Expanding the Family of Pyclen-Based Ligands Bearing Pendant

Mar 7, 2018 - Tb3+, Ho3+, Lu3+) also present radio-emissive isotopes and are then also prized in nuclear medicine for the development of diagnostic an...
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Article Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX

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Expanding the Family of Pyclen-Based Ligands Bearing Pendant Picolinate Arms for Lanthanide Complexation Mariane Le Fur,† Enikő Molnár,‡ Maryline Beyler,† Olivier Fougère,§ David Esteban-Gómez,⊥ Olivier Rousseaux,§ Raphael̈ Tripier,*,† Gyula Tircsó,*,‡ and Carlos Platas-Iglesias*,⊥ †

Université de Bretagne Occidentale, UMR-CNRS 6521, IBSAM, UFR des Sciences et Techniques, 6 avenue Victor le Gorgeu, C.S. 93837, 29238 Brest Cedex 3, France ‡ Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary § Groupe Guerbet, Centre de Recherche d’Aulnay-sous-Bois, BP 57400, 95943 Roissy CdG Cedex, France ⊥ Departamento de Química, Facultade de Ciencias & Centro de Investigaciones Científicas Avanzadas (CICA), Universidade da Coruña, 15071 A Coruña, Spain S Supporting Information *

ABSTRACT: We report a detailed characterization of lanthanide complexes with two azaligands based on the pyclen macrocycle containing two picolinate and one acetate pendant arms. The two picolinate arms are attached to either opposite (L3) or adjacent (L4) amine nitrogen atoms of the macrocyclic platform. The X-ray structures of the Yb3+ complexes show nine coordination of the ligand to the metal ion, a situation that is also observed for EuL4 in the solid state. The EuL3 complex forms centrosymmetric dimers in the solid state joined by μ2-η1:η1 carboxylate groups, which results in 10-coordinate Eu3+ ions. The emission spectra of EuL3 measured in H2O and D2O solution reveal the presence of a hydration equilibrium involving a nine-coordinate species lacking inner-sphere water molecules and a monohydrated 10-coordinate species. The Eu3+ complexes present modest emission quantum yields in buffered aqueous solution (Φ = 16 and 22% for EuL3 and EuL4, 0.1 M tris buffer, pH 7.4), while the corresponding Tb3+ complexes present very high emission quantum yields under the same conditions (∼90%). 1H NMR studies show that the complexes of L3 present a fluxional behavior in D2O solution, while those of L4 are more rigid. The analysis of the Yb3+-induced NMR shifts of YbL4 indicates that the complex presents a structure in solution similar to that observed in the solid state. The Gd3+ complexes present very high thermodynamic stability constants (log KGdL = 23.56(2) and 23.44(2) for GdL3 and GdL4, respectively). The corresponding pGd values (pGd = −log[Gd3+]free with cL = 1 × 10−5 M and cGd = 1 × 10−6 at pH 7.4) of 20.69 (GdL3) and 21.83 (GdL4) are higher than that of Gd(dota)− (pGd = 19.21). The Gd3+ complexes also show remarkable inertness with respect to their proton-assisted dissociation, with dissociation half-life times of 50 min (GdL3) and 20 h (GdL4) in 1 M HCl.

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and magnetic (Gd3+, Dy3+)7,8 properties. Some of them (i.e., Tb3+, Ho3+, Lu3+) also present radio-emissive isotopes and are then also prized in nuclear medicine for the development of diagnostic and therapeutic radiopharmaceuticals.9 Besides, metal ions such as Ac3+ and Y3+ present a coordination chemistry very similar to that of the Ln3+ ions and a great potential for radiopharmaceutical applications.10,11 Thus, it is easy to understand that the development of highly stable and inert Ln3+ chelates constitutes an important chemical challenge. Polyazamacrocycles show particularly high affinity for the lanthanides, when functionalized with carboxylic functions to complete (at least partially) the coordination sphere of the

INTRODUCTION Saturated azamacrocycles such as cyclam (1,4,8,11-tetraazacyclotetradecane),1 cyclen (1,4,7,10-tetraazacyclododecane),2 and tacn (1,4,7-triazacyclononane)3 are a class of ligands that, upon convenient functionalization, form very efficient complexes with a broad range of cationic metals, both in terms of thermodynamic stability and kinetic inertness.4 Complexes based on these ligand scaffolds are of great interest for numerous medical applications in diagnosis and therapy, where the metal center needs to be strongly complexed to avoid its release in vivo, a process that may be assisted by endogenous ligands and cations.5 Complexes of the trivalent lanthanide ions (Ln3+) are receiving great attention due to their important applications related to their optical (Eu3+, Tb3+, Yb3+, Sm3+, Er3+, Dy3+...)6 © XXXX American Chemical Society

Received: March 7, 2018

A

DOI: 10.1021/acs.inorgchem.8b00598 Inorg. Chem. XXXX, XXX, XXX−XXX

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Inorganic Chemistry metal center. Numerous chelators based on tacn,12,13 cyclen,14 and even cyclam,15 which was believed to be less suited for complexation of large metal ions, have been developed to form stable and/or inert lanthanide complexes for medical and bioanalytical applications.16 Among them, dota (Chart 1) is probably the most versatile ligand, as it is able to form stable complexes with a wide range of metal ions.17

a fourth N-functionalization. Despite this, pyclen ligands functionalized with three pendant arms, such as pcta and related chelators, form rather stable complexes with metal ions such as the lanthanides, both in terms of thermodynamic stability and dissociation kinetics.20 Pcta (or closely related derivatives) offers some advantages when compared with dota and dota-like analogues. First, the absence of one acetate arm leads to heptacoordinated Ln3+ complexes, allowing the access of two water molecules to the metal center.21 As a result, Gd3+ complexes of pcta and its derivatives show relaxivities that are considerably higher than that of Gd(dota) −. 22 It also forms charge-neutral Ln3+ complexes, which allows preparing lipophilic derivatives for selective targeting of cancer, altering biodistribution properties,23−25 or targeting amyloid aggregates.26 Pcta derivatives were found to present advantageous metal ion complexation kinetics for the design of radiopharmaceuticals.27 Finally, the presence of the aromatic moiety allows the indirect sensitization of Eu3+ or Tb3+ taking advantage of the antenna effect,28 which can be exploited for photophysical studies. In this case, the coordination sphere of the metal ions should be saturated by the ligand donor atoms to prevent the coordination of water molecules, thereby preventing the quenching of the Ln3+ excited state through O−H vibrational deactivation.29 Furthermore, the pyridyl unit could be easily functionalized to allow the conjugation of the ligand to an external moiety (i.e., a biovector), to increase lipophilicity of the ligand,30 or to shift the excitation wavelength to the visible region.31 The adequate selection of the N-appended functions of pyclen represents a straightforward strategy to modulate the properties of the corresponding Ln3+ complexes. In this context, we recently reported the synthesis of four pyclen based ligands, L1, L2, L3, and L4, presenting a combination of acetate and picolinate arms in a 2:1 or 1:2 ratio, and arranged in a symmetrical or a dissymmetrical manner (Chart 1).32,33 We proved that the dissymmetric arrangement in both ratios leads to an increase of the thermodynamic stability and kinetic inertness of complexes with yttrium(III).32,33 We also showed that the GdL2 complex presents higher thermodynamic stability, slower dissociation kinetics, and faster water exchange of the coordinated water molecule than GdL1.34 Thus, it is clear that the different arrangement of the pendant arms in this family of ligands has a profound impact in the properties of the corresponding metal complexes.

Chart 1. Ligands Discussed in This Study

Another important azamacrocyclic framework, so far less investigated, is pyclen (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene), which incorporates an aromatic pyridine moiety to the 12-membered macrocyclic unit.18 This offers a more rigid structure that may impose unusual coordination environments or provide unusual redox behavior.19 However, the sp2 character of the aromatic nitrogen atom implies the unavailability of a donor atom of the macrocycle for

Figure 1. View of the crystal structure of YbL3 (left) and the coordination polyhedron around the metal ion (right) with atom labeling; hydrogen atoms and water molecules are omitted for clarity. The ORTEP plot is at the 30% probability level. B

DOI: 10.1021/acs.inorgchem.8b00598 Inorg. Chem. XXXX, XXX, XXX−XXX

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Figure 2. View of the crystal structure of EuL3 (left) and the coordination polyhedron around the metal ion (right) with atom labeling; hydrogen atoms and water molecules are omitted for clarity. The ORTEP plot is at the 30% probability level.

Table 1. Bond Lengths (Å) of the Metal Coordination Environments Obtained from X-ray Diffraction Analysis for Eu3+ and Yb3+ Complexes of L3 and L4a EuL3 Eu1−N1I Eu1−N2I Eu1−N3I Eu1−N4I Eu1−N5I Eu1−N6I Eu1−O1I Eu1−O3I Eu1−O5I Eu1−O6I a

2.856(5) 2.619(5) 2.682(5) 2.711(5) 2.625(5) 2.592(5) 2.452(4) 2.408(4) 2.529(4) 2.433(4)

EuL4 Eu1−N1 Eu1−N2 Eu1−N3 Eu1−N4 Eu1−N5 Eu1−N6 Eu1−O1 Eu1−O3 Eu1−O5

2.640(3) 2.680(3) 2.600(3) 2.598(3) 2.501(3) 2.571(3) 2.363(3) 2.413(3) 2.383(3)

Yb1−N1A Yb1−N2A Yb1−N3A Yb1−N4A Yb1−N5A Yb1−N6A Yb1−O1A Yb1−O3A Yb1−O5A

YbL3

YbL4

2.594(6) 2.629(6) 2.596(6) 2.458(6) 2.459(6) 2.437(6) 2.392(5) 2.304(5) 2.311(4)

2.605(5) 2.515(5) 2.539(5) 2.591(4) 2.452(5) 2.483(5) 2.273(4) 2.304(4) 2.359(4)

See Figures 1 and 2 for labeling.

solution at pH ≈ 5 and isolated with excellent yields (87−99%) after purification using reversed-phase HPLC. The highresolution mass spectra (ESI+ ionization) show peaks due to the [LnHL]+ and [LnH2L]2+ entities (L = L3 or L4) that confirm the formation of the complexes (Figures S1−S10, Supporting Information). X-ray Crystal Structures. Slow evaporation of aqueous solutions of YbL3 and EuL3 provided single crystals suitable for X-ray diffraction analysis. The structures of the two complexes are shown in Figures 1 and 2, while Table 1 presents the bond distances of the coordination spheres of the metal ions. The crystal structure of YbL3 is very similar to that reported in our previous work for the yttrium analogue.33 The metal ion is directly coordinated to the six nitrogen atoms of the ligand and to three oxygen atoms of the carboxylate groups, providing a coordination polyhedron that can be best described as a muffin, an irregular 1:5:3 polyhedron containing five vertexes related by a 5-fold pseudosymmetry axis, three vertexes related by a 2-fold pseudosymmetry axis, and the remaining vertex sitting on the 5-fold axis (Figure 1).37 Crystals of EuL3 contain centrosymmetric dimers joined by μ2-η1: η1 carboxylate groups,38 which results in 10-coordinated Eu3+ ions. Similar bridging carboxylate groups were observed previously for

Given the potentially nonadentate nature of ligands L3 and L4, and the results obtained for their Y3+ complexes, we hypothesized that these ligands should present interesting complexation properties for the Ln3+ ions. Furthermore, picolinate groups are known to provide a rather efficient sensitization of the emission of Eu3+ and especially Tb3+, which emit in the visible region of the spectrum.21,35,36 Thus, in this paper we present the fourth chapter on Y3+ and/or Ln3+ complexes with this series of ligands that combine three main elements: pyclen, picolinate, and acetate arms. We report a detailed investigation of the structures of the Ln3+ complexes of L3 and L4 in the solid state and in solution. The photophysical properties of the Eu3+, Tb3+, and Yb3+ complexes were also investigated, and the thermodynamic stabilities of the Gd3+ complexes were determined. Finally, kinetic experiments were undertaken to assess the kinetic inertness of the complexes with respect to their acid-catalyzed dissociation.

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RESULTS AND DISCUSSION Synthesis. The synthesis of ligands L3 and L4 was reported in a recent paper.33 The corresponding LnL3 and LnL4 complexes (Ln3+ = Eu3+, Gd3+, Tb3+, Yb3+, or Lu3+) were prepared by reaction of the ligand with LnCl3·6H2O in aqueous C

DOI: 10.1021/acs.inorgchem.8b00598 Inorg. Chem. XXXX, XXX, XXX−XXX

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Figure 3. View of the crystal structures of EuL4 and YbL4 (top) and the corresponding coordination polyhedra around the metal ions (bottom) with atom labeling; hydrogen atoms and water molecules are omitted for clarity. The ORTEP plot is at the 30% probability level.

Table 2. Spectroscopic Properties of the Eu3+ and Tb3+ Complexes of Ligands L1−L4 τH2O/ms EuL1 EuL2 EuL3 EuL4 TbL1 TbL2 TbL3 TbL4

e

0.58 0.66e 0.98 1.52 1.71 1.68 2.48 2.40

τD2O/ms e

2.25 2.11e 2.12 2.07 3.15 2.59 2.79 2.54

Δkobs/ms−1a

qb

e

e

1.28 1.04e 0.55 0.17 0.27 0.21 0.04 0.02

1.2 0.9e 0.4 −0.1 1.04 0.8 −0.1 −0.2

Φ/%c

ΦEu/%d

ηsens/%

τR/ms

6 6 16 22 53 22 90 90

12 16 23 38

49 38 69 58

4.8 4.2 4.2 4.0

a Δkobs = kobs(H2O) - kobs(D2O), kobs = 1/τobs. bqEu = 1.2(Δkobs-0.25); qTb = 5.0(Δkobs-0.06). cEmission quantum yields determined at pH 7.4 (0.1 M tris buffer). dMetal centered luminescence quantum yield. eData from ref 34.

lanthanide complexes of do3a derivatives (Figure 2).39 The coordination polyhedron around the Eu3+ ions can be described as a bicapped square antiprism. The upper square face of the polyhedron is defined by O1I, O3I, O5I, and N3I (mean deviation from planarity 0.09 Å), while the lower plane is delineated by N2I, N4I, N5I, and O6I (mean deviation from planarity 0.10 Å). The two least-squares planes defined by the two square faces intersect at 4.5°. The mean twist angle of the upper and lower square faces amounts to 39.5 ± 5.7°, a value that is close to that expected for a square antiprism (45°). Donor atoms N6I and N1I are capping the upper and lower planes, respectively, defining a N6I−Eu1−N1I angle of 171.25(15)°. The structures of EuL4 and YbL4 (Figure 3) are similar to those reported recently for YL4.33 The ligand binds to the metal ions through the expected nine donor atoms, resulting in a muffin coordination polyhedron. The bond distances of the metal coordination environments are shorter for the Yb3+ complex compared to the Eu3+ analogue, as would be expected as a consequence of the lanthanide contraction.40 The macrocyclic pyclen units in YbL3, EuL4, and YbL4 adopt the [4242] conformation41 commonly observed for Ln3+ and Y3+ pyclen derivatives,23,24 as well as complexes with

divalent metal ions such as Mn2+ and Zn2+.42 As a result, the four five-membered chelate rings formed by the coordination of the pyclen moiety adopt a (δλδλ) conformation, which is characterized by the presence of a mirror plane that makes pyclen achiral.23 The complexes of Cu2+ with pyclen-based ligands appear to be a singular case, as both the mirror-planesymmetric43 and asymmetric conformations were observed.44 In EuL3, the macrocyclic entity of one of the units of the dimer adopts an unusual (δδδδ) conformation, while the other half of the dimer presents a (λλλλ) conformation imposed by the presence of an inversion center. The bond distances of the Eu3+ coordination environment in EuL3 are generally longer than those of EuL4, as a consequence of the higher coordination number observed for the first. The Eu1−N1I distance in EuL3 is particularly long, reflecting a weak coordination of the concerned amine nitrogen atom. The bond distances involving the donor atoms of the picolinate units in EuL3 and EuL4 are similar to those observed for nine- and 10-coordinate Eu 3+ complexes containing picolinate moieties.45 The individual Eu−N distances involving amine nitrogen atoms fall within a rather broad range (ca. 2.62−2.86 Å for EuL3 and 2.60−2.68 Å for EuL4). D

DOI: 10.1021/acs.inorgchem.8b00598 Inorg. Chem. XXXX, XXX, XXX−XXX

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Inorganic Chemistry Photophysical Properties. The absorption spectra of the Eu3+ and Tb3+ complexes of L3 and L4 present an absorption band with a maximum at ca. 273 nm attributed to π* ← π transitions centered on the pyridyl units.35,36 The molar absorption coefficients of the complexes of L3 and L4 are very similar (∼15000 M−1 cm−1), and ca. 40% higher than those of the L1 and L2 analogues, which reflects the increased number of pyridyl moieties (Table 2). The emission spectra of the EuL1 and EuL2 complexes, as well as the emission lifetimes recorded in H2O and D2O solutions, were reported in a previous paper.34 For the sake of completeness, we also report here a complete set of photophysical data for the Tb3+ complexes of L1 and L2, as well as the emission quantum yields of the Eu3+ complexes with these ligands. The emission spectra of the EuL3 and EuL4 complexes show the characteristic 5D0 → 7FJ transitions, with J = 0−4 (Figure 4).46 The spectra recorded for the two complexes present

emission spectra of complexes presenting hydration equilibria.48 The temperature and pressure dependence of the absorption bands indicated that the component with the longer wavelength corresponds to a species with a lower coordination number. In the spectrum of EuL3 the component at 580.0 nm shows a higher intensity with respect to that at 579.0 nm, which suggests that the speciation in solution is dominated by the species with q = 0, in agreement with the hydration number obtained from luminescence lifetime measurements. Thus, the dinuclear entities observed in the solid state for EuL3 likely break apart in aqueous solution, at least at the concentrations used for luminescence measurements. This is in contrast to some Ln3+ complexes, which were found to form stable aggregates in solution associated with the presence of bridging carboxylate groups.49 The coordination position occupied in the solid state by the oxygen atom of a carboxylate group of a neighboring complex unit is replaced by an inner-sphere water molecule, affording a 10 coordinate monohydrated species in equilibrium with a q = 0 form. The presence of hydration equilibria in solution involving 10-coordinate Eu3+ complexes has been reported previously.50 The overall emission quantum yields (Φ) determined for the EuL3 and EuL4 complexes, 16 and 22%, respectively, are in the upper range of those reported for Eu3+ complexes with ligands containing picolinate units (typically 5−24%).12,35,36 The quantum yields determined for EuL1 and EuL2 (6%) are considerably lower, which is related to the quenching effect caused by the presence of a coordinated water molecule. In order to gain further insight into the photophysical properties of the Eu3+ complexes, we calculated the metal centered emission quantum yields (ΦEu) following the procedure developed by Werts et al.51 This method relies on the strong magnetic dipole nature of the 5D0 → 7F1 transition of Eu3+, so that the intensity of this band can be considered as independent of the chemical environment of the metal center. This allows calculating the radiative lifetime τR of the metal centered emission using the following expression:

Figure 4. Emission spectra of the EuL3 and EuL4 complexes recorded in aqueous solution under excitation through the ligand bands at 272 nm (0.1 M tris buffer, pH 7.4). The inset shows an expansion of the 5 D0 → 7F0 and 5D0 → 7F1 transitions.

I 1 = AMD,0n3 tot τR IMD

different splitting patterns of the ΔJ = 1 and ΔJ = 2 transitions, which indicates that the coordination environments around Eu3+ in the two complexes are significantly different. Furthermore, the spectrum recorded for EuL3 shows two components for the 5D0 → 7F0 transition, which indicates the presence of two emissive Eu3+ species in solution. The emission lifetimes of the excited 5D0 state of Eu3+ in EuL3 could be however perfectly fitted to monoexponential decays, suggesting that the two species present in solution are in fast exchange with respect to the time scale of the luminescence decay rate.47 The luminescence lifetime of the Eu(5Do) excited state of EuL4 is rather long, in agreement with the absence of water molecules coordinated to the metal ion. Indeed, the lifetimes measured for the monoaquated EuL1 and EuL2 complexes are considerably shorter, while the lifetime measured for EuL3 displays an intermediate value (Table 2). This suggests that for EuL3 and equilibrium exists in solution involving a monohydrated species with coordination number 10 and a nine-coordinate nonhydrated (q = 0) species. The number of coordinated water molecules determined from the emission lifetimes recorded in H2O and D2O solutions confirms this hypothesis, providing a hydration number of 0.4. Two components of the 5D0→7F0 transition separated by ∼0.5− 1.0 nm were previously observed in the absorption and

(1)

where AMD,0 = 14.65 s−1 is the spontaneous emission probability of the 5D0 → 7F1 transition, n is the refractive index of the medium (1.333 for water at 589.3 nm), and Itot/ IMD is the ratio of the integrated corrected emission spectra to the area of the magnetic dipole 5D0 → 7F1 transition.51 The τR values obtained fall within the range 4.0−4.8 ms (Table 2). The metal centered quantum yields (ΦEu) were subsequently obtained using eq 2 using the emission lifetimes recorded in aqueous solution τH2O.

ϕEu =

τH2O τR

(2)

We obtained a ΦEu value of 38% for EuL4, while EuL1 and EuL2 present considerably lower values due to the presence of a coordinated water molecule (ΦEu = 12 and 16% respectively) and EuL3 shows an intermediate situation (ΦEu = 23%). The efficiency of the sensitization process can be subsequently obtained from the overall emission quantum yield determined in aqueous solution:

ΦH2O = ηsens × ΦEu E

(3) DOI: 10.1021/acs.inorgchem.8b00598 Inorg. Chem. XXXX, XXX, XXX−XXX

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Inorganic Chemistry The sensitization efficiencies were found to range from 38% for EuL2 to 69% for EuL3. The approach of Werts relies on several assumptions, so that the accuracy of the τR and ΦEu values is not known. Nevertheless, our results suggest modest efficiencies of the energy transfer processes taking place from the excited states of the ligand.35a,d The emission spectra of the Tb3+ complexes recorded upon excitation through the ligand bands (λexc = 272 nm) present the expected 5D4 → 7FJ transitions with J = 6−3, with the overall emission intensity being dominated by the 5D4 → 7F5 transition at ca. 545 nm (Figure 5, see also Figures S13−15, Supporting

Figure 6. Emission spectra of YbL3 and YbL4 recorded in aqueous solution (0.1 M tris buffer, pH 7.4, λexc = 272 nm, c = 4 × 10−5 M).

rather broad paramagnetically shifted signals in the range ∼ −18 to 27 ppm, which reflects the presence of dynamic exchange processes (Figure S16, Supporting Information). This behavior is likely connected to the presence of both nine- and 10-coordinate species in solution showing (δλδλ) and (δδδδ) conformations, respectively (see luminescence measurements above). The interconversion between these species requires inversion of the five-membered chelate rings formed by the coordination of the ethylenediamine moieties of the macrocycle. The 1H NMR spectrum of EuL4 is however wellresolved, showing 27 paramagnetically shifted resonances in the range 19 to −10 ppm (Figure S17, Supporting Information). This indicates a rather rigid structure of the EuL4 complex, which is in contrast to the fluxionality observed for EuL3. An analogous situation is observed when comparing the 1H NMR spectra of the diamagnetic Lu3+ complexes (Figure S18, Supporting Information). The 1H NMR paramagnetic shifts of Eu3+ complexes present significant contributions of both contact (δic) and pseudocontact (δipc) contributions.53 However, the paramagnetic 1H NMR shifts of Yb3+ complexes are dominated by the pseudocontact mechanism, which allows a more straightforward analysis of the structure of the complex in solution.52 Thus, we recorded the 1H NMR spectrum of YbL4, which presents 27 well-resolved signals in the approximate range +71 to −28 ppm (Figure 7). The diamagnetic contribution (δidia) to the paramagnetic shifts (δipara) of YbL4 were estimated by using the 1H chemical shifts of the diamagnetic Y3+ analogue reported earlier.33 The paramagnetic shifts were thus obtained from the observed chemical shifts (δiobs) by using eq 4:

Figure 5. Absorption (dashed line), excitation, and emission spectra of TbL3 recorded in aqueous solution (0.1 M tris buffer, pH 7.4, λexc = 272 nm, λem = 545 nm).

Information). It is also worth noting that the weak 5D4 → 7FJ (J = 2−0) transitions can be also observed at 650, 660, and 675 nm, respectively.6a The excitation spectra recorded upon metal centered emission and the absorption spectra are very similar, which indicates sensitization of the metal ion via ligand-tometal energy transfer. The emission lifetimes recorded in H2O and D2O solutions provide q values of about 1 for the complexes of L1 and L2, which confirms the results obtained for the Eu3+ analogues. In the case of TbL3 and TbL4, we obtained hydration numbers close to zero, indicating the absence of water molecules in the inner coordination spheres of these complexes. The actual q values obtained with the method proposed by Beeby are negative,29 which indicates that the ligands provide a rather efficient shielding of the Tb3+ ions from surrounding water molecules. The emission quantum yields determined for the TbL1 (53%) and TbL2 (22%) complexes are rather high, being similar to those reported for Tb3+ complexes containing the picolinate chromophore (20− 60%).12,35,36 The quantum yields determined for TbL3 and TbL4 are even higher (90%), approaching quantitative values. The YbL3 and YbL4 complexes show sizable emission in the NIR region of the spectrum upon excitation through the ligand bands (Figure 6). The emission pattern observed for the two complexes is characteristic of the 2F5/2 → 2F7/2 transition of Yb3+.6a,52b We notice a rather different intensity of the crystal field components in the two complexes, in line with the different arrangement of the donor atoms around the metal ion. Structure of the Complexes in Solution. The structure of the LnL3 and LnL4 complexes in solution was investigated using 1H and 13C NMR spectroscopies in D2O solutions. The 1 H NMR spectrum of the paramagnetic EuL3 complex shows

δipara = δiobs − δidia = δic + δipc

(4)

δiobs

where are the observed chemical shifts. The pseudocontact shifts can be approximated by using the following expression:54 δipc =

⎛ x 2 − y 2 ⎞⎤ ⎛ 3z 2 − r 2 ⎞ 1 ⎡ 3 ⎢ ⎟⎥ ⎜ Δ χ + Δ χ ⎜ ⎟ 2 rh ⎝ r 2 ⎠⎥⎦ 12πr 3 ⎢⎣ ax ⎝ r 2 ⎠

(5)

where r = x 2 + y 2 + z 2 and x, y, and z are the Cartesian coordinates of a nucleus i with respect to the Ln3+ ion placed at the origin, and Δχax and Δχrh are the axial and rhombic parameters of the symmetric magnetic susceptibility tensor. The paramagnetic shifts of YbL4 were analyzed using eq 5 and the Cartesian coordinates of the 1H nuclei obtained with F

DOI: 10.1021/acs.inorgchem.8b00598 Inorg. Chem. XXXX, XXX, XXX−XXX

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measurements. The relaxivities of both GdL3 and GdL4 increase below pH ≈ 2 as a result of complex dissociation, approaching a value of 13.2 mM−1 s−1 that is characteristic of the aquated ion [Gd(H2O)8]3+ at low pH (Figure 8).57

Figure 7. 1H NMR (300 MHz, 298 K, 30 mM) spectrum of YbL4 recorded in D2O solution and plot of the experimental shifts versus those calculated with the DFT optimized geometry and pseudocontact contributions. The solid line represents a perfect fit between experimental and calculated values. Figure 8. Proton relaxivities (r1p) of GdL3, GdL4, and Gd(pcta)34 as a function of pH and species distributions obtained from the analysis of the relaxivity data (25 °C, 0.15 M NaCl).

density functional theory (DFT) calculations (see computational details below). The DFT structure is very similar to that obtained with X-ray measurements. However, we preferred using the DFT data because the positions of ligand proton nuclei cannot be accurately located with X-ray analysis. The assignment of the 1H NMR signals was aided by 1H−1H COSY experiments and line width analysis.55 The COSY spectrum (Figure S49, Supporting Information) provided cross-peaks relating the geminal CH2 protons of the ligand and the protons of the pyridyl units. Linewidth analysis provided a straightforward assignment of the broader axial and sharper equatorial signals.55 The least-squares fit of the paramagnetic shifts followed the methodology described earlier, providing the Δχax and Δχrh values and a set of Euler angles that define the rotation of coordinates in the arbitrary reference frame used as input to the magnetic susceptibility frame.52 The calculated 1H NMR chemical shifts obtained with this analysis present an excellent agreement with the observed shifts (Figure 7), with deviations