Complexes in blood plasma

Andersson, A. and Ehrsson, H. (1995) Stability ofcisplatin and its monohydrated complex in blood, plasma and ultrafiltrate - implications for quantitative analysis. J. Pharm. Biomed. Anal., 13, 639-644. 

Chilvers, D.C., Dawson, J.B.. Bahregni-Toosi, M.H. and Hodgkinson. A. (1984). Identification and Determination of Copper- and Zinc-Protein Complexes in Blood Plasma after Separation DEAE Sepharose C1-6B. Analyst, 109,871. 

Reactions between the sulfur-containing amino acids cysteine and methionine (Fig. 2.18) and rufhenium(II) arene anticancer complexes are of much interest in view of the strong influence of sulfur amino acids on the intracellular chemistry of platinum drugs, their involvement in detoxification and resistance mechanisms [100]. We found [101] that [(ri -biphenyl)Ru(en)Cl][PF 5] reacts slowly with the thiol amino add L-cysteine in aqueous solution at 310 K, pH 2-5, and only to about 50% completion at a 1 2 mM ratio. Reactions appeared to involve aquation as the first step followed by initial formation of 1 1 adducts via substitution of water by S-bound or O-bound cysteine. Two dinuclear complexes were also detected as products from the reaction. In these reactions half or all of the chelated ethylene-diamine had been displaced and one or two bridging cysteines were present The unusual cluster species (biphenyl) Ru g was also formed espedaUy at higher cysteine concentrations. The reaction was suppressed in 50 mM triethylammo-nium acetate solution at pH > 5 or in 100 mM NaCl suggesting that thiols may not readily inactivate Ru(II)-en arene complexes in blood plasma or in cells. Similarly, reactions with the thioether sulfur of methionine appeared to be relatively weak. Only 27% of [(r -biphenyl)Ru(en)Cl][PF5] reacted with L-methionine (L-MetH) at an initial pH of 5.7 after 48 h at 310 K, and gave rise to only one adduct [(ri -biphenyl) Ru(en) (i-MetH -S)]. ... 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

Carotenoids are also present in animals, including humans, where they are selectively absorbed from diet (Furr and Clark 1997). Because of their hydrophobic nature, carotenoids are located either in the lipid bilayer portion of membranes or form complexes with specific proteins, usually associated with membranes. In animals and humans, dietary carotenoids are transported in blood plasma as complexes with lipoproteins (Krinsky et al. 1958, Tso 1981) and accumulate in various organs and tissues (Parker 1989, Kaplan et al. 1990, Tanumihardjo et al. 1990, Schmitz et al. 1991, Khachik et al. 1998, Hata et al. 2000). The highest concentration of carotenoids can be found in the eye retina of primates. In the retina of the human eye, where two dipolar carotenoids, lutein and zeaxan-thin, selectively accumulate from blood plasma, this concentration can reach as high as 0.1-1.0mM (Snodderly et al. 1984, Landrum et al. 1999). It has been shown that in the retina, carotenoids are associated with lipid bilayer membranes (Sommerburg et al. 1999, Rapp et al. 2000) although, some macular carotenoids may be connected to specific membrane-bound proteins (Bernstein et al. 1997, Bhosale et al. 2004). 

Lipids are transported in blood plasma bound to proteins, in complexes called lipoproteins... 

Instruments are offered in the market for clinical determination of electrolytes in blood, plasma or serum. One of them, for example, carries out simultaneous determinations of Na, K, Ca, Mg, hematocrit and pH. The cations are of the free type (see Section m.A) and are measured with specific ion-selective electrodes. In complex matrices such as blood or its derived fractions the concentration of free Ca and Mg is affected by the pH of the solution, for example, a slight change of pH will produce or neutralize anionic sites in the proteins, binding or releasing these cations furthermore, the response of the Mg-selective electrode is also affected by the concentration of free Ca(II). The correction... 

The tetracyclines Form an important group of antibiotics. The activity appears to result from their ability to chelate metal ions since the extent of antibacterial activity parallels the ability to form stable chelates. The metal in question appears to be magnesium or calcium since the addition of large amounts of magnesium can inhibit the antibiotic effects. In addition, it is known that in blood plasma the tetracyclines exist as calcium and magnesium complexes.,JS... 

Table 4 Percentage Occurrence of the Major Complexes (Non-protein) in Blood Plasma from Computer Simulation -1 ...

From potentiometric and spectroscopic studies it is concluded that the main species at neutral pH is a 1 1 tridentate chelate (11) with a log stability constant of ca. — 4. The claim55 that the stability of this species is comparable to that of the Cu(albumin) complex is rather surprising, since for this to occur the involvement of a histidine in the third amino add position is normally required, and furthermore others have concluded that in blood plasma at least the tripeptide is unlikely to compete against other ligands for the available Cu11.56,57 To illustrate the point that such conclusions from blood plasma simulations are only applicable to that medium, Pickart and Thaler58 have shown that in a cell culture medium the tripeptide considerably enhanced Cu uptake into cells and that this was not affected by a 300-fold molar excess of amino adds, including histidine. 

Mixed donor ligands. Thermodynamic parameters have been evaluated for the interaction of asparaginate with Fe2+ in aqueous solution at 25°C. On the basis of the results it is calculated that quite a large proportion of asparaginate in blood plasma may be complexed to iron(u) as well as to the expected copper(n).93 1.10-Phenanthro-line /V-oxide (phenNO) forms the complex [Fe(phenN0)3](C104)2 in which the ligands chelate by N- and O-donor atoms.96... 

RAPTA-C has been the subject of detailed reactivity, computational, in vitro and in vivo studies. In aqueous solution, one chloride ligand is usually hydrolysed, the extent of hydrolysis depending upon the concentration of the complex in solution, the concentration of chloride, the pH and temperature [20]. Once hydrolysed, RAPTA compounds can rapidly react with potential biomolecular targets such as DNA and proteins. However, hydrolysis does not appear to be a prerequisite for reaction with biomolecules as in blood plasma, where the chloride concentration is high enough to... 

N-NMR spectroscopy can be useful for ammine and amine complexes, but 14N is a quadrupolar nucleus, and quadrupolar relaxation is dominant when the environment of 14N has a low symmetry. This can lead to very broad lines and a consequent reduction in sensitivity. On the other hand, short relaxation times also have the advantage of allowing rapid pulsing so that a large number of transients can be acquired. Thus it is possible to follow reactions of cisplatin in blood plasma and cell-culture media at milli-molar drug concentrations and to detect ammine release [6],... 

Interest for the analysis of taxanes in biological fluids deals, in most cases, with the determination of the two pharmaceuticals, paclitaxel, and docetaxel, and their metabolites in blood plasma. The complexity of this matrix and the interference of endogenous compounds are, in... 

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