Gallium(III) catecholate complexes as probes for the kinetics and mechanism of inversion and isomerization of siderophore complexes

The catechol siderophore analog K-3[Ca(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, Delta-4 and Lambda-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 Delta G(298)(not equal) = 67.4(9) kJ mol(-1) in D2O at pD 12.1, with Delta H-not equal = 58.5(6) kJ mol(-1) and Delta S-not equal = -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-HML3 = 4.66(4) and log K-H2ML3 = 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 similar to 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 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 Lambda-trans-10 to Delta-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 Delta G(295)(not equal) = 60 kJ mol(-1) in D2O (pD 9.8) and Delta G(327)(not equal) = 67 kJ mol(-1) in DMSO-d(6).