Bioavailable Trace Metals in Neurological Diseases

Medical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron

Chelators in Iron and Copper Toxicity

Purpose of Review Chelation therapy is used for diseases causing an imbalance of iron levels (for example haemochromatosis and thalassaemia) or copper levels (for example Menkes’ and Wilson’s diseases). Currently, most pharmaceutical chelators are relatively simple but often have side effects. Some have been taken off the market. This review attempts to find theory and knowledge required to design or find better chelators. Recent Findings Recent research attempting to understand the biological mechanisms of protection against iron and copper toxicity is reviewed. Understanding of molecular mechanisms behind normal iron/copper regulation may lead to the design of more sophisticated chelators. The theory of metal ion toxicity explains why some chelators, such as EDTA, which chelate metal ions in a way which exposes the ion to the surrounding environment are shown to be unsuitable except as a means of killing cancer cells. The Lewis theory of acids and bases suggests which amino acids favour the attachment of the hard/intermediate ions Fe2+, Fe3+, Cu2+ and soft ion Cu+. Non-polar amino acids will chelate the ion in a position not in contact with the surrounding cellular environment. The conclusion is that only the soft ion binding cysteine and methionine appear as suitable chelators. Clearly, nature has developed proteins which are less restricted. Recent research on naturally produced chelators such as siderophores and phytochemicals show some promise as pharmaceuticals. Summary Although an understanding of natural mechanisms of Fe/Cu regulation continues to increase, the pharmaceutical chelators for metal overload diseases remain simple non-protein molecules. Natural and synthetic alternatives have been studied but require further research before being accepted

Synthesis, molecular structure, and binding properties of a hemispherand incorporating a phosphoryl hard donor group

Phosphahemispherand 3 was synthesized in 63 % yield from its macrocyclic precursor 2 and 1,3-propanediol ditosylate in the presence of NaH in THF. Host 3 exhibited temperature-dependent H-1, Cl-13 and P-31 NMR spectra owing to conformational exchange throughout the molecular framework. Exo and endo conformers are in equilibrium in solution, and the energy barrier between the two forms is 61 kJ mol(-1). Two exo conformers, with the P=O bond directed away from the macrocyclic cavity, were predominant at low temperature. The major form was assigned to the C-s symmetry exo conformation, The minor exo form was assigned to the asymmetric conformation that has one methoxy group on each face of the macroring. The energy barrier for interconversion between the two exo forms is 56 kJ mol(-1). The binding energies of alkali metal and ammonium cations to 2 and 3 wore measured by the picrate extraction technique, The highest K-a values were obtained for the complexes of 3 with K+ and Rb+. The conformational changes observed upon complexation were examined by NMR spectroscopy and X-ray analysis and are discussed in terms of pre organization, The formation of 1:1 complexes was only observed with the endo conformer

1:1 molecular complex between water and a macrocyclic crown phosphonamide

The 21-membered macrocycle 3-methyl-11,14,17,20-tetraoxa-2,4-diaza-3-phosphatricyclo[20.3.1.1(5,9)] heptacosa-1(26),5,7,9(27),22,24-hexaene 3-sulfide and water form a 1:1 inclusion compound, C21H29N2O4PS.H2O. The structure reveals host-guest hydrogen bonding with N and O binding sites. One NH ... OH2 hydrogen bond and close contacts with three consecutive O atoms of the polyether chain maintain the water molecule inside the macrocyclic cavity. The thiophosphoryl group is directed outward and the -OCH2CH2O- units adopt the (ag(+/-)a) conformation. The crystal is composed of centrosymmetrically related dimeric units of the complex

On the quantitative measure of a sonochemical effect in heterogeneous sonochemistry

The measurement of a sonochemical effect (SE) requires the definition of the reference conditions for the so-called “silent reaction”. It is shown that it is impossible to define SE correctly in the case of heterogeneous reactions, due to the dramatic effect of the agitation on reaction rates. This is true not only from the quantitative point of view (effect of ultrasound on reaction rates) but also from the qualitative perspective (change of reaction pathway when ultrasound is applied). The first, and most dramatic, example of chemical switching described in the literature, and claimed to be due to ultrasound, is proven also to be observable under efficient agitation conditions.FLWINinfo:eu-repo/semantics/publishe