Smart/intelligent contrast agent candidates for MRI based on Mn(II) ion are rare, as it usually forms labile complexes with polyaminocarboxylate-type ligands. Here, we report the first example of a complex that can be activated by changing pH its local environment. The PC2A-EA ligand an ethylamine pendant arm was found to form thermodynamically stable (log KMnL = 19.01, pMn 9.27) and kinetically inert respect trans-chelation metal such Cu(II). [MnH(PCA2-EA)] displays relatively slow water...

Toxicity concerns related to Gd(III)-based magnetic resonance imaging (MRI) agents prompted an intensive research toward their replacement by complexes of essential metal ions, like Mn(II). Here, we report a macrocyclic chelate, [Mn(PC2A-BP)], which possesses high thermodynamic stability (log KMnL = 14.86 and pMn=8.35) kinetic inertness (t1/2pH=7.4 286.2 h) as well remarkable relaxivity (r1p 23.5 mM-1 s-1, 0.49 T, 37 °C) in the presence human serum albumin, allowing significant MRI signal...

We report the synthesis of ligand Hnompa (6-((1,4,7-triazacyclononan-1-yl)methyl)picolinic acid) and a detailed characterization Mn(2+) complexes formed by this related ligands Hdompa (6-((1,4,7,10-tetraazacyclododecan-1-yl)methyl)picolinic Htempa (6-((1,4,8,11-tetraazacyclotetradecan-1-yl)methyl)picolinic acid). These form thermodynamically stable in aqueous solution with stability constants logKMnL = 10.28(1) (nompa), 14.48(1) (dompa), 12.53(1) (tempa). A study dissociation kinetics these...

During the past few years increasing attention has been devoted to Mn(II) complexes as possible substitutes for Gd(III) contrast agents in MRI. Equilibrium (log KMnL or pMn value), kinetic parameters (rates and half-lives of dissociation) relaxivity formed with 12-membered macrocyclic ligands were studied. The selected a way gain information on how ligand rigidity, nature donor atoms macrocycle (pyridine N, amine, etheric oxygen atom), pendant arms (carboxylates, phosphonates, primary,...

We report a detailed characterization of lanthanide complexes with two azaligands based on the pyclen macrocycle containing picolinate and one acetate pendant arms. The arms are attached to either opposite (L3) or adjacent (L4) amine nitrogen atoms macrocyclic platform. X-ray structures Yb3+ show nine coordination ligand metal ion, situation that is also observed for EuL4 in solid state. EuL3 complex forms centrosymmetric dimers state joined by μ2-η1:η1 carboxylate groups, which results...

We report the Mn(II) complexes with two pyclen-based ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized acetate pendant arms at either positions 3,6 (3,6-PC2A) or 3,9 (3,9-PC2A) of macrocyclic fragment. The 3,6-PC2A ligand was synthesized in five steps from pyclen oxalate by protecting one secondary amine groups using Alloc chemistry. complex 3,9-PC2A is characterized a higher thermodynamic stability [log KMnL 17.09(2)] than analogue 15.53(1); 0.15...

In the search for MnII MR and PET/MR imaging agents with optimal balance between thermodynamic stability, kinetic inertness, relaxivity, two novel bifunctional chelators (BFMnCs) based on CDTA (trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid) were synthesized. A six-step synthesis, involving buildup of a functionalized trans-1,2-diaminocyclohexane core, provided CuAAC-reactive 6a 6b bearing an alkyne or azide substituent cyclohexane ring, respectively (CuAAC = CuI-catalyzed...

The geometric features of two pyclen-based ligands possessing identical donor atoms but different site organization have a profound impact in their complexation properties toward lanthanide ions. ligand containing acetate groups and picolinate arm arranged symmetrical fashion (L1) forms Gd3+ complex being orders magnitude less stable than its dissymmetric analogue GdL2. Besides, GdL1 experiences much faster dissociation following the acid-catalyzed mechanism On contrary, exhibits lower...

We report the synthesis of two azaligands based on pyclen macrocyclic platform containing picolinate and one acetate pendant arms. The ligands differ in relative positions functions, which are arranged either a symmetrical (L3) or nonsymmetrical (L4) fashion. complexation properties toward natY3+ 90Y3+ were investigated to assess their potential as chelating units for radiopharmaceutical applications. X-ray structures YL3 YL4 complexes show nonadentate binding ligand metal ions. A...

Thanks to a smart regiospecific N-functionalization, pyclen based ligand bearing one picolinate and two acetate arms organized in dissymmetric manner was synthesized for Y3+ complexation, compared its symmetric analogue. The nature of the capping bonds around metal coordination environment has dramatic effect on properties chelate, natY3+ 90Y3+ derivatives presenting enhanced thermodynamic stability kinetic inertness.

A Zn II responsive Mn -based MRI contrast agent, [Mn(PC2A-DPA)], has been synthesized, investigated and applied in imaging studies. It shows high stability excellent inertness can be used to visualize glucose triggered release by MRI.

We report the synthesis of two pyclen-based regioisomer ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized with picolinic acid pendant arms either at positions 3,9-pc2pa (L5) or 3,6-pc2pa (L6) macrocyclic fragment. The were prepared by regiospecific protection one amine nitrogen atoms macrocycle using Boc and Alloc protecting groups, respectively. X-ray structure Gd(III) complex L5 contains trinuclear [(GdL5)3(H2O)3]3+ entities in which monomeric...

New “all-in-one” theranostic systems, combining a magnetic resonance imaging contrast agent with biphotonic photodynamic therapy photosensitiser generating cytotoxic singlet oxygen, were successfully developed and characterized.

We report the synthesis of a new family side-bridged pyclen ligands. The incorporation an ethylene bridge between two adjacent nitrogen atoms was reached from pyclen-oxalate precursor described previously. Three macrocycles, Hsb-3-pc1a, sb-3-pc1py, and Hsb-3-pc1pa, were obtained with aim to assess their coordination properties toward Cu2+ Zn2+ ions. also prepared nonreinforced analogues H3-pc1a, 3-pc1py, H3-pc1pa as comparative benchmarks. series ligands characterized investigated in detail....

Abstract We explore the potential of fluorine‐containing small Mn 2+ chelates as alternatives to perfluorinated nanoparticles, widely used 19 F MRI probes. In MnL1 , cyclohexanediamine skeleton and two piperidine rings, involving each a metal‐coordinating amide group an appended CF 3 moiety, provide high rigidity complex. This allows for good control Mn−F distance ( r MnF =8.2±0.2 Å determined from relaxation data), well kinetic inertness (a dissociation half‐life 1285 h is estimated...

Owing to the increasing importance of manganese(II) complexes in field magnetic resonance imaging (MRI), large efforts have been devoted find an appropriate ligand for Mn(II) ion encapsulation by providing balance between seemingly contradictory requirements (i.e., thermodynamic stability and kinetic inertness vs low denticity enabling water molecule(s) be coordinated its metal center). Among these ligands, a number pyridine or pyridol based open-chain macrocyclic chelators investigated so...

We report the Mn(II) complexes with two pyclen-based ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized acetate pendant arms either at positions 3,6 (3,6-PC2A) or 3,9 (3,9-PC2A) of macrocyclic fragment. The 3,6-PC2A ligand was synthesized in five steps from pyclen-oxalate by protecting one secondary amine groups pyclen using Alloc chemistry. complex 3,9-PC2A is characterized a higher thermodynamic stability (logKMnL 17.09(2) than analogue 15.53(1),...

We report the Mn(II) complexes with two pyclen-based ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized acetate pendant arms either at positions 3,6 (3,6-PC2A) or 3,9 (3,9-PC2A) of macrocyclic fragment. The 3,6-PC2A ligand was synthesized in five steps from pyclen-oxalate by protecting one secondary amine groups pyclen using Alloc chemistry. complex 3,9-PC2A is characterized a higher thermodynamic stability (logKMnL 17.09(2) than analogue 15.53(1),...

We report the synthesis of two pyclen-based regioisomer ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca1(15),11,13-triene) functionalized with picolinic acid pendant arms either at positions 3,9-pc2pa (L5) or 3,6-pc2pa (L6) macrocyclic fragment. The were prepared by regiospecific protection one amine nitrogen atom macrocycle using Boc and Alloc protecting groups, respectively. X-ray structure Gd(III) complex L5 contains trinuclear [(GdL5)3(H2O)3] 3+ entities in which monomeric...

New “all-in-one” theranostic systems, combining a magnetic resonance imaging (MRI) contrast agent with biphotonic photodynamic therapy (2P-PDT) photosensitiser generating cytotoxic singlet oxygen, were envisaged and synthesised. They are based on azamacrocycles, regiospecifically functionalised by two-photon PDT π-conjugated dibromobenzene-picolinate photosensitisers acetate, able to complex gadolinium(III) allow an MRI signal. Our approach was use two different macrocyclic platforms, tacn...

New “all-in-one” theranostic systems, combining a magnetic resonance imaging (MRI) contrast agent with biphotonic photodynamic therapy (2P-PDT) photosensitiser generating cytotoxic singlet oxygen, were envisaged and synthesised. They are based on azamacrocycles, regiospecifically functionalised by two-photon PDT π-conjugated dibromobenzene-picolinate photosensitisers acetate, able to complex gadolinium(III) allow an MRI signal. Our approach was use two different macrocyclic platforms, tacn...