p-NO2-Bn-DOTA , CAS No.116052-88-1

CAS: 116052-88-1 Cat. No.: P1443304 Formula: C₂₃H₃₃N₅O₁₀ Molecular Weight: 539.54

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

p-NO2-Bn-DOTAis a bifunctional chelator ( Bifunctional Chelator ; BFC ) and a macrocyclic DOTA derivative used for tumor pre-targeting. p-NO2-Bn-DOTA can be used for conjugation of peptides and radionuclides.

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: 539.54

Application Protocols

No supplier-tested bioassay protocols are provided for this catalog item. Typical literature workflows include:

• Preparation of p-NH2-Bn-DOTA from p-NO2-Bn-DOTA via catalytic hydrogenation, followed by conversion to p-SCN-Bn-DOTA for conjugation to amine-bearing biomolecules.
• Radiometal labeling of the purified bioconjugate in acetate buffer (pH ~4–5) at elevated temperature, with post-labeling purification by SEC or RP-HPLC.

Because exact conditions depend on the specific targeting vector, metal ion, and scale, users should consult the primary literature and validate conditions empirically. No item-specific dilutions, positive controls, or assay settings are specified for this item; refer to CoA/Spec Sheet and SDS.

Biological Roles

This product is a synthetic chelator derivative intended for research use; it does not possess intrinsic biological activity in the sense of a natural metabolite. The following points describe its role in biochemical research (literature/general):

• Metal sequestration: The DOTA framework forms kinetically inert, thermodynamically stable complexes with many trivalent and divalent metal ions. In biochemical assays, preformed DOTA–metal complexes can be used as tracers, imaging surrogates, or lanthanide tags for time-resolved fluorescence.
• Bioconjugation handle: The para-nitrobenzyl group serves as a precursor to functional groups (e.g., aniline, isothiocyanate) that enable covalent attachment to biomacromolecules (proteins/peptides) via lysine or N-terminus residues.
• Stability in biological milieu: DOTA–metal complexes are known (literature) for high in vitro stability against transchelation and transmetallation, an important attribute for reliable readouts in cell-based assays and biomarker studies.
• No clinical/therapeutic assertions: This product is for research use only, not for diagnostic or therapeutic applications.

Notes:

• In cell culture or lysate environments, free chelator can deplete essential metal ions; pre-chelation and purification of conjugates are recommended to avoid perturbing biological systems.
• Buffer selection (e.g., acetate/citrate, pH ~4–5 during complexation; HEPES/PBS, pH ~7.2–7.5 post-purification) should minimize competing metal chelators such as EDTA.

Buffer Applications

As a solid chelator derivative rather than a buffering agent, p-NO2-Bn-DOTA is not used to set or maintain pH. However, buffers are integral in its use for metal complexation and bioconjugation (literature/general):

• Metal complexation buffers: Acetate or citrate buffers at pH ~4–5 are commonly employed to load trivalent metals into DOTA derivatives, balancing deprotonation of donor atoms with suppression of hydrolysis. Avoid strong competing ligands (e.g., EDTA, phosphate at high concentration) that can sequester metals.
• Conjugation buffers: For coupling reactions of derived functionalities (e.g., p-SCN-Bn-DOTA) to biomolecules, carbonate (pH 8.5–9.0) or borate (pH 8.5) buffers are often used to promote amine nucleophilicity while preserving protein integrity. For amide couplings (EDC/NHS), MES or HEPES (pH 5.5–6.5 for activation; pH 7–8 for coupling) are typical.
• Purification/analytics: Use metal-depleted buffers and plastics to avoid unintended complexation. For LC-MS, volatile buffers (ammonium acetate/formate) are preferred.

Item-specific buffer recipes and pH ranges are not specified for this item; refer to method-specific literature and your CoA/Spec Sheet.

Green Alternatives

Greener choices relate to both solvent/reagent selection and workflow minimization for converting p-NO2-Bn-DOTA to a conjugation-ready chelator.

• Streamlined intermediates:

  • Choose p-NH2-Bn-DOTA directly when available to avoid a dedicated nitro-reduction step, reducing waste and metal catalysts (tradeoff: fewer options for in situ derivatization; check stability and supply).
  • Alternative bifunctional chelators (e.g., DBCO-DOTA, NHS-activated DOTA derivatives) can minimize harsh reagents, but may have shorter shelf life.

• Solvent considerations (literature/general):

  • Favor water/ethanol for catalytic hydrogenation where feasible, avoiding chlorinated solvents.
  • Use 2-MeTHF or CPME instead of THF/Et2O for extractions/workups when compatible with polarity.
  • For amide couplings, consider green(er) solvents such as EtOAc, Me-THF, propylene carbonate, or water-miscible systems; avoid DMF/DMSO where alternative media achieve comparable performance.

• Reagent choices:

  • Nitro reduction: Catalytic hydrogenation (H2, Pd/C) in EtOH/H2O is typically cleaner and generates water as a benign byproduct; avoid stoichiometric SnCl2 when possible due to tin waste.
  • Isothiocyanate formation: Consider thiocarbonyl diimidazole or equivalent over thiophosgene to reduce acute toxicity hazards (efficacy is system-dependent).

Tradeoffs:

• Highly polar chelators have limited solubility in many green solvents; judicious use of minimal DMF/DMSO as cosolvent may be necessary.
• Metal-free handling often requires acid-washed glassware and disposable plastics, which can increase solid waste; balance with reusables when purity allows.

Pharmaceutical Uses

This product is offered strictly for research use only. No clinical, diagnostic, or therapeutic claims are made. In a pharmaceutical development context (non-clinical R&D, literature/general):

• Excipient/formulation role: Not typical. DOTA derivatives function as active chelating components in conjugates rather than inert excipients.
• Process chemistry: Used to prepare chelator-bearing linkers and bioconjugates intended for preclinical evaluation (e.g., stability studies, radiolabeling process development, analytical standards).
• Reference standards: Preformed DOTA–metal complexes may serve as analytical comparators for radiochemical identity and stability assessments in development labs.

Item-specific pharmacopeial status, residual solvent limits, or GMP compliance: Not specified for this item; refer to CoA/Spec Sheet and regulatory guidance for any intended use beyond basic research.

Physical Properties

Item-specific physicochemical specifications have not been provided for this catalog entry. Values below are general/literature guidance for DOTA-type, benzyl-functionalized derivatives and must not be treated as product specifications.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet. (Many DOTA derivatives are high-melting solids; literature only.)
• Solubility (literature/general):
  • Polar aprotic solvents (DMSO, DMF, NMP): typically good to excellent for organic manipulations.
  • Water: variable; protonation state and counterions strongly influence aqueous solubility. Chelator salts often dissolve well in mildly acidic water (pH 4–6).
  • Alcohols (MeOH, EtOH): moderate; may require gentle warming/sonication.
• pKa/logP (literature/general for DOTA scaffolds):
  • Multiple basic pKa values (macrocyclic secondary/tertiary amines) and acidic pKa values (carboxylates); overall highly polar/ionic when deprotonated—logP typically very low (strongly hydrophilic upon deprotonation).
• Density, refractive index, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Practical notes (general):

• Hygroscopicity: Many polyaminocarboxylates are hygroscopic; weigh quickly in a low-humidity environment.
• Metal binding: Strongly chelates many di- and trivalent cations; trace metal content in solvents or glassware can affect solution behavior.

Quality and Grades

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

Guidance on quality considerations for this product class (general):

• Analytical characterization typically includes 1H/13C NMR, HRMS/ESI-MS, HPLC purity, and metal content (ICP-MS) because trace metals can associate with polyaminocarboxylate ligands.
• Residual solvents and inorganic salts (e.g., counterions) can influence apparent assay purity and solubility; comprehensive CoA should specify residuals when relevant.
• For bioconjugation/radiometal work, “metal-free” handling and packaging (acid-washed containers, chelex-treated water) are important to minimize pre-loading by adventitious metals.
• Stabilizers: None are typically needed for DOTA derivatives; if present (e.g., volatile bases or counterions), they should be disclosed on the CoA/Spec Sheet.
• UV/HPLC grade descriptors (when applicable): For materials advertised for HPLC-grade applications, low UV-absorbing impurities and sub-ppm metal levels are expected; verify against certificate data.

Batch-to-batch expectations:

• Consistent counterion form (free acid vs. salt) and hydration state should be stated, as these affect MW, assay, and stoichiometry in conjugation protocols.

Reaction and Applications

Use-case focus: p-NO2-Bn-DOTA is a protected/handle-bearing DOTA derivative employed as an intermediate toward conjugation-ready chelators and as a precursor for radiometal/lanthanide complexation in research settings.

Representative applications (literature/general):

• Nitro-to-amine conversion: Reduction of the para-nitro group (e.g., H2/Pd-C, Fe/HCl, or SnCl2) affords p-NH2-Bn-DOTA, a versatile intermediate for further functionalization (e.g., isothiocyanate formation).
• Isothiocyanate generation: Conversion of the aniline to p-SCN-Bn-DOTA (e.g., with thiophosgene or equivalent) yields a widely used bifunctional chelator for coupling to lysine residues in peptides/proteins.
• Amide coupling: The aniline or other derived handles can be coupled to activated esters or used to build linkers/spacers; carboxylates of DOTA arms can also be selectively activated for amide formation (route-dependent selectivity control required).
• Radiometal complexation: The DOTA framework forms very stable complexes with trivalent lanthanides and radiometals (e.g., 64Cu, 68Ga, 90Y, 177Lu, 111In) under mildly acidic, heated aqueous conditions (complexation conditions depend on metal; literature guidance only).
• Bioconjugation: Used to introduce DOTA to biomolecules (antibodies, peptides, small molecules) via the benzyl linkage, enabling downstream radiolabeling or Ln3+ tagging for assay development.

Practical tips:

• Maintain metal-free conditions prior to intended complexation (acid-washed glassware, chelex-treated water) to prevent premature chelation by adventitious metals.
• For reductions, select conditions compatible with any base-/acid-labile protecting groups on the chelator or linker. Filter off Pd/C thoroughly to avoid metal contamination.
• Validate chelation by analytical HPLC and MS; a shift in retention time and isotope pattern confirms complex formation.

Reaction Conditions

General, literature-based guidance for common transformations involving p-NO2-Bn-DOTA and its immediate derivatives (not product specifications):

• Nitro reduction to aniline:
  • H2 (1–3 atm), 5–10% Pd/C (5–10 wt% relative to substrate), EtOH/H2O or MeOH at 20–40°C; typical times 2–16 h. Filter through celite; thoroughly remove Pd traces (ICP check advised for radiometal workflows).
  • Alternative: Fe powder (5–10 equiv) in AcOH/H2O or SnCl2·2H2O (2–4 equiv) in EtOH/HCl, 50–80°C, 2–6 h. Generates inorganic waste; requires careful workup to remove salts.
• Isothiocyanate formation (from aniline):
  • Thiophosgene or thiocarbonyl diimidazole (TCI) in dry CH2Cl2/DMF with base (Et3N/DIPEA), 0–25°C, 1–4 h, giving p-SCN-Bn-DOTA suitable for conjugation to lysine residues (handle with extreme caution if using thiophosgene).
• Metal complexation (DOTA derivatives):
  • Aqueous acetate/citrate buffer, pH 4–5; metal salt (e.g., LnCl3); 60–95°C for 10–60 min depending on metal and ligand form. Monitor by radio-TLC/HPLC or LC-MS (non-radioactive).
• Bioconjugation (p-SCN-Bn-DOTA to proteins):
  • Carbonate buffer, pH 8.5–9.0, 20–25°C for 30–120 min; protein concentration 1–10 mg/mL; molar excess of chelator 3–20×. Quench with Tris or lysine; purify by desalting/SEC.

Notes:

• Degas solutions if oxygen-sensitive reagents are used. Maintain anhydrous conditions for moisture-sensitive steps. All parameters should be optimized for the specific substrate and scale.

Safety and Handling

Authoritative safety information is provided in the SDS. No item-specific GHS details were supplied for this listing; treat as a laboratory chemical and follow institutional safety practices.

• GHS classification, signal word, H-statements, pictograms: Not specified for this item; refer to SDS.
• Likely hazards (general for aromatic nitro-bearing chelators): May cause skin/eye/respiratory irritation. Dust may be irritating. Not expected to be volatile.
• PPE: Wear lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Handle powders in a fume hood to minimize dust inhalation.
• Incompatibilities (general):
  • Strong oxidizers/reducers when performing redox transformations (e.g., nitro reduction) should be used with caution and segregated.
  • Reactive acylation/thiocarbonyl reagents (if derivatizing to isothiocyanates) require strict anhydrous technique and proper containment.
  • Avoid contact with strong acids/bases if material bears base- or acid-labile protecting groups (consult CoA/SDS).
• Special risks with chelators: Can sequester essential metal ions; avoid ingestion and environmental release. Use dedicated glassware to prevent cross-contamination of trace-metal-sensitive experiments.
• First aid (general):
  • Skin/eye contact: Rinse with water for ≥15 minutes; remove contaminated clothing; seek medical attention as needed.
  • Inhalation: Move to fresh air; monitor for symptoms; seek medical attention if persistent.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire-fighting: Use standard media (CO2, dry chemical, foam). Combustion may produce NOx and COx; firefighters should wear SCBA.
• Waste: Collect solutions/solids as hazardous chemical waste per local regulations; chelator-containing waste should be segregated from metal-bearing waste streams to avoid downstream interference.

Solvent Selection

This item functions primarily as a bifunctional chelator precursor rather than as a reaction solvent. The following guidance reflects typical dissolution media used during synthesis or conjugation (literature/general):

• Polarity class: Highly polar, polyfunctional ligand; best handled in polar protic or polar aprotic media.
• Common dissolution choices:
  • DMSO or DMF (anhydrous): Excellent for stock solutions and for coupling chemistry; supports base-activated or carbodiimide-mediated reactions.
  • Water/buffer (pH 4–6): Useful for metal complexation steps and certain aqueous bioconjugations; adjust ionic strength to control solubility.
  • Alcohols (MeOH, EtOH): Moderate solubility; can serve as co-solvents.
• Poor choices: Nonpolar hydrocarbons and chlorinated solvents typically dissolve DOTA derivatives poorly.

Selection tips:

• For conjugation to amines after reduction to p-aminobenzyl: DMF/DMSO with a mild base (e.g., DIPEA) often gives good reactivity and solubility.
• For radiometal loading: Aqueous acetate/citrate buffers (pH ~4–5) are commonly used to favor complexation (literature). Remove organic co-solvents prior to radiolabeling when possible.
• For purification: Reverse-phase preparative HPLC with water–acetonitrile + 0.1% TFA/formic acid is typical; ensure compatibility with the specific derivative.

Storage and Reconstitution

• Storage conditions (item-specific): Store at -20°C (per Product Data). Protect from moisture and light. Keep container tightly closed. Minimize freeze–thaw by aliquoting upon first opening.
• Shipping (item-specific): Shipped in ice chest with ice pads.
• Research use note: For research use only.

Reconstitution (general guidance for DOTA derivatives; not a product specification):

• Solvents: Prepare stock solutions in anhydrous DMSO or DMF (e.g., 10–50 mM). For aqueous use, dissolve in metal-free water or mildly acidic buffer (pH 4–6) to aid solubilization, then adjust to working pH as needed.
• Metal-free technique: Use chelex-treated water and acid-washed containers to avoid adventitious metal contamination.
• Filtration: If particulate is present, filter through 0.22 µm PTFE (organic stocks) or PES (aqueous) syringe filters.
• Stability: Solutions in DMSO/DMF are generally stable short-term at 2–8°C and longer-term at -20°C; avoid repeated freeze–thaw. Aqueous solutions may slowly absorb trace metals; prepare fresh prior to metal complexation.

Any item-specific concentration limits, counterion/hydration state, or known solution stability data: Not specified for this item; refer to CoA/Spec Sheet.

Structure and Identity

Brief overview: p-NO2-Bn-DOTA is a para-nitrobenzyl-functionalized DOTA (1,4,7,10-tetraazacyclododecane tetraacetic acid) derivative used as a bifunctional chelator precursor in radiometal and lanthanide complexation.

• SKU: P1443304
• Product name: p-NO2-Bn-DOTA
• CAS: 116052-88-1
• 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: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general/literature description):

• Core macrocycle: 12-membered cyclen (1,4,7,10-tetraazacyclododecane) bearing four acetate-type pendant arms (DOTA scaffold) capable of octadentate metal coordination.
• Aroumatic handle: A para-nitrobenzyl substituent (–CH2–C6H4–NO2, para) installed as a reactive handle for downstream functional group interconversion (e.g., reduction to p-aminobenzyl).
• Functional groups: Tertiary and secondary amines within the macrocycle; carboxylate/acetate arms (as acids or esters, depending on exact substitution state); aromatic nitro group.
• 2D description in words: A macrocyclic tetraamine ring with four pendant acetate arms; one arm (or a tether to the macrocycle) terminates in a benzyl group bearing a para-nitro substituent, providing an orthogonal point for conjugation chemistry.

Notes:

• Exact substitution pattern/ionization state can vary among suppliers; consult the CoA/Spec Sheet for definitive structural representation of this specific lot/item.

Synthetic Utility

Key features enabling synthetic utility (literature/general for p-NO2-Bn-DOTA):

• Multifunctional core: The DOTA macrocycle provides four carboxylate arms and four nitrogens capable of selective protection/deprotection strategies, enabling installation of linking groups while preserving chelation capacity.
• Orthogonal handle: The para-nitrobenzyl group can be chemoselectively transformed without perturbing the macrocyclic core, e.g.,
  • Reduction to an aniline (p-NH2-Bn-DOTA) for further electrophile installation (e.g., isothiocyanate, NHS carbonate, sulfonyl chloride) to target amines on biomolecules.
  • Nucleophilic aromatic substitutions or diazotization-derived transformations from the aniline stage if different linkers are desired.
• Metal templating: Transient complexation with non-target metals can, in some routes, influence conformation/reactivity; however, for final materials, metal-free handling is required.
• Retrosynthesis: Disconnection at the benzyl–chelator linkage suggests assembly from a benzylated electrophile and a partially protected DOTA scaffold, or late-stage installation of the benzyl handle onto a mono-activated DOTA arm, followed by global deprotection.

Advantages vs. other chelators:

• DOTA confers high thermodynamic stability and kinetic inertness of metal complexes, advantageous over acyclic chelators (e.g., DTPA) for in vitro stability. Tradeoff: harsher conditions often required for complexation than with NOTA for some metals.

Target Specificity

Not an antibody, enzyme, or receptor-targeted ligand per se. No antigen/epitope or species specificity applies to this product. In research, the chelator can be appended to diverse targeting vectors (peptides, proteins, small molecules), but any specificity derives from the chosen vector rather than from p-NO2-Bn-DOTA itself.