Binuclear Gd³⁺ Complex of a 34-Membered Macrocycle with Six Carboxymethyl Arms: X-ray Structures, Formation Constants, NMR, EPR, and ¹H NMR Relaxivities

Abstract

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) Å, b = 10.968(1) Å, c = 16.133(2) Å, 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) Å, b = 15.036(1) Å, c = 17.396(1) Å, 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) Å. 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(GdpLHr), 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.