Binuclear Gd³⁺ complex of a 34-membered macrocycle with six carboxymethyl arms: X-ray structures, formation constants, NMR, EPR, and¹H NMR relaxivities

A 34-membered macrocyclic ligand with six pendant carboxymethyl groups has been synthesized by the coupling of two diethylenetriaminepentaacetate (dtpa) and two 1,4-diaminobutane units: the macrocycle is 2,12,19,29-tetraoxo-1,4,7,10,13,18,21,24,27,30-decaaza-4,7,10,21,24,27- cyclotetratriacontanehexaacetic acid, abbreviated as (34dtpabn)H₆. The macrocycle was crystallized as the acetone adduct (34dtpabn)H₆·2Me₂CO in the monoclinic space group P2₁/n with a = 14.566(2) ̊, b = 10.968(1) ̊, c = 16.133(2) ̊, β= 105.62(1)° , and Z = 2. The acetone molecules have close contacts with some carbon atoms of the macrocycle. The protonation constants determined by potentiometric titration (0.1 M KCl, 25 °C) were log K₁ = 9.70 (standard deviation = 0.01), log K₂ = 9.18 (0.05), log K₃ = 5.27 (0.02), log K₄ = 4.50 (0.03), log K₅ = 3.84 (0.01), and log K₆ = 3.23 (0.01). The corresponding protonation sites were identified by the pD dependence of ¹H NMR shifts; the central amino nitrogen of each dtpa moiety has the highest basicity. The binuclear Gd³⁺ complex of the macrocycle was crystallized as the 2-propanol adduct [Gd₂(34dtpabn)(H₂O) ₂]·2PrOH·7H₂O in the triclinic space group P1̄ with a = 11.880(1) ̊, b = 15.036(1) ̊, c = 17.396(1) ̊, α = 94.986(5)°, β= 103.340(5)°, γ = 98.286(5)°, and Z = 2. Each ligand molecule coordinates two Gd³⁺ ions forming a binuclear metal chelate with the Gd-Gd distance 10.8928(7) A. The coordination geometry around each metal ion is a tricapped trigonal prism consisting of three carboxylate oxygens, two amide oxygens, three amino nitrogens, and a water oxygen. Propanol molecules are located near the macrocyclic cavity with some close C-C contacts shorter than the sum of the van der Waals radii of methyl and methylene groups. The logarithmic overall formation constants, log β(Gd_pLH_r), were determined by potentiometry (0.1 M KCl, 25 °C): for GdLH₄, 35.85 (estimated uncertainty = 0.21); GdLH₃, 33.89 (0.36); GdLH₂, 30.27 (0.07); GdLH, 25.59 (0.04); GdL, 16.46 (0.04); GdLH_-1, 4.93 (0.19); Gd₂L, 30.36 (0.33). Dipolar interaction operative between the two Gd³⁺ ions in the binuclear complex collapses the hyperfine structure in the EPR spectrum. The ¹H NMR relaxivities are enhanced as a result of the binuclear complex formation.