Gallium(III) Catecholate Complexes as Probes for the Kinetics and Mechanism of Inversion and Isomerization of Siderophore Complexes¹

Abstract

The catechol siderophore analog K3[Ga(3)3], 4 (H2 3 = 2,3-dihydroxy-N,N‘-diisopropylterephthalamide), is D 3-symmetric in aqueous solution, and exists in two enantiomeric forms, Δ-4 and Λ-4. Variable temperature NMR experiments demonstrate that the inversion of the enantiomers of 4 in D2O is facile. The rate of inversion is independent of pH above pH 8. The mechanism is intramolecular. From line-shape analysis the free energy of activation ΔG ⧧ 298 = 67.4(9) kJ mol-1 in D2O at pD 12.1, with ΔH ⧧ = 58.5(6) kJ mol-1 and ΔS ⧧ = −0.030(9) kJ mol-1 K-1. Below pD 8 the rate of inversion for 4 is pD dependent and initially first order in [D+]. Potentiometric titrations reveal that 4 protonates in two one-proton steps with log K HML 3 = 4.66(4) and log K H 2 ML 3 = 3.99(7). In DMSO-d 6, formation of a tight contact ion pair between K+ and [Ga(3)3]3- ions increases the free energy barrier to inversion by ∼7 kJ mol-1. The complex K3[Ga(9)3], 10 (H2 9 = 2,3-dihydroxy-N-tert-butyl-N‘-benzylterephthalamide), was prepared to elucidate the mechanism of inversion by dynamic NMR spectroscopy, using the fact that 10 exists in two isomeric forms, cis-10 and trans-10, which are of C 3 and C 1 symmetry in solution. The ratio cis-10:trans-10 is 0.78(3) at ambient temperature in D2O or DMSO-d 6. Two processes are distinguishable on the NMR time scale in D2O or DMSO-d 6, cis- 10−trans- 10 isomerization and the inversion of the enantiomers of trans-10. Both processes proceed intramolecularly with T c = 295(1) K for Λ-trans-10 to Δ-trans-10 inversion and T c = 335(1) K for cis-10 to trans-10 isomerization in D2O at pD 9.5. The discrete exchange pattern of the tert-butyl resonances during inversion of trans-10 confirms that the reaction proceeds by a trigonal twist mechanism via a trigonal prismatic transition state. The free energy barriers to inversion are ΔG ⧧ 295 = 60 kJ mol-1 in D2O (pD 9.8) and ΔG ⧧ 327 = 67 kJ mol-1 in DMSO-d 6.

Supramolecular assembly dynamics

“…18). A mononuclear tris-catecholato complex (ML 3 ) racemizes rapidly in basic solution by way of a trigonal twist mechanism (19). When two tris-catecholate complexes are linked in a helicate, the racemization of the M 2 L 3 structure (from ⌬⌬ to ⌳⌳) slows by a factor of 100, demonstrating the mechanical coupling between the two metal centers (20).…”

“…Tris-catecholate structures: mononuclear ML3, dinuclear M2L3 helicate, and tetranuclear M4L6 tetrahedron. Racemization (⌬⌬ to ⌳⌳) of the helicate is slowed by the mechanical coupling of the metal centers, whereas the homochiral tetrahedron is inert to racemization (19,20). Scheme 2.…”

Quantitative 2D EXSY and Dynamic19F-NMR Studies of the Dynamic Behaviour of the Bidentate Chelate Complex Ga(fox)3 (fox = 5-fluoro-8-hydroxyquinoline)

“…The ∆H value was 70.6 kJmol -1 , which is of the same order of magnitude as values obtained in dipolar aprotic solvents and reported in the literature. [13] A positive moderate ∆S value (28.1 J K -1 mol -1 ) for the two processes (Bailar and Rây-Dutt) implies more disorder in the transition states than in the initial states. The apparent increase of entropy of 6.5 J K -1 mol -1 is only due to the contribution of the two mechanisms (2.2 ϭ e 6.5 / 8.32 ).…”

“…[13] Previously, we studied a new tripodal iron chelator, OTrensox, based on 8-hydroxyquinoline. [14] Subsquently, we studied, as a model, the coordination chemistry of Ga(III) [the diamagnetic analogue of Fe(III)] with a fluorine-labelled sub-unit, the 5-fluoro-8-hydroxy-quinoline (fox).…”

Potentially Multidentate Tripodal Amine Catechol Ligands as Chelators for Ga(III) and In(III)

“…10 It is worthwhile to mentioned that Fe(III) and Ga(III) showed similar affinity for a variety of ligands. 11,12 That is why, these natural and synthetic chelating agents of Fe(III) are also implemented as chelators for Ga(III) because of their common preference towards the hard donor atoms, such as oxygen and similar coordination behaviors. 13,14 Again, since the aqueous coordination chemistry of In(III) is moreover similar to Ga(III), the same Fe(III) chelators can also be applied for the development of In(III) sequestration with respect to their use as imaging agents.…”