1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid

• CAS: 60239-18-1
• Catalog Number: ACM60239181-4
• Category: Main Products
• Molecular Weight: 404.42g/mol
• Molecular Formula: C16H28N4O8
• Synonyms: J-650232; AJ-80871; MFCD00068657; CHEBI:61028; LS-187777; CS-0046228; 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid; ZINC22059268; BCP13075; 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid Europium
• IUPAC Name: 2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
• SMILES: C1CN(CCN(CCN(CCN1CC(=O)O)CC(=O)O)CC(=O)O)CC(=O)O
• InChI: InChI=1S/C16H28N4O8/c21-13(22)9-17-1-2-18(10-14(23)24)5-6-20(12-16(27)28)8-7-19(4-3-17)11-15(25)26/h1-12H2,(H,21,22)(H,23,24)(H,25,26)(H,27,28)
• InChI Key: WDLRUFUQRNWCPK-UHFFFAOYSA-N
• Application: Bifunctional DOTA aconjugates to peptides and has become an established strategy for constructing target-specific metal containing agents including targeted MRI contrast agents and diagnostic and ther; ; apeutic radiopharmaceuticals.
• Complexity: 447
• Covalently-Bonded Unit Count: 1
• EC Number: 611-959-5
• Exact Mass: 404.191g/mol
• H-Bond Acceptor: 12
• H-Bond Donor: 4
• Heavy Atom Count: 28
• Monoisotopic Mass: 404.191g/mol
• NSC Number: 681107
• Rotatable Bond Count: 8
• Topological Polar Surface Area: 162A^2
• UNII: 1HTE449DGZ

Case Study

DOTA as the Foundation for Advanced MRI Contrast Agents

Stasiuk, Graeme J., et al. Chemical Communications 49.27 (2013): 2732-2746.

1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) serves as the primary chelator for first-generation blood pool MRI contrast agents, utilized in 70% of contrast-enhanced MRI scans since 1980. Its gadolinium complex (Gd-DOTA/DOTAREM) represents the gold standard due to exceptional stability compared to alternatives like DTPA, providing reliable vascular imaging.
Structural Evolution
The cyclen macrocycle's versatility enabled targeted modifications: ProHance (a DO3A derivative with ethanol pendant arm) maintained sufficient stability despite reduced coordination sites, while advanced pendant arm modifications (amides, maleimides, triazoles, pyridyl groups) created next-generation functional MRI probes-including targeted agents and environmental sensors-without compromising Gd3+ stability in DO3A-based chelates.
Water Exchange Engineering
Steric engineering by replacing ethylene with propylene bridges increased crowding around Gd3+, accelerating water exchange rates 30-50× in Gd-DOTA analogues. This strategic trade-off marginally reduced thermodynamic stability but significantly enhanced contrast efficacy by optimizing dissociation kinetics of bound water molecules.
Significance
DOTA's unique triad of inherent thermodynamic stability, macrocyclic flexibility for functionalization, and tunable kinetic properties established the molecular foundation for evolving MRI diagnostics-from foundational blood-pool imaging to specialized probes-while maintaining clinical safety standards.

DOTA Enables Targeted Liver MRI Contrast Agent

Xiao, Yan, et al. Carbohydrate Research 395 (2014): 9-14.

In this study, a novel biocompatible macromolecule (AG-CM-EDA-DOTA-Gd) was synthesized from 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a contrast agent for liver magnetic resonance imaging (MRI). For mechanism, arabinogalactan-directed DOTA-Gd selectively bound hepatocyte asialoglycoprotein receptors, enabling liver-specific accumulation at 0.094 mmol Gd3+/kg.
Synthesis of Liver-Targeting Conjugate
A three-step synthesis created the DOTA-based contrast agent:
· Carboxymethyl-arabinogalactan (AG-CM): 2.0g arabinogalactan reacted with ClCH2COOH (4.5g) in NaOH (6M, 20ml) at 60°C for 90 min, purified by dialysis and lyophilization.
· Aminated derivative (AG-CM-EDA): AG-CM (1.2g) treated with ethylenediamine (2.2ml) via EEDQ coupling at pH 3 (25°C, 5h), dialyzed and lyophilized.
· DOTA conjugation: DOTA (0.8g) activated with sulfo-NHS/EDC·HCl, then reacted with AG-CM-EDA solution (40mg/ml, 10ml) at 4°C for 24h to form AG-CM-EDA-DOTA-Gd after gadolinium chelation.
Performance of AG-CM-EDA-DOTA-Gd
At 9.4T/25°C, the conjugate showed 1.86× higher T1-relaxivity (8.87 vs. 4.76 mmol-1·L·s-1) and 4.4× greater liver enhancement (85.2% vs. 19.3%) than Gd-DOTA at equivalent Gd3+ doses, with prolonged contrast duration.

Custom Q&A

What is the molecular formula of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

The molecular formula is C16H28N4O8.

What is another name for 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

Another name for it is DOTA.

What is the CAS number of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

The CAS number is 60239-18-1.

What is the role of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

It has a role as a chelator and a copper chelator.

How many nitrogen atoms are substituted with carboxymethyl groups in 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

Four nitrogen atoms at positions 1, 4, 7, and 10 of a twelve-membered ring are substituted with carboxymethyl groups.

What is the IUPAC name of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

The IUPAC name is 2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid.

What is the InChIKey of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

The InChIKey is WDLRUFUQRNWCPK-UHFFFAOYSA-N.

What is the molecular weight of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

The molecular weight is 404.42 g/mol.

What is the PubChem CID of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

The PubChem CID is 121841.

What is the physical description of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid?

It is described as light yellow.