Cyclen

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Cat Number

INT294906

CAS Number

294-90-6

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Product Detail Description Scientific Support Customer Q&A

CAS Number

294-90-6

EINECS

608-365-3

Storage

Room temperature

Synonyms

10-Tetraazacyclododecane

Molecular Formula

C8H20N4

Molecular Weight

172.27

Smiles

C1CNCCNCCNCCN1

Appearance

White to off-white powder

Melting Point

110-113℃

Boiling Point

292.61℃

Relative Density

1.04

pKa

10.53

General Description

Cyclen (1,4,7,10-tetraazacyclododecane) is a macrocyclic tetraamine featuring a 12-membered ring with four nitrogen atoms separated by two-carbon ethylene linkers. As a cyclam analog, cyclen is a well-known metal-chelating ligand that forms extremely stable complexes with transition metal and lanthanide ions. Its cavity size is optimal for binding to smaller metal ions (Cu2+, Zn2+, Ni2+) compared to the larger cyclam ring.

Mechanism of Action

Cyclen is a polyazamacrocyclic chelator that coordinates to metal ions through its four nitrogen donors in a square-planar or octahedral geometry. The macrocyclic effect (the thermodynamic advantage of macrocyclic over acyclic ligands) results in exceptionally high formation constants (log Kf) for metal-cyclen complexes. Cyclen can be functionalized at the nitrogen atoms (to N-alkyl derivatives) or at the carbon atoms (via tosylation and nucleophilic substitution) to create targeted metal-chelating agents.

Application

Cyclen is used as a key intermediate in the synthesis of bifunctional chelators for nuclear medicine (radiopharmaceuticals), MRI contrast agents (Gd-DOTA is based on cyclen), and luminescent lanthanide complexes. The 1,4,7,10-tetraazacyclododecane scaffold is also used in the synthesis of cyclam analogs for catalytic applications, in the preparation of molecular magnets, and in supramolecular chemistry as a building block for interlocked molecules.

Cyclen (1,4,7,10-tetraazacyclododecane) is a macrocyclic tetramine that serves as the fundamental building block for MRI contrast agents. Cyclen-based ligands form highly stable and kinetically inert Gd³⁺ chelates, which are safer for clinical use than acyclic counterparts. Key synthetic methods include Richman-Atkins (tosylate protection), Weisman-Reed (reductive ring expansion), and Athey-Kiefer (bis-imidazoline intermediate) approaches. Two major derivatives are DO3A (triacetic acid) and DOTA (tetraacetic acid), synthesized by N-alkylation of cyclen.
DO3A is heptadentate leaving one coordination site for water, while DOTA is octadentate providing higher stability. Gd³⁺ complexes exist in square antiprismatic (SA) and twisted square antiprismatic (TSA) geometries in solution, affecting water exchange rates. Relaxivity enhancement strategies include increasing hydration number, prolonging rotational correlation time via macromolecular conjugation, and optimizing water exchange. Cyclen-derived contrast agents are preferred for their thermodynamic stability, kinetic inertness, and lower toxicity, making them suitable for clinical MRI applications.

References

Rashid H U, et al. Cyclen-based Gd3+ complexes as MRI contrast agents: Relaxivity enhancement and ligand design. Bioorganic & medicinal chemistry, 2016, 24(22): 5663-5684.

What is the recommended storage condition for Cyclen?

It should be stored at controlled room temperature in a well-sealed container, protected from moisture and direct light, to maintain its chemical integrity throughout the shelf life.

What documentation is provided with each batch of Cyclen?

Each batch is accompanied by a Certificate of Analysis (COA) covering identity, potency, and relevant purity tests. Safety Data Sheets (SDS) are available upon request.

What is the primary synthetic application of Cyclen?

It is widely used as a key building block or intermediate in multi-step pharmaceutical synthesis workflows, providing versatile reactivity for constructing target molecular architectures.

Is Cyclen available in high-chemical-purity grade for pharmaceutical synthesis?

Yes, it is supplied in high chemical purity grades suitable for demanding pharmaceutical intermediate applications. Specifications and analytical data are available upon request.

Is Cyclen suitable for use in regulated pharmaceutical processes?

Yes, it is manufactured under quality standards consistent with regulated pharmaceutical applications, including in-process controls and release testing aligned with industry requirements.