BenzeneDiaMidoEthaneThiol N,N’-Bis(2-Mercaptoethyl)isophthalaMide

BenzeneDiaMidoEthaneThiol N,N’-Bis(2-Mercaptoethyl)isophthalaMide (CAS: 351994-94-0), also known as Emeramide or NBMI, is a novel lipophilic thiol-rich synthetic molecule widely used in heavy metal detoxification research, redox biology, and neuroprotective drug discovery. Featuring a unique molecular architecture that incorporates two reactive thiol groups attached to an isophthalamide aromatic core, it offers strong soft-metal chelation capacity, potent antioxidant activity, and enhanced blood-brain barrier permeability compared to conventional hydrophilic thiol chelators. Its well-defined metal-binding affinity, reliable synthetic accessibility, and established utility as a tool for probing thiol-dependent detoxification pathways and oxidative stress mechanisms make it a dependable standard for drug discovery, environmental toxicology, and molecular pharmacology research. Its primary applications are outlined below:

1. Medicinal Chemistry & Drug Discovery

Heavy Metal Chelation Therapy
N,N’-Bis(2-Mercaptoethyl)isophthalaMide serves as a leading clinical candidate for the detoxification of heavy metals, particularly mercury (Hg²⁺), lead (Pb²⁺), and cadmium (Cd²⁺). Its two thiol groups form stable, lipophilic complexes with soft metal ions, facilitating their removal from tissues—including the central nervous system—without redistributing metals to critical organs. Researchers employ this compound in preclinical and clinical studies for chronic metal poisoning, amalgam-related mercury exposure, and occupational heavy metal toxicity.

Neuroprotective Agent Development
The compound’s ability to cross the blood-brain barrier and chelate neurotoxic metals positions it as a promising therapeutic for neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). By reducing metal-induced oxidative stress and inhibiting metal-catalyzed protein aggregation, it supports neuroprotection in cellular and animal models. Scientists investigate its derivatives in SAR studies to optimize blood-brain barrier penetration and neuroprotective efficacy.

Antioxidant & Anti-inflammatory Therapeutics
Beyond metal chelation, the thiol groups confer potent free radical-scavenging activity. The compound has been evaluated as a cytoprotective agent against ischemia-reperfusion injury, acetaminophen hepatotoxicity, and inflammatory conditions. Its dual mechanism—both chelating pro-oxidant metals and directly neutralizing reactive oxygen species (ROS)—makes it a valuable scaffold for developing multifunctional therapeutics.

Anticancer Adjuvant Research
Emeramide is investigated as a chemosensitizer in cancer therapy. By modulating intracellular redox balance and depleting essential metal cofactors in tumor cells, it can enhance the efficacy of conventional chemotherapeutics (e.g., cisplatin, doxorubicin) while reducing their off-target toxicities. Researchers utilize this compound in combination therapy studies to improve therapeutic indices.

2. Environmental Toxicology & Occupational Health

Biomonitoring & Exposure Assessment
The compound is employed as a reference standard in analytical toxicology to develop methods for detecting heavy metal-thiol adducts in biological matrices (blood, urine, hair). Its well-characterized metal-binding stoichiometry supports the calibration of mass spectrometric assays for quantifying metal exposure in occupational and environmental settings.

Environmental Remediation Research
Derivatives of this scaffold are explored for the remediation of heavy metal-contaminated water and soil. The strong affinity of its thiol groups for mercury and other soft metals enables the design of immobilized chelating resins and functionalized materials for environmental cleanup applications.

Toxicological Mechanism Studies
Researchers use N,N’-Bis(2-Mercaptoethyl)isophthalaMide as a molecular tool to investigate the mechanisms of metal-induced cytotoxicity, oxidative damage, and mitochondrial dysfunction. By selectively chelating intracellular metals, it helps delineate the roles of specific metal ions in cell death pathways and inflammatory responses.

3. Biochemical Research & Enzyme Studies

Redox Signaling & Thiol Metabolism Probing
The compound’s thiol groups participate in reversible redox reactions (e.g., disulfide formation, S-glutathionylation), making it a useful probe for studying cellular redox homeostasis and thiol-disulfide exchange pathways. Researchers employ it to investigate the activity of thioredoxin reductase, glutathione peroxidase, and other redox-regulating enzymes.

Metalloproteinase & Metal-Enzyme Inhibition
N,N’-Bis(2-Mercaptoethyl)isophthalaMide is utilized as an inhibitor of zinc-dependent metalloproteinases (MMPs, ADAMs) and other metal-requiring enzymes. Its chelation of catalytic zinc ions provides a tool for studying the role of metalloproteinases in cancer metastasis, tissue remodeling, and inflammation.

Lipid Peroxidation & Oxidative Stress Assays
Due to its lipophilic nature, the compound effectively partitions into cell membranes and lipoproteins, where it inhibits lipid peroxidation chain reactions. Scientists use it in biochemical assays to evaluate oxidative stress in cardiovascular disease models, aging studies, and metabolic syndrome research.

4. Pharmaceutical Formulation & Drug Delivery

Liposome & Nanoparticle Encapsulation
The lipophilic character of Emeramide makes it amenable to encapsulation in lipid-based delivery systems, including liposomes, solid lipid nanoparticles, and nanoemulsions. Researchers optimize these formulations to improve oral bioavailability, sustained release, and targeted delivery to the brain or liver.

Prodrug & Derivative Design
Medicinal chemists modify the thiol groups (e.g., as disulfides, thioesters, or thioethers) to create prodrugs with improved stability, reduced gastrointestinal irritation, or enhanced tissue selectivity. The isophthalamide core provides multiple sites for conjugation, enabling the design of bifunctional molecules for combination therapies.

Pharmacokinetic & ADME Studies
The compound is used as a model lipophilic thiol in preclinical pharmacokinetic studies to investigate absorption, distribution, metabolism, and excretion (ADME) properties. Its well-defined metabolic pathway—including oxidation to disulfides and sulfonation—serves as a reference for predicting the behavior of other thiol-containing drug candidates.

5. Neuroscience & Central Nervous System Research

Blood-Brain Barrier Transport Studies
Due to its favorable lipophilicity and low molecular weight, N,N’-Bis(2-Mercaptoethyl)isophthalaMide is employed as a probe to study passive diffusion and transporter-mediated uptake across the blood-brain barrier. Researchers use it to validate in vitro BBB models and to assess the brain penetration of lipophilic chelators.

Metal-Induced Neurodegeneration Models
The compound is a standard tool in animal models of mercury-, lead-, or manganese-induced neurotoxicity. By mitigating metal accumulation and oxidative damage, it helps establish causal relationships between metal exposure and neurodegenerative phenotypes, supporting the development of disease-modifying strategies.

Amyloid-β & Tau Aggregation Studies
Investigators use Emeramide to study metal-catalyzed aggregation of amyloid-β and tau proteins in Alzheimer’s disease models. Its ability to chelate redox-active metals (e.g., Cu, Fe) and prevent protein crosslinking makes it a valuable reagent for probing the metal hypothesis of neurodegeneration.

6. Materials Science & Analytical Chemistry

Thiol-Functionalized Surfaces & Sensors
The compound serves as a model thiol for the functionalization of gold, silver, and platinum surfaces, enabling the development of electrochemical sensors for heavy metal detection. Researchers utilize its self-assembled monolayers (SAMs) on electrode surfaces to achieve selective and sensitive detection of Hg²⁺, Pb²⁺, and Cd²⁺ in aqueous samples.

Nanoparticle Stabilization & Conjugation
The strong affinity of thiols for noble metal nanoparticles (e.g., AuNPs, AgNPs) is exploited to stabilize and functionalize nanomaterials. N,N’-Bis(2-Mercaptoethyl)isophthalaMide is used to coat nanoparticles for bioimaging, drug delivery, and catalytic applications.

Reference Material for Analytical Method Development
Given its high purity and well-defined chemical structure, the compound is employed as a certified reference material in the development and validation of analytical methods, including HPLC, LC-MS/MS, and ICP-MS, for quantifying thiols and metal complexes in biological and environmental matrices.

7. Agricultural & Veterinary Research

Livestock Heavy Metal Toxicity Management
The compound is investigated as a veterinary therapeutic for heavy metal poisoning in livestock and aquaculture. Its favorable safety profile and effectiveness in reducing tissue metal burden support its use in animal health studies.

Crop Protection & Soil Remediation
Researchers explore the application of derivatives of this scaffold to mitigate heavy metal uptake in crops grown on contaminated soils. By chelating soil metals or by modulating plant metal-transporter expression, it may contribute to safer food production.

8. Handling & Storage

Storage Conditions
Store in tightly sealed, amber glass containers under inert atmosphere (N₂ or Ar) at 2–8 °C, protected from light, moisture, and oxidizing agents. The thiol groups are susceptible to oxidation to disulfides upon prolonged exposure to air or light. Desiccated storage is strongly recommended. Stock solutions should be prepared in degassed, oxygen-free solvents (e.g., DMSO, ethanol, or deoxygenated phosphate buffer) and stored at –20 °C under argon for extended periods.

Solubility & Preparation
Soluble in organic solvents including dimethyl sulfoxide (DMSO), ethanol, methanol, and acetone; sparingly soluble in water. For biological assays, dissolve in DMSO (prepared fresh) and dilute slowly with aqueous buffers (pH 7.0–7.4) to prevent precipitation. Note that the thiol groups may oxidize in alkaline or metal-containing buffers; addition of a mild reducing agent (e.g., TCEP or DTT) may be necessary for certain applications.

Chemical Stability Considerations
The compound is sensitive to oxidation; exposure to oxygen, light, or transition metals may promote disulfide dimer formation. Handle under inert atmosphere and use freshly prepared solutions for quantitative studies. Acidic or strongly basic conditions may hydrolyze the amide bonds; neutral pH is recommended for long-term stability.

Intended Use
This product is intended for research, development, and laboratory use only. It is not approved for human therapeutic use, clinical diagnostics, veterinary treatment, or food applications unless explicitly indicated for regulated clinical trials. Standard laboratory safety practices (chemical fume hood, impermeable gloves, safety goggles) should be followed during handling. Avoid inhalation of dust and contact with skin or eyes.

Summary

The value of BenzeneDiaMidoEthaneThiol N,N’-Bis(2-Mercaptoethyl)isophthalaMide (Emeramide, CAS: 351994-94-0) lies in its unique combination of lipophilicity, bidentate thiol chelation, and potent antioxidant activity, which together enable its application across multiple research disciplines. Its clinical-stage development as a heavy metal chelator positions it as a leading candidate for mercury and lead detoxification; its ability to cross the blood-brain barrier supports neuroprotective drug discovery; and its redox-active thiol groups make it a valuable tool for probing oxidative stress, thiol metabolism, and metal-dependent enzymatic pathways. Reliable synthetic accessibility, favorable safety profile, and proven utility in both in vitro biochemical assays and in vivo preclinical models make this compound a dependable standard for pharmaceutical research, environmental toxicology, and molecular pharmacology worldwide.

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