently, it has been shown that L and its N-trimethylated derivative are capable of stabilising iodine-dense three-dimensional networks that might be relevant for crystal engineering purposes and the design of solid-state conductors [34].…”

“…It was later in the spotlight for its ability to form metal complexes [ 6 , 7 , 8 ], but its wider success was achieved thanks to its utilisation as a scaffold for the preparation of new materials that have proven effective in a variety of applications. Indeed, L derivatives decorated with different hanging functionalities have been studied for several biomedical (MRI contrast agents [ 9 , 10 , 11 , 12 ], antiproliferative treatments [ 13 , 14 , 15 , 16 ], radiotherapy [ 17 , 18 ], enzyme mimicking [ 19 , 20 ] and antioxidant activity [ 21 , 22 , 23 ]), chemosensing [ 24 , 25 , 26 , 27 ] and catalytic [ 28 , 29 , 30 , 31 , 32 , 33 ] applications. Very recently, it has been shown that L and its N-trimethylated derivative are capable of stabilising iodine-dense three-dimensional networks that might be relevant for crystal engineering purposes and the design of solid-state conductors [ 34 ].…”

Chiral Pyclen-Based Heptadentate Chelates as Highly Stable MRI Contrast Agents

“…26−31 Albelda et al developed a pyclen-based complex exhibiting pH-responsive behavior, as the number of coordinated water molecules varies at different pH values from 1 to 2, which results in a change of relaxivity. 32 Tircso et al reported a pH-sensitive MRI probe, PC2A-EA, which contains an ethylamine moiety that can respond within the biologically relevant pH range. 11 In 2022, a heptadentate gadolinium complex called gadopiclenol was approved as a new MRI contrast agent for imaging the central nervous system and the body of adults and children aged 2 years and above.…”