Solution Structure of Ln(III) Complexes with Macrocyclic Ligands Through Theoretical Evaluation of ¹H NMR Contact Shifts

Herein, we present a new approach that combines DFT calculations and the analysis of Tb^III-induced ¹H NMR shifts to quantitatively and accurately account for the contact contribution to the paramagnetic shift in Ln^III complexes. Geometry optimizations of different Gd^III complexes with macrocyclic ligands were carried out using the hybrid meta-GGA TPSSh functional and a 46 + 4f⁷ effective core potential (ECP) for Gd. The complexes investigated include [Ln­(Me-DODPA)]⁺ (H₂Me-DODPA = 6,6′-((4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)­bis­(methylene))­dipicolinic acid, [Ln­(DOTA)­(H₂O)]⁻ (H₄DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate), [Ln­(DOTAM)­(H₂O)]³⁺ (DOTAM = 1,4,7,10- tetrakis­[(carbamoyl)­methyl]-1,4,7,10-tetraazacyclododecane), and related systems containing pyridyl units (Ln = Gd, Tb). Subsequent all-electron relativistic calculations based on the DKH2 approximation, or small-core ECP calculations, were used to compute the ¹H hyperfine coupling constants (HFCCs) at the ligand nuclei (<i>A</i>_iso values). The calculated <i>A</i>_iso values provided direct access to contact contributions to the ¹H NMR shifts of the corresponding Tb^III complexes under the assumption that Gd and Tb complexes with a given ligand present similar HFCCs. These contact shifts were used to obtain the pseudocontact shifts, which encode structural information as they depend on the position of the nucleus with respect to the lanthanide ion. An excellent agreement was observed between the experimental and calculated pseudocontact shifts using the DFT-optimized geometries as structural models of the complexes in solution, which demonstrates that the computational approach used provides (i) good structural models for the complexes, (ii) accurate HFCCs at the ligand nuclei. The methodology presented in this work can be classified in the context of model-dependent methods, as it relies on the use of a specific molecular structure obtained from DFT calculations. Our results show that spin polarization effects dominate the ¹H <i>A</i>_iso values. The X-ray crystal structures of [Ln­(Me-DODPA)]­(PF₆)·2H₂O (Ln = Eu or Lu) are also reported

Solution Structure of Ln(III) Complexes with Macrocyclic Ligands Through Theoretical Evaluation of ¹H NMR Contact Shifts

Herein, we present a new approach that combines DFT calculations and the analysis of Tb^III-induced ¹H NMR shifts to quantitatively and accurately account for the contact contribution to the paramagnetic shift in Ln^III complexes. Geometry optimizations of different Gd^III complexes with macrocyclic ligands were carried out using the hybrid meta-GGA TPSSh functional and a 46 + 4f⁷ effective core potential (ECP) for Gd. The complexes investigated include [Ln­(Me-DODPA)]⁺ (H₂Me-DODPA = 6,6′-((4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)­bis­(methylene))­dipicolinic acid, [Ln­(DOTA)­(H₂O)]⁻ (H₄DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate), [Ln­(DOTAM)­(H₂O)]³⁺ (DOTAM = 1,4,7,10- tetrakis­[(carbamoyl)­methyl]-1,4,7,10-tetraazacyclododecane), and related systems containing pyridyl units (Ln = Gd, Tb). Subsequent all-electron relativistic calculations based on the DKH2 approximation, or small-core ECP calculations, were used to compute the ¹H hyperfine coupling constants (HFCCs) at the ligand nuclei (<i>A</i>_iso values). The calculated <i>A</i>_iso values provided direct access to contact contributions to the ¹H NMR shifts of the corresponding Tb^III complexes under the assumption that Gd and Tb complexes with a given ligand present similar HFCCs. These contact shifts were used to obtain the pseudocontact shifts, which encode structural information as they depend on the position of the nucleus with respect to the lanthanide ion. An excellent agreement was observed between the experimental and calculated pseudocontact shifts using the DFT-optimized geometries as structural models of the complexes in solution, which demonstrates that the computational approach used provides (i) good structural models for the complexes, (ii) accurate HFCCs at the ligand nuclei. The methodology presented in this work can be classified in the context of model-dependent methods, as it relies on the use of a specific molecular structure obtained from DFT calculations. Our results show that spin polarization effects dominate the ¹H <i>A</i>_iso values. The X-ray crystal structures of [Ln­(Me-DODPA)]­(PF₆)·2H₂O (Ln = Eu or Lu) are also reported

Lanthanide(III) Complexes with Ligands Derived from a Cyclen Framework Containing Pyridinecarboxylate Pendants. The Effect of Steric Hindrance on the Hydration Number

Two new macrocyclic ligands, 6,6′-((1,4,7,10-tetraazacyclododecane-1,7-diyl)­bis­(methylene))­dipicolinic acid (H₂DODPA) and 6,6′-((4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)­bis­(methylene))­dipicolinic acid (H₂Me-DODPA), designed for complexation of lanthanide ions in aqueous solution, have been synthesized and studied. The X-ray crystal structure of [Yb­(DODPA)]­(PF₆)·H₂O shows that the metal ion is directly bound to the eight donor atoms of the ligand, which results in a square-antiprismatic coordination around the metal ion. The hydration numbers (<i>q</i>) obtained from luminescence lifetime measurements in aqueous solution of the Eu^III and Tb^III complexes indicate that the DODPA complexes contain one inner-sphere water molecule, while those of the methylated analogue H₂Me-DODPA are <i>q</i> = 0. The structure of the complexes in solution has been investigated by ¹H and ¹³C NMR spectroscopy, as well as by theoretical calculations performed at the density functional theory (DFT; mPWB95) level. The minimum energy conformation calculated for the Yb^III complex [Λ­(λλλλ)] is in good agreement with the experimental structure in solution, as demonstrated by the analysis of the Yb^III-induced paramagnetic ¹H shifts. The nuclear magnetic relaxation dispersion (NMRD) profiles recorded for [Gd­(Me-DODPA)]⁺ are typical of a complex with <i>q</i> = 0, where the observed relaxivity can be accounted for by the outer-sphere mechanism. However, [Gd­(DODPA)]⁺ shows NMRD profiles consistent with the presence of both inner- and outer-sphere contributions to relaxivity. A simultaneous fitting of the NMRD profiles and variable temperature ¹⁷O NMR chemical shifts and transversal relaxation rates provided the parameters governing the relaxivity in [Gd­(DODPA)]⁺. The results show that this system is endowed with a relatively fast water exchange rate <i>k</i>_<i>ex</i>²⁹⁸ = 58 × 10⁶ s^–1

Lanthanide(III) Complexes with Ligands Derived from a Cyclen Framework Containing Pyridinecarboxylate Pendants. The Effect of Steric Hindrance on the Hydration Number

Two new macrocyclic ligands, 6,6′-((1,4,7,10-tetraazacyclododecane-1,7-diyl)­bis­(methylene))­dipicolinic acid (H₂DODPA) and 6,6′-((4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)­bis­(methylene))­dipicolinic acid (H₂Me-DODPA), designed for complexation of lanthanide ions in aqueous solution, have been synthesized and studied. The X-ray crystal structure of [Yb­(DODPA)]­(PF₆)·H₂O shows that the metal ion is directly bound to the eight donor atoms of the ligand, which results in a square-antiprismatic coordination around the metal ion. The hydration numbers (<i>q</i>) obtained from luminescence lifetime measurements in aqueous solution of the Eu^III and Tb^III complexes indicate that the DODPA complexes contain one inner-sphere water molecule, while those of the methylated analogue H₂Me-DODPA are <i>q</i> = 0. The structure of the complexes in solution has been investigated by ¹H and ¹³C NMR spectroscopy, as well as by theoretical calculations performed at the density functional theory (DFT; mPWB95) level. The minimum energy conformation calculated for the Yb^III complex [Λ­(λλλλ)] is in good agreement with the experimental structure in solution, as demonstrated by the analysis of the Yb^III-induced paramagnetic ¹H shifts. The nuclear magnetic relaxation dispersion (NMRD) profiles recorded for [Gd­(Me-DODPA)]⁺ are typical of a complex with <i>q</i> = 0, where the observed relaxivity can be accounted for by the outer-sphere mechanism. However, [Gd­(DODPA)]⁺ shows NMRD profiles consistent with the presence of both inner- and outer-sphere contributions to relaxivity. A simultaneous fitting of the NMRD profiles and variable temperature ¹⁷O NMR chemical shifts and transversal relaxation rates provided the parameters governing the relaxivity in [Gd­(DODPA)]⁺. The results show that this system is endowed with a relatively fast water exchange rate <i>k</i>_<i>ex</i>²⁹⁸ = 58 × 10⁶ s^–1

Lanthanide(III) Complexes with a Reinforced Cyclam Ligand Show Unprecedented Kinetic Inertness

Lanthanide­(III) complexes of a cross-bridged cyclam derivative containing two picolinate pendant arms are kinetically inert in very harsh conditions such as 2 M HCl, with no dissociation being observed for at least 5 months. Importantly, the [Ln­(dota)]⁻ complexes, which are recognized to be extremely inert, dissociate under these conditions with lifetimes in the range ca. 1 min to 12 h depending upon the Ln³⁺ ion. X-ray diffraction studies reveal octadentate binding of the ligand to the metal ion in the [Eu­(cb-tedpa)]⁺ complex, while ¹H and ¹³C NMR experiments in D₂O point to the presence of a single diastereoisomer in solution with a very rigid structure. The structure of the complexes in the solid state is retained in solution, as demonstrated by the analysis of the Yb³⁺-induced paramagnetic shifts

Complexation of Ln³⁺ Ions with Cyclam Dipicolinates: A Small Bridge that Makes Huge Differences in Structure, Equilibrium, and Kinetic Properties

The coordination properties toward the lanthanide ions of two macrocyclic ligands based on a cyclam platform containing picolinate pendant arms have been investigated. The synthesis of the ligands was achieved by using the well-known bis-aminal chemistry. One of the cyclam derivatives (cb-tedpa^2–) is reinforced with a cross-bridge unit, which results in exceptionally inert [Ln­(cb-tedpa)]⁺ complexes. The X-ray structures of the [La­(cb-tedpa)­Cl], [Gd­(cb-tedpa)]⁺, and [Lu­(Me₂tedpa)]⁺ complexes indicate octadentate binding of the ligands to the metal ions. The analysis of the Yb³⁺-induced shifts in [Yb­(Me₂tedpa)]⁺ indicates that this complex presents a solution structure very similar to that observed in the solid state for the Lu³⁺ analogue. The X-ray structures of [La­(H₂Me₂tedpa)₂]³⁺ and [Yb­(H₂Me₂tedpa)₂]³⁺ complexes confirm the exocyclic coordination of the metal ions, which gives rise to coordination polymers with the metal coordination environment being fulfilled by oxygen atoms of the picolinate groups and water molecules. The X-ray structure of [Gd­(Hcb-tedpa)₂]⁺ also indicates exocyclic coordination that in this case results in a discrete structure with an eight-coordinated metal ion. The nonreinforced complexes [Ln­(Me₂tedpa)]⁺ were prepared and isolated as chloride salts in nonaqueous media. However, these complexes were found to undergo dissociation in aqueous solution, except in the case of the complexes with the smallest Ln³⁺ ions (Ln³⁺ = Yb³⁺ and Lu³⁺). A DFT investigation shows that the increased stability of the [Ln­(Me₂tedpa)]⁺ complexes in solution across the lanthanide series is the result of an increased binding energy of the ligand due to the increased charge density of the Ln³⁺ ion

Endeavor toward Redox-Responsive Transition Metal Contrast Agents Based on the Cross-Bridge Cyclam Platform

We present the synthesis and characterization of a series of Mn(III), Co(III), and Ni(II) complexes with cross-bridge cyclam derivatives (CB-cyclam = 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) containing acetamide or acetic acid pendant arms. The X-ray structures of [Ni(CB-TE2AM)]Cl2·2H2O and [Mn(CB-TE1AM)(OH)](PF6)2 evidence the octahedral coordination of the ligands around the Ni(II) and Mn(III) metal ions, with a terminal hydroxide ligand being coordinated to Mn(III). Cyclic voltammetry studies on solutions of the [Mn(CB-TE1AM)(OH)]2+ and [Mn(CB-TE1A)(OH)]+ complexes (0.15 M NaCl) show an intricate redox behavior with waves due to the MnIII/MnIV and MnII/MnIII pairs. The Co(III) and Ni(II) complexes with CB-TE2A and CB-TE2AM show quasi-reversible features due to the CoIII/CoII or NiII/NiIII pairs. The [Co(CB-TE2AM)]3+ complex is readily reduced by dithionite in aqueous solution, as evidenced by 1H NMR studies, but does not react with ascorbate. The [Mn(CB-TE1A)(OH)]+ complex is however reduced very quickly by ascorbate following a simple kinetic scheme (k0 = k1[AH–], where [AH–] is the ascorbate concentration and k1 = 628 ± 7 M–1 s–1). The reduction of the Mn(III) complex to Mn(II) by ascorbate provokes complex dissociation, as demonstrated by 1H nuclear magnetic relaxation dispersion studies. The [Ni(CB-TE2AM)]2+ complex shows significant chemical exchange saturation transfer effects upon saturation of the amide proton signals at 71 and 3 ppm with respect to the bulk water signal