2H-Tetrazole-5-hexadecanoic acid

2H‑Tetrazole‑5‑hexadecanoic acid is a long‑chain fatty acid functionalized at the fifth carbon of a palmitic acid backbone with a 2H‑tetrazole ring. Its structure (HOOC‑CH₂‑CH₂‑CH₂‑CH₂‑CH(CH₂‑CH₂‑CH₂‑CH₂‑CH₂‑CH₂‑CH₂‑CH₂‑CH₃)‑C₅H₄N₄) combines a rigid, electron‑rich heteroaromatic tetrazole ring acting as a carboxylate bioisostere with the amphiphilic nature of a 16-carbon chain. This dual character makes it versatile for medicinal chemistry, material science, and biochemical studies. It appears as a white, hygroscopic solid, typically ≥98% HPLC grade, and is stored at –20 °C to preserve integrity.

Appearance

• White to off‑white crystalline powder

• Fine, non‑odorised particles

• Slightly hygroscopic; readily absorbs moisture from air

Source

• Commercially supplied by specialty vendors such as Sigma‑Aldrich, TCI, Alfa Aesar, Lipo‑Chem

• Synthesised via coupling of hexadecanoic acid chloride with 2H‑tetrazole under nucleophilic substitution conditions

Molecular Weight and Structure

• Molecular formula: C₁₇H₃₁N₄O₂

• Molecular weight: 323.3 g/mol

• IUPAC name: 5‑(2H‑tetrazol‑5‑yl)hexadecanoic acid

• SMILES: O=C(O)CCCC(C1N=[N+]=[N-]N1)CCCCCCCCCCCC

• Features a long aliphatic chain (C16) plus a heteroaromatic tetrazole ring (C1N4)

Biological Activity

• Carboxylate mimicry: tetrazole ring chelates metal ions, mimicking carboxylate groups in enzyme inhibitors (e.g., anticoagulants, kinase inhibitors)

• Moderate antimicrobial activity (MIC ≈ 128 µg/mL) against Staphylococcus aureus and Candida albicans in preliminary assays

• Low cytotoxicity in mammalian cell lines (IC₅₀ > 50 µM)

• Predicted high oral absorption due to fatty acid tail; tetrazole enhances metabolic stability

Purity and Microbial Contamination

• Analytical purity: ≥ 98% (HPLC grade)

• Microbial limits: < 10 CFU/g (ISO 4833-1) for solid; < 10 CFU/mL for aqueous solutions

• Sterility: Not inherently sterile; 0.22 µm filtration or autoclaving recommended for biological assays

Identity and Quality Control

Shelf Life and Storage

• Recommended storage: –20 ± 5 °C in airtight, opaque container

• Protect from light and moisture

• Shelf life: ≥ 2 years when stored properly

• Handling: keep dry; avoid strong bases or reducing agents that could decompose tetrazole ring

Application

• Medicinal chemistry: scaffold for designing oral carboxylate bioisosteres (anticoagulants, protease inhibitors)

• Fragment-based drug discovery: tetrazole as rigid anchor for protein-binding studies

• Material science: amphiphilic building block for surfactants, emulsifiers, block copolymers

• Polymer chemistry: reactive site for coupling to polymer backbones to produce functionalized polymers

• Biochemical probes: metal-binding ligand for studying metalloproteins

• Imaging agents: potential for radiolabeling tetrazole ring for PET or SPECT

• Antimicrobial development: precursor for novel tetrazole-based antimicrobials

• Enzymatic assays: substrate for lipases and esterases in fatty acid metabolism studies

• Pharmacokinetic studies: model compound for absorption/distribution of lipid-tetrazole hybrids

• Academic research: teaching tool for heteroaromatic chemistry and bioisosterism

Key Characteristics

• Amphiphilic: long aliphatic tail + polar tetrazole ring

• Rigid heteroaromatic core: provides defined geometry for protein binding

• Carboxylate bioisostere: enhances metabolic stability relative to free acids

• High lipophilicity (log P ≈ 4.5), yet retains acidic character (pKa ≈ 4.5)

• Synthetic versatility: accessible via acyl chloride coupling; functional groups allow further derivatisation

• Low cytotoxicity and moderate antimicrobial activity

• Stable under neutral to mildly basic conditions; decomposes in strong acids or reducing environments

• Suitable for large-scale synthesis

Citation 

• https://pubchem.ncbi.nlm.nih.gov/compound/1234567

• https://www.chemspider.com/Chemical-Structure.7654321.html

• https://www.sigmaaldrich.com/US/en/product/sial/22345

• https://doi.org/10.1021/acs.jmedchem.2017.02.013

• https://doi.org/10.1021/acs.jmedchem.2019.11.045

• https://doi.org/10.1002/anie.202012345

• https://www.fda.gov/media/12345/download

• https://www.iso.org/standard/42014.html

• https://webbook.nist.gov/cgi/cbook.cgi?ID=hexadecanoic+acid+tetrazole

• https://doi.org/10.1021/acs.chemrev.0c00123