Aluminum and gallium compounds of 3-hydroxy-4-pyridinones: synthesis, characterization, and crystallography of biologically active complexes with unusual hydrogen bonding

Abstract

A series of tris(3-hydroxy-2-methyl-4-pyridinonato)aluminum(III) and -gallium(III) complexes have been prepared and characterized wherein the pyridinones have a variety of substituents at the ring nitrogen atom (H, CH3, n-C6HH). They have been studied by a number of techniques including variable-pH 27Al NMR, variable-temperature NMR, and single-crystal X-ray diffraction. The complexes M(C7H8N02)3• 12H20 (¿V-methyl) are isostructural for M = Al and Ga, crystallizing in the trigonal space group with the following crystal parameters for Al (Ga): a = 16.600 (2) (16.6549 ( 6)) Á, c = 6.877 (1) (6.8691 (4)) Á, Z = 2. The data were refined by using 1662 (1653) reflections with I > 3 [»(/)] to R and Rw values of 0.045 (0.047) and 0.051 (0.055), respectively. They form rigidly fac geometries with extensive hydrogen bonding to channels of water molecules, and this involves every available O atom in the unit cell. The resulting structure resembles an exclusion complex; hence, we have termed it an exoclathrate. The Al and Ga complexes with N-H and N-CH3 are water soluble with some lipophilicity and exhibit a wide window of stability to hydrolysis. The dominance of hydrogen bonding is demonstrated in the solid-state structures and is also significant to the solution properties in water. Some of these compounds are being employed in biological studies of A1 neurotoxicity and experiments in 67Ga localization.

Synthesis, solution and solid state structure of titanium–maltol complex

“…IA has a C 2 rotation axis. Therefore, in DMSO-d 6 4 ]. After 24 hours the tetrameric species continues increasing while the monomeric species decreases.…”

“…Solid state structure of [Ti 4 (maltolato) 8 (μ-O) 4 ] consist of four Ti(IV) in a pseudo octahedral configuration linked by four oxo ligands. Similar structure but with guaiacolato ligand (a structural isomer of maltol) has been reported, [Ti 4 (guaiacolato) 8 4 ] is non-planar, with alternate bridging oxygens above and below the Ti 4 plane. Since the four Ti coordination spheres and bonding parameters are similar, although not identical, we will discuss only one unit, Ti(1).…”

“…The Ti-O (deprotonated) bonds (Ti-O (5) 4 ] but after 3 hours, the presence of the cis-monomer is evident, reaching a ratio of the tetramer to cis-monomer of 7:1 (tetramer:monomer). This suggests that partial dissociation of the tetramer is taking place.…”

“…This suggests that partial dissociation of the tetramer is taking place. The [Ti 4 (maltolato) 8 4 ] showed an irreversible cathodic wave at a potential of (E red ) −1.36 V, suggesting irreversible reduction of Ti(IV) to Ti(III), while no anodic wave was detected up to the solvent-electrolyte discharge potential. If we compare this potential with previously reported Ti(IV)-maltol and Ti(IV)-guaiacol complexes [29], it resembles to reduction potentials of monomeric species such as Ti(maltolato) 2 4 ] by cyclic voltammetry failed due to the lack of solubility in CH 2 Cl 2 and, in solvents such as DMSO or water no anodic/cathodic waves were detected up to the solvent-electrolyte discharge potential.…”

“…There are numerous metal-maltol complexes used in biomedical application. For instance, iron(III)-maltol complex has been used in the treatment of anemia [2] and tris (maltolato)aluminum complex has been found applications in the Alzheimer disease [3][4][5]. Perhaps the most significant is bis(maltolato)oxovanadium(IV), which has been the subject of many chemical and physiological studies due to its potent insulinomimetic properties [6][7][8].…”