Photodecarboxylation of the Siderophore Aerobactin with the Lewis Acidic Metal Ions Fe(III), Ga(III), and Ti(IV)

The class of α-hydroxy carboxylic acid-containing ferric siderophore natural products undergo photochemical modification by decarboxylation. To date, there is only limited mechanistic understanding of the metal-ion-mediated photodegradation of photoactive siderophores. This study investigates the photoreactivity of the α-hydroxy carboxylic acid-containing siderophore aerobactin (AB) and the corresponding Ga3+ and Ti4+ metal complexes in direct comparison with their Fe3+-bound counterpart. Using UV-vis and nuclear magnetic resonance (NMR) spectroscopy, complemented by time-dependent density functional theory (TD-DFT) calculations, we demonstrate that ligand-to-metal charge transfer (LMCT)-driven photocleavage of aerobactin-metal complexes is feasible beyond Fe3+. We show that photoirradiation at shorter wavelengths of [Ga(AB)]3- and [Ti(AB)]2- results in decarboxylative photocleavage at two distinct sites. While [Fe(AB)]3- exhibits distinct reactivity upon photoexcitation from 254 to 575 nm, producing C-C bond cleavage to release CO2 and form the corresponding tautomer, the analogous [Ti(AB)]2- complex can be selectively exited. Lower energy excitation of [Ti(AB)]2- within the LMCT band centered at 295 nm induces decarboxylation in direct homology with the parent ferric complex, whereas secondary decarboxylation of the lysine carboxylate is observed using short wavelength irradiation of [Ga(AB)]3- and [Ti(AB)]2-. These experimental results, supported by TD-DFT findings, reveal that the coordinating hydroxamate groups, rather than the α-hydroxy carboxylate, are the source of efficient LMCT excitation and radical formation, challenging previous assumptions about aerobactin's photochemical decarboxylation mechanism. We provide a mechanistic framework for siderophore-mediated photochemistry and highlight its applicability to xenometal ions.