Retinol Palmitate (79-81-2) Physical and Chemical Properties
Retinol Palmitate
Long-chain retinyl ester used as a lipophilic vitamin A source for formulation, supplementation and R&D applications across cosmetic, nutraceutical and pharmaceutical development.
| CAS Number | 79-81-2 |
| Family | Retinoids (prenol lipids) |
| Typical Form | Powder or crystalline solid |
| Common Grades | EP, JP, USP |
Retinol palmitate is a retinoid class lipid: the fatty‑acid ester of all‑trans‑retinol with hexadecanoic (palmitic) acid, formally an all‑trans‑retinyl hexadecanoate. The structure combines a long saturated C16 acyl chain esterified to the primary alcohol of a C20 polyene retinoid (a substituted cyclohexenyl‑containing polyene). Key electronic features include an ester carbonyl, a conjugated tetraene system in the retinyl moiety and a relatively nonpolar saturated palmitoyl tail; the conjugated polyene confers chromophoric and oxidation‑sensitive character while the long alkyl chain dominates bulk lipophilicity.
As an amphiphilic lipid the molecule is strongly lipophilic and essentially nonpolar overall: the ester linkage and two oxygen atoms supply only minor polarity relative to the extensive hydrocarbon content. Acid–base behavior is negligible in customary conditions (no ionizable groups). Physicochemical consequences are high membrane affinity, low aqueous solubility, propensity to partition into lipid phases and formulation dependence (solubilized in oils or surfactant systems for topical/oral use). Chemical liabilities are hydrolysis of the ester to retinol plus palmitic acid (enzymatic or acid/base catalyzed), photo‑isomerization and oxidative cleavage or epoxidation of the conjugated polyene; these govern storage, delivery and stability in formulations.
Retinol palmitate has established roles in nutrition, dermatological and topical formulations as a vitamin A source and retinoid precursor. It is used in skin‑conditioning cosmetic preparations, as a food nutrient supplement form of vitamin A, and in certain medicinal applications where retinoid activity or vitamin A supplementation is intended. Common commercial grades reported for this substance include: EP, JP, USP.
Molecular Attributes
Molecular Weight and Composition
- Molecular formula: \(\ce{C36H60O2}\).
- Molecular weight: 524.9 \(\mathrm{g}\,\mathrm{mol}^{-1}\).
- Exact / monoisotopic mass: 524.45933115 (both values reported identically).
- Heavy atom count: 38; formal charge: 0.
- Topological polar surface area (TPSA): 26.3 Ų (reported as 26.3).
- Hydrogen bond donors / acceptors: 0 / 2.
- Rotatable bond count: 21; structural complexity (computed): 803.
- Defined bond stereocenters (double‑bond geometry): 4.
The dominance of nonpolar atoms and the large number of rotatable bonds reflect a flexible, highly lipophilic molecule with limited polar surface available for hydrogen bonding; TPSA is low relative to size, consistent with strong partitioning into nonpolar media.
LogP and Amphiphilicity
- Reported computed XLogP3: 13.6.
A computed XLogP in the double‑digit range indicates extreme lipophilicity and negligible water solubility under typical conditions. Practically this translates to very high affinity for lipid membranes, oils and hydrophobic excipients; formulation requires nonaqueous vehicles, microemulsions, surfactant solubilization or encapsulation for dispersion. High logP also implies slow aqueous diffusivity and a propensity for bioaccumulation in lipid compartments if released to the environment.
Biochemical Properties
Biosynthesis and Metabolic Context
Retinyl palmitate is an all‑trans‑retinyl ester formed by esterification of retinol with palmitic (hexadecanoic) acid. It serves physiologically as a storage and transport form of vitamin A in animals and is present in tissues such as adipose tissue, epidermis, fibroblasts, intestine and placenta. Cellular localizations reported include extracellular and membrane compartments, reflecting association with lipoproteins and membrane‑bound or secreted carrier proteins. Metabolically it is part of retinol metabolism and pathways relevant to vitamin A homeostasis and related deficiency states.
Biologically, retinyl palmitate can act as a provitamin A reserve: enzymatic hydrolysis releases retinol which can be oxidized further to retinal and retinoic acid, the latter classically mediating retinoid receptor signalling (cell differentiation, modulation of proliferation and gene expression). It also has antioxidant attributes in biological contexts linked to retinoid chemistry.
Reactivity and Transformations
Class‑typical reactions and transformations include: - Enzymatic hydrolysis by carboxylesterases and lipases to yield retinol plus palmitic acid. - Photo‑induced cis/trans isomerization of the conjugated tetraene and photodegradation of the polyene system. - Oxidative transformations of the polyene chain (epoxidation, cleavage, formation of oxidized metabolites) under exposure to oxygen, light or reactive oxygen species. - Acid‑ or base‑catalyzed ester hydrolysis under harsh chemical conditions.
These transformation pathways determine formulation stability, shelf life and biological activation; control of light, oxygen and hydrolytic conditions is essential to limit degradation.
Stability and Degradation
Retinyl palmitate is chemically labile relative to saturated lipids because of its conjugated polyene and ester linkage. It is sensitive to oxidation and photodegradation; exposure to light, heat and air accelerates isomerization and oxidative breakdown. The substance is also susceptible to enzymatic hydrolysis in biological environments.
Physical description and thermal property: - Physical description (experimental): Solid. - Melting point (experimental): 28.5 \(\mathrm{\degree C}\).
Melting near ambient temperature commonly yields a waxy solid or soft solid that may liquefy at modest elevations in temperature; this behavior influences handling, dosage form design and storage. Conformer generation for three‑dimensional modelling is reported as disallowed for this compound in automated workflows because the molecule is too flexible, reflecting the high rotatable bond count and conformational heterogeneity.
Chemical and Enzymatic Degradation Pathways
Primary degradation mechanisms relevant to industrial handling and formulation: - Hydrolysis: enzymatic (esterases/lipases) and chemical (acid/base) hydrolysis regenerates retinol and palmitic acid; hydrolysis is accelerated in aqueous or polar environments and by elevated temperature. - Oxidation and photodegradation: the conjugated tetraene is prone to oxygenation and photochemical reactions leading to isomerization and oxidative cleavage; antioxidants and opaque packaging reduce these routes. - Isomerization: thermal or photochemical cis/trans isomerization reduces retinoid activity and alters spectral and biological properties.
Mitigation strategies in formulation and storage include exclusion of light and oxygen, addition of antioxidants, selection of inert solvents or oil carriers, and cold‑chain or refrigerated storage for long‑term preservation.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS Registry Number: 79-81-2
- Molecular formula (reiterated): \(\ce{C36H60O2}\)
- InChI:
InChI=1S/C36H60O2/c1-7-8-9-10-11-12-13-14-15-16-17-18-19-25-35(37)38-30-28-32(3)23-20-22-31(2)26-27-34-33(4)24-21-29-36(34,5)6/h20,22-23,26-28H,7-19,21,24-25,29-30H2,1-6H3/b23-20+,27-26+,31-22+,32-28+ - InChIKey:
VYGQUTWHTHXGQB-FFHKNEKCSA-N - SMILES:
CCCCCCCCCCCCCCCC(=O)OC/C=C(\\C)/C=C/C=C(\\C)/C=C/C1=C(CCCC1(C)C)C - EC / EINECS number: 201-228-5
- UNII: 1D1K0N0VVC
- ChEBI: CHEBI:17616
- ChEMBL: CHEMBL1675
(Selected registry identifiers and structure keys are provided above as reported for unequivocal substance identification.)
Synonyms and Lipid Nomenclature
Common names and synonyms reported for this material include: retinyl palmitate; retinol palmitate; vitamin A palmitate; retinyl hexadecanoate; all‑trans‑retinyl palmitate; Retinol, hexadecanoate. A larger list of trade and historical synonyms exists in regulatory and pharmacopoeial contexts; the most widely used trivial names are "retinyl palmitate" and "vitamin A palmitate".
Industrial and Biological Applications
Roles in Formulations or Biological Systems
- Cosmetic applications: used as a skin conditioning agent and topical vitamin A source in dermatological and cosmetic formulations; its retinoid precursor activity underlies claimed benefits for skin texture, photoageing and dyschromias in formulations where conversion to active retinoids occurs in situ.
- Nutritional applications: employed as a dietary vitamin A source and food additive (nutrient supplement / color adjunct) in fortified foods and supplements.
- Pharmaceutical/therapeutic context: used as a source of vitamin A in medicinal preparations; has been investigated in contexts linked to retinoid biology (differentiation, anti‑proliferative effects) and carries regulatory designations in certain rare‑disease applications.
- Biological role: functions as a storage and transport ester of vitamin A in animal tissues, contributing to retinol homeostasis and serving as a substrate for conversion to active retinoid metabolites.
If a concise product application summary is required for procurement or formulation development, selection is typically based on the lipophilicity, ester stability and intended release/activation profile in the target matrix.
Safety and Handling Overview
- Hazard classifications reported (aggregated notifications): skin irritation (H315), reproductive toxicity with potential to damage fertility or the unborn child (H360; also H361 as suspected), and potential for long‑lasting harmful effects to aquatic life (H413). Precautionary statement codes reported include P203, P264, P273, P280, P302+P352, P318, P321, P332+P317, P362+P364, P405 and P501.
- Practical handling guidance: avoid inhalation or prolonged dermal exposure; use appropriate personal protective equipment (gloves, eye protection and laboratory clothing) when handling powders or concentrated materials. Control sources of ignition for solvent‑based operations and minimize generation of aerosols or dust. Prevent release to aquatic environments.
- Storage considerations: protect from light, heat and oxygen to limit photochemical and oxidative degradation; store in tightly closed, light‑opaque containers under a dry, inert atmosphere when long‑term stability is required.
- Environmental considerations: due to high lipophilicity and reported aquatic chronic hazard, prevent release to wastewater and natural waters; manage waste and rinses in accordance with local regulations.
For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
Handling and Storage of Lipid Materials
Retinyl palmitate should be handled using standard precautions for reactive, lipidic retinoids: minimize exposure to light and air, avoid prolonged heating, and formulate with appropriate antioxidants (e.g., BHT, where compatible) when stability is critical. Because the substance is solid near ambient temperature (melting point 28.5 \(\mathrm{\degree C}\)), thermal control during shipping and storage prevents softening or phase changes that complicate dosing and formulation. For laboratory use, transfer under inert atmosphere or in amber glassware is common practice to reduce oxidative and photolytic loss.
For further operational guidance and regulatory compliance, consult the product SDS, pharmacopeial monographs where applicable, and pertinent national or regional chemical safety regulations.
