14-azido-3,6,9,12-tetraoxatetradecan-1-amine hydrochloride (99%)
Molecular Formula: C10H23ClN4O4
CAS#: 3025839-69-1
SMILES: [NH3+]CCOCCOCCOCCOCCN=[N+]=[N-].[Cl-]
MDL#: MFCD35452378
Catalog#: AMTGC1459-AT25
Molecular weight: 298.77 g/mol
Appearance:
Purity: 99%
Storage: Long-term storage in a freezer at -20 °C
Solubility: Dichloromethane, Chloroform, Methanol
Other names:
- 14-azido-3,6,9,12-tetraoxatetradecan-1-aminium chloride
- Azido-PEG4-amine hydrochloride
Fields of Interest:
Bioconjugation, click chemistry, chemical biology, molecular probe development, medicinal chemistry, PEG linker synthesis, surface functionalization
Background
14-Azido-3,6,9,12-tetraoxatetradecan-1-amine hydrochloride (CAS 3025839-69-1) is the hydrochloride salt of a heterobifunctional polyethylene glycol (PEG) linker containing an azide and a primary amine. Its defined PEG4 spacer incorporates four ether oxygen atoms, providing a flexible, polar connection between the two terminal functional groups. This structure supports the design of molecular conjugates assembled through complementary amine-coupling and azide-click reactions.
In the hydrochloride form, the amine is protonated and paired with a chloride counterion. Amine-coupling conditions therefore need to provide sufficient unprotonated amine, typically through an appropriate base or reaction pH. The available primary amine can then react with an activated carboxylic acid to form an amide linkage while retaining the azide under compatible conditions. This enables staged assembly: one component is attached through the amine, followed by a second through azide–alkyne chemistry. The defined spacer also provides a consistent structural element for comparing linker lengths in probe and conjugate development.
Applications
The linker’s primary amine and azide provide complementary routes for exploring bioconjugation, molecular labeling, and functional materials.
Amide coupling and probe synthesis: After accounting for the hydrochloride salt, the primary amine can react with activated carboxyl-containing molecules, including suitable N-hydroxysuccinimide (NHS) esters. This offers a route for attaching the PEG4 linker to a ligand, reporter, or molecular building block while preserving an azide for subsequent functionalization.
Click chemistry and bioconjugation: The azide can participate in copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) with terminal alkynes, forming a triazole linkage. This chemistry provides a modular approach to joining appropriately functionalized labels, affinity tags, or biomolecular components through the PEG spacer.
Copper-free conjugation: The azide also offers a reaction site for strain-promoted azide–alkyne cycloaddition (SPAAC) with strained cyclooctyne reagents. This approach is relevant when designing conjugation workflows involving components sensitive to copper exposure. Reaction conditions should accommodate both the selected partner and the linker’s ammonium salt form.
Surface and polymer functionalization: Attachment through the amine offers a potential route for introducing a PEG-spaced azide onto appropriately activated carboxyl-containing surfaces or polymers. Subsequent click conjugation could install a reporter or recognition group, with the PEG4 segment separating the attached component from the supporting material.
Literature:
- European Journal of Medicinal Chemistry, 2020, vol. 201
- Montalbetti, C. A. G. N.; Falque, V. “Amide bond formation and peptide coupling.” Tetrahedron 2005, 61, 10827–10852. DOI: 10.1016/j.tet.2005.08.031
- Reviews carboxylic acid activation and amide-forming methods relevant to incorporating amine-functionalized PEG linkers into larger molecular constructs.
- Hong, V.; Presolski, S. I.; Ma, C.; Finn, M. G. “Analysis and Optimization of Copper-Catalyzed Azide–Alkyne Cycloaddition for Bioconjugation.” Angewandte Chemie International Edition 2009, 48, 9879–9883. DOI: 10.1002/anie.200905087
- Examines CuAAC conditions for biomolecular conjugation, providing practical context for coupling azide-functionalized linkers with alkyne-bearing partners.
- Baskin, J. M.; et al. “Copper-free click chemistry for dynamic in vivo imaging.” Proceedings of the National Academy of Sciences 2007, 104, 16793–16797. DOI: 10.1073/pnas.0707090104
- Demonstrates cyclooctyne-mediated labeling of azide-bearing biomolecules, illustrating the chemistry underlying copper-free conjugation strategies.