Biologically relevant metal complexes with mixed O, S donor ligands

Thio analogues of two 3-hydroxy-4-pyrones (Hma, Hema) and two 3-hydroxy-4- pyridinones (Hmpp, Hdpp) have been synthesized as a new class of ligand precursors. Reacting 3-hydroxy-4-pyrones with P₂ S₅ led to the formation of the respective 3- hydroxy-4-pyranthiones (Htma, Hetma) in reasonable yields. One of these pyranthiones, thiomaltol (Htma), was further reacted with aqueous NH₄OH and MeNH₂ to yield 3- hydroxy-4-pyridinethiones, Hmppt and Hdppt, respectively. During the synthesis of the 3-hydroxy-4-pyridinethiones, their dimeric forms Hmppt-dimer and Hdppt-dimer were also isolated and characterized. Solution studies of the monomeric compounds established that these thio compounds have lower pKa values than the corresponding oxygen analogues, as expected. X-ray crystallographic analyses of Htma and Hetma confirmed that only the carbonyl oxygen (C=0) had been substituted with a sulfur atom and C=S bond lengths in the resulting molecules are longer than the C=0 bond lengths in their synthetic precursors. X-ray crystallographic analysis of Hdppt-dimer demonstrated the presence of a disulfide bond in the dimeric organic compounds. The four monomeric ligand precursors were complexed with vanadium to yield eight complexes: four oxovanadium(IV) and four vanadium(III) complexes. Solution studies (potentiometric and spectrophotometric) of the four oxovanadium(IV) compounds indicated the formation of reasonably stable complexes with (VO)L₂ and (VO)L₂(OH) as the dominant species at physiological pH. X-ray crystallographic analysis demonstrated the presence of cis and trans isomers of VO(tma)₂. For both isomers, the two ligands are in the equatorial plane with the V=0 bond perpendicular to the ligands, forming a square pyramidal structure. Reaction of the four monomeric ligand precursors with Ga³⁺and In³⁺ ions yielded new tris(bidentate ligand) complexes. X-ray quality crystals of the/ac-isomer of Ga(tma)₃ were also obtained; two of the ligated S atoms were found in a cis configuration with respect to each other with the third sulfur atom and one of the oxygen atoms occupying the perpendicular axis. New complexes with a range of lanthanides (Ln³⁺) were also synthesized with the two pyranthiones, Htma and Hetma. The synthesis reactions yielded complexes of the type LnL₃•xH₂0 and LnL₂(OH) •xH₂0, supported by elemental analysis and spectroscopic evidence such as mass spectral data and IR and NMR spectra.Science, Faculty ofChemistry, Department ofGraduat

Hypaphorine Is Present in Human Milk in Association with Consumption of Legumes

In metabolomic analysis of human milk amines, we found a previously unidentified compound. This was tentatively identified as hypaphorine, an indole alkaloid composed of tryptophan and three methyls, and with neurological and glucose-lowering effects in rodents. Hypaphorine identity was confirmed by hypaphorine synthesis, and then a fluorometric method was developed to quantify hypaphorine in milk and foods. Using dietary records, we identified peanut products as probable sources of hypaphorine. Milk from 24 lactating women showed widely varying hypaphorine, with a mean ± SD 0.34 ± 0.33 μM, and the highest concentration of 1.24 μM. Peanuts showed high hypaphorine of 70 μg/g compared to 60 and 100 μg/g in dried chickpeas and lentils. Dietary challenge in lactating women with hypaphorine-rich foods demonstrated transfer of hypaphorine into milk with hypaphorine appearance peaking 5–18 h after consumption and prolonged disappearance indicative of slow excretion or metabolism. The potential functional roles of hypaphorine in human nutrition remain to be addressed