THP-PEG16-THP , CAS No.T1445164

CAS: T1445164 Cat. No.: T1445164 Formula: C₄₂H₈₂O₁₉ Molecular Weight: 891.09

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

THP-PEG16-THP is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

Specifications

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Names and Identifiers

Molecular Weight

891.09

Application Protocols

No standardized bioassay protocols apply to this protected PEG linker. Use is highly context‑dependent on the intended synthetic sequence.

• General workflow example (literature/general):
  1. Dissolve THP‑PEG16‑THP in dry DCM or THF under inert gas.
  2. Perform non‑acidic coupling/modification steps on other parts of your molecule while keeping termini protected.
  3. Deprotect with catalytic PPTS in EtOH at rt; monitor by 1H NMR.
  4. Convert the resulting diol to the desired difunctional species (e.g., ditosylate → diazide → diamine) and couple to targets.

For application‑specific conditions, consult the methods literature relevant to your substrate class. Always confirm compatibility on small‑scale trials.

Biological Roles

This product is a synthetic PEG linker and not a biological molecule per se. Nevertheless, PEG segments have well‑characterized roles in biomolecular contexts (literature/general):

• PEG as an interface modifier: Poly(ethylene glycol) confers hydrophilicity and reduces nonspecific protein adsorption on surfaces (“stealth” behavior), which is valuable in assay development and in vitro device coatings.
• Hydration and conformational effects: PEG chains form a dynamic hydration shell and exert entropic repulsion; a PEG16 spacer (~16 EO units) provides several nanometers of contour length, enabling decoupling of binding events from surfaces and minimizing steric hindrance between conjugated ligands (literature estimate: ~0.35 nm per EO unit in extended form; actual end‑to‑end distance is smaller in solution).
• Crowding and phase behavior: PEGs are used as macromolecular crowding agents and in phase‑separation systems (e.g., PEG/salt ATPS). However, the THP‑protected form is less suitable for aqueous biological media until deprotected.
• Biostability: Ether linkages resist hydrolysis under physiological pH; end‑group chemistry dominates stability. THP caps are acid‑labile and should be removed prior to any aqueous/biological application.

Note: These are general literature properties of PEG. This specific item is for research use only.

Buffer Applications

Not typically applicable. THP‑PEG16‑THP is a protected PEG linker and does not function as a buffering agent or pH stabilizer.

• Practical note: After acidic deprotection to HO‑PEG16‑OH, PEG can be dissolved in aqueous buffers for surface blocking or crowding studies, but buffering capacity still comes from conventional buffers (e.g., phosphate, HEPES). Use the present product only as a synthetic intermediate and deprotect before any aqueous biological usage.

Green Alternatives

Greener choices relate to solvent selection and protecting‑group strategy. Although THP is widely used, alternatives and solvent swaps can reduce environmental impact (literature/general):

• Greener solvent substitutions for common steps

  | Application | Conventional | Greener alternative | Trade‑offs | | --- | --- | --- | --- | | THP deprotection | DCM/MeOH + acid | EtOH or iPrOH + catalytic PPTS; aqueous EtOH with AcOH | Slightly slower rates; easier solvent recovery; lower toxicity | | PEG diol activation (tosylation) | DCM, CH2Cl2 | 2‑MeTHF or CPME | Different solubility; may need temperature optimization | | Azidation of ditosylate | DMF | Propylene carbonate or Cyrene | Higher viscosity; longer reaction times, but improved safety profile |

• Protecting‑group considerations:

  • THP is acid‑labile and removable under mild, green conditions (ethanol + catalytic acids). Alternative acetal PGs (e.g., MTHP) can offer similar profiles; however, changing PGs alters kinetics and byproducts.

• Workup/waste minimization:

  • Favor solvent switches to alcohols/esters for precipitation of PEG products (reduced halogenated solvent use).
  • Use catalytic loadings (PPTS) and aqueous ethanol quench to simplify neutralization.

• Energy footprint:

  • Many PEG transformations proceed at ambient temperature; avoid reflux when unnecessary and use efficient mixing to manage viscous media.

Always balance greenness with performance and product purity requirements.

Pharmaceutical Uses

No therapeutic/clinical claims. This product is intended strictly for research and development.

• Formulation/excipient context (literature/general): PEGs are widely used as excipients (solubilizers, plasticizers, ointment bases). However, THP‑PEG16‑THP is an end‑protected intermediate, not an excipient as‑is.
• Process development uses:
  • As a research linker to build PEGylated constructs or pro‑moieties; after deprotection and end‑group conversion, the PEG16 spacer can be incorporated into experimental delivery systems, conjugates, or polymer backbones.
  • Provides defined spacer length for structure–property studies (solubility, viscosity, interfacial behavior) in preformulation screening.
• Regulatory status: No pharmacopeial grade or compendial status is stated for this item. Any use in regulated products would require qualification and sourcing of appropriate grade.

Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Research Use Note: For research use only.

Physical Properties

Item-specific numerical specifications are not provided in the product data and should be confirmed on the CoA/Spec Sheet.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point / Glass transition: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not applicable/meaningful for polymeric oligomers; thermal decomposition may occur before boiling (general statement).
• Density/refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (literature/general):
  • Good solubility in polar aprotic organics (THF, DCM, CHCl3, DMF, DMSO, acetone).
  • Reduced water solubility relative to PEG diols due to hydrophobic THP caps; tends to be sparingly to moderately soluble in water depending on chain length (literature/general).
• Polarity/partitioning (literature/general): Amphiphilic PEG backbone; terminal THP groups increase overall hydrophobicity vs. HO‑PEG‑OH. No item-specific logP available.
• Viscosity/physical state (literature/general): PEG16 derivatives may be waxy solids or viscous oils at ambient temperature, depending on dispersity and end groups.
• Hygroscopicity: PEG segments are hygroscopic; protect from moisture to minimize THP hydrolysis (general guidance).

Quality & Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• What “protected PEG linker” implies (general):
  • Terminal hydroxyls are masked with THP groups to prevent undesired reactions during multistep syntheses. After assembly, deprotect under mild acidic conditions to reveal the diol for subsequent activation (e.g., tosylation, carbonate formation) or direct use.
• Typical quality considerations for PEG linkers (general/literature):
  • Dispersity: PEG oligomers are often a narrow distribution centered around the target repeat number; exact Mn/Mw should be listed on CoA when controlled.
  • Residual solvents, water content, and acid number can affect downstream reactions, especially acid‑catalyzed or moisture‑sensitive steps.
  • End‑group fidelity: Critical for bifunctional linkers; confirm by NMR and end‑group titration/HRMS where applicable.
• Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet.
• UV/fluorescence background: PEGs generally exhibit low UV absorbance above ~220–230 nm (literature); if using for analytical applications, verify UV cutoff on CoA.
• Documentation: For any regulated or high‑precision application, rely on the item’s CoA/Spec Sheet for exact purity, solvent content, and analytical data.

Reaction & Applications

This bifunctional, THP‑protected PEG is primarily a synthetic intermediate/linker. Key applications (literature/general):

• Protect–deprotect strategies:
  • Use the THP caps to passivate termini during steps incompatible with free diols (e.g., sensitive couplings on a central scaffold). Subsequently deprotect under mild acid to regenerate HO–PEG16–OH.
• Linker synthesis and diversification:
  • Convert the regenerated diol to ditosylate/dimesylate, then to diazide and further to diamine (Staudinger or hydrogenation). This enables a family of PEG16‑bis functional linkers (–NH2, –N3, –SH, –COOH via downstream transformations).
  • Formation of bis‑carbonates or bis‑carbamates for coupling to nucleophiles (alcohols, amines) on polymers, dendrimers, surfaces, or nanoparticles.
• Surface modification and materials:
  • Grafting to oxide, polymer, or carbon surfaces (post‑activation) to impart hydrophilicity and protein‑repellent character; tuning interfacial spacing with defined PEG length.
• Supramolecular/assembly:
  • Spacer in host–guest systems, hydrogels, and amphiphiles; THP protection can enable orthogonal assembly conditions before unveiling hydrophilic ends.
• Analytical/assay development:
  • Create well‑defined PEG spacing between recognition elements in biosensors after deprotection and end‑group conversion.

Practical notes:

• Maintain anhydrous, neutral/basic media until deprotection is desired.
• Monitor THP cleavage by 1H NMR (disappearance of THP acetal signals) and by SEC/GPC for integrity of PEG length.

Reaction Conditions

General literature guidance for common transformations of THP‑PEG16‑THP and its deprotected derivatives. Adjust to scale and substrate sensitivity.

• THP deprotection (to HO‑PEG16‑OH):
  • PPTS (5–10 mol%) in MeOH or EtOH, 20–25°C, 2–6 h; monitor by TLC/NMR. Neutralize with NaHCO3, evaporate alcohol, and co‑evaporate with toluene to remove residuals.
  • Aqueous acid: 0.05–0.1 M HCl or AcOH in THF/H2O (4:1 to 9:1), rt, 1–4 h; avoid over‑acidic conditions to prevent side reactions on acid‑sensitive motifs elsewhere in the molecule.
• Formation of ditosylate (from diol):
  • TsCl (2.2 equiv), pyridine or Et3N, cat. DMAP, 0°C to rt, 4–16 h in dry DCM or 2‑MeTHF. Typical literature yields: 70–90% for PEG oligomers with careful drying.
• Diazidation:
  • NaN3 (4–6 equiv) in dry DMF or propylene carbonate, 60–90°C, 6–16 h; work up by aqueous quench and extraction or precipitation. Use proper azide safety protocols.
• Diamine formation:
  • Staudinger reduction (PPh3, THF/H2O) or catalytic hydrogenation (Pd/C, H2, EtOH) from diazide; 0–25°C, 2–8 h.
• Carbonate activation:
  • p‑Nitrophenyl chloroformate (2.2 equiv), Et3N, dry DCM/THF, 0°C→rt, 2–4 h, to afford bis‑pNPC carbonate for coupling with amines.

Notes:

• Dry conditions prior to and during activation steps maintain high end‑group fidelity.
• Remove residual acids before base‑sensitive steps to avoid premature THP loss.

Safety & Handling

• GHS classification, pictograms, signal word, H‑statements: Not specified for this item; refer to the SDS for authoritative safety information.
• General hazards (literature/general): PEG materials are typically of low acute toxicity; THP ethers are acid‑labile acetals and may hydrolyze to liberate alcohols under acidic/moist conditions. Avoid strong acids that can trigger deprotection.
• PPE recommendations (good laboratory practice):
  • Wear lab coat, safety glasses or chemical splash goggles, and appropriate chemically resistant gloves (e.g., nitrile).
  • Handle in a fume hood when charging reagents/solvents or performing acid/base treatments.
• Incompatibilities (general):
  • Strong acids and acid catalysts (promote THP cleavage); oxidizing acids.
  • Prolonged exposure to moisture; store under dry, inert conditions.
  • Strong oxidants that may attack ether linkages under forcing conditions.
• First-aid overview (consult SDS for details):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; get medical advice if irritation develops.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire safety (general): Combustible organic; use CO2, dry chemical, or foam. Thermal decomposition may produce CO/CO2.
• Waste: Collect organic waste according to institutional and local regulations; segregate acidic streams used for deprotection.

Solvent Selection

Context: THP‑PEG16‑THP is an amphiphilic oligomer; terminal THP groups reduce hydrophilicity compared to HO‑PEG‑OH. Solvent choice impacts handling, deprotection, and subsequent functionalization.

• Polarity/miscibility (literature/general):
  • Highly soluble: DCM, CHCl3, THF, EtOAc, acetone, DMF, DMSO, MeCN.
  • Limited to moderate solubility: Alcohols (MeOH, EtOH, iPrOH) depending on temperature and concentration.
  • Water: Lower solubility than PEG diols; may form micellar/aggregate phases at higher n.
• Typical use scenarios:
  • Deprotection: MeOH or EtOH with catalytic acid (e.g., PPTS) or mixed aqueous organic (THF/H2O, MeCN/H2O) for controlled hydrolysis.
  • Activation of the revealed diol: Use dry DCM/DMF/THF for tosylation/mesylation/carbonate formation; ensure anhydrous conditions.
• Comparison guidance (literature/general):
  • DCM vs THF: DCM offers rapid dissolution and ease of phase separation; THF provides better miscibility with alcohols and bases during deprotection or activation.
  • DMF/DMSO: Best for nucleophilic substitutions (e.g., azidation) but harder to remove; consider workup via aqueous quench and extraction or precipitation into ether.
• Practical tips:
  • Pre‑dry solvents (molecular sieves or distillation) to preserve THP caps until intentional deprotection.
  • Warm gently (30–40°C) to aid dissolution; avoid prolonged heating with acid present.

Storage & Reconstitution

• Storage conditions (item‑specific): Store at −20°C.
• Shipping (item‑specific): Shipped in ice chest + ice pads.
• Atmosphere and container (general best practice):
  • Store under inert gas (N2 or Ar) in a tightly sealed container with desiccant to limit moisture ingress and prevent acid‑catalyzed THP hydrolysis.
  • Protect from acids and prolonged exposure to atmospheric humidity.
• Stability considerations (literature/general): THP end groups are acid‑labile; neutral to basic, anhydrous conditions help maintain integrity over time.
• Reconstitution/handling:
  • To prepare stock solutions, dissolve the material in dry, oxygen‑ and moisture‑free solvents such as DCM, THF, DMF, DMSO, or MeCN. Gentle warming (≤40°C) and sonication can aid dissolution of viscous samples.
  • For long‑term solution storage, keep at low temperature (≤−20°C) in dry, sealed vials; check periodically by 1H NMR for end‑group integrity.
• Freeze–thaw guidance: If stored as solution, aliquot to avoid repeated freeze–thaw cycles that can introduce moisture and promote hydrolysis.
• Compatibility note: Avoid storing with acidic reagents or in acidic glassware; rinse glassware thoroughly and dry before use.

Research Use Note: For research use only.

Structure & Identity

Brief overview: THP‑PEG16‑THP is a bifunctional polyethylene glycol (PEG) chain with approximately 16 ethylene glycol repeat units, terminally protected as tetrahydropyranyl (THP) ethers. It is intended as a moisture‑sensitive PEG linker/building block for synthetic chemistry.

• Item-specific identifiers

  • SKU: T1445164
  • CAS: T1445164 (catalog identifier; not a registered CAS RN)
  • Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Structural features (general/literature description)

  • Core: Linear PEG chain –[O–CH2–CH2]n– with n ≈ 16 (literature/nominal for “PEG16”).
  • End groups: Each terminal hydroxyl of PEG is masked as a THP ether (–O–CH2–(C5H8O)–), derived from 3,4‑dihydropyran.
  • Functional groups: Multiple ether linkages along the backbone; two acetal‑type THP protecting groups at termini (acid‑labile).
  • 2D structure (verbal): A flexible poly(ethylene oxide) chain terminated on both ends by a tetrahydropyran ring connected via an O‑CH2 acetal bridge.
  • Stereochemistry: None defined (achiral polymer segment; THP protection typically forms a mixture of hemiketal stereochemistry, not stereochemically controlled).

Synthetic Utility

THP‑PEG16‑THP offers orthogonal protection of PEG termini, enabling multistep sequences without interference from free diols (literature/general):

• End‑group chemistry platform:
  • Deprotect to HO‑PEG16‑OH, then derivatize to:
    • PEG16‑ditosylate/dimesylate → diazide → diamine → diisothiocyanate/di‑NHS carbamate.
    • Bis‑carbonates (e.g., p‑nitrophenyl carbonates) → coupling to amines/alcohols on biomolecules, surfaces, or polymers.
  • Access heterobifunctional variants by selective, stepwise protection/deprotection if asymmetry is introduced.
• Protecting‑group orthogonality:
  • THP resists many basic/nucleophilic conditions (e.g., amidations, carbodiimide couplings) yet is cleanly removed with catalytic acids (PPTS, CSA, dilute HCl) in alcoholic or mixed solvents.
• Assembly strategies:
  • Central‑core build: Attach the protected PEG to a multifunctional hub (e.g., dendrimer, scaffold) under non‑acidic conditions, then unveil diols for further growth or crosslinking.
  • Click‑ready linkers: After diazide formation, CuAAC or SPAAC can introduce diverse termini while retaining the PEG16 spacing.
• Analytical control:
  • Track transformations by 1H/13C NMR (THP acetal resonances, tosyl aromatic signals), FTIR (carbonate/urethane bands), and SEC/GPC for dispersity.

These are general synthetic utilities; verify conditions against your substrate compatibility.

Target Specificity

Not applicable. This product is a small‑molecule/oligomeric linker, not a biological targeting reagent or antibody. No antigen/epitope specificity applies.