This compound belongs to the class of organic compounds known as hydroxy fatty acids. These are fatty acids in which the chain bears a hydroxyl group.
External Descriptors
3-isopropylmalic acid
1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.
Certificati (CoA, COO, BSE/TSE e tabella di analisi)
C of A & Other Certificates(BSE/TSE, COO):
Analytical Chart:
Proprietà chimiche e fisiche
Peso molecolare
176.170 g/mol
XLogP3
0.000
Hydrogen Bond Donor Count
3
Hydrogen Bond Acceptor Count
5
Rotatable Bond Count
4
Exact Mass
176.068 Da
Monoisotopic Mass
176.068 Da
Topological Polar Surface Area
94.800 Ų
Heavy Atom Count
12
Formal Charge
0
Complexity
186.000
Isotope Atom Count
0
Defined Atom Stereocenter Count
2
Undefined Atom Stereocenter Count
0
Defined Bond Stereocenter Count
0
Undefined Bond Stereocenter Count
0
The total count of all stereochemical bonds
0
Covalently-Bonded Unit Count
1
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Recensioni
Recensioni dei clienti
Application Protocols
No supplier-validated protocols are provided in the Product Data for this item.
General example workflows (for research use only)
Enzyme kinetics (LeuB): Prepare 100 mM HEPES, pH 7.8, with 2 mM MgCl2. Make a 50 mM 3‑isopropylmalate stock in water (adjust pH to dissolve). In a quartz cuvette, mix buffer, NAD+ (0.5 mM), enzyme, and substrate (0.05–2 mM). Monitor A340 for NADH formation; fit initial rates to Michaelis–Menten.
LC–MS metabolite quantitation: Extract biological matrix with cold 80% MeOH containing an internal standard. Separate on HILIC or ion-pair reversed-phase; detect in negative ESI using MRM or SIM of the deprotonated ion. Calibrate with authentic 3‑isopropylmalate standards.
Note
These are literature-style illustrative procedures. Optimize concentrations, pH, and temperatures for your specific enzyme/source and instrumentation. Always consult primary references and your SDS/CoA.
Biological Roles
General/literature context (no clinical claims)
Metabolic intermediate: 3‑Isopropylmalate is a central intermediate in the leucine biosynthesis pathway in bacteria, fungi, and plants. It is generated from 2‑isopropylmalate by isopropylmalate isomerase (LeuC/LeuD) and subsequently oxidatively decarboxylated by isopropylmalate dehydrogenase (LeuB) to yield 2‑ketoisocaproate, a direct leucine precursor.
Enzyme interactions: Serves as a substrate/ligand for the above enzymes; binding and turnover are often Mg2+‑dependent. Some pathway enzymes exhibit stereospecificity toward the configuration at the hydroxyl-bearing carbon.
Regulation: Leucine biosynthesis is feedback-regulated by leucine at the level of acetolactate synthase and transcriptional regulators (e.g., Leu operon in bacteria). Intracellular 3‑isopropylmalate levels can reflect flux through this pathway.
Analytical marker: Detected in metabolomics of microorganisms under amino acid starvation or during growth on specific carbon/nitrogen sources; quantified by LC–MS/MS following ion-pair or hydrophilic interaction chromatography.
Salt/protonation state in biology: Predominantly exists as mono- or di-anionic species at physiological pH, influencing transport and enzyme binding.
Practical implications for researchers
When assaying enzymes, ensure buffer composition (pH 7–8), ionic strength, and Mg2+ concentration match literature optima for the organism/source enzyme.
Consider isotopically labeled 3‑isopropylmalate (13C/2H) for flux analysis and absolute quantitation.
Buffer Applications
Not typically used as a buffering agent.
Guidance for use in aqueous systems
Although 3‑isopropylmalate is a dicarboxylic acid and will contribute to solution buffering capacity near its pKa values, it is not a standard biochemical buffer. For enzyme assays involving this metabolite, choose a conventional buffer system (e.g., HEPES pH 7.5, Tris pH 7.5–8.0, or phosphate pH 7.0–7.5) and add 3‑isopropylmalate as a substrate/co-substrate.
Verify that your chosen buffer does not chelate essential metal ions if the target enzyme is metal-dependent; Good’s buffers (HEPES, MOPS) are often preferred for minimal metal binding.
Green Alternatives
Context
3‑Isopropylmalate is itself a small, non-halogenated organic acid with low volatility. Green chemistry considerations primarily concern solvent choice, protection/deprotection minimization, and bio-based sourcing.
Greener practice suggestions (literature/general guidance)
Aqueous media: Favor water or buffered aqueous solutions for enzymatic and analytical work; minimize DMSO/DMF use.
Bio-based sourcing: Where available, select material produced via fermentation/biocatalysis rather than purely petrochemical synthesis to reduce carbon intensity.
Solvent selection for derivatization: Use ethanol (bio-derived) rather than methanol or chlorinated solvents when feasible; consider solid-supported acid catalysts to reduce corrosive mineral acids.
Energy efficiency: Conduct reactions at ambient temperature and pressure when possible (e.g., EDC-mediated couplings in green solvents).
Tradeoffs
Aqueous systems may slow certain protection/activation steps and complicate isolations.
Bio-ethanol can introduce water that affects esterification equilibria—azeotropic drying or molecular sieves may be needed.
Illustrative comparison (general)
Water/buffer vs. DMSO stocks: Water avoids aprotic solvent hazards and simplifies waste; DMSO can be necessary for concentrated stocks but should be kept to minimal percentages in assays.
Ethyl lactate or propylene carbonate may serve as greener polar solvents in some transformations relative to DMF/ACN, subject to solubility and reaction compatibility.
Pharmaceutical Uses
No direct pharmaceutical or clinical use is indicated for 3‑isopropylmalate.
Formulation/manufacturing context (general)
Role as analytical standard: May be used as an internal or external standard in process analytics or metabolomics linked to microbial fermentation systems.
Excipients/compendial status: There is no common pharmacopeial monograph for 3‑isopropylmalate; it is not a typical excipient. If used in development-stage bioprocess analytics, ensure material traceability and impurity profiling (residual solvents, inorganic ions).
Regulatory note
For research use only (per Product Data). Not for human or veterinary use, not a drug substance, and not intended for diagnostic procedures without appropriate validation.
Physical Properties
Item-specific (from Product Data)
Appearance: Not specified for this item; refer to CoA/Spec Sheet.
Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
Literature/General values (for reference; not item specifications)
Typical molecular formula (free acid): C7H12O5 (literature, for neutral 3‑isopropylmalic acid).
Acid–base: Dicarboxylic acid with one secondary alcohol; expected to form mono-/di-anions near neutral to basic pH (literature). Reported pKa values for analogous malate derivatives are in the ranges pKa1 ~3–3.5 and pKa2 ~5–6 (compound-specific values should be confirmed in the primary literature).
Solubility: Free acids of malate derivatives are usually water soluble to moderately soluble; solubility is greatly increased as alkali or ammonium salts. Low solubility expected in nonpolar solvents; miscible with polar protic solvents such as methanol/ethanol to varying degrees (literature trends for hydroxy-dicarboxylic acids).
Hygroscopicity: Hydroxy-dicarboxylic acids and their salts may be hygroscopic; handle quickly in ambient air to minimize water uptake (general guidance).
Note: Precise item-specific constants (mp, bp, density, refractive index, UV cutoff, water/metal/peroxide limits) are not specified for this item; refer to CoA/Spec Sheet.
Quality and Grades
Item-specific (from Product Data)
Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
Stabilizers/antioxidants: Not specified for this item; refer to CoA/Spec Sheet.
Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
General guidance for this compound class
Biochemical/enzymology grade: For use as a substrate or standard in enzyme assays (e.g., isopropylmalate dehydrogenase/isomerase), low inorganic/organic impurities and accurate content are important. Trace metal content may affect metalloenzymes; users should review CoA for metal limits if assays are metal-dependent.
Chromatography/reference standard grade: When used as a calibration standard in LC/MS, low UV background and well-documented purity (e.g., quantitative NMR, HPLC area %) are valuable. Provide water content and counterion information for salts.
Enantiomeric composition: If stereochemistry matters (many leucine-pathway enzymes are stereoselective), suppliers may offer racemic material or a defined enantiomer/salt. Confirm enantiomeric excess and absolute configuration on the CoA where applicable.
What to check on receipt
Identity confirmation (NMR, HRMS) and purity assay methodology.
Residual solvents, water content (Karl Fischer), and counterion content (for salts).
Any declared UV cutoff or chromatographic baseline characteristics if intended for HPLC/UPLC.
Reaction and Applications
Applications (expanding on typical manufacturer use cases for this metabolite)
Biochemical substrate/standard: 3‑Isopropylmalate is a canonical intermediate in the leucine biosynthetic pathway. It is used as a substrate or standard in studies of isopropylmalate isomerase (LeuC/LeuD) and isopropylmalate dehydrogenase (LeuB), and in metabolomics for pathway flux analysis.
Enzyme kinetics and assay development: Useful for determining kinetic parameters (Km, Vmax) of the above enzymes; often monitored by coupled assays or LC/MS quantification.
Metabolic engineering: Supplementation or feeding studies in microbes/plants to probe regulation of leucine biosynthesis; tracer experiments possible with isotopically labeled analogs.
Synthetic/chemical transformations (general chemistry of hydroxy-dicarboxylic acids)
Esterification: Acid-catalyzed or coupling reagent-mediated formation of mono- or diesters (e.g., Me/Et esters) for derivatization, GC compatibility, or protection strategies.
Lactonization/dehydration: Under dehydrating conditions, β-hydroxy dicarboxylic acids can undergo water loss; reaction pathways depend on substitution and conditions.
Oxidation/reduction: Secondary alcohol can be oxidized to the corresponding keto-dicarboxylic acid; carboxyl groups may be reduced to alcohols under stronger conditions (e.g., borane) to access polyol frameworks.
Amide formation: Activation (e.g., carbodiimide, HATU/EDC) enables coupling to amines to give amides; selective mono- vs. di-acylation requires protecting group strategy.
Practical tips
Control protonation state: For aqueous enzymology, adjust pH to 7–8 to ensure dissolution and maintain enzyme activity.
Avoid metal contamination: Some pathway enzymes require divalent cations (e.g., Mg2+); extraneous metals may inhibit/activate—use high-purity reagents and chelexed buffers as appropriate.
Analytical quantification: Use ion-pair or HILIC/anion-exchange LC for the free acid; derivatize to esters for GC if needed.
Reaction Conditions
General enzymatic assay conditions (literature guidance; adjust per enzyme source)
Isopropylmalate isomerase (LeuC/LeuD): Typical buffers HEPES or Tris, pH 7.5–8.0; Mg2+ (1–5 mM) often required; temperature 25–37 °C. Substrate (3‑isopropylmalate) concentrations commonly 0.05–5 mM for kinetics; monitor interconversion with 2‑isopropylmalate by LC/MS or coupled UV assays.
Isopropylmalate dehydrogenase (LeuB): pH 7.5–8.0, Mg2+ or Mn2+ as cofactors depending on organism; NAD+ as co-substrate; 25–37 °C. Follow NADH formation at 340 nm or product formation by LC/MS.
Chemical transformations (general guidance)
Esterification: Alcohol (MeOH/EtOH), catalytic H2SO4 or HCl(g), 0–25 °C to reflux; remove water (Dean–Stark for higher alcohols) to drive to completion.
Amide coupling: EDC·HCl (1.1–2.0 equiv), NHS or HOBt additive, DMF or aqueous-organic media, pH control (5.0–6.0 for aqueous EDC); 0–25 °C, 1–16 h.
Oxidation of secondary alcohol: Jones or PCC (non-green) at 0–25 °C; or catalytic systems (e.g., TEMPO/bleach less effective on secondary alcohol; consider IBX/DMP variants with caution). Protect carboxyls if required to avoid side reactions.
Notes
Maintain defined protonation state: For aqueous work, adjust pH to enhance solubility; avoid high DMSO content for enzyme stability.
Metal sensitivity: Trace chelators (EDTA) can inhibit metalloenzymes; include only if intentionally studying metal dependence.
Safety and Handling
Item-specific (from Product Data)
GHS classification: Not specified for this item; refer to SDS.
Signal word / Pictograms / H-statements: Not specified for this item; refer to SDS.
Storage conditions: Room temperature (per Product Data).
General safety guidance (literature/standard laboratory practice; defer to SDS)
Likely hazards: Hydroxy-dicarboxylic acids are generally low volatility and of low acute hazard, but can cause irritation to eyes/skin upon contact. Avoid inhalation of dusts and ingestion.
PPE: Wear lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Use dust control (local exhaust) when weighing.
Handling: Avoid creating dust. If material is provided as an alkali/ammonium salt, it may be more hygroscopic—keep container tightly closed and minimize exposure to humid air.
Incompatibilities: Strong oxidizers (general precaution). Strong bases/acids can alter protonation state; avoid uncontrolled neutralization that may cause heat evolution or CO2 release if carbonate bases are used.
First aid (overview): Rinse eyes/skin with water for several minutes upon contact; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; seek medical attention as needed. Always follow the site SDS for authoritative instructions.
Spills: Avoid dust; sweep up gently or use HEPA vacuum. Dispose according to local regulations.
Fire fighting: Substance is non-volatile; use media appropriate for surrounding fire. Combustion may produce CO/CO2.
Solvent Selection
Applicability
3‑Isopropylmalate is a polar hydroxy-dicarboxylic acid (or its salt). Solvent selection is driven by ionization state and application (biochemical assay vs. synthetic transformation).
General solubility profile (literature trends)
Water: Good solubility as the mono/di-anion (adjust pH > pKa2). Free acid is variably soluble; mild basification (e.g., 1–10 mM NaOH) increases solubility substantially.
Alcohols: Methanol/ethanol often dissolve the free acid moderately; solubility improves with small amounts of water or base.
Polar aprotic solvents: Limited solubility of the free acid in acetonitrile/DMF/DMSO; small volumes of DMSO are commonly used to prepare concentrated stock solutions for biochemical assays, then diluted into aqueous buffers.
Nonpolar solvents: Poorly soluble.
Practical guidance
For enzyme assays: Prepare concentrated stocks in water or buffer at pH 7.0–8.0; if needed, briefly dissolve in minimal DMSO and dilute into buffer (<1–2% DMSO final to protect enzyme activity).
For derivatization/esterification: Use anhydrous alcohol solvents (MeOH, EtOH) with acid catalysts or coupling reagents; remove water to drive equilibria.
Salt selection: Sodium, potassium, or ammonium salts provide higher aqueous solubility; verify the exact counterion on product documentation.
Comparison notes
Versus malic acid: Similar polarity but higher hydrophobic character from the isopropyl group; slightly lower aqueous solubility expected for the free acid.
Versus 2‑isopropylmalate: Solubility characteristics are broadly similar; specific stereochemical/isomeric differences may influence crystallinity and dissolution rates.
Storage and Reconstitution
Item-specific (from Product Data)
Recommended storage: Room temperature.
General guidance
Container: Store tightly closed in a clean, dry container. If provided as a hygroscopic salt, limit exposure to ambient humidity; consider desiccation for long-term storage.
Light sensitivity: No special light sensitivity is commonly reported for this class; store protected from direct sunlight as good practice.
Stability: Hydroxy-dicarboxylic acids are generally stable at ambient conditions when dry. In solution, they may slowly undergo hydration/dehydration or microbial growth—prepare fresh aqueous solutions or filter-sterilize and refrigerate.
Reconstitution: For biochemical use, dissolve in high-purity water or appropriate buffer. Adjust pH (e.g., to 7.0–8.0 with NaOH) to aid dissolution of the free acid. If using an organic co-solvent (e.g., DMSO) for concentrated stocks, keep final co-solvent content low upon dilution into enzyme assays.
Freeze–thaw: For aqueous stocks intended for multiple uses, aliquot and store refrigerated or frozen to avoid repeated freeze–thaw cycles, which can concentrate salts and alter pH.
Always refer to the product’s CoA and SDS for definitive storage and handling instructions.
Structure and Identity
Item-specific (from Product Data)
Product name: 3-Isopropylmalate (SKU: I991466)
CAS: 126576-14-5
PubChem CID: 5462261
InChIKey: 321135 (as provided in Product Data)
SMILES: Not specified for this item; refer to CoA/Spec Sheet.
Literature/General structural information (for identity context; not item specifications)
Common chemical identity: 3-isopropylmalic acid; a hydroxy-dicarboxylic acid derived from malic acid with an isopropyl substituent.
Functional groups: two carboxylic acids (dicarboxylate in basic media), one secondary alcohol (β-hydroxy acid motif), one isopropyl (branched aliphatic) substituent.
Stereochemistry: the malate backbone contains a stereogenic center at the α-carbon (the carbon bearing –OH). Commercial materials may be racemic unless specified; enantiopurity is application-dependent in enzymology.
2D description in words: a four‑carbon malate backbone (–OOC–CH2–CH(OH)–COO–) in which the C-3 carbon (adjacent to the hydroxyl-bearing carbon) carries an isopropyl group; terminal carboxylates flank the chain.
Notes
This compound is a well-known metabolic intermediate in the leucine biosynthesis pathway (see Biological Roles). Always verify exact protonation state and counterions (free acid vs. salts) on the product’s CoA.
Synthetic Utility
Retrosynthetic value
3‑Isopropylmalate contains a β‑hydroxy dicarboxylic acid motif and a secondary alcohol adjacent to a substituted center, enabling access to diverse derivatives via redox and protection strategies.
Transformations (general)
Selective esterification: Mono- vs. diester formation using stoichiometry and protection tactics enables orthogonal functionalization of the two carboxyls.
Oxidation to keto-acid: The secondary alcohol can be oxidized (e.g., TEMPO or Dess–Martin is less suitable for unactivated secondary alcohols; more robust oxidants or catalytic systems with co-oxidants may be required) to yield the corresponding 3‑isopropyl‑oxaloacetic analog, enabling aldol-like downstream chemistry.
Decarboxylative strategies: Under thermal or oxidative conditions, substituted malates can undergo decarboxylation to give branched carboxylic acids; coupling with photoredox/copper catalysis enables decarboxylative C–C bond formations from activated esters.
Amide coupling: Activation (e.g., EDC·HCl/NHS) provides amides for probe attachment or immobilization on solid supports.
Chiral derivatization: If enantiopure material is available or resolved, it can serve as a chiral building block for β‑hydroxy acid derivatives.
Analytical chemistry
Derivatization (silylation or esterification) facilitates GC analysis; LC–MS typically uses negative ESI with formate/acetate buffers.
Target Specificity
This product is a small-molecule metabolite, not a biological affinity reagent. No target specificity data (e.g., antigen, epitope, isotype, clone, species reactivity) are applicable.
Item-specific
Target specificity: Not specified for this item; refer to CoA/Spec Sheet if any biological testing is provided.
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