Harmine (442-51-3) Physical and Chemical Properties
Harmine
A naturally occurring beta‑carboline (pyridoindole) alkaloid used as a research chemical and analytical reference in small‑molecule studies.
| CAS Number | 442-51-3 |
| Family | Pyridoindoles (beta‑carboline alkaloids) |
| Typical Form | Powder or crystalline solid |
| Common Grades | BP, EP |
Harmine is a naturally occurring beta-carboline (pyrido[3,4-b]indole) alkaloid of the pyridoindole structural class. Structurally it is a fused heteroaromatic system bearing two ring nitrogens, a 7-methoxy substituent and an N‑methyl substituent; the molecular formula is \(\ce{C13H12N2O}\). The conjugated heteroaromatic core produces a largely planar scaffold with a retained indolic N–H (one hydrogen-bond donor) and relatively small polar surface area, characteristics that determine its basic physicochemical and ADME-related behavior.
Electronically, the fused pyridine–indole system yields a delocalized π system; the 7‑methoxy group is an electron-donating substituent that modulates electron density on the aromatic framework and is a common site for biotransformation (O‑demethylation). Harmine is a weakly basic heteroaromatic amine with limited polar surface area and modest hydrogen-bonding capacity, and therefore displays moderate lipophilicity and membrane permeability consistent with its pharmacological activity as a reversible monoamine oxidase inhibitor (MAOI) and CNS‑active alkaloid.
Common commercial grades reported for this substance include: BP, EP.
Basic Physicochemical Properties
Density and Solid-State Form
Physical description: Solid. Crystalline forms and crystal-structure data have been reported for harmine; unit-cell and space-group information are available in crystallographic reports. No single, experimentally established bulk density value is available in the current data context.
Melting Point
Reported melting point: \(264 - 265\ ^\circ\mathrm{C}\). This relatively high melting point is consistent with a rigid, planar aromatic lattice and indicates thermal stability of the free base up to the melting range.
Solubility and Dissolution Behavior
No experimentally established value for this property is available in the current data context.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
No experimentally established value for this property is available in the current data context.
Qualitatively, harmine contains one NH hydrogen (indolic) and nitrogen atoms within the fused heterocycle; the basicity is weaker than typical aliphatic amines due to aromatic delocalization. Protonation equilibria, when present, are expected to be shifted toward the non‑protonated form at physiological pH, which contributes to membrane permeability and CNS access.
Reactivity and Stability
Harmine is an aromatic heterocycle that is chemically stable under neutral to mildly acidic conditions but is susceptible to metabolic oxidative transformations. Human metabolic pathways reported include O‑demethylation (producing harmol) and hydroxylation (e.g., 6‑hydroxy derivatives such as 6‑Hydroxy‑harmaline). As a heteroaromatic alkaloid, it is generally resistant to hydrolysis but can undergo oxidative metabolism and N‑demethylation under biological conditions. Typical storage stabilization approaches for related alkaloids include protection from light and moisture to minimize slow oxidative degradation.
Molecular Parameters
Molecular Weight and Formula
- Molecular formula: \(\ce{C13H12N2O}\)
- Molecular weight: 212.25 (given as 212.25)
Exact/monoisotopic mass values (as reported): \(212.094963011\) (ExactMass / MonoisotopicMass)
Other computed heavy-atom and structural descriptors reported: Heavy atom count 16; Complexity 258; Formal charge 0; Isotope atom count 0.
LogP and Structural Features
- Computed XLogP3: 3.6
- Experimental LogP: 3.56
- Topological polar surface area (TPSA): 37.9
- Hydrogen-bond donor count: 1
- Hydrogen-bond acceptor count: 2
- Rotatable bond count: 1
The combination of XLogP ≈ 3.6 and TPSA ≈ 38 Ų indicates moderate lipophilicity with sufficient membrane partitioning for CNS exposure while retaining minimal polar surface for limited aqueous solubility. Low rotatable-bond count and a rigid fused-ring system favor good passive permeability but reduce conformational flexibility.
Structural Identifiers (SMILES, InChI)
- SMILES:
CC1=NC=CC2=C1NC3=C2C=CC(=C3)OC - InChI:
InChI=1S/C13H12N2O/c1-8-13-11(5-6-14-8)10-4-3-9(16-2)7-12(10)15-13/h3-7,15H,1-2H3 - InChIKey:
BXNJHAXVSOCGBA-UHFFFAOYSA-N
(NB: SMILES, InChI and InChIKey are provided for structural interoperability and spectrometric annotation.)
Additional molecular spectrometric descriptors: exact mass and monoisotopic mass both \(212.094963011\).
Identifiers and Synonyms
Registry Numbers and Codes
- CAS RN: 442-51-3
- EC Number: 207-131-4
- UNII: 4FHH5G48T7
- InChIKey: BXNJHAXVSOCGBA-UHFFFAOYSA-N
Synonyms and Brand-Independent Names
Common synonyms and systematic names recorded include: - Harmine - 7‑methoxy‑1‑methyl‑9H‑pyrido[3,4‑b]indole - 7‑Methoxy‑1‑methyl‑9H‑beta‑carboline - Banisterine - Telepathine - Leucoharmine - Yageine - Harmin - 1‑Methyl‑7‑methoxy‑beta‑carboline
(These alternative names and trivial synonyms are useful for procurement, literature searching, and specification matching.)
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Harmine is a bioactive alkaloid with activity as a reversible monoamine oxidase inhibitor (MAOI, EC 1.4.3.4) and has been investigated in early‑stage pharmacology and small clinical investigations (maximum clinical trial phase reported: Phase I). It appears as a natural product constituent in several plant species and has historical significance as a pharmacologically active component of traditional preparations. Documented biological activities include MAO inhibition and other bioactivity screens (including investigational antiviral annotations in some test systems).
Formulation and Development Contexts
Because harmine is a lipophilic, crystalline alkaloid with limited aqueous solubility (see LogP and TPSA above), formulation approaches for pharmaceutical development typically consider solubilization strategies (cosolvents, lipid-based delivery, or salt/derivative formation where chemically feasible) and stability in solid formulations. No approved therapeutic indication is established for harmine in standard pharmacopeial contexts; its selection in research and development is primarily based on its pharmacology and CNS permeability profile.
If a concise application summary is not otherwise supplied in documentation, in practice this substance is selected for research or development projects based on its MAOI activity, CNS permeability potential, and use as a natural‑product reference standard.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Typical commercial grade distinctions that apply to small‑molecule alkaloids include pharmaceutical (for advanced development), analytical / reference standard (high purity, for assay and spectroscopy), and technical grades (for non‑clinical research, where tighter impurity control is not required). Analytical reference materials are commonly supplied with certificate of analysis (COA) showing identity and spectral confirmation.
Reported commercial grades for this substance include: - BP - EP
General Quality Attributes (Qualitative Description)
Quality attributes commonly reviewed for harmine batches are: - Identity confirmation by MS (m/z 212 dominant in EI/ESI), NMR, IR and UV spectra. - Purity assessment by HPLC and GC‑MS (typical principal peak at m/z 212 in EI spectra). - Water content and residual solvent limits where applicable. - Physical form (free base vs. salt, crystalline morphology) and melting-point consistency (expected \(264 - 265\ ^\circ\mathrm{C}\) for the free base). - Storage stability data and impurity profile (including known degradants and O‑demethylation products).
No standardized assay or specific impurity limits are provided here; individual suppliers provide COAs detailing numeric specifications.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
Harmine is classified in hazard communications as acutely toxic at higher exposure levels and as an eye irritant in notified classifications. Aggregated hazard statements reported include: - H302+H312+H332: Harmful if swallowed, in contact with skin or if inhaled. - H302: Harmful if swallowed. - H312: Harmful in contact with skin. - H319: Causes serious eye irritation. - H332: Harmful if inhaled.
As a biologically active monoamine oxidase inhibitor, harmine can influence neurotransmitter metabolism; potential systemic pharmacological effects should be considered in exposure scenarios. Known human metabolites include harmol and 6‑hydroxy‑harmaline; metabolic activation or biotransformation can alter toxicological properties.
Exposure-control recommendations (general, class‑based): - Use appropriate personal protective equipment (PPE): gloves resistant to organic chemicals, eye protection, and lab coat. - Avoid inhalation of dusts or aerosols; use local exhaust or containment for weighed solids. - Prevent skin contact and ingestion; practice good hygiene and do not eat or drink in work areas.
For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
Storage and Handling Guidelines
- Store in a tightly closed container in a cool, dry, well‑ventilated area protected from light and oxidants.
- Minimize exposure to heat and moisture to retain crystalline integrity and minimize slow oxidative changes.
- Use dust control measures when handling solids at scale; use inert atmosphere if required for long‑term storage of sensitive lots (per vendor guidance).
For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
