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1.
Polyaminocarboxylate-based luminescent lanthanide complexes have unusual emission properties, including millisecond excited-state lifetimes and sharply spiked spectra compared to common organic fluorophores. There are three distinct sections in the structure of the luminescent lanthanide chelates: a polyaminocarboxylate backbone to bind the lanthanide ions tightly, an antenna molecule to sensitize the emission of lanthanide ions, and a reactive group to attach to biomolecules. We have previously reported the modifications on the chelates, on the antenna molecules (commonly cs124), and on the reactive sites. In searching for stronger binding chelates and better protection from solvent hydration, here we report the modification of the coordination number of the chelates. A series of 9- and 10-dentate chelates were synthesized. Among them, the 1-oxa-4,7-diazacyclononane (N2O)-containing chelate provides the best protection to the lanthanide ions from solvent molecule attack, and forms the most stable lanthanide coordination compounds. The TTHA-based chelate provides moderately good protection to the lanthanide ions.  相似文献   

2.
Luminescent lanthanide complexes consisting of a lanthanide-binding chelate and organic-based antenna molecule have unusual emission properties, including millisecond excited state lifetimes and sharply spiked spectra, compared to standard organic fluorophores. We have previously used carbostyril (cs124, 7-amino-4-methyl-2(1H)-quinolinone) as an antenna molecule (Li and Selvin, J. Am. Chem. Soc., 1995) attached to a polyaminocarboxylate chelate such as DTPA. Here, we report the chelate syntheses of DTPA conjugated with cs124 derivatives substituted on the 1-, 3-, 4-, 5-, 6-, and 8-position. Among them, the DTPA chelate of cs124-6-SO(3)H has similar lifetime and brightness for both Tb(3+) and Eu(3+) compared to the corresponding DTPA-cs124 complexes, yet it is significantly more soluble in water. The Tb(3+) complex of DTPA-cs124-8-CH(3) has significantly longer lifetime compared to DTPA-cs124 (1.74 vs 1.5 ms), indicating higher lanthanide quantum yield resulting from the elimination of back emission energy transfer from Tb(3+) to the antenna molecule. Thiol-reactive forms of chelates were made for coupling to proteins. These lanthanide complexes are anticipated to be useful in a variety of fluorescence-based bioassays.  相似文献   

3.
The preparation and characterization of new model complexes for the molybdenum cofactor are reported. The new models are distinctive for the inclusion of pterin-substituted dithiolene chelates and have the formulation Tp(*)MoX(pterin-R-dithiolene) (Tp(*)=tris(3,5,-dimethylpyrazolyl)borate), X=O, S, R=aryl. Syntheses of Mo(4+) and (5+) complexes of two pterin-dithiolene derivatives as both oxo and sulfido compounds, and improved syntheses for pterinyl alkynes and [Et(4)N][Tp(*)Mo(IV)(S)S(4)] reagents are described. Characterization methods include electrospray ionization mass spectrometry, electrochemistry, infrared spectroscopy, electron paramagnetic resonance and magnetic circular dichroism. Cyclic voltammetry reveals that the Mo(5+/4+) reduction potential is intermediate between that for dithiolenes with electron-withdrawing substituents and simple dithiolates chelates. Electron paramagnetic resonance and magnetic circular dichroism of Mo(5+) complexes where X=O, R=aryl indicates that the molybdenum environment in the new models is electronically similar to that in Tp(*)MoO(benzenedithiolate).  相似文献   

4.
The triazolopyrimidine scaffold represents one of the privileged structure in chemistry, and there has been an increase in number of studies utilizing this scaffold and its derivatives. Optimization of synthetic protocols such as aza-Wittig reaction, [3 + 2] cycloaddition reaction along with previous methods including condensation with 1,3-dicarbonyl substrates and oxidation of aminopyrimidine Schiff bases have been performed to obtain desired triazolopyrimidines. The triazolopyrimidine ring has been extensively used as a template in medicinal chemistry for its diverse pharmacological properties. Several medicinally active molecules possessing triazolopyrimidine scaffold, either fused or coupled with other heterocycles, have been reported in the literature, highlighting the significance of this nucleus. Interestingly, the unique triazolopyrimidine scaffold also exhibits an impressive potential as a ligand for the synthesis of several metal complexes with significant biological potential. Literature provides enough evidence of exhaustive exploration of this scaffold as a ligand for the chelates of platinum, ruthenium and other metals. This review aims to be a comprehensive and general summary of the different triazolopyrimidine syntheses, their use as ligands for the synthesis and development of metal complexes as medicinal agents and their main biological activities.  相似文献   

5.
Organocobalt(III) complexes with Schiff bases derived from a β-diketone bearing both an alkyl and an aryl group have been prepared. The template syntheses using benzoylacetone and ethylenediamine as complexing agents provide a route to alkylcobalt chelates with the corresponding tri- and tetradentate Schiff bases. However, if a β-diketone with two aryl groups, e.g. dibenzoylmethane, was employed as the starting ketoenol component, no organometallic products were detected; a new mixed-ligand ‘inorganic’ chelate of cobalt(II), [Co{O=C(Ph)CH=C(Ph)O}2(en)], was isolated instead. Its structure as well as that of one of the alkylcobalt complexes with a tridentate Schiff base composed of benzoylacetone and ethylenediamine have been established by X-ray techniques. The current scope of the template synthesis of alkylcobalt complexes with Schiff bases is summarized.  相似文献   

6.
Myeloperoxidase was purified from normal human leukocytes in a crystalline state. Two types of crystals were obtained by the batchwise and dialysis crystallization methods, one of which had a bipyramidal shape belonging to the orthorhombic system. Three multiple forms of human myeloperoxidase were separated from the crystalline enzyme by CM-Sepharose chromatography with sodium chloride gradient elution. These three multiple forms were found to have very similar enzymatic, spectroscopic, and chemical properties. However, slight differences were observed in their amino acid compositions and the molecular weights of their large subunits determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Hemi-myeloperoxidase was prepared from holo-myeloperoxidase by reduction with dithiothreitol and modification with iodoacetamide, and the molecular shapes of the holo- and hemi-enzymes were determined by analytical ultracentrifugation. The axial ratios were calculated to be 2.4-3.5 for the holo-enzyme and 2.9-3.1 for the hemi-enzyme. These results suggest that the shapes of the two enzymes are more spherical in solution than the proposed structural model previously reported.  相似文献   

7.
Gliocladium virens (ATCC 24290) produces two monohydroxamates (cis- and trans-fusarinine) and a dihydroxamate (dimerum acid) as the major siderophores in the culture filtrate. This fungus also produces minor quantities of three trihydroxamates (the deferri forms of ferricrocin, coprogen B, and coprogen). Structural features of the free ligands and the metal complexed forms of cis-fusarinine (cF), trans-fusarinine (tF), and dimerum acid (DA) have been investigated using electronic (visible), circular dichroism (CD), and NMR spectroscopy. In aqueous solution, in the pH range of 6.5-8.0, all of the ferric complexes of cF (and tF) exist as 3:1 chelates. Fe(cF)3 [or Fe(tF)3] forms both lambda and delta coordination isomers, but the former in a slight excess. DA forms a 3:2 ferric complex in the pH range of 5.0-8.0. Iron coordination in Fe2(DA)3 is predominantly delta. DA ligands in Ga2(DA)3 exist as two different conformers at a ratio of 2:1. In mixed solution cF, tF, and DA form a large number of homogeneous and heterogeneous Fe(III) chelates.  相似文献   

8.
The asorbic acid (AH-) auto-oxidation rates catalyzed by copper chelates of 1,10-phenanthroline (OP) or by iron chelates of bleomycin (BLM) are only slightly higher than the oxidation rates catalyzed by the metal ions. AH- oxidation in the presence of DNA is accompanied by degradation of the DNA. The rates of DNA scission by the metal chelates are markedly higher than the rates induced by the free metal ions. AH- oxidation is slowed down in the presence of DNA which forms ternary complexes with the chelates. The ternary complexes react slowly with AH- but induce DNA double strand breaks more efficiently than the free metal chelates. With OP, DNA is degraded by the reaction of the ternary complex, DNA-(OP)2Cu(I), withH2O2

AH- oxidation in the presence of DNA was biphasic, showing a marked rate increase after DNA was cleaved. We suggest that this sigmoidal pattern of the oxidation curves reflects the low initial oxidative activity of the ternary complexes, accelerating as DNA is degraded.

Using O2-produced by pulse radiolysis as a reductant, we found that AH- oxidation with (OP)2Cu(II) induced more DNA double strand breaks per single strand break than bipyridine-copper.

The site specific DNA damaging reactions indicated by these results are relevant to the mechanism of cytotoxic activities of bleomycin and similar antibiotics or cytotoxic agents.  相似文献   

9.
A new solid-phase labeling strategy for the preparation of (99m)Tc and Re chelate complexes and associated peptide derivatives, was developed. Resin-bound monoamide monoamine (MAMA) chelates were prepared in such a manner that upon the addition of a suitable Re(V) and Tc(V) precursor the target metal complexes were selectively released from the resin. The desired products were isolated from unreacted ligand by a simple filtration/solid-phase extraction procedure. In addition to the preparation of a series of functionalized ligands, a peptide conjugate was constructed from one of the resin-bound chelates using a conventional automated peptide synthesizer. The yields of the Re chelate complexes were typically greater than 70%, while the maximum yield for reactions run at the tracer level using (99m)Tc was 50%. The reported approach has a number of attractive features, including the opportunity to prepare libraries of novel agents, the ability to isolate macroscopic amounts of Re complexes for use in in vitro screening studies and as well-characterized standards for tracer level work, and the ability to produce (99m)Tc complexes that are free of any unreacted starting material without having to employ preparative HPLC.  相似文献   

10.
Formation constants and structures of copper(II) complexes with oxidized glutathione (L) have been determined by computer modelling of spectrophotometric and NMR relaxation measurements data over a wide range of pH (1-13) and metal and ligand concentrations in aqueous KNO(3) (1M) at 298K. Among 11 found complexes, four forms were characterized for the first time. Based on a comparison of thermodynamic, relaxation, and optical and EPR spectroscopy parameters the structural conclusions were made. In particular, the CuLH(2) and CuLH(-) complexes both contain two isomers which are similar to mono- and bis-aminoacid copper(II) complexes. In the Cu(2)L and Cu(3)L(2)(2-) species one of the copper atoms is bound only with the carboxylate or carbonyl groups and the others are coordinated similarly to aminoacid chelates. Along with the last, in Cu(2)LH(-2)(2-) two bridging OH(-) groups in one isomer or two chelate rings including deprotonated peptide nitrogen and glycinyl carboxylate oxygen in another are also present. In Cu(3)L(2)H(-4)(6-) the mixed variant of coordination between CuL(2-) (CuN(2)O(2)) and Cu(2)LH(-4)(4-)(CuN(3)O) is realized. The structures of polynuclear complexes have been optimized in density functional theory computations. Rate constants of ligand exchange reactions of Cu(LH)(2)(4-) and CuL(2)(6-) with participation of the LH(3-) and L(4-) forms were determined for the first time. Factors determining rates of these processes have been revealed and their proceeding by associative substitution mechanism shown.  相似文献   

11.
The cyanine dyes Cy3 and Cy5 have proven valuable in numerous applications involving conjugation with proteins. Practical syntheses of lysine-selective, succinimidyl ester derivatives of these dyes have been published, and succinimidyl esters are commercially available. However, the published syntheses of cysteine-selective derivatives produce relatively low yields from expensive starting materials, or produce molecules with marginal water solubility for protein labeling. We report here facile syntheses (four steps, >50% overall yield) of iodoacetamide, sulfhydryl-reactive derivatives of the Cy3 and Cy5 fluorophores. These novel derivatives have good water solubility (>2.5 mM) and bear only one reactive side chain, reducing possible protein cross-linking encountered with previous derivatives.  相似文献   

12.
Complexes formed between labelled proteolytic enzymes (trypsin, subtilopeptidase A) and the alpha-macroglobulins of plasma are rapidly and selectively taken up by rabbit alveolar macrophages. The uptake occurs over a narrow zone of pH. Kinetics of the uptake is affected by temperature; in particular, incubation of macrophages at 37 degrees C before the addition of the labelled complex reduces the capacity to take up complexes. EDTA prevents the association of labelled complexes with macrophages, and can dissociate previously bound label. The effect of EDTA is reversed by the addition of calcium or magnesium or both. Iodoacetamide does not prevent the uptake of complexes but causes them to remain available for dissociation from the cells by EDTA. Incubation of complexes with macrophages at 37 degrees C with no iodoacetamide results in the appearance of trichloroacetic acid soluble products of the enzyme in the supernatant fluid. These observations indicate that the selective uptake of proteinase-alpha-macroglubin complexes by rabbit alveolar macrophages can be resolved into three phases: (1) membrane binding which depends upon divalent cations and is pH sensitive, (2) endocytosis inhibitable by iodoacetamide and (3) temperature-dependent hydrolysis of the contained labelled enzyme.  相似文献   

13.
3-Deoxy-D-erythro-hexos-2-ulose bis(thiosemicarbazone) (1) acts as a tetradentate ligand of the N2S2 type which forms stable coordination complexes with metal(II) cations. The Cu(II), Pt(II), and Pd(II) chelates (2, 4, and 6, respectively) of 1 were synthesized and characterized by elemental analysis and NMR spectroscopy. The NMR spectra of the Pt complex (4) showed the coupling of H-1 and C-1, C-2 of the bis(thiosemicarbazone) with 195Pt (33.7% naturally occurring), which supports the structure proposed for the chelate. The complexes 2, 4, and 6 were acetylated to give the corresponding tri-O-acetyl derivatives 3, 5, and 7. Elimination of Cu(II) from 3 with hydrogen sulfide afforded 8, the tri-O-acetyl derivative of 1. Preliminary studies have shown antiviral activity of chelates 2, 4, and 6 against poliovirus type 1.  相似文献   

14.
Three novel Mn(II) complexes bearing benzyloxymethyl functionalities are reported and their ability to enhance water (1H and 17O) relaxation times is investigated in detail. Two of them contain one coordinated water molecule and display relaxivity values only slightly smaller than those shown by the most clinically used contrast agents (e.g. [Gd(DTPA)(H2O)]2-). Moreover, in these Mn(II) chelates the exchange rate of the coordinated water is ca. one order of magnitude higher if compared to the exchange rates previously reported for Gd(III) complexes with octadentate ligands. The occurrence of such fast exchange rates of the coordinated water is exploited in the formation of macromolecular adducts with human serum albumin to attain systems displaying relaxivity values in the upper range of those so far reported for analogous Gd(III) systems. These results strongly support the view that Mn(II) complexes, in spite of the lower effective magnetic moment, can be considered as viable alternatives to the currently used Gd(III) complexes as contrast agents for MRI applications.  相似文献   

15.
In the pelagic environment, iron is a scarce but essential micronutrient. The iron acquisition capabilities of selected marine bacteria have been investigated, but the recent proliferation of marine prokaryotic genomes and metagenomes offers a more comprehensive picture of microbial iron uptake pathways in the ocean. Searching these data sets, we were able to identify uptake mechanisms for Fe(3+), Fe(2+) and iron chelates (e.g. siderophore and haem iron complexes). Transport of iron chelates is accomplished by TonB-dependent transporters (TBDTs). After clustering the TBDTs from marine prokaryotic genomes, we identified TBDT clusters for the transport of hydroxamate and catecholate siderophore iron complexes and haem using gene neighbourhood analysis and co-clustering of TBDTs of known function. The genomes also contained two classes of siderophore biosynthesis genes: NRPS (non-ribosomal peptide synthase) genes and NIS (NRPS Independent Siderophore) genes. The most common iron transporters, in both the genomes and metagenomes, were Fe(3+) ABC transporters. Iron uptake-related TBDTs and siderophore biosynthesis genes were less common in pelagic marine metagenomes relative to the genomic data set, in part because Pelagibacter ubique and Prochlorococcus species, which almost entirely lacked these Fe uptake systems, dominate the metagenomes. Our results are largely consistent with current knowledge of iron speciation in the ocean, but suggest that in certain niches the ability to acquire siderophores and/or haem iron chelates is beneficial.  相似文献   

16.
Complexes formed between labelled proteolytic enzymes (trypsin, subtilopeptidase A) and the α-macroglobulins of plasma are rapidly and selectively taken up by rabbit alveolar macrophages. The uptake occurs oxver a narrow zone of pH. Kinetics of the uptake is affected by temperature; in particular, incubation of macrophages at 37° C before the addition of labeled complex reduces the capacity to take up complexes. EDTA prevents the association of labelled complexes with macrophages, and can dissociate previously bound label. The effect of EDTA is reversed by the addition of calcium or magnesium or both. Iodoacetamide does not prevent the uptale of complexes but causes them to remain available for dissociation from the cells by EDTA. Incubation of complexes with macrophages at 37° C with no iodoacetamide results in the appearance of trichloroacetic acid soluble products of the enzyme in the supernatant fluid. These observations indicate that the selective uptake of proteinase-α-macroglubin complexes with rabbit alveolar macrophages can be resolved into three phases: (1) membrane binding which depends upon divalent cations and is pH sensitive, (2) endocytosis inhibitable by iodoacetamide and (3) temperature-dependent hydrolysis of the contained labelled enzyme.  相似文献   

17.
《Free radical research》2013,47(4-6):241-258
The asorbic acid (AH?) auto-oxidation rates catalyzed by copper chelates of 1,10-phenanthroline (OP) or by iron chelates of bleomycin (BLM) are only slightly higher than the oxidation rates catalyzed by the metal ions. AH? oxidation in the presence of DNA is accompanied by degradation of the DNA. The rates of DNA scission by the metal chelates are markedly higher than the rates induced by the free metal ions. AH? oxidation is slowed down in the presence of DNA which forms ternary complexes with the chelates. The ternary complexes react slowly with AH? but induce DNA double strand breaks more efficiently than the free metal chelates. With OP, DNA is degraded by the reaction of the ternary complex, DNA-(OP)2Cu(I), withH2O2

AH? oxidation in the presence of DNA was biphasic, showing a marked rate increase after DNA was cleaved. We suggest that this sigmoidal pattern of the oxidation curves reflects the low initial oxidative activity of the ternary complexes, accelerating as DNA is degraded.

Using O2?produced by pulse radiolysis as a reductant, we found that AH? oxidation with (OP)2Cu(II) induced more DNA double strand breaks per single strand break than bipyridine-copper.

The site specific DNA damaging reactions indicated by these results are relevant to the mechanism of cytotoxic activities of bleomycin and similar antibiotics or cytotoxic agents.  相似文献   

18.
Tri(2-pyridylmethyl)amineCu complex-linked iron meso-tetraphenylporphyine derivatives were prepared to model the active site of cytochrome c oxidase. Exposure to oxygen converted the reduced forms of the complexes to the corresponding stable mu-peroxo species in spite of the presence of three coordination sites, two on the heme and one on the Cu. The oxy forms were characterized spectroscopically. Kinetic analyses of the oxygenation reactions of the reduced forms suggests that preferential O2 binding occurs at the Cu site over the heme. This mechanism is also supported by examination of the redox potentials of the two metal ions. Since the peroxy complexes of the models exhibit a structure similar to that of the previously reported fully-oxidized form, the relevance of the model chemistry to the enzyme reaction is discussed.  相似文献   

19.
It has been repeatedly postulated that the high heat resistance of bacterial spores is due to stabilization of biopolymers in the spore interior by a solid deposit of protective cement consisting of coordination complexes of ligands with divalent metal ions. This report presents data on metal-binding characteristics of some of the ligands related to spores as determined by means of potentiometric equilibrium measurements under conditions of temperature and ionic strength (t = 25.0°C; μ = 1.0 KNO3) identical with those reported earlier by the authors in order to facilitate correlation by using comparable data. The spore ligands investigated in this study included 2,6-pyridinedicarboxylic acid (DPA), α,ε-diaminopimelic acid, D-glutamic acid, and D-alanine in a ratio of 1:1 with metal ions which are known to play a role in heat resistance of spores. Stability constants of the chelates of these spore ligands with metal ions such as Ca(II), Mg(II), Cu(II), Ni(II), Zn(II), Co(II), and Mn(II) have been determined. In general the metal chelates of DPA exhibited the greatest stability. On the basis of a consideration of the stability data together with the known configurations of the ligand and the coordination requirements of the metal ions, possible structures indicating the coordinate binding of the spore ligands with the metal ions are presented. All the metal chelates except those of Ca(II) were found to undergo hydrolysis and separation of solid phase in the pH range 7-8.5. The relatively greater hydrolytic stability of Ca(II) chelates and the high affinity of DPA for metal ions appear to be of biological significance insofar as these two spore components are more widely associated with the heat resistance of bacterial spores.  相似文献   

20.
The effects of sulfhydryl inhibitors (iodoacetamide and N-ethylmaleimide) on the electron spin resonance spectra of two maleimide and two iodoacetamide spin labels in erythrocyte ghosts were found to correlate with their relative “lipid”/water partition coefficients. But the spectral characteristics of the maleimide spin labels, and their ghost concentrations after iodoacetamide inhibition, are not consistent with the hypothesis that interprets their spectra solely on the basis of a heterogenous membrane distribution. An alternative hypothesis is suggested which is compatible with relative “lipid solubilities” and the iodoacetamide inhibition spectra.  相似文献   

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