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Biomedical subjects

L Que

Publications and source records attributed to L Que.

At least 37 records · Page 2Linked to original sources
PubMed2000

N-donor effects on carboxylate binding in mononuclear iron(II) complexes of a sterically hindered benzoate ligand.

Using the sterically hindered 2,6-dimesitylbenzoate ligand Mes2ArCO2-, a series of mononuclear Fe(II) carboxylate complexes has been obtained with the general formula (Mes2ArCO2)2Fe(base)2 (base = 1-methylimidazole (MeIm), pyridine (Py), 2-picoline (2-Pic), 2,5-lutidine (2,5-Lut), 2,6-lutidine (2,6-Lut), (base)2 = N,N,N',N'-tetramethylethylenediamine (TMEDA)). For the monodentate base adducts, single-crystal X-ray diffraction studies revealed several different structural types ranging from distorted tetrahedral to distorted octahedral that correlate with the degree of alpha-substitution of the N-donors. Increasing alpha-substitution leads to the lengthening of the Fe-N bond, which in turn results in a change in carboxylate binding mode from eta 1 to eta 2. We surmise that this change is due to an electrostatic effect and is driven by increasing the Lewis acidity of the Fe center. Such a simple process for inducing carboxylate shifts could play a critical role in biological systems.

Benzoates↗
PubMed2000

Copper(II) complexes of pyridyl-appended diazacycloalkanes: synthesis, characterization, and application to catalytic olefin aziridination.

As part of an ongoing effort to rationally design new copper catalysts for olefin aziridination, a family of copper(II) complexes derived from new tetradentate macrocyclic ligands are synthesized, characterized both in the solid state and in solution, and screened for catalytic nitrene transfer reactivity with a representative set of olefins. The pyridylmethyl-appended diazacycloalkane ligands L6(py)2, L7(py)2, and L8(py)2 are prepared by alkylation of the appropriate diazacycloalkane (piperazine, homopiperazine, or diazacyclooctane) with picolyl chloride in the presence of triethylamine. The ligands are metalated with Cu(ClO4)(2).6H2O to provide the complexes [(L6(py)2)Cu(OClO3)]ClO4 (1), [(L7(py)2)Cu(OClO3)]ClO4 (2), and [(L8(py)2)Cu](ClO4)2 (3), which, after metathesis with NH4PF6 in CH3CN, afford [(L6(py)2)Cu(CH3CN)](PF6)2 (4), [(L7(py)2)Cu(CH3CN)](PF6)2 (5), and [(L8(py)2)Cu](PF6)2 (6). All six complexes are characterized by X-ray crystallography, which reveals that complexes supported by L6(py)2 and L7(py)2 (1, 2, 4, 5) adopt square-pyramidal geometries, while complexes 3 and 6, ligated by L8(py)2 feature tetracoordinate, distorted-square-planar copper ions. Tetragonal geometries in solution and d(x2 - y2), ground states are confirmed for the complexes by a combination of UV-visible and EPR spectroscopies. The divergent flexibility of the three supporting ligands influences the Cu(II)/Cu(I) redox potentials within the family, such that the complexes supported by the larger ligands L7(py)2 and L8(py)2 (5 and 6) exhibit quasi-reversible electron transfer processes (E1/2 approximately -0.2 V vs Ag/AgCl), while the complex supported by L6(py)2 (4), which imposes a rigid tetragonal geometry upon the central copper(II) ion, is irreversibly reduced in CH3CN solution. Complexes 4-6 are efficient catalysts (in 5 mol % amounts) for the aziridination of styrene with the iodinane PhINTs (in 80-90% yields vs PhINTs), while only 4 exhibits significant catalytic nitrene transfer reactivity with 1-hexene and cyclooctene.

Alkenes↗
PubMed2000

Catalytic oxidation with a non-heme iron complex that generates a low-spin Fe(III)OOH intermediate

The antitumor drug bleomycin (BLM) is proposed to act via a low-spin iron(III) hydroperoxide intermediate called "activated bleomycin". To gain more insight into the mechanistic aspects of catalytic oxidation by these intermediates we have studied the reactivity of [(N4Py)Fe(CH3CN)](ClO4)2 (1) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) with excess H2O2. Under these conditions a transient purple species is generated, [(N4Py)FeOOH]2- (2), which has spectroscopic features and reactivity strongly reminiscent of activated bleomycin. The catalytic oxidation of alkanes such as cyclohexane, cyclooctane, and adamantane by 1 with H2O2 gave the corresponding alcohols and ketones in up to 31% yield. It was concluded, from the O2 sensitivity of the oxidation reactions, the formation of brominated products in the presence of methylene bromide, and the nonstereospecificity of the oxidation of cis- or trans-dimethylcyclohexane, that long-lived alkyl radicals were formed during the oxidations. Oxidation of alkenes did not afford the corresponding epoxides in good yields but resulted instead in allylic oxidation products in the case of cyclohexene, and cleavage of the double bond in the case of styrene. Addition of hydroxyl radical traps, such as benzene and acetone, led to only partial quenching of the reactivity. The kinetic isotope effects for cyclohexanol formation, ranging from 1.5 in acetonitrile to 2.7 in acetone with slow addition of H2O2, suggested the involvement of a more selective oxidizing species in addition to hydroxyl radicals. Monitoring the UV/Vis absorption of 2 during the catalytic reaction showed that 2 was the precursor for the active species. On the basis of these results it is proposed that 2 reacts through homolysis of the O-O bond to afford two reactive radical species: [(N4Py)Fe(IV)O]2+ and *OH. The comparable reactivity of 1 and Fe-BLM raises the possibility that they react through similar mechanistic pathways.

Journal Article↗
PubMed2000

Third-body wear of cobalt-chromium-molybdenum implant alloys initiated by bone and poly(methyl methacrylate) particles.

The potential for bone and poly(methyl methacrylate) (PMMA) debris to initiate wear on ASTM-F75 and ASTM-F799 CoCrMo alloys articulating against ultrahigh molecular weight polyethylene (UHMWPE) was investigated. Third-body wear particles of bone and PMMA bone cement (with and without the radiopacifier, barium sulfate) were introduced between CoCrMo and UHMWPE in a reciprocating sliding wear test. A scanning electron microscope and a white light interference surface profilometer were used to study the surface damage and quantify the surface roughnesses of the worn alloys. The CoCrMo alloys, which are widely used as the femoral components in total artificial knees and hips, showed surface damage as the result of wear in the presence of bone or PMMA debris. Severe scratches were generated within 2700 cycles (94.5-m sliding distance) on the alloy's surface. Ploughing was the major wear mechanism. Carbides in the F75 alloy surface appeared to be unaffected by the debris. A quantitative study was performed on the surface roughness (average roughness, R(a), and root mean square roughness, RMS) of the alloy after wear testing. A nonparametric Wilcoxon rank sum test of wear severity (R(a) and RMS) was performed based on the surface roughness data. The surfaces of the specimens tested with the PMMA and bone particles were significantly rougher than those of the controls (p < 0.01). Small scratches also occurred on some of the control specimen surfaces and may have been second-body wear caused by defects and impurities in the UHMWPE.

Animals↗
PubMed2000

Coordination chemistry of co(II)-bleomycin: its investigation through NMR and molecular dynamics.

Previous studies on the coordination chemistry of Co-bleomycin have suggested the secondary amine in beta-aminoalanine, the N5 and N1 nitrogens in the pyrimidine and imidazole rings, respectively, and the amide nitrogen in beta-hydroxyhistidine as equatorial ligands to the cobalt ion. The primary amine in beta-aminoalanine and the carbamoyl group of the mannose have been proposed alternatively as possible axial ligands. The first coordination sphere of Co(II) in Co(II)BLM has been investigated in the present study through the use of NMR and molecular dynamics calculations. The data collected from the NMR experiments are in agreement with the equatorial ligands previously proposed, and also support the participation of the primary amine as an axial ligand. The paramagnetic shifts of the gulose and mannose protons could suggest the latter as a second axial ligand. This possibility was investigated by way of molecular dynamics, with distance restraints derived from the relaxation times measured through NMR. The molecular dynamics results indicate that the most favorable structure is six-coordinate, with the primary amine and either the carbamoyl oxygen or a solvent molecule occupying the axial sites. The analysis of the structures previously derived for HOO-Co(III)-bleomycin and HOO-Co(III)-pepleomycin led us to propose the six-coordinate structure with only endogenous ligands, as the one held in solution by the Co(II) derivative of bleomycin.

Bleomycin↗
PubMed2000

Copper-induced conformational changes in the N-terminal domain of the Wilson disease copper-transporting ATPase.

The Wilson disease copper-transporting ATPase plays a critical role in the intracellular trafficking of copper. Mutations in this protein lead to the accumulation of a toxic level of copper in the liver, kidney, and brain followed by extensive tissue damage and death. The ATPase has a novel amino-terminal domain ( approximately 70 kDa) which contains six repeats of the copper binding motif GMTCXXC. We have expressed and characterized this domain with respect to the copper binding sites and the conformational consequences of copper binding. A detailed analysis of this domain by X-ray absorption spectroscopy (XAS) has revealed that each binding site ligates copper in the +1 oxidation state using two cysteine side chains with distorted linear geometry. Analysis of copper-induced conformational changes in the amino-terminal domain indicates that both secondary and tertiary structure changes take place upon copper binding. These copper-induced conformational changes could play an important role in the function and regulation of the ATPase in vivo. In addition to providing important insights on copper binding to the protein, these results suggest a possible mechanism of copper trafficking by the Wilson disease ATPase.

Adenosine Triphosphatases↗
PubMed2000

Surface roughness of retrieved CoCrMo alloy femoral components from PCA artificial total knee joints.

In this study, we analyzed the surface roughness of retrieved cobalt-chromium-molybdenum (CoCrMo) femoral components of porous coated anatomic (PCA) artificial total knee joints, using a white light interference surface profilometer (WLISP). Thirty-eight PCA retrieved specimens obtained from the Anderson Clinic (Arlington, VA) were used. The artificial knees were originally implanted between 1982-1993, and the specimens were retrieved during revision surgeries between 1988-1996. We examined specimens damaged by three wear modes: femoral component against the ultra high molecular weight polyethylene (UHMWPE) articular surface (mode I), femoral component against the metal tibial tray (because of UHMWPE tibial component wear-through) (mode II), and femoral component against metal-debris-embedded-UHMWPE (with metal debris from the porous coating) (mode III). The mean surface roughness of each femoral component was the average of 80 surface roughness measurements. The in vivo alloy femoral component surfaces were rougher by an order of magnitude over controls, and the alloy surfaces were predominantly worn by the formation of parallel scratches in the direction of articulation. There was no correlation between the surface roughness of the femoral components and patient age, sex, weight, and total time of implantation. Significant surface roughness increases accompanied mode II and mode III wear. Different carbide morphologies were found on different femoral component surfaces, indicating that a variety of sintering processes, with different times and temperatures, may have been applied to the alloy femoral components during manufacture. Metal component roughness may be important to the wear of UHMWPE components and the success of total artificial knee joint.

Adult↗
PubMed2000

"FUR"--one size suits all.

This work used amalgamated data from previous projects in order to test the concept that when organ function is expressed in terms of tracer kinetics, the results are independent of patient size or gender. Dynamic gamma camera studies were analysed by measuring the rate of movement of tracers from the blood into various organs. These rates were expressed as a "fractional uptake rate" (FUR), which is the fraction of tracer in the blood taken up by the organ per unit time. As these values were small, it was convenient to express the FUR per million seconds. The FUR was calculated using the expression FUR = SLOPE (of Rutland-Patlak plot), multiplied by B(0) (the blood curve value back-extrapolated to time zero), and divided by the TOTAL amount of tracer injected. Data were used from adult patients between the ages of 20 and 49 years who had normal organ function. Organ/tracer groups studied were the skeletal uptake of 99mTc-MDP, the renal uptake of 99mTc-MAG3, the renal uptake of 99mTc-MDP, the renal uptake of 99mTc-DTPA, the hepatic uptake of 99mTc-colloid, the splenic uptake of 99mTc-colloid, and the hepatic uptake of 99mTc-DISIDA. Each organ/tracer group was divided into three subgroups according to patient size (smallest, middle and largest), and also into subgroups according to gender. Comparison of these subgroups did not show any significant size- or gender-related differences in FUR values. It is concluded that for patients with normally functioning organs the FUR is independent of patient size or gender. Thus, the FUR is a valuable way of expressing organ function, particularly in patients with unusual or rapidly changing body size, such as children.

Adult↗
PubMed1999

Herbicide-degrading alpha-keto acid-dependent enzyme TfdA: metal coordination environment and mechanistic insights.

TfdA is a non-heme iron enzyme which catalyzes the first step in the oxidative degradation of the widely used herbicide (2, 4-dichlorophenoxy)acetate (2,4-D). Like other alpha-keto acid-dependent enzymes, TfdA utilizes a mononuclear Fe(II) center to activate O(2) and oxidize substrate concomitant with the oxidative decarboxylation of alpha-ketoglutarate (alpha-KG). Spectroscopic analyses of various Cu(II)-substituted and Fe(II)-reconstituted TfdA complexes via electron paramagnetic resonance (EPR), electron spin-echo envelope modulation (ESEEM), and UV-vis spectroscopies have greatly expanded our knowledge of the enzyme's active site. The metal center is coordinated to two histidine residues as indicated by the presence of a five-line pattern in the Cu(II) EPR signal, for which superhyperfine splitting is attributed to two equivalent nitrogen donor atoms from two imidazoles. Furthermore, a comparison of the ESEEM spectra obtained in H(2)O and D(2)O demonstrates that the metal maintains several solvent-accessible sites, a conclusion corroborated by the increase in multiplicity in the EPR superhyperfine splitting observed in the presence of imidazole. Addition of alpha-KG to the Cu-containing enzyme leads to displacement of an equatorial water on copper, as determined by ESEEM analysis. Subsequent addition of 2,4-D leads to the loss of a second water molecule, with retention of a third, axially bound water. In contrast to these results, in Fe(II)-reconstituted TfdA, the cosubstrate alpha-KG chelates to the metal via a C-1 carboxylate oxygen and the alpha-keto oxygen as revealed by characteristic absorption features in the optical spectrum of Fe-TfdA. This binding mode is maintained in the presence of substrate, although the addition of 2,4-D does alter the metal coordination environment, perhaps by creating an O(2)-binding site via solvent displacement. Indeed, loss of solvent to generate an open binding site upon the addition of substrate has also been suggested for the alpha-keto acid-dependent enzyme clavaminate synthase 2 [Zhou et al. (1998) J. Am. Chem. Soc. 120, 13539-13540]. Nitrosyl adducts of various Fe-TfdA complexes have also been investigated by optical and EPR spectroscopy. Of special interest is the tightly bound NO complex of Fe-TfdA.(alpha-KG).(2,4-D), which may represent an accurate model of the initial oxygen-bound species.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1999

Role of the nonheme Fe(II) center in the biosynthesis of the plant hormone ethylene.

The final step of ethylene biosynthesis in plants is catalyzed by the enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACCO). In addition to ACC, Fe(II), O2, CO2, and ascorbate are required for in vitro enzyme activity. Direct evidence for the role of the Fe(II) center in the recombinant avocado ACCO has now been obtained through formation of enzyme.(substrate or cofactor).NO complexes. These NO adducts convert the normally EPR-silent ACCO complexes into EPR-active species with structural properties similar to those of the corresponding O2 complexes. It is shown here that the ternary Fe(II)ACCO.ACC.NO complex is readily formed, but no Fe(II)ACCO.ascorbate.NO complex could be observed, suggesting that ascorbate and NO are mutually exclusive in the active site. The binding modes of ACC and the structural analog alanine specifically labeled with 15N or 17O were examined by using Q-band electron nuclear double resonance (ENDOR). The data indicate that these molecules bind directly to the iron through both the alpha-amino and alpha-carboxylate groups. These observations are inconsistent with the currently favored mechanism for ACCO, in which it is proposed that both ascorbate and O2 bind to the iron as a step in O2 activation. We propose a different mechanism in which the iron serves instead to simultaneously bind ACC and O2, thereby fixing their relative orientations and promoting electron transfer between them to initiate catalysis.

Amino Acid Oxidoreductases↗
PubMed1999

Surface roughness quantification of CoCrMo implant alloys.

The articulating surfaces of CoCrMo alloy wear specimens and retrieved femoral components of artificial total knee joints are subject to uneven wear. A repeatable and reliable measurement method is necessary to evaluate the surface damage. In this study, the surface roughness of CoCrMo alloy specimens subjected to in vitro third-body wear, and retrieved femoral components of knee joints were analyzed using a white light interference surface profilometer. Each third-body wear specimen was divided into a 19x19 grid of 1-mm(2) squares (361 squares) and each femoral condyle of retrieved specimens was divided into two 10x10 grids of 1-mm(2) squares (100 squares). The surface roughness average (Ra) and root mean square roughness (RMS) were measured for each of the squares. The average of all points measured was defined as the true surface roughness mean (TSRM). Measurements were then performed on 40-60 (in vitro specimens) or 30 (retrieved specimens) randomly selected points on each surface and a cumulative average was calculated. The cumulative average surface roughness value from only a few (5-15) measurement points generated large deviations (>40%) from the TSRM, but converged to the TSRM as the number of measurements increased. The number of randomly selected points necessary for the cumulative average roughness to be within 10% of the TSRM was defined as the representative measurement number (RMN). The RMN for the third-body wear specimens (surface area of 573 mm(2)) was 40 points, and the RMN for the retrieved femoral components (surface area of 100 mm(2)) was 20 points. To obtain the cumulative surface roughness average within a desired percentage of the TSRM, it is important to define or experimentally determine the critical minimum number of measurements, RMN. Several types of measurements may be necessary to understand wear and damage on metal components of artificial knee joints. The TSRM represents a consistent and reproducible measure of surface damage, and a starting point to develop appropriate measurement protocols to quantify damage on a specific surface.

Arthroplasty, Replacement, Knee↗
PubMed1999

EPR properties of mixed-valent mu-oxo and mu-hydroxo dinuclear iron complexes produced by radiolytic reduction at 77 K.

Radiolytic reduction at 77 K of oxo/hydroxo-bridged dinuclear iron(III) complexes in frozen solutions forms kinetically stabilized, mixed-valent species in high yields that model the mixed-valent sites of non-heme, diiron proteins. The mixed-valent species trapped at 77 K retain ligation geometry similar to the initial diferric clusters. The shapes of the mixed-valent EPR signals depend strongly on the bridging ligands. Spectra of the Fe(II)OFe(III) species reveal an S = 1/2 ground state with small g-anisotropy as characterized by the uniaxial component (gz-gav/2 < 0.03) observable at temperatures as high as approximately 100 K. In contrast, hydroxo-bridged mixed-valent species are characterized by large g-anisotropy (gz-gav/2 > 0.03) and are observable only below 30 K. Annealing at higher temperatures causes structural relaxation and changes in the EPR characteristics. EPR spectral properties allow the oxo- and hydroxo-bridged, mixed-valent diiron centers to be distinguished from each other and can help characterize the structure of mixed-valent centers in proteins.

Anisotropy↗
PubMed1999

Double-strand DNA hydrolysis by dilanthanide complexes.

Although there has been progress in developing artificial hydrolytic DNA cleaving agents, none of these has been shown to carry out the double-strand hydrolysis of DNA. We demonstrate that La(III) or Ce(IV) combined with the ligand 1,3-diamino-2-hydroxypropane-N,N,N', N'-tetraacetate (HPTA) in a 2 : 1 ratio can efficiently cleave supercoiled plasmid DNA at 55 degrees C within a 3-h period. Analysis of end-labeled restriction fragments cleaved by these complexes reveals 3'- and 5'-ends consistent with a hydrolytic mechanism. Unlike for other polydentate carboxylate complexes, plasmid DNA cleavage by La(2)(HPTA) or Ce(2)(HPTA) affords a significant amount of linear DNA with a considerable fraction of the supercoiled form still remaining. This result implies that La(2)(HPTA) and Ce(2)(HPTA) can carry out double-strand cleavage of plasmid DNA. La(2)(HPTA) and Ce(2)(HPTA) represent the first metal complexes demonstrated to be capable of double-strand hydrolytic cleavage of plasmid DNA.

DNA↗
PubMed1999

A comparison of the renal handling of 99Tcm-DTPA and 99Tcm-MAG3 in hypertensive patients using an uptake technique.

The renal uptake and outflow of 99Tcm-DTPA and 99Tcm-MAG3 were compared by analysing renal studies performed in two different departments, but with analysis techniques and computer programs using algorithms that were almost identical. Comparison was performed by a retrospective review of results from patients who were referred for renal investigations because of hypertension but who had apparently normal kidneys. The analysis of tracer outflow rates in the form of whole-kidney transit times and renal cortical transit times showed no significant difference between the two tracers. The fractional uptake rate of tracer for each patient (both kidneys) indicated that MAG3 was extracted from the blood 3.3 times faster than DTPA in patients aged 20-69 years, with a lower ratio above the age of 70. When used to measure relative renal function, there was no overall difference between the two tracers. The fractional uptake rates were also converted to flow rates, producing values of 95.8 +/- 28.0 ml.min(-1).1.73 m-2 for DTPA and 320 +/- 75 ml.min(-1).1.73 m-2 for MAG3, in hypertensive patients aged 20-40 years. These values showed a good correlation with other published GFR and MAG3 clearance rates (obtained using blood sampling methods) in normal patients of similar ages.

Adult↗