Cetrimonium bromide (
16H33)N(CH3)3">C16H33)N(CH3)3r; cetyltrimethylammonium bromide; hexadecyltrimethylammonium bromide; CTAB) is a
quaternary ammonium
In chemistry, quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure , R being an alkyl group or an aryl group. Unlike the ammonium ion () and the primary, secondary, or tertiary ammonium cations ...
surfactant.
It is one of the components of the topical
antiseptic
An antiseptic (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") is an antimicrobial substance or compound that is applied to living tissue/skin to reduce the possibility of infection, sepsis, or putre ...
cetrimide
Cetrimide, or alkyltrimethylammonium bromide, is an antiseptic which is a mixture of three quaternary ammonium compounds: tetradonium bromide (TTAB or MITMAB), cetrimonium bromide (CTAB), and laurtrimonium bromide (DTAB or LTAB). It was first d ...
. The cetrimonium (hexadecyltrimethylammonium) cation is an effective antiseptic agent against bacteria and fungi. It is also one of the main components of some buffers for the
extraction of DNA.
It has been widely used in synthesis of gold nanoparticles (''e.g.'', spheres, rods, bipyramids), mesoporous silica nanoparticles (''e.g.'', MCM-41), and hair conditioning products. The closely related compounds
cetrimonium chloride and
cetrimonium stearate are also used as topical antiseptics and may be found in many household products such as shampoos and cosmetics. CTAB, due to its relatively high cost, is typically only used in select cosmetics.
As with most surfactants, CTAB forms
micelles in aqueous solutions. At 303 K (30 °C) it forms micelles with
aggregation number An aggregation number is a description of the number of molecules present in a micelle once the critical micelle concentration (CMC) has been reached. In more detail, it has been defined as the average number of surfactant monomers in a spherical mi ...
75-120 (depending on method of determination; average ~95) and degree of ionization, α = 0.2–0.1 (fractional charge; from low to high concentration). The binding constant (K°) of Br
− counterion to a CTA
+ micelle at 303 K (30 °C) is ''ca.'' 400 M-1. This value is calculated from Br
− and CTA
+ ion selective electrode measurements and
conductometry data by using literature data for micelle size (r = ~3 nm), extrapolated to the
critical micelle concentration
In colloidal and surface chemistry, the critical micelle concentration (CMC) is defined as the concentration of surfactants above which micelles form and all additional surfactants added to the system will form micelles.
The CMC is an important c ...
of 1 mM. However, K° varies with total surfactant concentration so it is
extrapolated to the point at which micelle concentration is zero.
Applications
Biological
Cell lysis
Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
is a convenient tool to isolate certain
macromolecules that exist primarily inside of the cell. Cell membranes consist of
hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are ...
and
lipophilic
Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipo ...
endgroups. Therefore,
detergents are often used to dissolve these membranes since they interact with both
polar and nonpolar endgroups. CTAB has emerged as the preferred choice for biological use because it maintains the integrity of precipitated
DNA during
its isolation. Cells typically have high concentrations of macromolecules, such as
glycoproteins and
polysaccharides, that co-precipitate with DNA during the extraction process, causing the extracted DNA to lose purity. The positive charge of the CTAB molecule allows it to denature these molecules that would interfere with this isolation.
Medical
CTAB has been shown to have potential use as an
apoptosis-promoting anticancer agent for head and neck cancer (HNC). ''In vitro'', CTAB interacted additively with γ radiation and
cisplatin
Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, ...
, two standard HNC therapeutic agents. CTAB exhibited anticancer cytotoxicity against several HNC cell lines with minimal effects on normal
fibroblasts, a selectivity that exploits cancer-specific metabolic aberrations. ''In vivo'', CTAB
ablated tumor-forming capacity of FaDu cells and delayed growth of established tumors. Thus, using this approach, CTAB was identified as a potential apoptogenic quaternary ammonium compound possessing ''in vitro'' and ''in vivo'' efficacy against HNC models. CTAB is also recommended by the World Health Organisation (WHO) as a purification agent in the downstream vaccine processing of polysaccharide vaccines.
Protein electrophoresis
Glycoproteins form broad, fuzzy bands in SDS-PAGE (Laemmli-electrophoresis) because of their broad distribution of negative charges. Using positively charged detergents such as CTAB will avoid issues associated with glycoproteins. Proteins can be blotted from CTAB-gels in analogy to
western blot
The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...
s ("eastern blot"), and Myelin-associated high hydrophobic protein can be analyzed using CTAB 2-DE.
DNA extraction
CTAB serves as an important surfactant in the DNA extraction buffer system to remove membrane lipids and promote cell lysis. Separation is also successful when the tissue contains high amounts of
polysaccharides.
CTAB binds to the polysaccharides when the salt concentration is high, thus removing polysaccharides from solution. A typical recipe can be to combine 100 mL of 1 M Tris HCl (pH 8.0), 280 mL 5 M NaCl, 40 mL of 0.5 M
EDTA
Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes ev ...
, and 20 g of CTAB then add
double distilled water (ddH
2O) to bring total volume to 1 L.
Nanoparticle synthesis
Surfactants play a key role in
nanoparticle
A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 10 ...
synthesis by adsorbing to the surface of the forming nanoparticle and lowering its surface energy. Surfactants also help to prevent aggregation (''e.g.'' via
DLVO mechanisms).
Au nanoparticle synthesis
Gold
Gold is a chemical element with the symbol Au (from la, aurum) and atomic number 79. This makes it one of the higher atomic number elements that occur naturally. It is a bright, slightly orange-yellow, dense, soft, malleable, and ductile me ...
(Au) nanoparticles are interesting to researchers because of their unique properties that can be used in applications such as
catalysis
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
,
optics
Optics is the branch of physics that studies the behaviour and properties of light, including its interactions with matter and the construction of instruments that use or detect it. Optics usually describes the behaviour of visible, ultrav ...
,
electronics
The field of electronics is a branch of physics and electrical engineering that deals with the emission, behaviour and effects of electrons using electronic devices. Electronics uses active devices to control electron flow by amplification ...
,
sensing, and
medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pr ...
. Control of nanoparticle size and shape is important in order to tune its properties. CTAB has been a widely used reagent to both impart stability to these nanoparticles as well as control their morphologies. CTAB may play a role in controlling nanoparticle size and shape by selectively or more strongly binding to various emerging
crystal facets.
Some of this control originates from the reaction of CTAB with other reagents in the gold nanoparticle synthesis. For example, in aqueous gold nanoparticle syntheses,
chlorauric acid (HAuCl
4) may react with CTAB to create a CTA
+-AuCl complex. The gold complex is then reacted with
ascorbic acid to produce
hydrochloric acid
Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid
Acid strength is the tendency of an acid, symbol ...
, an ascorbic acid radical, and CTA-AuCl
3. The ascorbic acid radical and CTA-AuCl
3 react spontaneously to create metallic Au
0 nanoparticles and other byproducts. An alternative or simultaneous reaction is the substitution of Cl
− with Br
− about the Au(III) center. Both complexation with the ammonium cation and/or speciation of the Au(III) precursor influence the kinetics of the nanoparticle formation reaction and therefore influence the size, shape, and (size and shape) distributions of the resulting particles.
Mesoporous materials
CTAB is used as the template for the first report of ordered
mesoporous materials. Microporous and mesoporous inorganic solids (with pore diameters of ≤20 Å and ~20–500 Å respectively) have found great utility as catalysts and sorption media because of their large internal surface area. Typical microporous materials are crystalline framework solids, such as
zeolite
Zeolites are microporous, crystalline aluminosilicate materials commonly used as commercial adsorbents and catalysts. They mainly consist of silicon, aluminium, oxygen, and have the general formula ・y where is either a metal ion or H+. These p ...
s, but the largest pore dimensions are still below 2 nm which greatly limit application. Examples of mesoporous solids include
silicas and modified layered materials, but these are invariably
amorphous or
paracrystalline
In materials science, paracrystalline materials are defined as having short- and medium-range ordering in their lattice (similar to the liquid crystal phases) but lacking crystal-like long-range ordering at least in one direction.
Origin and ...
, with pores that are irregularly spaced and broadly distributed in size. There is a need to prepare highly ordered mesoporous material with good mesoscale crystallinity. The synthesis of mesoporous solids from the calcination of
aluminosilicate
Aluminosilicate minerals ( IMA symbol: Als) are minerals composed of aluminium, silicon, and oxygen, plus countercations. They are a major component of kaolin and other clay minerals.
Andalusite, kyanite, and sillimanite are naturall ...
gels in the presence of surfactants was reported. The material possesses regular arrays of uniform channels, the dimensions of which can be tailored (in the range of 16 Å to >100 Å) through the choice of surfactant, auxiliary chemicals, and reaction conditions. It was proposed that the formation of these materials takes place by means of a liquid-crystal 'templating' mechanism, in which the silicate material forms inorganic walls between ordered surfactant
micelles. CTAB formed micelles in the solution and these micelles further formed a two dimensional
hexagonal mesostructure. The silicon precursor began to hydrolyze between the micelles and finally filled the gap with silicon dioxide. The template could be further removed by calcination and left a pore structure behind. These pores mimicked exactly the structure of mesoscale soft template and led to highly ordered mesoporous silica materials.
Toxicity
CTAB has been used for applications from nanoparticle synthesis to cosmetics. Due to its use in human products, along with other applications, it is essential to be made aware of the hazards this agent contains
The Santa Cruz Biotechnology, Inc.offers a comprehensive
MSDS for CTAB and should be referred to for additional questions or concerns.
Animal testing has shown ingestion of less than 150 g of the agent can lead to adverse health effects or possibly death by CTAB causing chemical burns throughout the esophagus and
gastrointestinal tract that can be followed by nausea and vomiting.
If the substance continues through the gastrointestinal tract, it will be poorly absorbed in the intestines followed by excretion in feces.
Toxicity has also been tested on aquatic life including
Brachydanio rerio (zebra fish) and
Daphnia magna (Water flea). Zebra fish showed CTAB toxicity when exposed to 0.3 mg/L for 96 hours, and water fleas showed CTAB toxicity when exposed to 0.03 mg/L for 48 hours.
CTAB along with other
quaternary ammonium salts
In chemistry, quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure , R being an alkyl group or an aryl group. Unlike the ammonium ion () and the primary, secondary, or tertiary ammonium cations ...
have frequently been used in cosmetics at concentrations up to 10%. Cosmetics at that concentration must only be used as rinse-off types such as shampoos. Other leave-on cosmetics are considered only safe at or below 0.25% concentrations. Injections into the body cavity of pregnant mice showed
embryotoxic and
teratogenic effects. Only
teratogenic effects were seen with 10 mg/kg doses, while both effects were seen at 35 mg/kg doses. Oral doses of 50 mg/kg/day showed embryotoxic effects as well.
Similar tests were completed by giving rats 10, 20, and 45 mg/kg/day of CTAB in their drinking water for one year. At the 10 and 20 mg/kg/day doses, the rats did not have any toxic symptoms. At the highest dose, the rats began experiencing weight loss. The weight loss in the male rats was attributed to less efficient food conversion. The tests showed no microscopic alterations to the gastrointestinal tract of the rats.
Other toxicity tests have been conducted using incubated human skin HaCaT
keratinocyte
Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells.
Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...
cells. These human cells were incubated with gold nanorods that were synthesized using seed-mediated, surfactant-assisted growth of gold nanoparticles. Gold nanoparticles are shown to be nontoxic, however once the nanoparticles are put through the growth solutions, the newly formed nanorods are highly toxic. This large increase in toxicity is attributed to the CTAB that is used in the growth solutions to cause
anisotropic growth.
Experiments also showed the toxicity of bulk CTAB and the synthesized gold nanorods to be equivalent. Toxicity tests showed CTAB remaining toxic with concentrations as low as 10 μM. The human cells show CTAB being nontoxic at concentrations less than 1 μM. Without the use of CTAB in this synthesis, the gold nanorods are not stable; they break into nanoparticles or undergo
aggregation.
The mechanism for
cytotoxicity has not been extensively studied, but there has been possible mechanisms proposed. One proposal showed two methods that led to the cytotoxicity in U87 and A172
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ...
cells. The first method showed CTAB exchanging with
phospholipids causing rearrangement of the membrane allowing β-
galactoside to enter into the cell by way of cavities. At low concentrations, there are not enough cavities to cause death to the cells, but with increasing the CTAB concentration, more phospholipids are displaced causing more cavities in the membrane leading to cell death. The second proposed method is based on the dissociation of CTAB into CTA
+ and Br
− within the
mitochondrial membrane. The positively charged CTA
+ binds to the
ATP synthase not allowing H
+ to bind stopping the synthesis of ATP and resulting in cell death.
See also
*
Cetrimonium chloride - The corresponding chloride salt
*
Behentrimonium chloride
Behentrimonium chloride, also known as docosyltrimethylammonium chloride or BTAC-228, is a yellow waxlike organic compound with chemical formula , used as an antistatic agent and, sometimes, a disinfectant. It is commonly found in cosmetics su ...
- A C
25 structural analogue
References
Further reading
*''Merck Index'', 11th Edition, 1989.
Drug information
{{Throat preparations
Antiseptics
Household chemicals
Quaternary ammonium compounds
Cationic surfactants
Bromides