COORDINATION CHEMISTRY OF MICROBIAL IRON TRANSPORT .42. STRUCTURAL AND SPECTROSCOPIC CHARACTERIZATION OF DIASTEREOMERIC CR(III) AND CO(III) COMPLEXES OF DESFERRIFERRITHIOCIN

Desferriferrithiocin, DFFTH2 (1), is a novel siderophore produced by Streptomyces antibioticus and acts as a mediator for iron uptake in this organism. It contains neither catecholate nor hydroxamate functional groups and is tridentate, via a central nitrogen, a phenolate oxygen, and a carboxylate oxygen. It is known to form 2 to 1 complexes with ferric ion. There are potentially several geometric isomers for the ML2 complex. In order to prepare kinetically stable complexes of this chiral ligand, Fe3+ has been replaced by Cr3+ and Co3+. There are two diastereomeric Co3+ complexes that form from Na3[CO(CO3)3] and DFFTH2 in aqueous solution. These have been separated by chromatographic (HPLC) techniques and characterized by electrophoresis, FAB mass spectra, NMR spectra, and VIS/UV and CD spectra. Reaction of the siderophore ligand with CrCl3-3THF in dry acetone in the presence of excess triethylamine gives a mixture of two diastereomeric chromium complexes, [Et3NH] [Cr(DFFT)2], in 70% yield. These diastereomers have been separated by HPLC and characterized by microanalysis, FAB mass spectroscopy, VIS/UV and CD spectroscopy, and single-crystal X-ray diffraction. The structure analyses have established that the complexes are meridional isomers that differ in their chirality at the metal center. The first isomer, A (produced in relative abundance of 62.5%), is a greenish-brown solid whose color in solution varies greatly with the solvent. According to the IUPAC convention, this isomer has a (or A) absolute configuration. When isolated from acetonitrile/water solutions as the tetramethylammonium salt of A, the compound [(CH3)4N][Cr(DFFT)2]•0.5H2O (2) crystallizes in the orthorhombic space group P212121 with a = 10.592 Å, b = 18.702 (7) Å, c = 27.407 (5) Å, V = 5429 (4) Å3 4, and Z = 8; the two metal complexes in the asymmetric unit are essentially identical. The absolute configuration of the ligand is confirmed to be 5. The second isomer, with a Δ(or C) absolute configuration (isolated in relative abundance of 37.5%), crystallizes from methanol/2-propanol as the potassium salt K[Cr(DFFT)2]•2C3H8O (3). Crystals of this salt conform to space group P21 with a = 9.643 (2) Å, b= 13.913(3) Å, c = 12.350 (4) Å, β = 112.14(2)°, V= 1536.6 (13) Å3, and Z = 2. The structure of 2 was determined from 12 422 unique data (h, k ± 1) measured at -105 °C. Refinement of 694 variables against 10587 observed data gave R = 3.7%, Rw = 4.8, and GOF = 1.97. The structure of 3 was determined from 3655 unique data (±, A ± 1) measured at -105 °C. Refinement of 378 variables against 2126 observed data gave R = 3.2%, Rw = 3.4%, and GOF = 1.08. Although isomers A and C have metal coordination geometries that are essentially mirror images, the chirality of the ligand makes these diastereomers rather than enantiomers. The solid-state structures of these isomers are discussed in relation to their CD spectra, which are novel in being essentially the same for the low-energy T2g manifold while mirror image for the T1g manifold. [The same spectral features are apparent for the Co3+ complexes.] The CD spectra are qualitatively explained on the basis of these electronic transitions for an octahedral complex; the two isomers both have a distorted octahedral geometry that is approximately D2d in symmetry. The further perturbation of this ligand field involves an S4 symmetry distortion which affects, T1 and T2 symmetries differently and can be used as a simple rationale for the unusual relationship of the spectra. © 1990, American Chemical Society. All rights reserved.