Thiol-PEG3-phosphonic acid , CAS No.1360716-36-4

CAS: 1360716-36-4 Cat. No.: T1445155 Formula: C₈H₁₉O₆PS Peso molecolare: 274.27

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Panoramica

Thiol-PEG3-phosphonic acid is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

Specifications

Condizioni di conservazione di stoccaggio

Store at -20°C

Spedito in

Ice chest + Ice pads

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Nomi e identificatori

• Peso molecolare: 274.27

Application Protocols

No validated biological assay protocols are provided in the Product Data for this item. The following are general workflow outlines (literature-based) and should be optimized by the user:

• Oxide surface functionalization (phosphonate anchoring):

  1. Clean/dehydrate substrate (e.g., UV-ozone or solvent rinse and bake).
  2. Immerse in 1–10 mM linker solution in EtOH/H2O (e.g., 95:5), optionally mildly acidic; exclude competing anions.
  3. Incubate 2–24 h at RT to 80°C (substrate dependent).
  4. Rinse thoroughly; optional anneal to strengthen binding.

• Thiol–maleimide coupling to a maleimide-functional partner:

  1. Dissolve partner at 0.1–5 mM in pH 6.5–7.5 buffer; degas.
  2. Add Thiol-PEG3-phosphonic acid (1.0–1.2 eq), with minimal DMSO cosolvent if required.
  3. React 30–120 min at RT; monitor by LC/MS.
  4. Quench residual maleimide (e.g., with cysteine or mercaptoethanol) and purify.

These outlines are provided as general guidance only and are not item-specific validated procedures.

Biological Roles

This compound is a synthetic, non-natural bifunctional PEG linker and does not have an endogenous biological role. The notes below reflect general biochemical interactions relevant to its functional groups (literature/general information).

• PEG segment: Poly(ethylene glycol) is widely used to increase hydrophilicity and reduce nonspecific protein adsorption on surfaces (“antifouling”). Short PEG3 spacers provide some hydration layer yet retain compact geometry.
• Thiol functionality:
  • Reacts selectively with accessible cysteine residues on proteins via maleimide or haloacetyl handles introduced on the counterpart molecule, enabling site-selective conjugation.
  • Can form disulfides under oxidizing conditions, providing reversible linkages exploitable in redox-responsive systems.
• Phosphonic acid functionality:
  • Polyanionic at neutral pH (typically –2 charge when fully deprotonated), enabling electrostatic interactions with cationic surfaces or metal centers.
  • Mimics aspects of phosphate binding to metal ions, leading to strong coordination on metal oxides.
• Biocompatibility context: PEGylated surfaces are often used in biomaterials to mitigate protein adsorption and cell adhesion; however, any application of this product must remain within research use, with compatibility validated empirically for each biological system.

No pharmacological, enzymatic, or signaling roles are attributed to this compound; it serves purely as a chemical tool for constructing or modifying biomolecular/supramolecular assemblies in research.

Buffer Applications

This product is not a buffering agent and is not used to maintain pH in biochemical assays. However, its chemistry intersects with buffer selection during conjugation (literature guidance):

• Thiol–maleimide coupling: Prefer buffers at pH 6.5–7.5 (e.g., phosphate, HEPES) to balance thiolate formation and maleimide stability; avoid primary amines (e.g., Tris) if competing reactions are possible.
• Thiol–haloacetyl alkylation: Often run near neutral pH; chloride/iodide salts do not generally interfere, but strong nucleophiles should be minimized.
• Phosphonate solubility: Aqueous solubility improves with increasing pH due to deprotonation; carbonate or phosphate buffers can aid dissolution but may introduce competitive anions in metal-binding steps.

For oxide surface modification, water/alcohol mixtures or mildly acidic aqueous media are commonly employed rather than classical biological buffers.

Green Alternatives

Selection of linkers and deposition media can influence environmental footprint. While a PEG3 phosphonic acid/thiol linker is specialized, greener choices often relate to solvent systems and alternative anchors.

• Greener solvents (literature guidance):

  • Prefer water/ethanol mixtures for oxide functionalization over chlorinated solvents or high-boiling amides, where compatible.
  • For stock solutions, minimize DMSO/DMF volumes; use ethanol or water when stability permits.

• Alternative anchoring chemistries (contextual tradeoffs):

  • Catechol/DOPA-PEG–thiol: Strong oxide adhesion in aqueous media; catechols can undergo oxidation/polymerization—requires antioxidant management.
  • Silane-PEG–thiol: Silanes cure readily on silica/oxide surfaces; however, they may release alcohols and can require anhydrous conditions and careful moisture control to avoid polymeric byproducts.
  • Carboxylate-PEG–thiol: Greener synthesis routes exist, but oxide binding is typically weaker than phosphonates; may desorb under harsh aqueous conditions.

Small comparison (literature-based):

• Phosphonate vs silane anchors: phosphonates offer robust binding across a range of metal oxides with less propensity for uncontrolled polymerization; silanes are excellent on silica but often less stable on non-silica oxides.
• Phosphonate vs catechol: both bind strongly; catechols allow aqueous-only processing but can be redox-sensitive.

Overall, the most impactful “green” lever is replacing high-toxicity solvents and avoiding heavy-metal catalysts during downstream conjugations.

Pharmaceutical Uses

No clinical/therapeutic claims are made for this research reagent. In formulation and process development contexts (literature/general):

• Surface modification of particulates: Phosphonate anchoring enables robust PEGylation of metal oxide nanoparticles (e.g., iron oxide) to improve colloidal stability in various media. The thiol terminus can serve as an attachment point for further ligands.
• Device coatings and diagnostic platforms: PEGylated phosphonate layers are employed on oxide-rich substrates (e.g., glass/ITO) to reduce nonspecific adsorption in analytical devices. The thiol can be leveraged to immobilize thiol-reactive probes or capture layers.
• Conjugation intermediate: Functions as a spacer in the assembly of bioconjugates for in vitro assays, imaging agents, or analytical standards.

Regulatory/compendial status:

• Pharmacopeial monographs: None known for this specific linker (literature/context). Any use in regulated manufacturing would require internal qualification and impurity profiling.
• Excipients: PEG-based materials are common excipients; however, a PEG3 linker with thiol/phosphonate termini is a specialized research intermediate and should be qualified for any specific application.

Always limit to research and development activities unless independently validated for process use.

Physical Properties

Item-specific physical constants are not provided in the Product Data. The following are general expectations for this class of PEGylated bifunctional linkers; treat as literature guidance only.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight / formula: Not specified for this item; refer to CoA/Spec Sheet.
• Acidity/basicity: Phosphonic acid is a strong dibasic acid (pKa1 typically ~1–2; pKa2 ~6–8, literature for alkylphosphonic acids). Actual pKa can shift due to PEG and linker architecture.
• Polarity: Highly polar due to multiple ether oxygens and terminal phosphonic acid; typically water-miscible (literature expectation for short PEG linkers with acidic termini).
• Solubility (literature expectations):
  • Water: good to excellent when deprotonated; moderate in strongly acidic media due to reduced ionization.
  • Alcohols (MeOH/EtOH/iPrOH): generally soluble.
  • Polar aprotic solvents (DMSO, DMF): highly soluble.
  • Nonpolar solvents (hexanes, toluene): poorly soluble.
• Boiling/melting points, density, refractive index, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Practical implications (general):

• Solutions are hygroscopic and can retain water due to PEG ether oxygens.
• The thiol may slowly oxidize to disulfide in aerated solutions; minimize air exposure.

Quality and Grades

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

Context and guidance (general):

• For surface chemistry, nanomaterials, and bioconjugation work, users often require high chemical purity and low levels of oxidized byproducts (e.g., disulfides) and inorganic impurities that might compete for binding to metal oxides.
• If HPLC or LC–MS analytics are part of your workflow, consider grades advertised as HPLC or LC–MS suited, which typically emphasize low UV background and stringent impurity control (literature/generic guidance).
• If stabilizers or additives are used to protect thiols from oxidation, they will be indicated on the product CoA/spec; none are listed in the Product Data here.

Verification:

• Request the Certificate of Analysis (CoA) for batch-specific assay, residual solvents, and byproduct profile.
• For critical applications (e.g., monolayer formation), perform a quick iodometric or Ellman’s test (literature method) to confirm free thiol content on receipt and after storage.

Reaction and Applications

Thiol-PEG3-phosphonic acid is a versatile bifunctional linker enabling orthogonal surface attachment and conjugation.

Key application families (literature/generic):

• Surface anchoring to metal oxides: Phosphonic acids form robust mono-/bi-/tridentate complexes on TiO2, ZrO2, Fe3O4, Al2O3, and ITO. Used to fabricate self-assembled monolayers (SAMs), antifouling layers, and ligand shells on nanoparticles/quantum dots.
• Gold/silver interfacing: The terminal thiol chemisorbs to Au/Ag surfaces, enabling mixed monolayers or bridging between oxide-bound substrates and noble metals.
• Bioconjugation linker:
  • Thiol–maleimide coupling (Michael addition) for selective cysteine labeling.
  • Thiol–haloacetyl alkylation (SN2) to generate thioethers.
  • Disulfide exchange/formation for reversible linkages (redox-cleavable constructs).
• Polymer/film modification: Incorporation into PEGylated coatings to increase hydrophilicity and reduce nonspecific adsorption on device surfaces while providing a second functional handle.

Practical notes (general):

• Maintain free-thiol state by minimizing oxygen; verify with Ellman’s reagent prior to critical coupling.
• For oxide binding, pre-clean and dehydrate surfaces; mild heating (50–120°C, substrate dependent) or extended soak improves coverage (literature practice). Avoid conditions that degrade substrates.
• Control ionic strength and pH in aqueous deposition to balance solubility and binding kinetics; phosphonate anchoring is often effective from mildly acidic ethanol/water mixtures.

Manufacturer Applications: Not specified in Product Data; the above expands typical literature uses for this functionality.

Reaction Conditions

General literature guidance for the two reactive termini; optimize per substrate.

• Thiol–maleimide coupling:

  • Solvent: Aqueous buffer (phosphate/HEPES) with 0–20% DMSO or ethanol cosolvent.
  • pH: 6.5–7.5 (limits maleimide hydrolysis and ring opening).
  • Temperature: 20–25°C.
  • Time: 0.5–2 h typically; monitor by LC/MS.
  • Additives: Degas buffers; include low oxygen to prevent thiol oxidation. EDTA can chelate adventitious metals.

• Thiol–haloacetyl (alkylation):

  • Solvent: Aqueous or mixed aqueous–organic.
  • pH: ~7.5–8.2 to increase thiolate fraction without excessive side reactions.
  • Temperature: 0–25°C.
  • Time: 1–4 h.

• Thiol–ene (radical):

  • Solvent: EtOH, ACN, or neat; oxygen-free conditions.
  • Photoinitiation: 365–405 nm with a suitable photoinitiator (e.g., DMPA, literature) or thermal initiator (AIBN) for ene substrates.
  • Temperature: Ambient; minutes to hours depending on light intensity.

• Phosphonate surface grafting (oxide substrates):

  • Media: EtOH/H2O (e.g., 95:5) or dry polar aprotic solvent.
  • pH: Often mildly acidic to neutral to promote condensation/coordination.
  • Temperature: RT to 80–120°C (substrate dependent) for 1–24 h; post-anneal can improve robustness (literature practice).

All parameters are literature/general guidelines; verify compatibility with your specific substrates and avoid conditions that compromise the PEG or thiol integrity.

Safety and Handling

Follow standard laboratory safety practices. Item-specific GHS details are not provided in the Product Data; consult the SDS for authoritative information.

• GHS/Hazards:
  • Signal word / H-statements / Pictograms: Not specified for this item; refer to SDS.
• Primary hazards (general for functionality):
  • Thiol group: May exhibit strong odor; can oxidize to disulfides on exposure to air/oxidants. Some thiols can cause skin/eye irritation and sensitization (literature generality).
  • Phosphonic acid: Corrosive/irritant potential due to acidity; may cause eye/skin irritation. Avoid contact with bases and reactive metals in concentrated form.
• Recommended PPE: Lab coat, safety glasses or face shield, and appropriate chemically resistant gloves (e.g., nitrile). Work in a fume hood when weighing or preparing solutions to control vapors/odors and to limit oxidation.
• Handling tips (general):
  • Use inert atmosphere (N2/Ar) when feasible to limit thiol oxidation.
  • Keep containers tightly closed; minimize headspace oxygen.
  • Prepare fresh solutions when possible; add a reducing environment only if compatible with your application.
• Incompatibilities (general): Strong oxidizing agents (thiol oxidation), strong bases/acids may alter speciation/solubility; reactive metal salts may complex with the phosphonate.
• First-aid overview (general):
  • Skin/eye contact: Rinse with water for several minutes; remove contaminated clothing; seek medical attention as needed.
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.

Always defer to the official SDS for classification, response, and disposal guidance.

Solvent Selection

This amphiphilic, PEGylated bifunctional acid typically shows strong affinity for polar solvents (literature expectations). Item-specific solubilities are not provided; verify experimentally for your batch.

• Polarity class (general): Highly polar protic/aprotic compatible due to PEG ether oxygens and phosphonic acid.
• Expected miscibility/solubility (literature):
  • Water and aqueous buffers: good, particularly above pH ~2 where partial deprotonation enhances solubility.
  • DMSO/DMF/NMP: excellent solubility for stock solutions.
  • Alcohols (MeOH/EtOH/iPrOH): typically good.
  • Acetone/ACN: moderate to good, depending on ionization state.
  • Nonpolar media (toluene/hexanes): poor.
• When to choose which solvent (general):
  • Surface functionalization of oxides: Aqueous ethanol, isopropanol, or dry polar aprotics are frequently used for phosphonate anchoring; adjust pH to promote binding without hydrolyzing substrates.
  • Thiol conjugation (maleimide/haloacetyl): Aqueous buffers (pH 6.5–7.5) with limited DMSO cosolvent to improve solubility while minimizing maleimide hydrolysis (literature practice).
• Small comparison (literature-based):
  • PEG-acids (carboxylate terminus) often require higher pH to dissolve fully; phosphonates are generally soluble across a broader acidic-to-neutral range.

Note: Remove dissolved oxygen when free thiol integrity is critical (argon sparge/degassing).

Storage and Reconstitution

• Storage conditions (from Product Data): Store at −20°C. Shipped in ice chest with ice pads.
• Packaging/handling: Keep container tightly closed under dry, inert atmosphere where possible to limit thiol oxidation and moisture uptake.
• Stability considerations (general):
  • Free thiols can form disulfides on exposure to air/oxidants, especially in solution.
  • PEG segments are hygroscopic; avoid repeated opening in humid environments.

Reconstitution and solution handling (general/literature guidance):

• Solvents: Water, ethanol, or polar aprotic solvents (DMSO/DMF) typically dissolve PEG3 linkers well; confirm solubility for your batch.

• Concentration: Prepare concentrated stocks (e.g., 10–100 mM) in dry DMSO or water as needed; filter if required.

• Aliquoting: Make single-use aliquots; minimize headspace; store aliquots at −20°C.

• Inert handling: Degas solutions and blanket with nitrogen/argon for sensitive applications.

• Freeze–thaw: Minimize cycles; avoid repeated thawing. Thaw at RT, mix gently, and use promptly.

• Specifications not provided: Water content, residual solvents, stabilizers, or inhibitors are not specified for this item; refer to CoA/Spec Sheet.

Always verify compatibility of your solvent/buffer with downstream reactions (e.g., avoid amines for maleimide coupling) and confirm free-thiol content before critical conjugations.

Structure and Identity

A bifunctional PEGylated linker featuring a terminal thiol and a terminal phosphonic acid, useful for surface anchoring and conjugation.

• SKU: T1445155
• Product name: Thiol-PEG3-phosphonic acid
• CAS: 1360716-36-4
• Category: Small molecules and compound library (research use)
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES / InChI / InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general description based on name; literature):

• Backbone: A short poly(ethylene glycol) spacer with approximately three ethylene glycol (–CH2–CH2–O–) units ("PEG3"), imparting hydrophilicity and flexibility.
• Termini:
  • Thiol (–SH): Soft nucleophile that coordinates strongly to coinage metals (e.g., Au, Ag) and participates in thiol-specific conjugation chemistries.
  • Phosphonic acid (–PO3H2): Acidic, chelating/anchoring group with strong affinity to many metal oxide surfaces (e.g., TiO2, ZrO2, Fe3O4, Al2O3) via mono-/bi-/tridentate binding modes.
• 2D structure (verbal): A linear PEG chain (~three oxyethylene repeats) connecting one end-capped with a free thiol and the other end with a phosphonic acid; no rings, no stereocenters; multiple ether oxygens spaced every two carbons.

Notes:

• The above are general/literature-based structural features inferred from the compound name. Item-specific identifiers (formula, exact MW, line notation) are not provided in the Product Data.

Synthetic Utility

As a bifunctional PEG linker, Thiol-PEG3-phosphonic acid is a modular building block enabling orthogonal transformations on each terminus (literature/general):

• Thiol terminus (soft nucleophile):
  • Michael addition to maleimides/acrylates to form stable thioethers.
  • SN2 reaction with haloacetyl/alkyl halides (iodide/bromide > chloride) to give thioethers.
  • Thiol–ene radical addition under photoinitiation.
  • Disulfide formation/exchange for reversible linkages.
• Phosphonic acid terminus (hard Lewis base/acidic):
  • Strong chelation/coordination to metal oxides for surface immobilization.
  • Conversion to phosphonate esters under dehydrative conditions (if desired in synthesis), or activation (e.g., via chlorination) for further coupling—subject to compatibility with the PEG and thiol.
• PEG spacer: Provides solubility and spacing, often improving reaction outcomes in aqueous or mixed solvents and reducing steric/electrostatic interference near surfaces or biomolecules.

Retrosynthetic value:

• Useful as a “handle” to introduce a surface anchor (phosphonate) while keeping a reactive counterpart (thiol) available for late-stage diversification, enabling parallel synthesis and modular assembly of surface-bound libraries, nanoparticle ligands, or bioconjugates.

Target Specificity

Not an antibody, protein, or biological targeting agent. No antigen/epitope specificity applies to this small-molecule linker.

• Tested species/reactivity, clone, isotype: Not applicable.
• Any target-binding behavior arises from chemical affinity: thiol to noble metals; phosphonic acid to metal oxides (literature/general).