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Complex Concentration (complex + concentration)

Distribution by Scientific Domains

Chemistry	75%

Selected Abstracts

Mass spectrometry study of hemoglobin-oxaliplatin complexes in colorectal cancer patients and potential association with chemotherapeutic responses

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2006
Rupasri Mandal
Oxaliplatin is the most active platinum (Pt)-containing anticancer drug for the treatment of advanced colorectal cancer. We report here the study of potential association of the levels of oxaliplatin-protein complexes in 19 cancer patients with treatment efficacy using size-exclusion high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC/ICPMS) and nanoelectrospray ionization mass spectrometry (nanoESI-MS) techniques. Blood samples from 19 colorectal cancer patients were collected at 1 and 48,h after the first infusion of oxaliplatin. HPLC/ICPMS quantification of the oxaliplatin-protein complexes showed that the levels of Pt-protein complexes in plasma samples at 48,h were reduced by approximately 50% compared to those at 1,h, whereas those in hemolysates did not change significantly. The concentrations of hemoglobin (Hb)-oxaliplatin complexes determined by HPLC/ICPMS ranged from 3.1 to 8.7,µM. NanoESI-MS analysis of the patient hemolysates showed three distinct mass spectral profiles of the Hb-oxaliplatin complexes: (1) 1:1, (2) 1:1 with 1:2, and (3) multiple complexes of 1:1, 1:2, 1:3, and 1:4, corresponding to the Hb-oxaliplatin complex concentrations determined by HPLC/ICPMS. Potential association of variables including Hb-oxaliplatin complex concentrations with time to progress as the treatment efficacy indicator was analyzed using the Cox model. Multivariate analysis of the potential predictors showed that the statistically significant variables were Hb-oxaliplatin complex concentration (p,=,0.02), performance status (p,=,0.02), baseline neutrophil count (p,=,0.05), and the site of the primary cancer (colon vs. rectal, p,=,0.01). The hazard ratio for the concentration of the Hb-oxaliplatin complexes was 2.4, suggesting that the risk of cancer progression significantly increased with increasing of Hb-oxaliplatin complexes in patients. These results demonstrate that the level of the Hb-oxaliplatin complexes in erythrocytes is a potential biomarker for indicating inter-patient variations in oxaliplatin treatment efficacy. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Cyclic Carbonate Synthesis Catalysed by Bimetallic Aluminium,Salen Complexes

CHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2010
William Clegg Prof.
Abstract The development of bimetallic aluminium,salen complexes [{Al(salen)}2O] as catalysts for the synthesis of cyclic carbonates (including the commercially important ethylene and propylene carbonates) from a wide range of terminal epoxides in the presence of tetrabutylammonium bromide as a cocatalyst is reported. The bimetallic structure of one complex was confirmed by X-ray crystallography. The bimetallic complexes displayed exceptionally high catalytic activity and in the presence of tetrabutylammonium bromide could catalyse cyclic carbonate synthesis at atmospheric pressure and room temperature. Catalyst-reuse experiments demonstrated that one bimetallic complex was stable for over 60 reactions, though the tetrabutylammonium bromide decomposed in situ by a retro-Menschutkin reaction to form tributylamine and had to be regularly replaced. The mild reaction conditions allowed a full analysis of the reaction kinetics to be carried out and this showed that the reaction was first order in aluminium complex concentration, first order in epoxide concentration, first order in carbon dioxide concentration (except when used in excess) and unexpectedly second order in tetrabutylammonium bromide concentration. Further kinetic experiments demonstrated that the tributylamine formed in situ was involved in the catalysis and that addition of butyl bromide to reconvert the tributylamine into tetrabutylammonium bromide resulted in inhibition of the reaction. The reaction kinetics also indicated that no kinetic resolution of racemic epoxides was possible with this class of catalysts, even when the catalyst was derived from a chiral salen ligand. However, it was shown that if enantiomerically pure styrene oxide was used as substrate, then enantiomerically pure styrene carbonate was formed. On the basis of the kinetic and other experimental data, a catalytic cycle that explains why the bimetallic complexes display such high catalytic activity has been developed. [source]

Mass spectrometry study of hemoglobin-oxaliplatin complexes in colorectal cancer patients and potential association with chemotherapeutic responses

Histidine-stimulated divalent metal uptake in human erythrocytes and in the erythroleukaemic cell line HEL.92.1.7

THE JOURNAL OF PHYSIOLOGY, Issue 2 2004
F. Oakley
The uptake of 65Zn by human erythrocytes was investigated in the presence of high (40 mm) and low (5 mm) concentrations of histidine and 0,500 ,m cobalt, nickel, manganese and zinc. Varying concentrations of metal mono- and bis-histidine complexes will be formed and the inhibition of 65Zn uptake could be correlated with the calculated complex concentrations to investigate competition between metals. For each metal, the calculated concentrations of bis-histidine complex giving 50% inhibition of 65Zn uptake were similar at both 5 mm and 40 mm histidine. Manganese,bis-histidine appeared to have a much higher affinity for the binding site than the other metal,bis-histidine complexes, which had similar affinities to each other. Studies of the inhibition of histidine-stimulated 54Mn uptake by the addition of manganese confirmed that manganese,bis-histidine does act as a substrate for the transporter in a similar fashion to the other metals studied. In addition, human erythroleukaemic cells (HEL cells) were used as a model for erythroid precursor cells. l -histidine, but not d -histidine, stimulated 65Zn uptake in a saturable fashion. The other metals competed with zinc in a similar manner to that seen in erythrocytes, and the affinity for manganese,bis-histidine was much greater than for the bis-histidine complexes of the other three metals. Both the capacity for metal transport per cell, and the affinity of the transporter for the metal,bis-histidine complexes, were much greater in the HEL cells than in the erythrocyte. It is suggested that histidine-stimulated metal transport may play a role in the supply of metals to maturing erythroid cells. [source]