Thiol-PEG4-t-butyl ester - ≥95% , CAS No.564476-33-1

CAS: 564476-33-1 Cat. No.: T597501 Summenformel: C₁₅H₃₀O₆S Molekulargewicht: 338.46 PubChem CID: 12082267

GRADE & PURITY ≥95%

Synonyms

t-Butyl 3-mercapto(peg4)propionate | tert-Butyl1-mercapto-3,6,9,12-tetraoxapentadecan-15-oate | Thiol-PEG4-t-butyl ester | HY-141328 | t-Butyl 15-Mercapto-4,7,10,13-tetraoxa-pentadecanoate | SCHEMBL5144409 | BP-20978 | HS-PEG4-CH2CH2COOtBu | Thio-PEG4-t-b

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Übersicht

Thiol-PEG4-t-butyl ester is a PEG derivative containing a thiol group and a t-butyl ester. The hydrophilic PEG spacer increases solubility in aqueous media. The thiol group reacts with maleimide, OPSS, vinylsulfone and transition metal surfaces including gold, silver, etc. The t-butyl protected carboxyl group can be deprotected under acidic conditions.

Specifications

Synonyme

t-Butyl 3-mercapto(peg4)propionate | tert-Butyl1-mercapto-3,6,9,12-tetraoxapentadecan-15-oate | Thiol-PEG4-t-butyl ester | HY-141328 | t-Butyl 15-Mercapto-4,7,10,13-tetraoxa-pentadecanoate | SCHEMBL5144409 | BP-20978 | HS-PEG4-CH2CH2COOtBu | Thio-PEG4-t-b

Spezifikationen & Reinheit

≥95%

Storage

Store at -20°C

Verschickt in

Ice chest + Ice pads

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Reinheit

≥95%

Namen und Kennungen

Kanonisches Lächeln

CC(C)(C)OC(=O)CCOCCOCCOCCOCCS

IUPAC Name

tert-butyl 3-[2-[2-[2-(2-sulfanylethoxy)ethoxy]ethoxy]ethoxy]propanoate

InChIKey

NKLWGDQDZRFINM-UHFFFAOYSA-N

INCHI

1S/C15H30O6S/c1-15(2,3)21-14(16)4-5-17-6-7-18-8-9-19-10-11-20-12-13-22/h22H,4-13H2,1-3H3

Isomere SMILES

CC(C)(C)OC(=O)CCOCCOCCOCCOCCS

PubChem CID

12082267

Molekulargewicht

338.46

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic acids and derivatives
    • Klasse Carboxylic acids and derivatives
      • Subclass Carboxylic acid derivatives

• Kingdom: Organic compounds
• Superclass: Organic acids and derivatives
• Klasse: Carboxylic acids and derivatives
• Subclass: Carboxylic acid derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Carboxylic acid esters
• Alternative Parents: Monocarboxylic acids and derivatives Dialkyl ethers Alkylthiols Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aliphatic acyclic compounds
• Substituents: Carboxylic acid ester - Monocarboxylic acid or derivatives - Ether - Dialkyl ether - Alkylthiol - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organosulfur compound - Organooxygen compound - Carbonyl group - Aliphatic acyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as carboxylic acid esters. These are carboxylic acid derivatives in which the carbon atom from the carbonyl group is attached to an alkyl or an aryl moiety through an oxygen atom (forming an ester group).
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Chemische und physikalische Eigenschaften

• Molekulargewicht: 338.500 g/mol
• XLogP3: 0.700
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 16
• Exact Mass: 338.176 Da
• Monoisotopic Mass: 338.176 Da
• Topological Polar Surface Area: 64.200 Ų
• Heavy Atom Count: 22
• Formal Charge: 0
• Complexity: 267.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No vendor‑validated application protocols are provided for this item.

General workflows (literature guidance):

• Thiol–maleimide conjugation
  • Prepare thiol‑containing partner in HEPES or PBS at pH 6.8–7.2; ensure it is in reduced form (treat with TCEP, then remove excess reductant by desalting).
  • Dissolve Thiol‑PEG4‑tBu in a compatible co‑solvent (DMF/DMSO). Add to the reaction to achieve 1.1–2.0 molar equivalents relative to maleimide sites. Incubate at room temperature, 0.5–2 h. Purify by SEC or RP‑HPLC.
• tBu deprotection and amide coupling
  • Treat with TFA/DCM (or alternative acid) at 0–25 °C until LC‑MS shows complete conversion. Evaporate volatiles, co‑evaporate with toluene or EtOAc to remove residual TFA. Neutralize if needed, then activate with EDC/NHS (aqueous) or HATU/DIPEA (DMF) and couple to amines.

These are starting points only. Optimize stoichiometry, pH, and time for your system. For scale‑up, perform risk and safety assessments.

Biological Roles

This compound is a synthetic heterobifunctional PEG linker rather than a naturally occurring metabolite. It does not have intrinsic biological roles.

General/literature context for PEG linkers in biochemical workflows (no clinical claims):

• PEGylation spacer: The PEG4 segment provides a hydrophilic, flexible spacer between a surface/biomolecule and a functional payload, often reducing nonspecific adsorption and improving solubility/dispersion in aqueous media once ionizable groups are present.
• Chemoselective attachment: The thiol can selectively conjugate to maleimide‑bearing biomolecules or materials. After deprotecting the tert‑butyl ester to the acid, standard carbodiimide chemistry can couple to primary amines on peptides/proteins or amine‑functionalized surfaces.
• Surface passivation: PEG motifs are widely used to passivate interfaces in biosensors and microfluidic devices, reducing protein fouling and improving assay reproducibility.

If your application interfaces with living cells or proteins, evaluate:

• Stability of the thiol linkage (maleimide thioethers can undergo exchange; ring‑opened succinimide adducts are more stable).
• Post‑deprotection charge state (carboxylates introduce negative charge at physiological pH, influencing binding and distribution on surfaces).

For any biological experiments, confirm compatibility in small‑scale tests and adhere to your institution’s biosafety policies.

Buffer Applications

This item is a small‑molecule linker and is not itself a buffering agent.

Practical notes for bioconjugation workflows (general guidance):

• Thiol–maleimide coupling: Use mildly acidic to neutral buffers (e.g., phosphate, HEPES) at pH 6.5–7.5 to minimize thiol oxidation and maleimide hydrolysis. Avoid high concentrations of primary amines (e.g., Tris) that can compete in some reactions.
• Maintaining thiol in reduced state: Immediately prior to coupling, reduce thiols on biomolecules with TCEP (compatible with maleimides) and desalt to remove excess reductant.
• Post‑deprotection coupling (carboxyl to amine): After converting the tert‑butyl ester to the acid, employ MES buffer (pH 5.0–6.5) with EDC/NHS for amide formation; then adjust to pH 7–8 for reaction with amines.

These are literature best practices and should be optimized for your specific system. The product itself does not provide buffering capacity.

Green Alternatives

While the product is a linker rather than a solvent, greener choices can be made in the processing and coupling steps. The guidance below is literature-based and general.

• Prefer safer solvents where compatible with reactivity:

  • Replace DCM with ethyl acetate, 2‑MeTHF, or cyclopentyl methyl ether (CPME) for extractions and some couplings.
  • Use MeCN, EtOAc, or 2‑MeTHF instead of THF/DCM when feasible.
  • For aqueous bioconjugations, run reactions in buffered water with co‑solvents like MeCN or EtOH.

• Acid deprotection of tert‑butyl esters:

  • Conventional: TFA/DCM (effective but high EHS burden). Greener variant: TFA in EtOAc or HCl in dioxane/MeOH where compatible; or use solid acids (e.g., acidic ion‑exchange resins) for certain substrates.

• Reducing environmental load:

  • Conduct couplings at higher concentrations to reduce solvent use.
  • Employ water‑soluble carbodiimides (EDC) and catalytic NHS in aqueous media post‑deprotection to minimize chlorinated waste.

Tradeoffs (summary):

• 2‑MeTHF/CPME: improved safety and recyclability vs DCM/THF, but may solubilize PEG linkers less efficiently; check solubility.
• Aqueous media: greener and protein‑friendly, yet the tert‑butyl ester reduces water solubility; deprotect first if water solubility is needed.

Implement solvent selection with small‑scale trials to ensure conversion, selectivity, and manageable workup.

Pharmaceutical Uses

No pharmacopeial grade or excipient designation is provided for this item; it is supplied for research use only.

General formulation/manufacturing context for similar PEG linkers (no therapeutic claims):

• Conjugation intermediates: Heterobifunctional PEGs are widely used during research and process development to create drug–polymer conjugates, antibody–drug conjugates (ADCs), and surface‑modified delivery systems. The thiol terminus enables selective attachment to maleimide‑bearing components; the tert‑butyl ester can be deprotected to introduce a carboxyl for further coupling.
• Solubility modulation: The PEG4 spacer can improve solubility/dispersion of hydrophobic payloads in intermediate processing steps.
• Process considerations: Control residual reagents (e.g., TFA after deprotection, carbodiimides after coupling) by appropriate quench and purification. For cGMP or clinical manufacturing, alternative grades and full regulatory support would be required.

Item‑specific status:

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

All uses are restricted to laboratory research and development settings.

Physical Properties

Item-specific physicochemical specifications are not provided in the 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.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Melting/boiling point: Not specified for this item; refer to CoA/Spec Sheet.
• Density/refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Water/peroxide/metal content: Not specified for this item; refer to CoA/Spec Sheet.

General/literature expectations for PEG4-based linkers (for planning only; not product specifications):

• Physical state: Often viscous oil or low‑melting waxy solid depending on end groups and exact structure.
• Solubility: Typically highly soluble in polar organic solvents (DMF, DMSO, MeCN, MeOH, EtOH) and often soluble in dichloromethane and THF; variable in water depending on terminal groups. The tert‑butyl ester reduces aqueous solubility relative to the acid.
• Hygroscopicity: PEG chains can be hygroscopic; minimize moisture exposure during weighing and solution prep.

Always verify exact values from the Certificate of Analysis (CoA) for your lot when parameters are critical (e.g., concentration calculations, process scale-up).

Quality and Grades

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

Guidance on interpreting grades for PEG linkers (general information):

• Research grade materials are suitable for method development, screening, and routine bioconjugation in discovery settings. Purity is typically assessed by NMR and HPLC/LC‑MS, but exact thresholds vary by supplier and lot; consult the CoA.
• High‑purity or >95% grade (when stated on CoA) is preferred for precise stoichiometry in conjugations and for minimizing side products in polymer/material syntheses.
• Stabilizers: Some thiol reagents are supplied with trace amounts of reducing agent or under inert gas to preserve free –SH. For this item, any stabilizer or additive is Not specified; refer to CoA/SDS.
• Residual solvents/metals: Not specified for this item; refer to CoA/Spec Sheet.

Recommendations:

• Verify lot‑specific assay/purity and identity (e.g., 1H NMR integration consistent with PEG4, mass spectrum for the thiol/tert‑butyl ester end groups).
• For regulated or scale‑up work, request additional documentation such as residual solvent analysis, elemental impurities, and stability data where applicable.

Reaction and Applications

Use cases below expand on typical applications of heterobifunctional PEG linkers bearing a thiol and a tert‑butyl ester. These are literature/practice guidelines, not item-specific claims.

• Thiol conjugation chemistry:

  • Thiol–maleimide Michael addition: Rapid, chemoselective coupling at pH ~6.5–7.5 to maleimide‑functionalized proteins, polymers, or surfaces. The PEG4 spacer improves aqueous compatibility and reduces steric hindrance.
  • Thiol–ene (radical) coupling: UV or thermal initiation across activated alkenes (e.g., acrylates, vinyl sulfones). Suitable for network formation and surface functionalization.
  • Disulfide formation/exchange: Oxidative dimerization or exchange with activated disulfides to introduce cleavable linkages. Control oxidation state with TCEP/DTT as needed.

• Protected acid handle (t‑Bu ester):

  • The tert‑butyl ester is acid‑labile; treatment with TFA/DCM (typical) unveils the carboxylic acid, which can be activated (EDC/NHS, HATU, PyBOP) for amide coupling to amines on small molecules, peptides, or surfaces.
  • Enables orthogonal, sequential coupling: perform thiol conjugation first (neutral pH), then deprotect and couple the acid second, or vice versa depending on substrate sensitivity.

• Materials science (aligns with category):

  • Fabrication of PEGylated surfaces and hydrogels, spacing functional groups from substrates to mitigate fouling.
  • Introduction of adhesion/anchoring motifs via thiol–gold interactions on Au surfaces; subsequent acid deprotection for further derivatization.

Practical tips:

• Work under inert atmosphere to maintain thiol in reduced form. Include trace antioxidant/reductant only if compatible with downstream steps.
• Verify coupling by LC‑MS or MALDI; PEG distributions may show minor adducts.

Reaction Conditions

Typical conditions for reactions involving thiol‑PEG4‑tert‑butyl esters (literature guidance; adjust to your system):

1. Thiol–maleimide coupling

• Solvent/buffer: Aqueous PBS or HEPES (pH 6.5–7.5) with 0–30% co‑solvent (MeCN, DMF) as needed for solubility.
• Temperature: 20–25 °C.
• Time: Minutes to a few hours; monitor by LC‑MS.
• Notes: Avoid amine buffers like Tris. Keep thiol reduced (pre‑treat with TCEP, then desalt).

2. Thiol–ene (radical) addition

• Solvent: DCM, MeCN, or bulk monomer; degassed.
• Initiation: UV (e.g., 365 nm) with photoinitiator (DMPA) or thermal AIBN (for ene partners suitable for radical addition).
• Temperature: Ambient to 60 °C.
• Time: 0.5–4 h depending on substrate.

3. tert‑Butyl ester deprotection

• Reagent: TFA (50–100%) in DCM or EtOAc; or HCl/dioxane.
• Temperature: 0–25 °C.
• Time: 0.5–2 h (monitor by TLC/LC‑MS). Avoid prolonged exposure to prevent side reactions at sensitive partners.

4. Carboxyl activation and amide coupling (post‑deprotection)

• Reagents: EDC (1.1–1.5 eq) + NHS (1.1–1.5 eq) in MES buffer (pH 5.5–6.0) or HATU with DIPEA in DMF for nonaqueous systems.
• Temperature: 0–25 °C.
• Time: 0.5–4 h activation; 1–16 h coupling.

These conditions are representative from the literature and should be optimized by small‑scale trials. No item‑specific specifications are implied.

Safety and Handling

GHS and hazard statements are not provided in the Product Data for this item. Always consult the SDS for authoritative information and your institution’s EHS guidance.

• GHS classification / pictograms: Not specified for this item; refer to SDS.
• Signal word / H‑statements: Not specified for this item; refer to SDS.

General safety considerations for thiol‑PEG linkers (literature/practice guidance):

• Thiol functionality: May oxidize to disulfides on air exposure; can have a strong odor. Handle in a well‑ventilated area or fume hood. Keep containers tightly closed under inert gas where possible.
• Peroxide formation: PEG ethers are not classical peroxide formers like dialkyl ethers, but long‑term storage with air and light can still lead to oxidative byproducts. Use inhibitors/reducing agents in solution as appropriate (e.g., TCEP or DTT in aqueous workups) to maintain thiol in reduced form.
• Incompatibilities: Avoid strong oxidizers (can form disulfides), strong bases plus nucleophiles (may induce transesterification), and strong acids if tert‑butyl ester integrity must be preserved (TFA will deprotect).
• PPE: Lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Avoid skin contact due to possible sensitization by thiols.
• First aid overview: Skin/eye contact—rinse with water for 15 minutes; inhalation—move to fresh air; ingestion—seek medical attention. Follow institutional procedures.
• Waste: Collect organic solutions/solids in halogenated or non‑halogenated organic waste per local regulations.

Storage (product data): Store at −20 °C. Shipments are sent on ice packs. Protect from light and moisture.

Solvent Selection

This linker is a polar, nonionic PEG derivative with broad compatibility in polar organic media. The following guidance is general/literature-based and intended for method planning; it is not item-specific specification.

• Polarity class: Polar aprotic–compatible; miscible with many organic solvents.
• Typical good solvents: DMF, DMSO, MeCN, MeOH, EtOH, THF, DCM, and mixtures thereof. Aqueous solubility is often moderate to low for the tert‑butyl ester form but improves markedly after deprotection to the free acid.
• Dry conditions: For thiol‑mediated coupling or when moisture‑sensitive partners are present, use anhydrous solvents and inert atmosphere to limit oxidation and hydrolysis.

When to choose vs alternatives:

• Choose Thiol‑PEG4‑tBu when you need (a) thiol chemoselectivity to maleimides/ene partners and (b) a protected acid that can later be unveiled to couple to amines (via EDC/NHS/HATU) or surfaces.
• If immediate water solubility is needed, consider using the free acid or carboxylate salt variant instead of the tert‑butyl ester.
• For click‑type reactions lacking thiol handles, consider azido‑PEG or alkyne‑PEG linkers.

Small comparison (general):

• Thiol‑PEG4‑tBu: best for sequential thiol-first, acid‑later strategies; more hydrophobic due to tBu.
• Thiol‑PEG4‑acid: better aqueous handling; no acid‑labile protection.
• Maleimide‑PEG4‑tBu: flips the thiol reactivity partner; useful for direct conjugation to thiols on biomolecules.

Storage and Reconstitution

• Storage conditions (product data): Store at −20 °C. Shipment is on ice packs in an insulated container.
• Packaging and handling: Keep container tightly closed. Minimize exposure to air and moisture to prevent thiol oxidation and hydrolysis of sensitive groups.

General reconstitution and handling guidance (not item-specific specifications):

• Atmosphere: Handle under inert gas (N2/Ar), especially when preparing stock solutions.
• Solvents for stock solutions: Use anhydrous DMF, DMSO, THF, or MeCN. For aqueous use, consider deprotecting the tert‑butyl ester to the acid to enhance water compatibility.
• Concentration: Prepare concentrated stocks (e.g., 10–100 mM) as solubility allows; store aliquots to avoid repeated freeze–thaw.
• Stability: Thiols can slowly oxidize; if oxidation occurs, reduce in situ (e.g., TCEP) just prior to coupling, provided the reductant is compatible.
• Light/moisture: Protect from light and humidity. Use desiccant in storage.

If precipitation or discoloration is observed after storage, assess integrity by LC‑MS or NMR before use. For any lot‑specific stability, water content, or inhibitor details, consult the CoA and SDS.

Research Use Only: This product is intended for laboratory research and development; not for human or veterinary use.

Structure and Identity

Thiol-PEG4-t-butyl ester is a heterobifunctional polyethylene glycol (PEG) linker bearing a terminal thiol and a tert‑butyl ester-protected carboxylate at opposite ends.

• SKU: T597501
• Product name: Thiol-PEG4-t-butyl ester
• CAS: 564476-33-1 (product data)
• PubChem CID: 12082267 (product data)
• InChIKey: 240879 (product data)
• 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.

Structural features (general/literature description):

• Contains a PEG4 spacer: four ethylene glycol repeat units [–CH2–CH2–O–]4 providing hydrophilicity and flexibility.
• One terminus is a thiol (–SH), enabling chemoselective conjugation via thiol–maleimide, thiol–ene, or disulfide chemistry.
• The other terminus is a tert‑butyl ester (–COOtBu) that serves as an acid‑labile protecting group for a carboxylic acid; it can be deprotected (e.g., with TFA) to reveal a free –CO2H for coupling.
• 2D depiction in words: HS–(CH2CH2O)4–(linker methylene, if present)–C(=O)–O–C(CH3)3. Exact atom count and any intervening methylenes depend on the commercial variant; consult the CoA for definitive structure.

Notes:

• The PEG backbone is nonionic and typically reduces aggregation and nonspecific interactions in conjugates.
• No stereogenic centers are expected in a simple PEG4 linker; functional groups are achiral.

Synthetic Utility

Functional group set and reactivity (general guidance for PEG4 linkers with thiol and tert‑butyl ester):

• Thiol (–SH): Nucleophilic soft center. Engages in:

  • Michael additions to maleimides, acrylates, vinyl sulfones (fast, selective under mild conditions).
  • Thiol–ene radical additions across alkenes under UV/thermal initiation.
  • Disulfide formation/exchange to install cleavable linkages.
  • Au–S coordination for self‑assembled monolayers on gold.

• tert‑Butyl ester: Acid‑labile protection for a carboxyl group.

  • Deprotection with TFA or other strong acids reveals –CO2H for amide/ester formation (EDC/NHS, HATU, DIC/DMAP).
  • Orthogonality: Survives many neutral/basic steps; avoid strong acids until deprotection is desired.

• PEG4 spacer: Enhances solubility in polar organics, increases effective reach from surfaces/biomolecules, and reduces steric encumbrance.

Retrosynthetic value:

• Enables modular assembly of conjugates where one end is installed via thiol chemistry and the other via carboxyl activation. Useful for creating bifunctional materials, link‑out handles on small molecules, and surface grafts.

Practical considerations:

• Handle under inert gas to prevent thiol oxidation; if disulfide forms, reduce prior to use (e.g., with TCEP) and promptly consume.
• After deprotection, neutralize acid and remove volatile acids (e.g., TFA) thoroughly to avoid interference in subsequent couplings.

Target Specificity

Not applicable. This product is a small‑molecule linker and does not possess biological target specificity, epitopes, isotypes, or species reactivity. No antibody or protein target information is associated with this item.