114873-37-9

Basic information

• Product Name: 1,4,7,10-TETRAAZACYCLODODECAAN-1,4,7-TRIYLTRIAZIJNZUUR
• Synonyms: 1,4,7,10-TETRAAZACYCLODODECAAN-1,4,7-TRIYLTRIAZIJNZUUR;1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic acid
• CAS NO: 114873-37-9
• Molecular Formula: C₁₄H₂₆N₄O₆
• Molecular Weight: 346.37944
• Mol File: 114873-37-9.mol

Chemical Properties

• Melting Point: 260℃
• Boiling Point: 617.6±55.0 °C(Predicted)
• Appearance: /
• Density: 1.242±0.06 g/cm3(Predicted)
• PKA: 2.46±0.10(Predicted)
• CAS DataBase Reference: 1,4,7,10-TETRAAZACYCLODODECAAN-1,4,7-TRIYLTRIAZIJNZUUR(CAS DataBase Reference)
• NIST Chemistry Reference: 1,4,7,10-TETRAAZACYCLODODECAAN-1,4,7-TRIYLTRIAZIJNZUUR(114873-37-9)
• EPA Substance Registry System: 1,4,7,10-TETRAAZACYCLODODECAAN-1,4,7-TRIYLTRIAZIJNZUUR(114873-37-9)

Safety Data

• Hazardous Substances Data: 114873-37-9(Hazardous Substances Data)

Usage

Uses

Used in Medical Imaging:
1,4,7,10-TETRAAZACYCLODODECAAN-1,4,7-TRIYLTRIAZIJNZUUR is used as a potential contrast agent for magnetic resonance imaging (MRI). The compound enhances the visibility of certain tissues and structures within the body, allowing for more accurate diagnosis and monitoring of various conditions.
Used in Oncology:
In the field of oncology, 1,4,7,10-TETRAAZACYCLODODECAAN-1,4,7-TRIYLTRIAZIJNZUUR is used for the targeting, treatment, and diagnosis of tumors. Its ability to form complexes with lanthanides allows for the development of lanthanide-azacrown coordination complexes, which can be utilized in the imaging and treatment of cancerous cells.
Used in Drug Delivery Systems:
Similar to gallotannin, DONA can also be employed in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells. By incorporating DONA into various organic and metallic nanoparticles, its delivery, bioavailability, and therapeutic outcomes can be improved, potentially leading to more effective cancer treatments.

Upstream product

• 294-90-6 1,4,7,10-tetraazacyclododecan 
• 122555-91-3 1,4,7-tris-tert-butoxycarbonylmethyl-1,4,7,10-tetraazacyclododecane 
• 79-11-8 chloroacetic acid 
• 79-08-3 bromoacetic acid 

Downstream Products

• 112188-16-6 [Gd(DO3A)] 
• 120041-08-9 1,4,7-tris(carboxymethyl)-10-(2'-hydroxypropyl)-1,4,7,10-tetraazacyclododecane 
• 143229-09-8 10-[2-Hydroxy-3-(4-(carboxy)-cyclohexyloxy)-propyl]-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane 
• 143229-08-7 10-[2-Hydroxy-3-(4-(carboxymethyl)-phenoxy)propyl]-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane 
• 143229-10-1 10-[2-Hydroxy-3-(4-(2-carboxyethyl)-phenoxy)-propyl]-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane 
• 174700-60-8 10-[5-(2-Carboxyphenyl)-2-hydroxy-5-oxo-4-aza-pentyl]-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane 

Relevant articles and documents

Tri- and tetranuclear RuII-Gd III 2 and RuII-Gd III 3 d-f heterometallic complexes as potential bimodal imaging probes for MRI and optical imaging

The synthesis of tri- and tetranuclear RuII-GdIII2 and RuII-GdIII3 d-f heterometallic complexes of 4-aminopyridine-appended DO3A (DOTA-AMpy, 4) with 1,10-phenanthroline and 4′-(p-tolyl)-2,2′:6′,2′′-terpyridine ancillary ligands and their relaxometry and in vitro cytotoxicity studies are reported. Complexes [Ru(phen)2{Gd(DOTA-AMpy)(H2O)}2]Cl2 (7) and [Ru(ttpy){Gd(DOTA-AMpy)(H2O)}3]Cl2 (9) exhibit the "per Gd" longitudinal relaxivity of 6.19 and 7.47 mM-1 s-1 and 15.37 and 18.61 mM-1 s-1, respectively, in aqueous solution and in the presence of HSA (20 MHz, pH = 7.4, phosphate buffer saline, 37 °C). Complex 7 exhibits an emission band at 590 nm. The cell viability and cytotoxicity studies of complexes 7 and 9 against the HeLa cell lines by MTT assay demonstrate their cytotoxic activity with the IC50 values of 52.1 and 27.9 μM, respectively. Morphological assessment of apoptosis by acridine orange and ethidium bromide staining and by Hoechst-33342 assay shows marked morphological signs of apoptosis in a dose-dependent manner. Flow cytometric analysis by propidium iodide staining indicates the inhibition of HeLa cell proliferation and DNA ladder assay shows apoptotic cell death, lending support to the antitumor activity of 7 and 9. A molecular docking study reveals that these complexes intercalate with DNA and bind to HSA. Relaxometry and cytotoxicity studies indicate that complexes 7 and 9 could be used as potential bimodal imaging probes and as anticancer agents.

Synthesis and relaxivity studies of a gadolinium(III) complex of ATP-conjugated DO3A as a contrast enhancing agent for MRI

A gadolinium(III) complex of adenosine 5′-triphosphate (ATP)-appended DO3A has been synthesized in order to attain higher relaxivity and to reduce the in vivo toxicity. DO3A (2) was synthesized as the exclusive product by a single step direct trialkylation of cyclen with chloroacetic acid in water (pH 10, -4°C). ATP was then covalently appended to the DO3A framework through a propyl linker. The 3-bromopropane spacer appended DO3A (3) was synthesized by the reaction of DO3A with 1,3-dibromopropane in water/DMF in the presence of triethylamine as proton scavenger. The ATP-appended DO3A (DOSA-Pr-ATP) was synthesized by the reaction of 3 with ATP in water at room temperature. [Gd(DOSA-Pr-ATP)(H2O)2] (4) was synthesized by the reaction of DOSA-Pr-ATP with gadolinium(III) perchlorate hydrate in water. The X- and Q-band EPR spectra of 4 contain a broad band with no hyperfine splitting at both room temperature and liquid nitrogen temperature. The g-values are 2.167 and 2.033 at X- and Q-band, respectively. The magnetic moment of 4 is 7.45 BM which is close to the value for free GdIII ion. The longitudinal relaxivity, r1p, of [Gd(DO3A-Pr-ATP)(H2O)2] is 6.51 mM-1s-1 (24 MHz and 35±0.1°C), which is higher than that of [Gd(DOTA)(H2O)]- (r1p = 3.50 mM-1s-1, 20 MHz, 39°C, pH 7.3) and [Gd(DO3A)-(H2O)2] (r1p = 4.8 mM -1s-1, 20 MHz, 40°C). The higher relaxivity of 4 than for other systems with q = 2 is due to the increase in the molecular dimension of the complex by the conjugation of ATP. The relaxivity of 4 at pH 8.4 (TRIS buffer) decreases to 5.64 mM-1s-1, probably due to a change in the hydration number by the replacement of the coordinated water molecules by TRIS. The r1p relaxivity of 4 in the presence of β-cyclodextrin is 8.97 mM-1s-1 due to the increase in the molecular weight and dimension of the inclusion complex formed by the noncovalent host-guest interaction of the ATP pendant arm with the hydrophobic cavity of β-cyclodextrin. The transverse relaxivity, r2p, of 4 is 7.48 mM-1s-1 (24 MHz and 35±0.1°C). The r2p/r1p ratio of 1.16 indicates that 4 is a T 1-weighted contrast agent. The ATP moiety remains as an extended pendant arm and does not bind with the metal ion, nor does it block the coordination sites for the inner-sphere water molecules. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

A new potential contrast agent for magnetic resonance imaging: Synthesis and relaxivity studies of a gadolinium(III) complex of glucose-6-phosphate conjugated 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid

Synthesis and longitudinal and transverse relaxivities of a gadolinium(III) complex, [Gd(DO3A-Pr-Glu-6-phos)(H2O)2] (4), of glucose-6-phosphate conjugated DO3A (DO3A-Pr-Glu-6-phos = 10-(3-(glucose-6- phosphate)oxypropyl)-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane and DO3A = 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) are reported. DO3A-Pr-Glu-6-phos (L1) is synthesized by the reaction of bromopropane appended DO3A (3) with glucose-6-phosphate at room temperature. The magnetic moment of 4 is 7.49 BM, which is close to that of the free gadolinium(III) ion. The X- and Q-band epr spectra of 4 at LNT show a broad band with g-values of 2.167 and 2.033, respectively. The higher longitudinal relaxivity of 4 (r1p = 6.99 mM-1 s-1, 24 MHz, 35 °C ± 0.1) than that of [Gd(DOTA)(H2O)]- (r1p = 3.56 mM-1 s-1, 20 MHz, 39°C, pH 7.3) and [Gd(DO3A)(H2O)2] (r1p = 4.8 mM -1 s-1, 20 MHz, 40°C) is attributed to the nature of the glucose-6-phosphate pendant arm. The longitudinal relaxivity of the complex in the presence of β-cyclodextrin increases to 9.62 mM-1 s -1 due to the formation of the inclusion complex. The transverse relaxivity of 4 is 7.02 mM-1 s-1 and the r 2p/r1p ratio of 1.01 indicates that it is a T 1-weighted contrast agent.

Synthesis, relaxivity, and in vitro fluorescence imaging studies of a novel d-f heterometallic trinuclear complex as a potential bimodal imaging probe for MRI and optical imaging

A new trinuclear heterometallic RuII-GdIII2 complex of 4-aminopyridine appended DO3A (DO3A = 1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) with 2,2′-bipyridine as ancillary ligands is synthesized and its relaxometry and in vitro fluorescence imaging studies are reported. The complex [Ru(bpy)2{Gd(DOTA-AMpy)(H2O)}2]Cl2 (7) exhibits a "per Gd" longitudinal relaxivity (r1p) of 5.80 and 14.30 mM-1 s-1 in aqueous solution and in the presence of HSA, respectively (20 MHz, pH = 7.4, PBS, 37 °C). The complex 7 exhibits an intense 1MLCT absorption band at 480 nm and luminesces at 595 nm with a luminescence quantum yield of 3.2%. The fluorescence microscopy imaging study of HeLa cells incubated with 7 and stained with ethidium bromide and acridine orange confirms that the cells are viable throughout the imaging experiments and its cytotoxicity against HeLa cells, studied by the MTT assay, demonstrates its use for bioimaging studies. HeLa cell lines treated with the complex 7 and stained with Hoechst-33342 showed marked morphological signs of apoptosis in a dose-dependent manner by inducing changes in cell cycle arrest at the G2/M phase. Furthermore, apoptosis of HeLa cells, studied by the DNA ladder assay, indicates apoptotic cell death lending support for the antitumor activity of 7. A molecular docking study reveals that the complex 7 intercalates into the major groove of the DNA stabilized by hydrogen bonding and it binds with HSA by electrostatic- and hydrogen bonding interactions. The relaxometry, luminescence and fluorescence imaging studies indicate that the RuII-GdIII2 complex 7 has a good cell membrane permeability and could be considered as a potential bimodal imaging probe.

Optimized co-solute paramagnetic relaxation enhancement for the rapid NMR analysis of a highly fibrillogenic peptide

Co-solute paramagnetic relaxation enhancement (PRE) is an attractive way to speed up data acquisition in NMR spectroscopy by shortening the T 1 relaxation time of the nucleus of interest and thus the necessary recycle delay. Here, we present the rationale to utilize high-spin iron(III) as the optimal transition metal for this purpose and characterize the properties of its neutral chelate form Fe(DO3A) as a suitable PRE agent. Fe(DO3A) effectively reduces the T 1 values across the entire sequence of the intrinsically disordered protein α-synuclein with negligible impact on line width. The agent is better suited than currently used alternatives, shows no specific interaction with the polypeptide chain and, due to its high relaxivity, is effective at low concentrations and in 'proton-less' NMR experiments. By using Fe(DO3A) we were able to complete the backbone resonance assignment of a highly fibrillogenic peptide from α1-antitrypsin by acquiring the necessary suite of multidimensional NMR datasets in 3 h.

Gadobutrol intermediate, preparation method thereof and application of gadobutrol intermediate in preparation of gadobutrol

The invention discloses a gadobutrol intermediate, a preparation method thereof and application of the gadobutrol intermediate in preparation of gadobutrol. The gadobutrol intermediate is represented by a chemical formula 4 in the specification. The invention also discloses a method for preparing gadobutrol by using the gadobutrol intermediate. The method is reasonable in route design, low in raw material price, high in total yield, high in product purity, low in purification cost and good in economical efficiency, and can fully meet the requirements of industrial production of products.

NOVEL PROCESS FOR THE PREPARATION OF MACROCYCLIC CHELANT 2,2',2''-(10-(2-HYDROXYPROPYL)-1,4,7,10-TETRA AZACYCLODODECANE-1,4,7-TRIYL) TRIACETIC ACID AND IT'S COMPLEXES WITH PARAMAGNETIC METAL IONS

The present invention relates to an improved process for the preparation of macrocyclic chelant 2,2',2''-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1). The present invention further relates to the process for the preparation of metal complexes of macrocyclic chelant 2,2',2''-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1) with purity greater than 99.0% by HPLC. The present invention also relates to an improved process for the preparation of gadolinium complex of formula (1a) with macrocyclic chelant 2,2',2''-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1). The present invention further relates to a novel process for the preparation of calcium complex of formula (1b) with macrocyclic chelant 2,2',2''-(10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid of formula (1).

A 1, 4, 7, 10 - tetraazacyclododecane - 1, 4, 7 - four three-acetic acid in preparation method (by machine translation)

A 1, 4, 7, 10 - tetraazacyclododecane - 1, 4, 7 - triacetic acid preparation method. The invention the technical problem to be solved is to provide a high-efficiency, low-cost method for preparing the gadolinium cloth is mellow impurity (DO3A) and [...] complex (DO3A - Gd) process, is used for the quality control of the gadolinium cloth is mellow. In order to [...] (M1) as the starting material, first with the chloroactic acid lithium reaction synthesis impurity DO3A crude, DO3A crude with gadolinium oxide into to get DO3A - Gd, recrystallization of crude product high purity DO3A - Gd. DO3A - Gd under acidic conditions to obtain high purity xie luo DO3A. The reaction process is simple, line clear, without column chromatography, the target compound has high purity and yield, greatly reduces the production of waste gas. (by machine translation)

Lanthanide(iii) complexes of monophosphinate/monophosphonate DOTA-analogues: Effects of the substituents on the formation rate and radiolabelling yield

H4dota and its analogues are routinely used for complexation of lanthanide radioisotopes in nuclear medicine. Many of the radioisotopes have short half-lives and, thus, the complexation rate plays an important role. Notwithstanding that, the relationship between ligand structures and complexation rates is not well understood. Here we report a complexation study of H4dota and its analogues bearing one phosphonate or phosphinate pendant arm. The substituents on the phosphinate group were non-coordinating (-H) or contained another coordinating group (-CH2N(CH2COOH)2, -CH2PO2H2 or -CH2NH2). The basicity of ligands, stability of reaction intermediates, formation rates of CeIII complexes, and 177LuIII radiolabelling were studied. The complexation rates and labelling yields do not show any correlation with ligand basicity. In contrast, the additional chelating group attached to the pendant arm plays an important role. A decreased complexation rate and lower labelling yield were found for compounds bearing an additional amino group, whereas improved properties were found for the compound bearing a geminal bis(phosphinate) pendant arm. It indicates that the introduction of chelating pendant arms with acidic coordinating groups might be a promising strategy to improve radiolabelling of macrocyclic carriers with metal radioisotopes.

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