Long Wavelength Excitation of Europium Luminescence in Extended, Carboline-Based Cryptates

Two new β-carboline-based tris­(biaryl) europium cryptates are introduced. The extended antenna moiety incorporated into the cryptand frameworks enables the sensitization of europium emission with excitation wavelengths well above 450 nm. In aqueous solution, the cryptates show great complex stability, luminescence lifetimes around 0.5 ms, and absolute quantum yields of ca. 3%. In addition, the europium luminescence shows a well-defined pH-dependence in the physiologically interesting pH range 7–9

Monopicolinate Cyclen and Cyclam Derivatives for Stable Copper(II) Complexation

The syntheses of a new 1,4,7,10-tetraazacyclododecane (cyclen) derivative bearing a picolinate pendant arm (H<b>L1</b>), and its 1,4,8,11-tetraazacyclotetradecane (cyclam) analogue H<b>L2</b>, were achieved by using two different selective-protection methods involving the preparation of cyclen-bisaminal or phosphoryl cyclam derivatives. The acid–base properties of both compounds were investigated as well as their coordination chemistry, especially with Cu²⁺, in aqueous solution and in solid state. The copper­(II) complexes were synthesized, and the single crystal X-ray diffraction structures of compounds of formula [Cu­(HL)]­(ClO₄)₂·H₂O (L = <b>L1</b> or <b>L2</b>), [Cu<b>L1</b>]­(ClO₄) and [Cu<b>L2</b>]­Cl·2H₂O, were determined. These studies revealed that protonation of the complexes occurs on the carboxylate group of the picolinate moiety. Stability constants of the complexes were determined at 25.0 °C and ionic strength 0.10 M in KNO₃ using potentiometric titrations. Both ligands form complexes with Cu²⁺ that are thermodynamically very stable. Additionally, both H<b>L1</b> and H<b>L2</b> exhibit an important selectivity for Cu²⁺ over Zn²⁺. The kinetic inertness in acidic medium of both complexes of Cu²⁺ was evaluated by spectrophotometry revealing that [Cu<b>L2</b>]⁺ is much more inert than [Cu<b>L1</b>]⁺. The determined half-life values also demonstrate the very high kinetic inertness of [Cu<b>L2</b>]⁺ when compared to a list of copper­(II) complexes of other macrocyclic ligands. The coordination geometry of the copper center in the complexes was established in aqueous solution from UV–visible and electron paramagnetic resonance (EPR) spectroscopy, showing that the solution structures of both complexes are in excellent agreement with those of crystallographic data. Cyclic voltammetry experiments point to a good stability of the complexes with respect to metal ion dissociation upon reduction of the metal ion to Cu⁺ at about neutral pH. Our results revealed that the cyclam-based ligand H<b>L2</b> is a very attractive receptor for copper­(II), presenting a fast complexation process, a high kinetic inertness, and important thermodynamic and electrochemical stability

Cooperative Anion Recognition in Copper(II) and Zinc(II) Complexes with a Ditopic Tripodal Ligand Containing a Urea Group

The ability of Cu^II and Zn^II complexes of the ditopic receptor H₂L [1-(2-((bis­(pyridin-2-ylmethyl)­amino)­methyl)­phenyl)-3-(3-nitrophenyl)­urea] for anion recognition is reported. In the presence of weakly coordinating anions such as ClO₄^–, the urea group binds to the metal ion (Cu^II or Zn^II) through one of its nitrogen atoms. The study of the interaction of the metal complexes with a variety of anions in DMSO shows that SO₄^2– and Cl^– bind to the complexes through a cooperative binding involving simultaneous coordination to the metal ion and different hydrogen-bonding interactions with the urea moiety, depending on the shape and size of the anion. On the contrary, single crystal X-ray diffraction studies show that anions such as NO₃^– and PhCO₂^– form 1:2 complexes (metal/anion) where one of the anions coordinates to the metal center and the second one is involved in hydrogen-bonding interaction with the urea group, which is projected away from the metal ion. Spectrophotometric titrations performed for the Cu^II complex indicate that this system is able to bind a wide range of anions with an affinity sequence: MeCO₂^– ∼ Cl^– (log <i>K</i>₁₁ > 7) > NO₂^– > H₂PO₄^– ∼ Br^– > HSO₄^– > NO₃^– (log <i>K</i>₁₁ < 2). In contrast to this, the free ligand gives much weaker interactions with these anions. In the presence of basic anions such as MeCO₂^– or F^–, competitive processes associated with the deprotonation of the coordinated N–H group of the urea moiety take place. Thus, N-coordination of the urea unit to the metal ion increases the acidity of one of its N–H groups. DFT calculations performed in DMSO solution are in agreement with both an anion-hydrogen bonding interaction and an anion–metal ion coordination collaborating in the stabilization of the metal salt complexes with tetrahedral anions

Monopicolinate Cyclen and Cyclam Derivatives for Stable Copper(II) Complexation

The syntheses of a new 1,4,7,10-tetraazacyclododecane (cyclen) derivative bearing a picolinate pendant arm (H<b>L1</b>), and its 1,4,8,11-tetraazacyclotetradecane (cyclam) analogue H<b>L2</b>, were achieved by using two different selective-protection methods involving the preparation of cyclen-bisaminal or phosphoryl cyclam derivatives. The acid–base properties of both compounds were investigated as well as their coordination chemistry, especially with Cu²⁺, in aqueous solution and in solid state. The copper­(II) complexes were synthesized, and the single crystal X-ray diffraction structures of compounds of formula [Cu­(HL)]­(ClO₄)₂·H₂O (L = <b>L1</b> or <b>L2</b>), [Cu<b>L1</b>]­(ClO₄) and [Cu<b>L2</b>]­Cl·2H₂O, were determined. These studies revealed that protonation of the complexes occurs on the carboxylate group of the picolinate moiety. Stability constants of the complexes were determined at 25.0 °C and ionic strength 0.10 M in KNO₃ using potentiometric titrations. Both ligands form complexes with Cu²⁺ that are thermodynamically very stable. Additionally, both H<b>L1</b> and H<b>L2</b> exhibit an important selectivity for Cu²⁺ over Zn²⁺. The kinetic inertness in acidic medium of both complexes of Cu²⁺ was evaluated by spectrophotometry revealing that [Cu<b>L2</b>]⁺ is much more inert than [Cu<b>L1</b>]⁺. The determined half-life values also demonstrate the very high kinetic inertness of [Cu<b>L2</b>]⁺ when compared to a list of copper­(II) complexes of other macrocyclic ligands. The coordination geometry of the copper center in the complexes was established in aqueous solution from UV–visible and electron paramagnetic resonance (EPR) spectroscopy, showing that the solution structures of both complexes are in excellent agreement with those of crystallographic data. Cyclic voltammetry experiments point to a good stability of the complexes with respect to metal ion dissociation upon reduction of the metal ion to Cu⁺ at about neutral pH. Our results revealed that the cyclam-based ligand H<b>L2</b> is a very attractive receptor for copper­(II), presenting a fast complexation process, a high kinetic inertness, and important thermodynamic and electrochemical stability

Cooperative Anion Recognition in Copper(II) and Zinc(II) Complexes with a Ditopic Tripodal Ligand Containing a Urea Group

The ability of Cu^II and Zn^II complexes of the ditopic receptor H₂L [1-(2-((bis­(pyridin-2-ylmethyl)­amino)­methyl)­phenyl)-3-(3-nitrophenyl)­urea] for anion recognition is reported. In the presence of weakly coordinating anions such as ClO₄^–, the urea group binds to the metal ion (Cu^II or Zn^II) through one of its nitrogen atoms. The study of the interaction of the metal complexes with a variety of anions in DMSO shows that SO₄^2– and Cl^– bind to the complexes through a cooperative binding involving simultaneous coordination to the metal ion and different hydrogen-bonding interactions with the urea moiety, depending on the shape and size of the anion. On the contrary, single crystal X-ray diffraction studies show that anions such as NO₃^– and PhCO₂^– form 1:2 complexes (metal/anion) where one of the anions coordinates to the metal center and the second one is involved in hydrogen-bonding interaction with the urea group, which is projected away from the metal ion. Spectrophotometric titrations performed for the Cu^II complex indicate that this system is able to bind a wide range of anions with an affinity sequence: MeCO₂^– ∼ Cl^– (log <i>K</i>₁₁ > 7) > NO₂^– > H₂PO₄^– ∼ Br^– > HSO₄^– > NO₃^– (log <i>K</i>₁₁ < 2). In contrast to this, the free ligand gives much weaker interactions with these anions. In the presence of basic anions such as MeCO₂^– or F^–, competitive processes associated with the deprotonation of the coordinated N–H group of the urea moiety take place. Thus, N-coordination of the urea unit to the metal ion increases the acidity of one of its N–H groups. DFT calculations performed in DMSO solution are in agreement with both an anion-hydrogen bonding interaction and an anion–metal ion coordination collaborating in the stabilization of the metal salt complexes with tetrahedral anions

Hyperfine Coupling Constants on Inner-Sphere Water Molecules of a Triazacyclononane-based Mn(II) Complex and Related Systems Relevant as MRI Contrast Agents

We report the synthesis of the ligand H₂MeNO2A (1,4-bis­(carboxymethyl)-7-methyl-1,4,7-triazacyclononane) and a detailed experimental and computational study of the hyperfine coupling constants (HFCCs) on the inner-sphere water molecules of [Mn­(MeNO2A)] and related Mn²⁺ complexes relevant as potential contrast agents in magnetic resonance imaging (MRI). Nuclear magnetic relaxation dispersion (NMRD) profiles, ¹⁷O NMR chemical shifts, and transverse relaxation rates of aqueous solutions of [Mn­(MeNO2A)] were recorded to determine the parameters governing the relaxivity in this complex and the ¹⁷O and ¹H HFCCs. DFT calculations (TPSSh model) performed in aqueous solution (PCM model) on the [Mn­(MeNO2A)­(H₂O)]·<i>x</i>H₂O and [Mn­(EDTA)­(H₂O)]^2–·<i>x</i>H₂O (<i>x</i> = 0–4) systems were used to determine theoretically the ¹⁷O and ¹H HFCCs responsible for the ¹⁷O NMR chemical shifts and the scalar contributions to ¹⁷O and ¹H NMR relaxation rates. The use of a mixed cluster/continuum approach with the explicit inclusion of a few second-sphere water molecules is critical for an accurate calculation of HFCCs of coordinated water molecules. The impact of complex dynamics on the calculated HFCCs was evaluated with the use of molecular dynamics simulations within the atom-centered density matrix propagation (ADMP) approach. The ¹⁷O and ¹H HFCCs calculated for these complexes and related systems show an excellent agreement with the experimental data. Both the ¹H and ¹⁷O HFCCs (<i>A</i>_iso values) are dominated by the spin delocalization mechanism. The <i>A</i>_iso values are significantly affected by the distance between the oxygen atom of the coordinated water molecule and the Mn²⁺ ion, as well as by the orientation of the water molecule plane with respect to the Mn–O vector

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

Gd³⁺-Based Magnetic Resonance Imaging Contrast Agent Responsive to Zn²⁺

We report the heteroditopic ligand H₅L, which contains a DO3A unit for Gd³⁺ complexation connected to an NO2A moiety through a <i>N</i>-propylacetamide linker. The synthesis of the ligand followed a convergent route that involved the preparation of 1,4-bis­(<i>tert</i>-butoxycarbonylmethyl)-1,4,7-triazacyclononane following the orthoamide strategy. The luminescence lifetimes of the Tb­(⁵D₄) excited state measured for the TbL complex point to the absence of coordinated water molecules. Density functional theory calculations and ¹H NMR studies indicate that the EuL complex presents a square antiprismatic coordination in aqueous solution, where eight coordination is provided by the seven donor atoms of the DO3A unit and the amide oxygen atom of the <i>N</i>-propylacetamide linker. Addition of Zn²⁺ to aqueous solutions of the TbL complex provokes a decrease of the emission intensity as the emission lifetime becomes shorter, which is a consequence of the coordination of a water molecule to the Tb³⁺ ion upon Zn²⁺ binding to the NO2A moiety. The relaxivity of the GdL complex recorded at 7 T (25 °C) increases by almost 150% in the presence of 1 equiv of Zn²⁺, while Ca²⁺ and Mg²⁺ induced very small relaxivity changes. In vitro magnetic resonance imaging experiments confirmed the ability of GdL to provide response to the presence of Zn²⁺

Stabilizing Divalent Europium in Aqueous Solution Using Size-Discrimination and Electrostatic Effects

We report two macrocyclic ligands containing a 1,10-diaza-18-crown-6 fragment functionalized with either two picolinamide pendant arms (bpa18c6) or one picolinamide and one picolinate arm (ppa18c6^–). The X-ray structure of [La­(ppa18c6)­(H₂O)]²⁺ shows that the ligand binds to the metal ion using the six donor atoms of the crown moiety and the four donor atoms of the pendant arms, 11-coordination being completed by the presence of a coordinated water molecule. The X-ray structure of the [Sr­(bpa18c6)­(H₂O)]²⁺ was also investigated due to the very similar ionic radii of Sr²⁺ and Eu²⁺. The structure of this complex is very similar to that of [La­(ppa18c6)­(H₂O)]²⁺, with the metal ion being 11-coordinated. Potentiometric measurements were used to determine the stability constants of the complexes formed with La³⁺ and Eu³⁺. Both ligands present a very high selectivity for the large La³⁺ ion over the smaller Eu³⁺, with a size-discrimination ability that exceeds that of the analogous ligand containing two picolinate pendant arms reported previously (bp18c6^2–). DFT calculations using the TPSSh functional and the large-core pseudopotential approximation provided stability trends in good agreement with the experimental values, indicating that charge neutral ligands derived from 1,10-diaza-18-crown-6 enhance the selectivity of the ligand for the large Ln³⁺ ions. Cyclic voltammetry measurements show that the stabilization of Eu²⁺ by these ligands follows the sequence bp18c6^2– < ppa18c6^– < bpa18c6 with half-wave potentials of −753 mV (bp18c6^2–), −610 mV (ppa18c6^–), and −453 mV (bpa18c6) versus Ag/AgCl. These values reveal that the complex of bpa18c6 possesses higher stability against oxidation than the aquated ion, for which an <i>E</i>_1/2 value of −585 mV has been measured