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

The catechol siderophore analog K 3 [Ga( 3 ) 3 ], 4 (H 2 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 D 2 O 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 Δ G ⧧ 298 = 67.4(9) kJ mol - 1 in D 2 O at pD 12.1, with Δ H ⧧ = 58.5(6) kJ mol - 1 and Δ S ⧧ = −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 K 3 [Ga( 9 ) 3 ], 10 (H 2 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 D 2 O or DMSO -d 6 . Two processes are distinguishable on the NMR time scale in D 2 O 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 D 2 O 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 Δ G ⧧ 295 = 60 kJ mol - 1 in D 2 O (pD 9.8) and Δ G ⧧ 327 = 67 kJ mol - 1 in DMSO -d 6 .