S-benzoyl mercaptoacetyltriglycine (S-Bz-MAG3) was synthesized and labeled with carrier-free 188Re. The overall yield of S-Bz-MAG3 is higher than those published in the literature. Dependence of the labeling yield of 188Re-MAG3 upon concentration of reducing agent, pH, reaction time, and other parameters was examined and optimum conditions were obtained. The labeling yield of 188Re-MAG3 was more than 98%. The concentration procedure was succeeded with Sep-Pak C18 column to obtain highly concentrated 188Re-MAG3. The experimental conditions of labeling of IgG with carrier free 188Re via S-Bz-MAG3 as a bifunctional chelating agent (BFCA) by pre-radiolabeling of the chelate was studied. The conjugation conditions were optimized. The stability of 188Re-MAG3-IgG in vitro was high. The results of this studiy may be useful for 188Re labeling of MAbs for radioimmunotherapy. 相似文献
The synthesis of 188Re-MAG3 is described using 188Re, which was obtained from the alumina based 188W/188Re generator. Dependence of the radiolabeling yields of 188Re-MAG3 on reducing agent concentration, Bz-MAG3 concentration, pH, temperature and incubation time was examined. In the case of optimum conditions the yield of 188Re-MAG3 was 98%. TLC and HPLC techniques were employed to monitor the different species formed. Biodistribution study of 188Re-MAG3 was carried out in rats and compared with behavior of 99mTc-MAG3. 相似文献
Element-Organic Amine/Imine Compounds, XXXI. - Cyclometallation with N-tert-Butyl-Phosphorus-Nitrogen Iridium Complexes The interaction of R1R2N–PNR3 ( 1 ) (R1 SiMe3, tBu, iC3H7; R2 R3 SiMe3, tBu) with [M(COD)(μ-Cl)]2 ( 2 ), M Rh, Ir, affords the amino(imino)phosphane complexes 3 , whose PN bond adds methanol with formation of the diamidophosphite complexes 4 . Already below 0°C the iridium compounds of 4 undergo cyclometallation of a tBu methyl group (R2) with formation of the hydrido-iridium metallaheterocycles 5 . The structures of 4b and 5a are elucidated by X-ray analyses. 相似文献
Radiolabeling of biologically active molecules with fac-[188Re(CO)3(H2O)3]+ unit has been of primary interest in recent years. Therefore, we herein report ligands L1−L4 (L1=histidine, L2=nitrilotriacetic acid, L3=2-picolylamine-N,N-diacetic acid, L4=bis(2-pyridymethy)amine) that have been evaluated by radiochemical reactions with fac-[188Re(CO)3(H2O)3]+. These reactions yielded the radioactive complexes of fac-[188Re(CO)3L] (L = L1−L4, 188Re tricarbonyl complexes 1–4), which were identified by HPLC. Complexes 1–4, with log Po/w values ranging from −2.23 to 2.18, were obtained with yields of ≥95% using ligand concentrations within 10−6–10−4M range. Thus, specific activities of 220 GBq/μmol could be achieved. Challenge studies with cysteine and histidine revealed
high stability for all of these radioactive complexes, and biodistribution studies in mice indicated a fast rate of blood
clearance and high rate of total radioactivity excretion occurring primarily through the renal-urinary pathway. In summary,
the ligands L1–L4 are potent chelators for the future functionalization of biomolecules labeling with fac-[188Re(CO)3(H2O)3]+. 相似文献
Due to physical decay properties commonly associated with therapeutic radionuclides, 188Re (t1/2 = 16.98 h, Emax = 2.12 MeV) is of high interest for endovascular brachytherapy and endoradiotherapy in general. Rhenium precursors in the
low oxidation state +I, such as the organometallic fac-[Re(H2O)3(CO)3]+ are promising lead compounds compared to those with oxidation states +III and +V since they can be prepared under mild conditions
and do not tend to reoxidize to oxidation state +VII while multidentate ligands can be attached under substitution of coordinated
water molecules. This study comprises the application of the Free-Ion Selective Radiotracer Extraction (FISRE) technique in
order to determine dissociation rate constants of complexes bearing the [188Re(CO)3]+-core at tracer levels in vitro with regards to their time-dependent kinetic speciation. As ligands, the tridentate l-histidine as well as the dipeptides l-carnosine (β-alanyl-l-histidine) and glycyl-l-histidine were chosen in order to study the effects of different moieties attached to the primary amine of l-histidine. 相似文献
In this paper, we investigated three ligand systems, symmetric and asymmetric pyridyl-containing tridentate ligands (L1NH2 = (bis(2-pyridylmethyl)-amino)-ethylamine, L2H = (bis(2-pyridylmethyl)-amino)-acetic acid, L3NH2 = [(6-amino-hexyl)-pyridyl-2-methyl-amino]-acetic acid) as bifunctional chelating agents for labeling biomolecules. These
ligands reacted with the precursor fac-[188Re(CO)3(H2O)3]+ and yielded the radioactive complexes fac-[188Re(CO)3L] (L = three ligands), which were identified by RP-HPLC. The corresponding stable rhenium tricarbonyl complexes (1–3) were
allowed for macroscopic identification of the radiochemical compounds. 188Re tricarbonyl complexes, with log Po/w values ranging from −1.36 to −0.32, were obtained with yields of ≥90% using ligand concentrations within the 10−6−10−4M range. Challenge studies with cysteine and histidine revealed the high stability properties of these radioactive complexes,
and biodistribution studies in normal mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion,
primarily through the renal-urinary pathway. In summary, these asymmetric and symmetric pyridyl-containing tridentate ligands
are potent bifunctional chelators for the future biomolecules labeling of fac-[188Re(CO)3(H2O)3]+. 相似文献
The synthesis of enantiomerically pure aluminium, gallium and indium complexes supported by chiral (R,R)‐(HHONNOHH) ( 1 ), (R,R)‐(MeHONNOHMe) ( 2 ), (R,R)‐(tButBuONNOtButBu) ( 3 ), (R,R)‐(MeNO2ONNOMeNO2) ( 4 ), (R,R)‐(HOMeONNOHOMe) ( 5 ) and (R,R)‐(ClClONNOClCl) ( 6 ) (1,2)‐diphenylethylene‐salen ligands is described. Several of these complexes have been crystallographically authenticated, which highlights a diversity of coordination patterns. Whereas all Ga complexes form [Ga2(CH2SiMe3)4(ONNO)] bimetallic species (ONNO= 1 – 3 ), aluminium [AlR(ONNO)] (R=Me, CH2SiMe3) and indium [In(CH2SiMe3)(ONNO)] derivatives are monometallic for ONNO= 1 , 2 and 4 – 6 , and only form the bimetallic complexes [Al2R4(ONNO)] and [In2(CH2SiMe3)4(ONNO)] for the most sterically crowded ligand 3 . The [AlMe(ONNO)] complexes react with iPrOH to give [AlOiPr(ONNO)] complexes that are robust towards further iPrOH. The [In(CH2SiMe3)(ONNO)] congeners are inert towards excess alcohol, whereas the Ga compounds decompose easily. All these alkyl complexes, as well as the [AlOiPr(ONNO)] derivatives, catalyse the ring‐opening polymerisation (ROP) of racemic lactide (rac‐LA). The [AlMe(ONNO)] complexes require additional alcohol to afford controlled reactions, but [AlOiPr(ONNO)] complexes are single‐component catalysts for the isoselective ROP of rac‐LA, with values of Pm in the range 0.80–0.90. Experimental evidence unexpectedly shows that chain‐end control leads to the isoselectivity of these aluminium catalysts; also, the more crowded the coordination sphere, the higher the isoselectivity. The bimetallic Ga complexes do not afford controlled reactions, but the binary [In(ONNO)(CH2SiMe3)/(PhCH2OH)] systems competently mediate non‐stereoselective ROP; evidence is given that an activated monomer mechanism is at work. Kinetic studies show that catalytic activity decreases when electronic density and steric congestion at the metal atom increase. 相似文献
The capacity of gated hosts for controlling a kinetic discrimination between stereoisomers is yet to be understood. To conduct corresponding studies, however, one needs to develop chiral, but modular and gated hosts. Accordingly, we used computational (RI‐BP86/TZVP//RI‐BP86/SV(P)) and experimental (NMR/CD/UV/Vis spectroscopy) methods to examine the transfer of chirality in gated baskets. We found that placing stereocenters of the same kind at the rim (R1=CH3, so‐called bottom) and/or top amide positions (R2=sec‐butyl) would direct the helical arrangement of the gates into a P or M propeller‐like orientation. With the assistance of 1H NMR spectroscopy, we quantified the intrinsic (thermodynamic) and constrictive (kinetic) binding affinities of (R)‐ and (S)‐1,2‐dibromopropane 5 toward baskets (S3b/P)‐ 2 , (S3t/M)‐ 3 , and (S3bt/P)‐ 4 . Interestingly, each basket has a low ( ≤1.3 kcal mol?1), but comparable (de<10 %) affinity for entrapping enantiomeric (R/S)‐ 5 . In terms of the kinetics, basket (S3b/P)‐ 2 , with a set of S stereocenters at the bottom and P arrangement of the gates, would capture (R)‐ 5 at a faster rate (kinR/kinS=2.0±0.2). Basket (S3t/M)‐ 3 , with a set of S centers at the top and M arrangement of the gates, however, trapped (S)‐ 5 at a faster rate (kinR/kinS=0.30±0.05). In light of these findings, basket (S3bt/P)‐ 4 , with a set of S stereocenters installed at both top and bottom sites along with a P disposition of the gates, was found to have a lower ability to differentiate between enantiomeric (R/S)‐ 5 (kinR/kinS=0.8). Evidently, the two sets of stereocenters in this “hybrid” host acted concurrently, each with the opposite effect on the entrapment kinetics. Gated baskets are hereby established to be a prototype for quantifying the kinetic discrimination of enantiomers through gating and elucidating the electronic/steric effects on the process. 相似文献
The rapidly increasing therapeutic applications of 188Re in nuclear medicine, oncology and interventional cardiology require routine production of large, multi-Curie levels of the 188W parent. The capability and effective coordination of back-up production sites is important to insure that high level 188W/188Re generators are continually available. We have coordinated 188W production at the High Flux Isotope Reactor (HFIR - Oak Ridge, US) with production at the BR2 Reactor (Mol, Belgium) characterized by peak thermal neutron fluxes of 2.51·015 (HFIR) and 1·1015 (BR2) neutrons/cm2·sec, respectively. The long 69-day physical half-life permits receipt of 188W from BR2 within 0.25 T1/2's, even after the 12-day post irradiation cooling required for 187W decay (T1/2 = 24 hours). Since 188W production by double neutron capture of enriched 186W is a function of the square of the thermal neutron flux, HFIR production (4-5 Ci 188W/g 186W/cycle) is higher than at the BR2 (1.0-1.1 Ci/g 186W/cycle). However, the specific activity (SA) of BR2-produced 188W is still about 0.8-0.9 Ci/g after processing at ORNL following shipment from Belgium. This SA is sufficiently high to permit fabrication of 1 Ci generators suitable for clinical use, since simple post elution concentration of the saline bolus (30-50 ml) obtained from the generator can provide samples with high specific volume (1 ml volume). The time periods from reactor push in Mol and completion of processing, fabrication and shipment of generators from Oak Ridge have been 19-21 days. Six campaigns have been successfully completed since 1998, with processed levels of 188W in Oak Ridge from 8-26 Curies/campaign. 188W has been provided to MAP Medical technologies Oy (Tikkakoski, Finland) for fabrication and distribution of generators for use at IAEA-supported research projects in developing countries. We have thus established and demonstrated an effective collaboration between the Studiecentrum voor Kernenergie-Centre d'Etude de l'Energie Nucléaire (SCK·CEN) and ORNL for back-up production of 188W. This collaboration continues to be especially helpful during periods when interruption of HFIR operation is necessary for maintenance and upgrades. 相似文献
The synthesis and full characterization of the sterically demanding ditopic lithium bis(pyrazol‐1‐yl)borates Li2[p‐C6H4(B(Ph)pzR2)2] is reported (pzR = 3‐phenylpyrazol‐1‐yl ( 3 Ph), 3‐t‐butylpyrazol‐1‐yl ( 3 tBu)). Compound 3 Ph crystallizes from THF as THF‐adduct 3 Ph(THF)4 which features a straight conformation with a long Li···Li distance of 12.68(1) Å. Compound 3 tBu was found to function as efficient and selective scavenger of chloride ions. In the presence of LiCl it forms anionic complexes [ 3 tBuCl]− with a central Li‐Cl‐Li core (Li···Li = 3.75(1) Å). 相似文献
A series of bis‐chelate pseudo‐octahedral mononuclear coordination complexes of manganese with the chromophore [MnN4O2]n+ (n=0, 1) have been generated in all three principal oxidation states of this transition‐metal center under ambient conditions by utilizing a readily tunable, versatile phenolic pyridylhydrazone ligand system (i.e., H2(3,5‐R1,R2)‐L; L=ligand). Strategic combinations of the nature and position of a variety of substituent groups afforded selective, spontaneous stabilization of multiple spin states of the manganese center, which, upon close crystallographic scrutiny, appears to be in part due to the occurrence or absence of hydrogen‐bonding interactions that involve the phenolate/phenolic oxygen atom. The divalent complexes are isolable in two forms, namely, molecular [MnII{H(3,5‐R1,R2)‐L}2] and ionic [MnII{H2(3,5‐R1,R2)‐L}{H(3,5‐R1,R2)‐L}]ClO4, with the latter complex converting easily into the former complex on deprotonation. Accessibility of the higher‐valent states is achievable only when the phenolate oxygen atom is sterically hindered from participation in hydrogen bonding. The [MnIII{H(3,5‐tBu2)‐L}2]ClO4 complex is the first example of a hydrazone‐based MnIII complex to exhibit spin crossover. Formation of the tetravalent complexes [MnIV{(3,5‐R1,R2)‐L}2] (R1=tBu, R2=H; R1=R2=tBu) necessitates base‐assisted abstraction of the hydrazinic proton. 相似文献
Chain‐length‐dependent termination rate coefficients of the bulk free‐radical polymerization of styrene at 80 °C are determined by combining online polymerization rate measurements (DSC) with living RAFT polymerizations. Full kt versus chain‐length plots were obtained indicating a high kt value for short chains (2 × 109 L · mol−1 · s−1) and a weak chain‐length dependence between 10 and 100 monomer units, quantified by an exponent of −0.14 in the corresponding power law 〈kti,i〉 = kt0 · P−b.
Double logarithmic plots of 〈kti,i〉 versus P, evaluated from experimental time‐resolved Rp data according to the procedure described in the text, for different CPDA and AIBN concentrations. The best linear fit for (10 < P < 100) is indicated as full line. 相似文献
The dipyrromethene (DPM) ligand is the key to isolation of monomeric Zn hydride complexes with tricoordinate zinc centers. A range of RDPM ligands with various substituents in the pole position (1,9-positions) were prepared: R = tBu, adamantyl (Ad), mesityl (Mes), 2,6-diisopropylphenyl (DIPP), 2,4,6-triphenylphenyl (Mes*), or 9-anthracenyl (Anth). Reaction of the ligands with Et2Zn gave a series of (RDPM)ZnEt complexes, which were converted with I2 to the corresponding (RDPM)ZnI compounds. The latter reacted by salt metathesis with KN(iPr)HBH3 to the series of Zn hydride complexes (RDPM)ZnH. For ligands with the larger Mes* and Anth substituents, (RDPM)ZnEt was converted to (RDPM)ZnOSiPh3, which after reaction with PhSiH3 gave the hydrides. While Zn hydride complexes with R = tBu or Ad are dimeric, all complexes with aryl-substituents are monomeric. The aryl groups span a cavity around the metal, blocking dimerization and causing a high-field shift of the 1H NMR signals due to the ASIS effect. Attempted abstraction of the hydride with B(C6F5)3 led to cleavage of the B-C6F5 bond. 相似文献
The lipophilicity of the novel 12 products of the reaction of N3-substituted amidrazones with cis-1,2-cyclohexanedicarboxylic anhydride (4 linear, 4 triazole-like and 4 isoindole ones) with potential pharmacologic activity was evaluated by thin layer and liquid chromatography. Using organic-aqueous eluent systems (with methanol or acetonitrile) on RP18 plates and C18 column, a linear relationship between the volume fraction of modifiers and the retention indices was obtained. The retention values, log k or RM were extrapolated to zero organic modifier content to obtain the log kw or RMW values. 12 compounds with known literature lipophilicity were used as a calibration dataset. The results were compared in a multivariate way with in silico methods (ALOGPs, AC_logP, AB/LogP, COSMOFrag, miLogP, ALOGP, MLOGP, KOWWIN, XLOGP3).
The polymerization of acrylonitrile (M) initiated by the Ce(IV)–acetophenone (AP) redox pair has been studied in acetic–sulfuric acid mixtures in a nitrogen atmosphere. The rate of polymerization is proportional to [M]3/2, [AP]1/2 and [Ce(IV)]1/2. The rate of disappearance of ceric ion,–RCe, is proportional to [AP], [M], and [Ce(IV)]. The effect of certain salts, solvent, acid and temperature on both the rates have been investigated. A suitable kinetic scheme has been proposed, and the composite rate constants kp2(k/k/t) and k0/ki are reported. 相似文献
The lipophilicity of a library of 30 derivatives of dihydrofuran‐2(3H)‐one (γ‐butyrolactone) was determined by MEKC. Calibration curve prepared for ten reference drugs enabled to calculate partition coefficient (log P) for novel compounds. The results of MEKC analysis were compared with lipophilicity coefficients determined by RP‐TLC (RM0) and computational (Mlog P, Clog P) methods. Good correlation was observed between the results obtained by both experimental methods: the MEKC parameters log k and relative lipophilicity RMO. The relationship between determined log P values and results of the computational prediction was weaker. Analysis of the relationship between lipophilicity and anticonvulsant activity showed statistically significant differences between mean values of log P coefficients for group of active (2.18) and inactive (1.51) compounds in the maximal electroshock test. 相似文献