Abstract

Dihomo-γ-linolenic acid (DGLA), systematically named (8Z,11Z,14Z)-icosa-8,11,14-trienoic acid, is a 20-carbon polyunsaturated fatty acid with molecular formula C₂₀H₃₄O₂. This ω-6 fatty acid features three cis-configured double bonds at positions Δ⁸, Δ¹¹, and Δ¹⁴. DGLA exists as a colorless to pale yellow viscous liquid at room temperature with a melting point of approximately -45°C and boiling point of 381°C at atmospheric pressure. The compound demonstrates characteristic chemical reactivity of polyunsaturated carboxylic acids, including susceptibility to oxidation, hydrogenation, and esterification reactions. DGLA serves as a key metabolic intermediate in the biosynthesis of various eicosanoids and exhibits distinctive spectroscopic signatures in NMR and IR spectroscopy. Its molecular structure features a bent hydrocarbon chain with restricted rotation around double bonds, resulting in specific conformational preferences.

Introduction

Dihomo-γ-linolenic acid represents an important intermediate in the metabolic pathway of essential fatty acids. Classified as an unsaturated carboxylic acid, this C₂₀ compound belongs to the broader category of polyunsaturated fatty acids (PUFAs) with significant biochemical implications. The systematic IUPAC nomenclature identifies the compound as (8Z,11Z,14Z)-icosa-8,11,14-trienoic acid, precisely defining the position and stereochemistry of its three double bonds. The compound's discovery emerged from investigations into fatty acid metabolism during the mid-20th century, with structural elucidation achieved through combined chemical degradation studies and spectroscopic analysis. Early synthetic work established the complete stereochemistry and confirmed the all-cis configuration of the triene system.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The molecular structure of dihomo-γ-linolenic acid features a 20-carbon unbranched hydrocarbon chain with a carboxylic acid terminus at C1. The three double bonds at positions C8-C9, C11-C12, and C14-C15 all exhibit Z (cis) configuration, creating bends in the molecular structure with approximately 30° angles at each double bond. The carbon atoms at the double bonds exhibit sp² hybridization with bond angles of approximately 120°, while the saturated segments maintain sp³ hybridization with tetrahedral geometry. The electronic structure demonstrates conjugation between the double bonds, though the methylene-interrupted arrangement (C-C single bonds between double bonds) limits full electronic delocalization. Molecular orbital calculations predict highest occupied molecular orbitals localized primarily around the triene system with contributions from the carboxylic oxygen orbitals.

Chemical Bonding and Intermolecular Forces

Covalent bonding in dihomo-γ-linolenic acid follows typical patterns for unsaturated fatty acids. Carbon-carbon double bonds measure approximately 1.34 Å with bond dissociation energies of 264 kJ/mol, while single bonds range from 1.53-1.54 Å with dissociation energies of 347 kJ/mol. The carboxylic acid group features a carbonyl carbon-oxygen bond length of 1.21 Å and hydroxyl carbon-oxygen bond of 1.36 Å. Intermolecular forces are dominated by London dispersion forces along the hydrocarbon chain and hydrogen bonding capability through the carboxylic acid functionality. The calculated dipole moment measures approximately 1.8 D, primarily oriented along the C-O bond axis. The compound's polarity permits limited solubility in polar organic solvents while maintaining hydrophobicity characteristic of long-chain fatty acids.

Physical Properties

Phase Behavior and Thermodynamic Properties

Dihomo-γ-linolenic acid exists as a viscous liquid at room temperature with a clear, pale yellow appearance. The compound demonstrates a melting point of -45°C and boiling point of 381°C at 760 mmHg. Under reduced pressure of 0.1 mmHg, distillation occurs at 180-185°C. The density measures 0.905 g/mL at 25°C, with a refractive index of 1.482 at 20°C. Thermodynamic parameters include heat of combustion of -11892 kJ/mol, heat of vaporization of 85.6 kJ/mol, and specific heat capacity of 2.1 J/g·K. The compound exhibits low volatility with vapor pressure of 2.7×10⁻⁶ mmHg at 25°C. Viscosity measurements indicate 28.5 cP at 25°C, decreasing exponentially with temperature increase.

Spectroscopic Characteristics

Infrared spectroscopy reveals characteristic absorptions at 3005 cm⁻¹ (=C-H stretch), 2920 cm⁻¹ and 2850 cm⁻¹ (C-H stretch), 1710 cm⁻¹ (C=O stretch), 1650 cm⁻¹ (C=C stretch), and 1280 cm⁻¹ (C-O stretch). Proton NMR spectroscopy shows distinctive signals: δ 0.88 ppm (t, 3H, CH₃), 1.25-1.35 ppm (m, 10H, CH₂), 1.62 ppm (quintet, 2H, CH₂CH₂COOH), 2.05 ppm (m, 8H, CH₂CH=CH), 2.34 ppm (t, 2H, CH₂COOH), 5.30-5.40 ppm (m, 6H, CH=CH). Carbon-13 NMR displays signals at δ 14.1 ppm (CH₃), 22.6 ppm (CH₂CH₃), 24.6 ppm (CH₂CH₂COOH), 25.6 ppm, 27.2 ppm, 27.3 ppm, 29.0-29.7 ppm (multiple CH₂), 31.5 ppm (CH₂CH₂CH₃), 34.0 ppm (CH₂COOH), 127.8-130.4 ppm (CH=CH), 180.2 ppm (COOH). UV-Vis spectroscopy shows weak absorption at 205 nm (ε = 1800 M⁻¹cm⁻¹) and 230 nm (ε = 3500 M⁻¹cm⁻¹) corresponding to π→π* transitions.

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

Dihomo-γ-linolenic acid undergoes characteristic reactions of both carboxylic acids and polyunsaturated hydrocarbons. Esterification reactions proceed with standard alcohol catalysts at rates comparable to other fatty acids, with second-order rate constants of approximately 0.015 M⁻¹min⁻¹ at 25°C. Hydrogenation catalyzed by palladium or platinum metals proceeds sequentially with relative rates of 1:0.8:0.6 for the three double bonds under standard conditions. Autoxidation represents a significant degradation pathway, proceeding through free radical mechanisms with initiation rate constants of 10⁻⁶ M⁻¹s⁻¹ at 25°C. The compound demonstrates relative stability in anhydrous environments but undergoes rapid decomposition in the presence of oxygen, particularly when exposed to light or metal catalysts. Thermal decomposition begins at 150°C with activation energy of 85 kJ/mol.

Acid-Base and Redox Properties

The carboxylic acid functionality exhibits typical weak acid behavior with pKa of 4.95 in aqueous solution at 25°C. Titration curves show buffering capacity between pH 4.0 and 6.0. Redox properties include standard reduction potential of -0.32 V for the fatty acid/aldehyde couple. Electrochemical oxidation occurs at +1.05 V versus standard hydrogen electrode, primarily involving the double bond system. The compound demonstrates moderate stability toward reducing agents but undergoes rapid oxidation with strong oxidizing agents including potassium permanganate and ozone. Ozonolysis cleaves each double bond quantitatively, producing azelaic acid, succinic acid, and hexanoic acid fragments.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

Laboratory synthesis of dihomo-γ-linolenic acid typically proceeds through elongation of γ-linolenic acid (GLA) using homologation strategies. The most efficient method employs a Wittig reaction between the C18 aldehyde derivative of GLA and the phosphorane of 2-(triphenylphosphoranylidene) acetate, yielding the C20 acid with preservation of cis stereochemistry. Alternative approaches include malonic ester synthesis with appropriate halide precursors, though this method often results in lower stereochemical purity. Modern synthetic routes utilize cross-metathesis strategies with protected fatty acid derivatives, achieving overall yields of 65-75% with stereochemical purity exceeding 98%. Purification typically involves column chromatography on silica gel followed by recrystallization at low temperature (-20°C) from acetone or ethyl acetate.

Analytical Methods and Characterization

Identification and Quantification

Gas chromatography-mass spectrometry provides the primary analytical method for identification and quantification of dihomo-γ-linolenic acid. Capillary GC columns with polar stationary phases (cyanopropyl polysiloxane) achieve excellent separation with retention index of 2150 relative to n-alkanes. Characteristic mass spectral fragments include m/z 108 (C₇H₁₂O⁺), 150 (C₁₀H₁₄O₂⁺), 193 (C₁₂H₁₇O₂⁺), and the molecular ion at m/z 306 (C₂₀H₃₄O₂⁺). High-performance liquid chromatography with UV detection at 205 nm provides quantitative analysis with detection limits of 0.1 μg/mL and linear range from 1-1000 μg/mL. Reverse-phase C18 columns with acetonitrile/water mobile phases (85:15 v/v) yield retention times of 12-14 minutes under standard conditions.

Purity Assessment and Quality Control

Purity assessment typically employs complementary chromatographic techniques including GC-FID, HPLC-UV, and silver-ion chromatography. Acceptable purity standards require minimum 98% chemical purity by area normalization in GC analysis. Common impurities include positional isomers with double bond migration, trans-isomerization products, and oxidation derivatives including hydroperoxides and aldehydes. Quality control protocols specify maximum peroxide value of 2.0 mEq/kg and acid value between 185-195 mg KOH/g. Storage under nitrogen atmosphere at -20°C maintains stability for extended periods, with recommended shelf life of 12 months from preparation.

Applications and Uses

Industrial and Commercial Applications

Dihomo-γ-linolenic acid finds limited industrial application as a specialty chemical intermediate in organic synthesis. The compound serves as a starting material for production of various prostaglandin analogs and eicosanoid derivatives through selective chemical transformations. In materials science, DGLA derivatives function as reactive monomers in polymer systems, particularly in cross-linked networks where the multiple double bonds provide sites for polymerization. Ester derivatives find application as plasticizers and lubricant additives, offering improved low-temperature properties compared to saturated analogs. Commercial production remains limited to specialized chemical suppliers, with global production estimated at 100-200 kg annually.

Conclusion

Dihomo-γ-linolenic acid represents a structurally interesting polyunsaturated fatty acid with distinctive chemical and physical properties. The combination of carboxylic acid functionality with three cis-configured double bonds creates a molecule with specific reactivity patterns and conformational behavior. Its spectroscopic signatures provide clear identification characteristics, while its chemical reactivity follows established pathways for unsaturated carboxylic acids. The compound's limited natural occurrence and metabolic significance have driven development of efficient synthetic methodologies. Future research directions may explore novel derivatives for materials applications and further investigation of its electrochemical properties. Challenges remain in improving stability during storage and handling, particularly regarding oxidative degradation pathways.