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Martin W Brechbiel - One of the best experts on this subject based on the ideXlab platform.
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In vitro and in vivo characterization of 67Ga3+ complexes with cis,cis-1,3,5-triamino-cyclohexane-N,N′,N″-Triacetic Acid derivatives
Nuclear Medicine and Biology, 2001Co-Authors: Ekaterina Dadachova, Natashia Eberly, Changwon Park, Dangshe Ma, Chang H. Paik, Martin W BrechbielAbstract:Abstract The aim of this study was to investigate the in vitro and in vivo performance of a 67 Ga complex with cis,cis -1,3,5-triaminocyclohexane-N,N′,N″-Triacetic Acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET imaging. The radiolabeling procedure, electrophoretic properties, lipophilicity, Acid stability, human serum stability and biodistribution in mice of 67 Ga(tachta) were investigated. The 67 Ga(tachta) complex forms at 10 −3 M tachta concentration at 40°C in 100% yield; it is neutral, non-lipophilic, 90% stable at pH=4 and 5 and 100% stable at pH=6, for at least 8 d. Serum stability experiments demonstrated that at 5 hr 67 Ga(tachta) exists in serum as a free complex. At 24 hr, 30% of 67 Ga(tachta) is reversibly bound to transferrin-albumin fraction of serum, and that this percentage remains unchanged for a period of 4 d. Biodistribution in mice showed that 67 Ga(tachta) rapidly clears via the kidneys from the body with less than 10% of injected activity left in the body at 3 hours and only 6% remaining after 24 hr. The complex also cleared rapidly from all of the major organs, with bone showing some slightly increased (1.15% ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based upon these data, 67 Ga(tachta) may be considered as a candidate for developing new Ga(III) radiopharmaceuticals for PET.
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in vitro and in vivo characterization of 67ga3 complexes with cis cis 1 3 5 triamino cyclohexane n n n Triacetic Acid derivatives
Nuclear Medicine and Biology, 2001Co-Authors: Ekaterina Dadachova, Natashia Eberly, Changwon Park, Chang H. Paik, Martin W BrechbielAbstract:Abstract The aim of this study was to investigate the in vitro and in vivo performance of a 67 Ga complex with cis,cis -1,3,5-triaminocyclohexane-N,N′,N″-Triacetic Acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET imaging. The radiolabeling procedure, electrophoretic properties, lipophilicity, Acid stability, human serum stability and biodistribution in mice of 67 Ga(tachta) were investigated. The 67 Ga(tachta) complex forms at 10 −3 M tachta concentration at 40°C in 100% yield; it is neutral, non-lipophilic, 90% stable at pH=4 and 5 and 100% stable at pH=6, for at least 8 d. Serum stability experiments demonstrated that at 5 hr 67 Ga(tachta) exists in serum as a free complex. At 24 hr, 30% of 67 Ga(tachta) is reversibly bound to transferrin-albumin fraction of serum, and that this percentage remains unchanged for a period of 4 d. Biodistribution in mice showed that 67 Ga(tachta) rapidly clears via the kidneys from the body with less than 10% of injected activity left in the body at 3 hours and only 6% remaining after 24 hr. The complex also cleared rapidly from all of the major organs, with bone showing some slightly increased (1.15% ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based upon these data, 67 Ga(tachta) may be considered as a candidate for developing new Ga(III) radiopharmaceuticals for PET.
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syntheses and characterizations of metal complexes derived from cis cis 1 3 5 triaminocyclohexane n n n Triacetic Acid
Inorganic Chemistry, 2001Co-Authors: Natashia Eberly, Robin D Rogers, Martin W BrechbielAbstract:A convenient six-step procedure is developed to routinely prepare the hexadentate ligand cis,cis-1,3,5-triaminocyclohexane-N,N‘,N‘ ‘-Triacetic Acid (H3tachta) as an HCl salt. Complexes of gallium(III) and indium(III), [Ga(tachta)] and [In(tachta)], are synthesized from the reactions of the ligand and the corresponding metal precursors. Copper(II), palladium(II), and cobalt(II) complexes, [Cu(Htachta)], [Pd(Htachta)], and [Co(Htachta)], are obtained from the reactions of H3tachta with the corresponding metal chlorides. The structures of H3tachta·3HCl·2H2O (C12H28Cl3N3O8) and [Ga(tachta)] (C12H18GaN3O6) are characterized. The crystal of H3tachta·3HCl·2H2O is monoclinic, of the space group P21/c, with a = 15.1688(4) A, b = 8.4708(2) A, c = 15.9408(2) A, β = 108.058(1)°, and Z = 4; that of [Ga(tachta)] is cubic, of space group Pa3, with a = 14.0762(1) A and Z = 8. The gallium atom of [Ga(tachta)] is six-coordinated in the solid state, and the complex assumes a pseudooctahedronal geometry with the completely d...
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Design of ligands containing the o-hydroxybenzyl group. Metal-complexing properties of N,N″-bis(2-hydroxybenzyl)diethylenetriamine-N,N′,N″-Triacetic Acid
Journal of The Chemical Society-dalton Transactions, 1994Co-Authors: Robert D. Hancock, Martin W Brechbiel, Ignacy Cukrowski, Ewa Cukrowska, Gladys D. Hosken, Vimal Iccharam, Otto A. GansowAbstract:The ligand N,N″-bis(2-hydroxybenzyl)diethylenetriamine-N,N′,N″-Triacetic Acid (H5L) has been synthesised and the protonation constants for L determined by potentiometric methods in 0.5 mol dm–3 NaNO3, and spectrophotometric methods in 0.5 and 0.1 mol dm–3 NaCl, all at 25 °C. The sites of protonation have been inferred from 1H NMR studies in D2O. The complex formation constants of CaII, ZnII CdII, CuII, PbII and BiIII have been determined at 25 °C by potentiometric methods in 0.5 mol dm–3 NaNO3, and spectrophotometric methods in 0.5 mol dm–3 NaCl. The results show that at biological pH the hydroxybenzyl groups tend to remain protonated, and over most of the pH range protonated complexes dominate, with fully deprotonated complexes occurring only at pH values above 9 or 10. The ligand L is, compared to some of its analogues, effectively a weak complexing agent. This is rationalised in terms of the six-membered chelate rings formed in the complex, which include the hydroxybenzyl group. The six-membered chelate rings destabilize complexes of the larger metal ions with which the octadentate ligand should prefer to co-ordinate.
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Synthesis of 2-(p-thiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-Triacetic Acid: application of the 4-methoxy-2,3,6-trimethylbenzenesulfonamide protecting group in the synthesis of macrocyclic polyamines.
Bioconjugate Chemistry, 1993Co-Authors: Thomas J. Mcmurry, Martin W Brechbiel, Chuanchu Wu, Otto A. GansowAbstract:A synthesis of the bifunctional chelator 2-(p-thiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-Triacetic Acid [2-(p-NCS-Bz)-NOTA] is described which illustrates the especial utility of the (4-methoxy-2,3,6-trimethylphenyl)sulfonyl (Mtr) protecting group as an alternative to the p-tolylsulfonyl (Ts) moiety commonly used for Richman-Atkins type cyclizations. Reaction of N,N'-bis(p-tolylsulfonyl)-1-(p-benzamidobenzyl)ethylenediami ne with N,N-bis[2-[(p-tolylsulfonyl)oxy]ethyl]-p-toluenesulfonamide gave 2-(p-benzamidobenzyl)-1,4,7-tris(p-tolylsulfonyl)-1,4,7-tria zacyclononane in 55% yield, whereas the analogous reaction using the Mtr-protected starting materials gave the corresponding Mtr-protected macrocycle in 34% yield. However, deprotection of the Ts- and Mtr-protected macrocycles (H2SO4, 90 degrees C) afforded 2-(p-benzamidobenzyl)-1,4,7-triazacyclononane in 23% and 60% yield, respectively, illustrating the relatively facile cleavage of the Mtr moiety. A modest improvement in overall percent conversion of (p-nitrobenzyl)ethylenediamine into substituted macrocyclic polyamine was observed when comparing the Mtr vs Ts protection (12.6 vs 10.6%). The macrocyclic triamine was converted to 2-(p-NCS-Bz)-NOTA by alkylation with bromoacetic Acid (pH 9, 73%) followed by hydrolysis of the benzamide protecting group (6 M HCl, 70 degrees C, 87%) and reaction with thiophosgene (90%). The serum stability of the 67Cu complexes of 1,4,7-triazacyclononane (I), 2-(p-nitrobenzyl)-1,4,7,10-tetraazacy-clododecane (II), 2-(p-nitrobenzyl)-1,4,8,11-tetraazacyclotetradecane (III), 2-(p-PhCONH-Bz)-NOTA (IV), 2-(p-nitrobenzyl)-1,4,7,10-tetraazadodecane-1,4,7,10-tetraacetic Acid (V), 2-(p-nitrobenzyl)-1,4,8,11-tetraazatetradecane-1,4,8,11-tetraaceti c Acid (VI), and the acyclic ligand 1-(p-nitrobenzyl)-4-methyldiethylenetriamine-N,N,N',N", N"-pentaacetic Acid (VII) was measured at 37 degrees C (5% CO2) and showed the following order of relative stability: I < VII
Jana Klimentová - One of the best experts on this subject based on the ideXlab platform.
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Lanthanide Complexes of 2,2′,2″-(10-{[Hydroxy(phenyl)phosphoryl]methyl}-1,4,7,10-tetraazacyclododecan-1,4,7-triyl)Triacetic Acid: Structural Characterisation of Intermediates from the Proposed Complexation Mechanism in the Systems of LnIII-dota-Type
European Journal of Inorganic Chemistry, 2008Co-Authors: Pavel Vojtíšek, Jan Rohovec, Jana KlimentováAbstract:The crystal and molecular structures of ten lanthanide complexes of H4do3aPPh [2,2′,2″-(10-{[hydroxy(phenyl)phosphoryl]methyl}-1,4,7,10-tetraazacyclododecan-1,4,7-triyl)Triacetic Acid] are presented here. These complexes constitute a new type of coordination compounds within the Ln-dota family. They represent an intermediate stage on the way from the ligand to the classical in-cavity complexes. The important role of intramolecular H-bonds for the process was observed. These intermediate complexes in the solid state form several isostructural groups with the different coordination polyhedra (square antiprisma or dodecahedron) of lanthanide ions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
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lanthanide complexes of 2 2 2 10 hydroxy phenyl phosphoryl methyl 1 4 7 10 tetraazacyclododecan 1 4 7 triyl Triacetic Acid structural characterisation of intermediates from the proposed complexation mechanism in the systems of lniii dota type ligands
European Journal of Inorganic Chemistry, 2008Co-Authors: Pavel Vojtíšek, Jan Rohovec, Jana KlimentováAbstract:The crystal and molecular structures of ten lanthanide complexes of H4do3aPPh [2,2′,2″-(10-{[hydroxy(phenyl)phosphoryl]methyl}-1,4,7,10-tetraazacyclododecan-1,4,7-triyl)Triacetic Acid] are presented here. These complexes constitute a new type of coordination compounds within the Ln-dota family. They represent an intermediate stage on the way from the ligand to the classical in-cavity complexes. The important role of intramolecular H-bonds for the process was observed. These intermediate complexes in the solid state form several isostructural groups with the different coordination polyhedra (square antiprisma or dodecahedron) of lanthanide ions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Bhumasamudram Jagadish - One of the best experts on this subject based on the ideXlab platform.
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improved synthesis of 10 2 alkylamino 2 oxoethyl 1 4 7 10 tetraazacyclododecane 1 4 7 Triacetic Acid derivatives bearing Acid sensitive linkers
Synthetic Communications, 2014Co-Authors: Bhumasamudram Jagadish, Tarik J Ozumerzifon, Sue A Roberts, Gabriel B Hall, Eugene A Mash, Natarajan RaghunandAbstract:Abstract Alkylation of the hydrobromide salts of 1,4,7-tris(methoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane and 1,4,7-tris(ethoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane with appropriate α-bromoacetamides, followed by hydrolysis, provides convenient access to 10-(2-alkylamino-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-Triacetic Acid derivatives that contain Acid-sensitive functional groups. The utility of the method is demonstrated by improved syntheses of two known 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic Acid monoamides bearing Acid-sensitive ω-tritylthio alkyl chains in much greater yields based on cyclen as the starting material. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]
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design synthesis and evaluation of 1 4 7 10 tetraazacyclododecane 1 4 7 Triacetic Acid derived redox sensitive contrast agents for magnetic resonance imaging
Journal of Medicinal Chemistry, 2010Co-Authors: Natarajan Raghunand, Eugene A Mash, Gerald P Guntle, Vijay Gokhale, Gary S Nichol, Bhumasamudram JagadishAbstract:The design and synthesis of three 1,4,7,10-tetraazacyclododecane-1,4,7-Triacetic Acid (DO3A) derivatives bearing linkers with terminal thiol groups and a preliminary evaluation of their potential for use in assembling redox-sensitive magnetic resonance imaging contrast agents are reported. The linkers were selected on the basis of computational docking with a crystal structure of human serum albumin (HSA). Gd(III)-DO3A and Eu(III)-DO3A complexes were synthesized, and the structure of one complex was established by X-ray crystallographic analysis. The binding to HSA of a Gd(III)-DO3A complex bearing a thiol-terminated 3,6-dioxanonyl chain was competitively inhibited by homocysteine and by the corresponding Eu chelate. Binding to HSA was abolished when the terminal thiol group of this complex was absent. The longitudinal water-proton relaxivities (r1) of the three Gd(III)-DO3A complexes and of two Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTA) complexes were measured in saline at 7 ...
Michael F. Tweedle - One of the best experts on this subject based on the ideXlab platform.
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Effect of Ligand Basicity on the Formation and Dissociation Equilibria and Kinetics of Gd3+ Complexes of Macrocyclic Polyamino Carboxylates
Inorganic Chemistry, 1994Co-Authors: Krishan Kumar, Xiangyun Wang, Jean F. Desreux, Michael F. TweedleAbstract:Formation and dissociation equilibria and reaction kinetics for Gd(III) complexes of GdL(L is HE-DO3A = 10-(2-hydroxyethyl)-1,4,7,10-tetraazacyclodecance-1,4,7-Triacetic Acid, HP-DO3A = 10-(2-hydroxyisopropyl)1,4,7,10-tetraazacyclododecane-1,4,7-Triacetic Acid, AND HIP-DO3A = 10-(2-hydroxyisopropyl)-1,4,7,10-tetraazacyclododecnae-1,4,7-Triacetic Acid). Stability constants were measured and reaction kinetics were studied. Relationships of ligand basicity to reaction rate and stability was discussed.
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True tracer radiolabeling of gadolinium complex of 10‐(2‐hydroxypropyl)‐1,4,7,10‐tetraazacyclododecane‐1,4,7 Triacetic Acid (HP‐DO3A)
Journal of Labelled Compounds and Radiopharmaceuticals, 1993Co-Authors: Krishan Kumar, K. Sukumaran, C. Allen Chang, Michael F. Tweedle, W. C. EckelmanAbstract:True tracer radiolabeling, purification, and analysis of a gadolinium complex of HP-DO3A (10-(2-hydroxy-propyl)-1,4,7,10-tetraazacyclo dodecane-1,4,7-Triacetic Acid) was achieved by the reaction of carrier-added 153GdCl3 and excess free ligand. Two analytical methods (ITLC and HPLC) were developed to determine the purity of radiolabeled samples.
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true tracer radiolabeling of gadolinium complex of 10 2 hydroxypropyl 1 4 7 10 tetraazacyclododecane 1 4 7 Triacetic Acid hp do3a
Journal of Labelled Compounds and Radiopharmaceuticals, 1993Co-Authors: Krishan Kumar, K. Sukumaran, Michael F. Tweedle, Allen C Chang, W. C. EckelmanAbstract:True tracer radiolabeling, purification, and analysis of a gadolinium complex of HP-DO3A (10-(2-hydroxy-propyl)-1,4,7,10-tetraazacyclo dodecane-1,4,7-Triacetic Acid) was achieved by the reaction of carrier-added 153GdCl3 and excess free ligand. Two analytical methods (ITLC and HPLC) were developed to determine the purity of radiolabeled samples.
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synthesis characterization and crystal structure of the gadolinium iii chelate of 1r 4r 7r alpha alpha alpha trimethyl 1 4 7 10 tetraazacyclododecane 1 4 7 Triacetic Acid do3ma
Inorganic Chemistry, 1993Co-Authors: Sang I Kang, Krishan Kumar, Rama S Ranganathan, John E Emswiler, Jack Z Gougoutas, Mary F Malley, Michael F. TweedleAbstract:The tetraazatricarboxylic macrocycle, (1R,4R,7R)-α,α',α«-trimethyl-1,4,7,10-tetraazacyclododecanol,4,7-Triacetic Acid (DO3MA) (4) was synthesized by the simultaneous hydrogenolysis and deformylation of 10-formyl-1,4,7-tris(benzyloxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane(N-CHO-DO3MA-TBE).
V. Snieckus - One of the best experts on this subject based on the ideXlab platform.
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a new convenient synthesis of bifunctional chelating agent 1 4 aminobenzyl 1 4 8 11 tetraazacyclotetradecane n n n Triacetic Acid 1 h2nbn teta
Tetrahedron Letters, 1998Co-Authors: M. Maillet, C. S. Kwok, A. A. Noujaim, V. SnieckusAbstract:A convenient and short synthesis (3 steps, 50% overall yield) of the bifunctional chelating agent 1-(4-aminobenzyl)-1,4,8,11-tetraazacyclotetradecane-N′-,N″-,N‴-Triacetic Acid (4) via a boron-protection strategy is reported.
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A new convenient synthesis of bifunctional chelating agent 1-(4-aminobenzyl)-1,4,8,11-tetraazacyclotetradecane-N′,N″,N‴-Triacetic Acid [1-(H2NBn-TETA)]
Tetrahedron Letters, 1998Co-Authors: M. Maillet, C. S. Kwok, A. A. Noujaim, V. SnieckusAbstract:A convenient and short synthesis (3 steps, 50% overall yield) of the bifunctional chelating agent 1-(4-aminobenzyl)-1,4,8,11-tetraazacyclotetradecane-N′-,N″-,N‴-Triacetic Acid (4) via a boron-protection strategy is reported.
