Spectroscopic studies on the interaction of bilirubin with symmetrical alkyl diamines

The interactions of symmetrical alkyldiamines with bilirubin-IX α have been examined in dichloromethane and dioxane solutions, by visible region difference spectroscopy and florescence methods. In dioxane solutions a clear difference is observed between the complexes of the shorter chain diamines (number of spacer methylene groups (n ≤ 4) ) and the longer chain diamines (n ≥ 6) . The variations in spectral features with diamine chain length are less pronounced in dichloromethane. The spectroscopic results are consistent with the occurrence of distinct bilirubin conformations depending upon the solvent and the geometry of the interacting receptor. Based on molecular modelling two conformations are proposed. A 'ridge-tile' model similar to that observed in crystals is favoured for binding to the longer diamines, while a 'quasi-cyclic' structure is preferred for interaction with the short chain diamines

17β-estradiol protects male mice from cuprizone-induced demyelination and oligodendrocyte loss

In addition to regulating reproductive functions in the brain and periphery, estrogen has trophic and neuroprotective functions in the central nervous system (CNS). Estrogen administration has been demonstrated to provide protection in several animal models of CNS disorders, including stroke, brain injury, epilepsy, Parkinson’s disease, Alzheimer’s disease, age-related cognitive decline and multiple sclerosis. Here, we use a model of toxin-induced oligodendrocyte death which results in demyelination, reactive gliosis, recruitment of oligodendrocyte precursor cells and subsequent remyelination to study the potential benefit of 17β-estradiol (E2) administration in male mice. The results indicate that E2 partially ameliorates loss of oligodendrocytes and demyelination in the corpus callosum. This protection is accompanied by a delay in microglia accumulation as well as reduced mRNA expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα), and insulin-like growth factor-1 (IGF-1). E2 did not significantly alter the accumulation of astrocytes or oligodendrocyte precursor cells, or remyelination. These data obtained from a toxin-induced, T cell-independent model using male mice provide an expanded view of the beneficial effects of estrogen on oligodendrocyte and myelin preservation

Solubilization of bilirubin by cholate micelles. Spectroscopic and gel permeation studies

The interactions of bilirubin with bile salts were studied by fluorescence, CD, and 1H NMR methods. Enhancement of bilirubin fluorescence and induction of optical activity in bilirubin in the presence of cholate has been obsd. Fluorescence enhancement is pronounced above the crit. micelle concn., whereas induced CD bands are detectable even in the premicellar region. Dehydrocholate and deoxycholate did not increase fluorescence, but did induce CD bands for bilirubin. Gel-permeation chromatog. on Sephadex G-50 yielded a single bilirubin-cholate species at alk. pH, whereas 2 species were obtained at neutral pH. 1H NMR and CD spectral characterizations of these complexes are reported. A 4:1 cholate-bilirubin mixt. was analyzed by difference NOE spectroscopy. Observation of strong, neg. NOE, both intermol. and intramol., suggests that specific Me groups on bilirubin and cholate are proximal in the mixed micelle

Solubilization of bilirubin by cholate micelles. Spectroscopic and gel permeation studies

The interactions of bilirubin with bile salts have been studied using fluorescence, circular dichroism and<SUP>1</SUP>H NMR methods. Enhancement of bilirubin fluorescence and induction of optical activity in bilirubin in the presence of cholate has been observed. Fluorescence enhancement is pronounced above the critical micelle concentration, while induced CD bands are detectable even in the premicellar region. Dehydrocholate and deoxycholate did not cause a fluorescence increase, but induced CD bands were observed for bilirubin in these cases. Gel permeation chromatography on Sephadex G-50 yielded a single bilirubin-cholate species at alkaline pH, while two species were obtained at neutral pH.<SUP>1</SUP>H NMR and CD spectral characterizations of these complexes are reported. A 4&#166;1 cholate-bilirubin mixture has been analysed by difference (nuclear Overhauser effect) NOE spectroscopy. Observation of strong, negative NOE, both intermolecular and intramolecular leads to the conclusion that specific methyl groups on bilirubin and cholate are proximal in the mixed micelle

Spectroscopic studies on the interaction of bilirubin with symmetrical alkyl diamines

The interactions of symmetrical alkyldiamines with bilirubin-IX $\alpha$ have been examined in dichloromethane and dioxane solutions, by visible region difference spectroscopy and florescence methods. In dioxane solutions a clear difference is observed between the complexes of the shorter chain diamines (number of spacer methylene groups $(n \leq 4)$ and the longer chain diamines $(n \geq 6)$. The variations in spectral features with diamine chain length are less pronounced in dichloromethane. The spectroscopic results are consistent with the occurrence of distinct bilirubin conformations depending upon the solvent and the geometry of the interacting receptor. Based on molecular modelling two conformations are proposed. A 'ridge-tile' model similar to that observed in crystals is favoured for binding to the longer diamines, while a 'quasi-cyclic' structure is preferred for interaction with the short chain diamines

A proton-NMR study of bilirubin IX\alpha solubilization by cholate micelles: application of nuclear Overhauser effects.

The solubilization of bilirubin IX\alpha (I) in aq. soln. by Na cholate micelles was examd. by 270-MHz 1H NMR spectroscopy. The incorporation of I into the micelles was accompanied by specific shifts of I vinyl and bridgehead protons and the C18 and C19 Me groups of the steroid. The obsd. chem. shifts showed a monotonic concn. dependence suggesting that changes in aggregation size are continuous. Nuclear Overhauser effects (NOE) were shown to be a useful probe or micellization. A 4:1 cholate (II)/I mixt. was investigated by difference NOE spectroscopy. The observation of intermol. NOE between peripheral protons of I and II were diagnostic of spatially proximate groups. Inter-II NOE increased in magnitude upon I incorporation, suggesting closer packing of steroid mols. on solubilization of the pigment. Intramol. NOE obsd. for solubilized I were consistent with a compact intramolecularly H-bonded conformation