Benzaldehyde-PEG4-azide , CAS No.1151451-77-2

CAS: 1151451-77-2 Cat. No.: B1449121 Formule: C₁₅H₂₁N₃O₅ Poids moléculaire: 323.34 PubChem CID: 146026155

Storage

Store at 2-8°C,Argon charged

Shipped In

Wet ice

Vue d’ensemble

Benzaldehyde-PEG4-azide is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs. Benzaldehyde-PEG4-azide is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.

Specifications

Conditions de stockage de stockage

Store at 2-8°C,Argon charged

Expédié en

Wet ice

Ce produit nécessite l'expédition en chaîne froide. Les services terrestres et autres services économiques ne sont pas disponibles.

Noms et identifiants

• Sourires canoniques: C1=CC(=CC=C1C=O)OCCOCCOCCOCCN=[N+]=[N-]
• IUPAC Name: 4-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]benzaldehyde
• InChIKey: MJNGKISXZKKSNN-UHFFFAOYSA-N
• INCHI: 1S/C15H21N3O5/c16-18-17-5-6-20-7-8-21-9-10-22-11-12-23-15-3-1-14(13-19)2-4-15/h1-4,13H,5-12H2
• PubChem CID: 146026155
• Poids moléculaire: 323.34

Application Protocols

Not applicable to this product.

• No validated bioassay protocols (WB, IHC, IF, FC) are defined for a small-molecule linker. For practical guidance, see Reaction Conditions and Buffer Applications sections for general conjugation workflows.

Biological Roles

Item-specific facts (from Product Data)

• None provided; this product is designated for research use only.

General context (literature; no therapeutic/clinical claims)

• Endogenous role: The compound is synthetic and not known to have intrinsic biological roles. Its benzaldehyde unit can engage in reversible imine chemistry with primary amines on biomolecules (e.g., N-termini or lysines), which is exploited for labeling or capture under controlled conditions.
• Bioconjugation utility: The azide enables bioorthogonal reactions (CuAAC/SPAAC) with alkyne-bearing probes, permitting site-selective modifications in complex biological mixtures with minimal off-target reactivity.
• Spacer effects: PEG4 improves aqueous compatibility, reduces nonspecific protein binding, and can decrease immunogenicity/aggregation in conjugates compared to non-PEGylated linkers (general PEG behavior).
• Analytical/biochemical workflows: Frequently used to introduce aldehyde handles onto clicked constructs or, conversely, to add triazole-linked tags to aldehyde-presenting biomolecules. Resulting conjugates are amenable to MS, fluorescence, or affinity readouts depending on the partner.

Note: Any use in live cells/organisms should be fully validated for cytotoxicity and compatibility; follow institutional biosafety and chemical safety procedures.

Buffer Applications

Item-specific facts (from Product Data)

• None provided.

Applicability to buffers (literature/general)

• This is not a buffering agent. However, pH and buffer choice are critical for its typical ligation reactions:
  • Oxime/hydrazone ligation: Use 50–200 mM acetate or citrate buffers at pH 4.5–6.0; aniline (50–100 mM) can catalyze formation significantly. Maintain mild temperatures (20–37 °C).
  • Schiff base formation (for reductive amination): Perform imine formation in mildly acidic conditions (pH 5.5–6.5) followed by reduction (e.g., NaBH3CN or picoline borane) in acetate/phosphate buffers; avoid strong acid/base that degrades azide.
  • CuAAC: Commonly run in PBS, HEPES, or Tris buffers (pH 7.0–8.0) with 1–2 mM CuSO4, 5–10 mM sodium ascorbate, and a ligand (e.g., 0.1–1 mM TBTA/THPTA/BTTAA). Aeration control and chelators influence copper availability.
• Solubility aids: Up to 10–30% DMSO, DMF, or ethanol may be added to aqueous buffers to dissolve PEGylated linkers.

Note: These are general literature conditions and not product specifications. Optimize for your substrate and analytical endpoints.

Green Alternatives

Context (literature/guidance)

• The reagent itself is a specialized bifunctional linker; “greener” considerations focus on solvent and catalyst choices during use.

Greener practice suggestions (general)

• Prefer aqueous or water-miscible media for click and ligations. Use ethanol or 2-propanol as co-solvents when feasible instead of DMF/NMP.
• For click chemistry, copper-free SPAAC (strain-promoted) eliminates Cu(I) waste and potential biomolecule damage; tradeoff is the need for cyclooctyne partners (cost/availability).
• If using CuAAC, select benign ligands (e.g., BTTAA/THPTA) that allow lower copper loadings in water and facilitate downstream removal.
• Replace NaBH3CN in reductive amination with picoline borane or sodium triacetoxyborohydride, which can be easier to handle and reduce cyanide hazards.

Compact comparison (literature; not item-specific specifications)

• Option: DMF vs EtOH/H2O
  • Pros (EtOH/H2O): lower toxicity, easier waste handling, renewable component
  • Cons: potential lower solubility/rate; may need co-solvent
• Option: CuAAC vs SPAAC
  • Pros (SPAAC): metal-free, biocompatible
  • Cons: Requires strained alkyne; slower with some partners
• Option: DCM workups vs EtOAc/MTBE
  • Pros (EtOAc/MTBE): lower chlorinated solvent usage
  • Cons: May change extraction efficiency for PEGylated products

Pharmaceutical Uses

Item-specific facts (from Product Data)

• None provided.

General formulation/manufacturing context (no therapeutic claims)

• Conjugation intermediate: Benzaldehyde-PEG4-azide is a useful heterobifunctional spacer for assembling complex small-molecule or bioconjugate architectures (e.g., payload attachment to biomacromolecules) in discovery and process development labs.
• Process considerations: PEGylated linkers can improve solubility and processability of hydrophobic APIs or probes during intermediate steps. The azide/triazole motif is robust to many process conditions, enabling late-stage diversification by CuAAC.
• Excipient status: This specific molecule is not a standard pharmacopeial excipient. Any use in cGMP settings requires full qualification (identity, purity, residual solvents/metals, extractables/leachables) and risk assessments for aldehyde/azide content.
• Analytical control: Track aldehyde content (e.g., DNPH derivatization, quantitative NMR) and azide integrity (IR ~2100 cm−1, LC–MS) through storage and process steps.
• Removal of catalysts/impurities: For CuAAC processes, plan for copper removal (chelating resins, diafiltration) and demonstrate acceptable residual levels per ICH Q3D if applicable.

Physical Properties

Item-specific facts (from Product Data)

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Other specifications (bp, mp, density, refractive index, UV cutoff, water/peroxide/metal limits): Not specified for this item; refer to CoA/Spec Sheet.

General/literature expectations for benzaldehyde–PEG4–azide linkers (not product specifications)

• Physical state: PEGylated azide–aldehyde linkers are often low-melting solids or viscous oils; hygroscopic tendencies are common due to PEG content.
• Solubility: typically highly soluble in polar aprotic solvents (DMF, DMSO, acetonitrile) and alcohols; moderate to high solubility in water depending on exact end-group structures; low solubility in nonpolar hydrocarbons.
• Partitioning: PEG spacers reduce logP relative to neat benzaldehyde; expect amphiphilic behavior (literature qualitative trend).
• Spectroscopic handles: benzaldehyde shows a strong 1H NMR formyl singlet near 9.8–10.1 ppm; azide IR stretch typically ~2100 cm−1; PEG methylenes at ~3.4–3.8 ppm (1H) and ~70 ppm (13C). These are qualitative identifiers, not specifications.

Note: For exact material attributes of this lot (mp, purity, residual solvents, water content), consult the product CoA/SDS.

Quality and Grades

Item-specific facts (from Product Data)

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers: Not specified for this item; refer to CoA/Spec Sheet.

General guidance for this class of linker (literature/industry practice)

• Typical expectations: For bioconjugation and library synthesis, materials are often supplied at ≥95% purity by HPLC/LC–MS, with low residual solvents and well-characterized identity (NMR, HRMS). UV profile is usually benign across 220–400 nm except for the benzaldehyde chromophore around 250–280 nm.
• What grade implies: “Bioconjugation grade” or “Reagent grade” commonly indicates strict control of water content and aldehyde integrity (minimized hydrate/acid impurity), and low azide decomposition products (amines/imidates). Absent an explicit grade, verify suitability with a small-scale pilot reaction.
• Stabilizer/antioxidant: Generally not required for aldehyde–PEG–azides; some vendors bottle under argon and include desiccants to preserve aldehyde functionality. This item is Argon charged per Product Data.
• Documentation: Request CoA for exact assay, residual solvent profile, and analytical traces (HPLC, NMR, MS) relevant to your regulatory or analytical needs.

Reaction and Applications

Item-specific facts (from Product Data)

• Manufacturer Applications: Not specified beyond “For research use only.”

Applications for benzaldehyde–PEG4–azide linkers (literature/general)

• Orthogonal conjugation: Dual-reactive handle enables sequential or convergent assembly—CuAAC/SPAAC at the azide terminus and reversible/derivatizable chemistry at the aldehyde.
• Click chemistry: Azide participates in CuAAC with terminal alkynes (Huisgen cycloaddition) to form stable 1,2,3-triazoles. For biomolecule labeling, use CuSO4/sodium ascorbate with a ligand (TBTA, THPTA, BTTAA) to minimize protein oxidation; SPAAC with cyclooctynes avoids copper.
• Imine chemistry at aldehyde: Forms Schiff bases with primary amines; hydrazone/oxime ligations with hydrazides/alkoxyamines are faster and more stable. Reductive amination (NaBH3CN, picoline borane) converts imines to secondary amines, giving permanent linkages.
• Spacer utility: PEG4 improves aqueous accessibility, reduces steric/binding interference in bioconjugates, and enhances solubility of hydrophobic payloads.
• Library synthesis: Useful as a bifunctional building block for triazole-linked combinatorial libraries incorporating benzaldehyde-derived motifs.
• Surface modification: Immobilize via click to alkyne-functionalized surfaces/nanomaterials, leaving the aldehyde free for ligand capture (e.g., hydrazide beads) or vice versa.
• Analytical tagging: The aromatic aldehyde UV chromophore aids HPLC tracking; triazole formation provides mass shift confirmation in LC–MS.

Reaction Conditions

Item-specific facts (from Product Data)

• None provided.

Representative literature conditions (general guidance; not product specifications)

• CuAAC (azide + terminal alkyne):
  • Solvent: t-BuOH/H2O (1:1), ACN/H2O, or DMF/H2O.
  • Catalysis: 0.5–2 mol% CuSO4 with 2–10 mol% ligand (TBTA/THPTA/BTTAA); 5–20 mM sodium ascorbate to generate Cu(I) in situ.
  • Temp/time: 20–25 °C, 0.5–4 h (often complete within 1 h for small molecules). Protect from air for optimal rates.
• SPAAC (copper-free):
  • Solvent: neat aqueous buffer (PBS/HEPES) or with 10–30% DMSO.
  • Temp/time: 20–37 °C, 1–24 h depending on cyclooctyne partner (e.g., DBCO, BCN).
• Oxime/hydrazone ligation at aldehyde:
  • Buffer: 100 mM acetate or citrate, pH 4.5–5.5, optionally 50–100 mM aniline catalyst.
  • Temp/time: 20–37 °C, 1–6 h; shift to neutral pH after formation to enhance stability.
• Reductive amination:
  • Conditions: aldehyde + primary amine in MeOH/DMF or buffered aqueous MeOH; NaBH3CN (1.5–3 equiv) or picoline borane at pH 5.5–6.5.
  • Temp/time: 20–25 °C, 2–16 h.

Always optimize with test reactions and consult primary literature for your specific substrates.

Safety and Handling

Item-specific facts (from Product Data)

• GHS classification, pictograms, signal word, H-statements: Not specified for this item; refer to SDS.
• Storage: Store at 2–8 °C, Argon charged. Shipped on wet ice.

General safety guidance (literature/good laboratory practice; defer to SDS)

• Hazard profile: Contains an aldehyde (can be a skin/eye irritant and sensitizer) and an organic azide (may pose thermal decomposition/pressure risks if overheated or contaminated; typically less hazardous than inorganic azides but handle with care). Avoid strong acids with heavy metals that can form metal azides in waste streams.
• Incompatibilities: strong oxidizers; strong reducing agents; acids/bases that can degrade the azide; nucleophiles that may react with the aldehyde. Avoid copper powder and other reactive metals in dry state unless performing controlled CuAAC.
• PPE: lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Work in a fume hood to control vapors and to contain click-chemistry copper catalysts/ligands.
• Handling: keep container tightly closed under inert gas; minimize exposure to moisture to reduce aldehyde hydration and PEG-associated hygroscopic uptake.
• First aid (overview): eye/skin contact—rinse with water for ≥15 min; inhalation—fresh air; ingestion—rinse mouth, do not induce vomiting; seek medical attention. Always consult the SDS for authoritative instructions.
• Waste: segregate copper-containing aqueous click waste; avoid contact of azides with lead/copper plumbing.

Solvent Selection

Item-specific facts (from Product Data)

• No item-specific solvent recommendations are provided for this SKU.

General solvent behavior (literature/typical for PEG4 aldehyde–azides)

• Polarity/miscibility: PEG4 imparts strong affinity for polar aprotic media. Expect excellent solubility in DMSO, DMF, NMP, acetonitrile, and methanol/ethanol; moderate in water; poor in alkanes and toluene unless co-solvent is used.
• Choosing solvents by transformation:
  • CuAAC click: DMF, DMSO, t-BuOH/H2O (1:1), or ACN/H2O are common. Add TBTA/BTTAA ligands for copper stabilization.
  • SPAAC (copper-free): purely aqueous buffers (PBS, HEPES) often suffice; add small % DMSO/DMF if needed.
  • Oxime/hydrazone formation: aqueous acetate/citrate buffers (pH 4.5–6.0) with 10–50% ACN, DMF, or alcohol cosolvent enhance solubility and rates. Aniline or p-phenylenediamine can catalyze (literature practice).
• Dry media: Use anhydrous solvents when preserving free aldehyde, especially prior to conjugation; molecular sieves can suppress aldehyde hydration.
• Comparison notes:
  • DMSO vs DMF: DMSO is more benign/toxicologically preferred for bio-compatibility but may complicate MS; DMF is easier to remove but is a reproductive toxin.
  • ACN/H2O blends provide fast CuAAC kinetics and easy workup; alcohols can participate in side acetalization under strongly acidic conditions (usually minimal at pH 5–6).

Storage and Reconstitution

Item-specific facts (from Product Data)

• Storage: Store at 2–8 °C, Argon charged.
• Shipping: Shipped on wet ice.

General guidance (literature/best practice)

• Atmosphere: Keep tightly sealed under inert gas (Ar or N2) to preserve aldehyde integrity and limit moisture uptake by the PEG chain.
• Light/moisture: Protect from light and humidity; include desiccant in secondary containment if long-term storage is anticipated.
• Stability: Organic azides are generally stable at refrigerated temperatures when uncontaminated; avoid heat and contact with heavy metals in dry waste. Aldehydes can hydrate/oxidize; periodic QC by NMR/LC–MS is prudent for long storage.
• Reconstitution: For stock solutions, use anhydrous DMSO, DMF, or acetonitrile. Typical working concentrations for conjugations are 10–100 mM (prepare fresh or aliquot and freeze to minimize freeze–thaw cycles). If aqueous use is required, dissolve in minimal DMSO/DMF then dilute into buffer at target pH.
• Freeze–thaw: If freezing solutions, store at −20 °C or −80 °C in aliquots to avoid repeated cycles; warm to room temperature before opening to reduce condensation.
• Labeling: Note preparation date/solvent and monitor for changes (odor/color, new peaks in HPLC) indicating aldehyde degradation.

For definitive stability limits and shelf life, refer to the product CoA/SDS.

Structure and Identity

Item-specific facts (from Product Data)

• Product name: Benzaldehyde-PEG4-azide (SKU: B1449121)
• CAS: 1151451-77-2
• CID: 146026155
• InChIKey: 220777 (as provided)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

General structural description (literature/typical for this scaffold)

• Functional groups: an aromatic aldehyde (benzaldehyde) at one terminus and an organic azide (–N3) at the other, connected by a tetraethylene glycol (PEG4) spacer.
• PEG4 spacer: typically –(CH2–CH2–O)4–; confers hydrophilicity and flexibility, increases aqueous/polar solvent compatibility, and spaces reactive termini ~18–20 Å apart (literature estimate for fully extended PEG4).
• Connectivity: the benzaldehyde is commonly attached via an ether or benzylic linker to PEG4; the distal terminus bears a primary azide suitable for CuAAC/SPAAC. Exact regiochemistry for this catalog item is not specified here; refer to CoA/Spec Sheet.
• Stereochemistry: none expected (no stereocenters in the minimal scaffold as commonly supplied).

Synthetic Utility

Item-specific facts (from Product Data)

• None provided.

General synthetic value (literature)

• Functional orthogonality: Combines an electrophilic aldehyde with a latent 1,3-dipole (azide), enabling divergent synthetic routes—imine formation/reduction on one end and cycloaddition on the other.
• Named reactions:
  • CuAAC/SPAAC to furnish triazoles from the azide terminus.
  • Reductive amination of the benzaldehyde to give secondary amines; oxime/hydrazone ligations followed by reduction (NaBH3CN, NaBH(OAc)3, or picoline borane) to stabilize linkages.
  • Acetal protection of the aldehyde (e.g., ethylene glycol, PTSA) if orthogonal protection is required during azide transformations.
• Retrosynthetic handle: Serves as a linchpin to introduce PEG spacing into small molecules while maintaining a modular point of diversification at the aryl position.
• Late-stage functionalization: The aldehyde allows attachment to amine-containing fragments/biomolecules under mild conditions; the azide can be “clicked” at the end to install reporters, affinity tags, or drug fragments.
• Purification considerations: PEG chains can smear on silica; reverse-phase HPLC or normal-phase with polar modifiers (MeOH, i-PrOH, 1–5% NH3 or AcOH) often improves chromatographic behavior.

Target Specificity

Not applicable to this product.

• This is a small-molecule linker, not an antibody, enzyme, or ligand with defined biological targets. No antigen/epitope, species reactivity, clone, or isotype information applies.