The Chemistry of Peels :
A Hypothesis of Action Mechanisms ( L.Dewandre) and
A proposal of New Classification of Chemical Peelings
Luc Dewandre - Alain Tenenbaum
The following definition of chemical peels found in the literature has been chosen and adaptated by the authors for the purposes of this chapter
A chemical peel is a treatment technique used to improve and smooth the facial and/or body skin's texture using a chemical solution that causes the dead skin to slough off and eventually peel off. The regenerated skin is usually smoother and less wrinkled than the old skin.
It is advised to seek professional help from a plastic surgeon, or otolaryngologist ( facial plastic surgeon), a maxillo facial surgeon and/or a dermatologist on a specific type of chemical peel before a procedure is performed.
It is our goal to propose a hypothesis for the mechanism of action of chemical peelings solutions as a new classification of chemical peelings.The traditionally accepted mechanism has been based on the concept that the effect of a peeling solution on the skin is based purely on its acidity. By using elementary concepts in chemistry three separate mechanisms of action for chemical peeling solutions will be explained:
3. metabolic interactions.
The literature devoted to chemical peels is full of informations about the methodology, indications, contraindications, side effects, as obtained results. Without any proof, acidity has always been assumed to be the solely mechanism of action of peeling agents. All peeling agents were assumed to induce the three stages of tissue replacement; namely, destruction, elimination, and regeneration, all accompanied by a controlled stage of inflammation.
A brief study of the chemistry of the molecules and solutions used in chemical peels immediately questions the hypothesis that acidity is the only basis for the action of peeling solutions. In fact, with the exception of trichloroacetic acid (TCA) and non-neutralized glycolic acid solutions, the most commonly used peeling solutions are only weakly acidic, and phenol and resorcinol mixtures may not be acidic at all, having a pH greater than 7 in some formulations.
You will find detailed below descriptions of some elementary chemistry concepts which, along with a review of the chemistry of the skin, should help to explain the possible interactions between different peelings solutions and the skin. Finally, will be proposed two new classifications of solutions for peelings :
One according to their mechanisms of action.( Classification of L.Dewandre)
The other one according to chemical parameters (structure of the molecula, pKa ,etc ) or Classification of A.Tenenbaum
Useful Elements of Basic Chemistry
Understanding some of the basic concepts of chemistry is necessary to truly understand chemical peels. Mineral and organic chemistry as biochemistry are taught to medical students but most practicing physicians do not remember these fundamental sciences .
Also chemistry has been unfortunately evicted in cosmetic dermatology as aesthetic medicine courses , masters, workshops and congresses . A brief review of useful information should help to update most practitioners.
An acid (from the Latin acidus meaning sour) is traditionally considered any chemical compound that, when dissolved in water, gives a solution with a hydrogen ion activity greater than in pure water, i.e. a pH less than 7.0. That approximates the modern definition of Johannes Nicolaus Brønsted and Martin Lowry, who independently defined an acid as a compound which donates a hydrogen ion (H+) to another compound (called a base). Acid/base systems are different from redox reactions in that there is no change in oxidation state. Acids can occur in solid, liquid or gaseous form, depending on the temperature. They can exist as pure substances or in solution.
Chemicals or substances having the property of an acid are said to be acidic (adjective).
The Arrhenius concept is the easiest one retained by majority of peelers,because most of peelings acids are ionic compounds.acting as a source of H3O+ when dissolved in water.
The Swedish chemist Svante Arrhenius attributed the properties of acidity to hydrogen in 1884. An Arrhenius acid is a substance that increases the concentration of the hydronium ion, H3O+, when dissolved in water. This definition stems from the equilibrium dissociation of water into hydronium and hydroxide (OH-) ions:
H2O(l) + H2O(l) H3O+(aq) + OH-(aq)
In pure water the majority of molecules exist as H2O, but a small number of molecules are constantly dissociating and re-associating. Pure water is neutral with respect to acidity or basicity because the concentration of hydroxide ions is always equal to the concentration of hydronium ions. An Arrhenius base is a molecule which increases the concentration of the hydroxide ion when dissolved in water. Note that chemists often write H+(aq) and refer to the hydrogen ion when describing acid-base reactions but the free hydrogen nucleus, a proton, does not exist alone in water, it exists as the hydronium ion, H3O+.
While the Arrhenius concept is useful for describing many reactions, it is also quite limited in its scope.
Brønsted acids act by donating a proton to water and at the difference of Arrhenius acids , can also be used to describe molecular compounds, whereas Arrhenius acids must be ionic compounds.
In 1923 chemists Johannes Nicolaus Brønsted and Thomas Martin Lowry independently recognized that acid-base reactions involve the transfer of a proton. A Brønsted-Lowry acid (or simply Brønsted acid) is a species that donates a proton to a Brønsted-Lowry base. Brønsted-Lowry acid-base theory has several advantages over Arrhenius theory. Consider the following reactions of acetic acid (CH3COOH), ( used as chemical peel for the décolleté by some great peelers like L. Wiest ) the organic acid that gives vinegar its characteristic taste:
Both theories easily describe the first reaction: CH3COOH acts as an Arrhenius acid because it acts as a source of H3O+ when dissolved in water, and it acts as a Brønsted acid by donating a proton to water. In the second example CH3COOH undergoes the same transformation, donating a proton to ammonia (NH3), but cannot be described using the Arrhenius definition of an acid because the reaction does not produce hydronium. .
As with the acetic acid reactions, both definitions work for the first example, where water is the solvent and hydronium ion is formed. The next reaction do not involve the formation of ions but can still be viewed as proton transfer reaction.
The Brønsted-Lowry definition is the most widely used definition; unless otherwise specified acid-base reactions are assumed to involve the transfer of a proton (H+) from an acid to a base.
A third concept was proposed by Gilbert N. Lewis which includes reactions with acid-base characteristics that do not involve a proton transfer. A Lewis acid is a species that accepts a pair of electrons from another species; in other words, it is an electron pair acceptor. Brønsted acid-base reactions are proton transfer reactions while Lewis acid-base reactions are electron pair transfers. All Brønsted acids are also Lewis acids, but not all Lewis acids are Brønsted acids. Contrast the following reactions which could be described in terms of acid-base chemistry.
In the first reaction a fluoride ion, F-, gives up an electron pair to boron trifluoride to form the product tetrafluoroborate. Fluoride "loses" a pair of valence electrons because the electrons shared in the B—F bond are located in the region of space between the two atomic nuclei and are therefore more distant from the fluoride nucleus than they are in the lone fluoride ion. BF3 is a Lewis acid because it accepts the electron pair from fluoride. This reaction cannot be described in terms of Brønsted theory because there is no proton transfer. The second reaction can be described using either theory. A proton is transferred from an unspecified Brønsted acid to ammonia, a Brønsted base; alternatively, ammonia acts as a Lewis base and transfers a lone pair of electrons to form a bond with a hydrogen ion. The species that gains the electron pair is the Lewis acid; for example, the oxygen atom in H3O+ gains a pair of electrons when one of the H—O bonds is broken and the electrons shared in the bond become localized on oxygen. Depending on the context, Lewis acids may also be described as a reducing agent or an electrophile.
Dissociation and equilibrium
Reactions of acids are often generalized in the form HA H+ + A-, where HA represents the acid and A- is the conjugate base. Acid-base conjugate pairs differ by one proton, and can be interconverted by the addition or removal of a proton (protonation and deprotonation, respectively). Note that the acid can be the charged species and the conjugate base can be neutral in which case the generalized reaction scheme could be written as HA+ H+ + A. In solution there exists an equilibrium between the acid and its conjugate base. The equilibrium constant K is an expression of the equilibrium concentrations of the molecules or the ions in solution. Brackets indicate concentration, such that [H2O] means the concentration of H2O. The acid dissociation constant Ka is generally used in the context of acid-base reactions. The numerical value of Ka is equal to the concentration of the products divided by the concentration of the reactants, where the reactant is the acid (HA) and the products are the conjugate base and H+.
The stronger of two acids will have a higher Ka than the weaker acid; the ratio of hydrogen ions to acid will be higher for the stronger acid as the stronger acid has a greater tendency to lose its proton. Because the range of possible values for Ka spans many orders of magnitude, a more manageable constant, pKa is more frequently used, where pKa = -log10 Ka. Stronger acids have a smaller pKa than weaker acids. Experimentally determined pKa at 25°C in aqueous solution are often quoted in textbooks and reference material.
For peelers , this notion is very important because stronger acids have a higher Ka and a lower pKa than weaker acids.
For our classification,2 parameters have to be taken in consideration for peelers :
1- The pKa synonym of acids aggressivity and linked to the acid strength
2- The pH , synonym of penetration for the selected acid
For chemists, the strength of an acid refers to its ability or tendency to lose a proton. A strong acid is one that completely dissociates in water; in other words, one mole of a strong acid HA dissolves in water yielding one mole of H+ and one mole of the conjugate base, A-, and none of the protonated acid HA. In contrast a weak acid only partially dissociates and at equilibrium both the acid and the conjugate base are in solution.. In water each of these essentially ionizes 100%. The stronger an acid is, the more easily it loses a proton, H+. Two key factors that contribute to the ease of deprotonation are the polarity of the H—A bond and the size of atom A, which determines the strength of the H—A bond. Acid strengths are also often discussed in terms of the stability of the conjugate base.
According to the classification of A.Tenenbaum , which is further described in this chapter, peelers should be careful with the dangerous distinction between so called ,, cosmetic,, peelings for acids with pKa > 3 and ,, medical,, peelings for acids with pKa <3, because some acids like salicylic acid with a pKa near 3 , as the phenol , toxic substance with a pKa > 3 need to be exclusively used by trained physicians.
Polarity and the inductive effect
The polarity of the H-A bond is the 1 st factor contributing to the acid strength
As the electron density on hydrogen decreases , it is more acidic. Moving from left to right across a row on the periodic table elements become more electronegative (excluding the noble gases).
In several compound classes, collectively called carbon acids, the C-H bond can be sufficiently acidic for proton removal. Unactivated C-H bonds are found in alkanes and are not adjacent to a heteroatom]] (O, N, Si, etc). Such bonds usually only participate in radical substitution.
Polarity refers to the distribution of electrons in a bond, the region of space between two atomic nuclei where a pair of electrons is shared. When two atoms have roughly the same electronegativity (ability to attract electrons) the electrons are shared evenly and spend equal time on either end of the bond. When there is a significant difference in electronegativities of two bonded atoms, the electrons spend more time near the nucleus of the more electronegative element and an electrical dipole, or separation of charges, occurs, such that there is a partial negative charge localized on the electronegative element and a partial positive charge on the electropositive element. Hydrogen is an electropositive element and accumulates a slightly positive charge when it is bonded to an electronegative element such as oxygen or chlore .
The electronegative element need not be directly bonded to the acidic hydrogen to increase its acidity. An electronegative atom can pull electron density out of an acidic bond through the inductive effect. The electron-withdrawing ability diminishes quickly as the electronegative atom moves away from the acidic bond.
Carboxylic acids are organic acids that contain an acidic hydroxyl group and a carbonyl (C=O bond). Carboxylic acids can be reduced to the corresponding alcohol; the replacement of an electronegative oxygen atom with two electropositive hydrogens yields a product which is essentially non-acidic. The reduction of acetic acid to ethanol using LiAlH4 (lithium aluminum hydride or LAH) and ether is an example of such a reaction.
The pKa for ethanol is 16, compared to 4.76 for acetic acid
Atomic radius and bond strength
The size of the atom A or atomic radius is the 2 nd factor contributing to the acid strength.
Moving down a column on the periodic table atoms become less electronegative but also significantly larger, and the size of the atom tends to dominate its acidity when sharing a bond to hydrogen.(see table1)
Hydrogen sulfide, H2S, is a stronger acid than water, even though oxygen is more electronegative than sulfur. Just , this is because sulfur is larger than oxygen and the H—S bond is more easily broken than the H—O bond
Another factor that contributes to the ability of an acid to lose a proton is the strength of the bond between the acidic hydrogen and the atom that bears it. This, in turn, is dependent on the size of the atoms sharing the bond. For an acid HA, as the size of atom A increases, the strength of the bond decreases, meaning that it is more easily broken, and the strength of the acid increases. Bond strength is a measure of how much energy it takes to break a bond. In other words, it takes less energy to break the bond as atom A grows larger, and the proton is more easily removed by a base. ..
It is important to keep in mind the difference between monoprotic acids ( having one unique pKa and polyprotic acids ( having 2 or more pKa ) .
Monoprotic acids are those acids that are able to donate one proton per molecule during the process of dissociation (sometimes called ionization) as shown below (symbolized by HA):
HA(aq) + H2O(l) H3O+(aq) + A−(aq) Ka
Common examples of monoprotic acids in organic acids indicate the presence of one carboxyl group and mostly these acids are known as monocarboxylic acid. Examples in organic acids include acetic acid (CH3COOH) ,glycolic acid and lactic acid
Polyprotic acids are able to donate more than one proton per acid molecule, in contrast to monoprotic acids that only donate one proton per molecule. Specific types of polyprotic acids have more specific names, such as diprotic acid (two potential protons to donate) and triprotic acid (three potential protons to donate).
A diprotic acid (here symbolized by H2A) can undergo one or two dissociations depending on the pH. Each dissociation has its own dissociation constant, Ka1 and Ka2.
H2A(aq) + H2O(l) H3O+(aq) + HA−(aq) Ka1
HA−(aq) + H2O(l) H3O+(aq) + A2−(aq) Ka2
The first dissociation constant is typically greater than the second; i.e., Ka1 > Ka2. For example, the weak unstable carbonic acid (H2CO3) can lose one proton to form bicarbonate anion (HCO3-) and lose a second to form carbonate anion (CO32-). Both Ka values are small, but Ka1 > Ka2 .
Diprotic acids used for peelings are malic ,tartaric and azelaic acids.
2 dissociations depending on the pH mean that such acids can generate 2 peelings with the 2 nd one less acidic than the 1 st one , in case we consider one peeling reaction per one dissociation.
A triprotic acid (H3A) can undergo one, two, or three dissociations and has three dissociation constants, where Ka1 > Ka2 > Ka3.
H3A(aq) + H2O(l) H3O+(aq) + H2A−(aq) Ka1
H2A−(aq) + H2O(l) H3O+(aq) + HA2−(aq) Ka2
HA2−(aq) + H2O(l) H3O+(aq) + A3−(aq) Ka3
An organic example of a triprotic acid is citric acid, which can successively lose three protons to finally form the citrate ion. Even though the positions of the protons on the original molecule may be equivalent, the successive Ka values will differ since it is energetically less favorable to lose a proton if the conjugate base is more negatively charged.
Weak acid/weak base equilibria
In order to lose a proton, it is necessary that the pH of the system rise above the pKa of the protonated acid. The decreased concentration of H+ in that basic solution shifts the equilibrium towards the conjugate base form (the deprotonated form of the acid). In lower-pH (more acidic) solutions, there is a high enough H+ concentration in the solution to cause the acid to remain in its protonated form, or to protonate its conjugate base (the deprotonated form).
Solutions of weak acids and salts of their conjugate bases form buffer solutions.
A buffer solution is an aqueous solution consisting of a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid. It has the property that the pH of the solution changes very little when a small amount of acid or base is added to it. Buffer solutions are used as a means of keeping pH at a nearly constant value in a wide variety of chemical applications. Many life forms thrive only in a relatively small pH range; an example of a buffer solution is blood.
Le Chatelier s principle
In a solution there is an equilibrium between a weak acid, HA, and its conjugate base, A- :
HA + H2O H3O+ + A−
• When hydrogen ions (H+) are added to the solution, equilibrium moves to the left, as there are hydrogen ions (H+ or H3O+) on the right-hand side of the equilibrium expression.
• When hydroxide ions (OH-) are added to the solution, equilibrium moves to the right, as hydrogen ions are removed in the reaction (H+ + OH- → H2O).
Thus, in both cases, some of the added reagent is consumed in shifting the equilibrium in accordance with Le Chatelier's principle and the pH changes by less than it would if the solution were not buffered.
Henderson Hasselbach Equation
The acid dissociation constant for a weak acid, HA, is defined as
Simple manipulation with logarithms gives the Henderson-Hasselbach equation, which describes pH in terms of pKa
In this equation [A−] is the concentration of the conjugate base and [HA] is the concentration of the acid. It follows that when the concentrations of acid and conjugate base are equal, often described as half-neutralization, pH=pKa. In general, the pH of a buffer solution may be easily calculated, knowing the composition of the mixture, by means of an ICE table.
One should remember that the calculated pH may be different from measured pH.
Legend : Buffer capacity for pKa=7 as percentage of maximum
Buffer capacity is a quantitative measure of the resistance of a buffer solution to pH change on addition of hydroxide ions. It can be defined as follows.
buffer capacity = Equation 6
where dn is an infinitesimal amount of added base and d(pH) is the resulting infinitesimal change in pH. With this definition the buffer capacity can be expressed as
where Kw is the self-ionization constant of water and CA is the analytical concentration of the acid, equal to [HA]+[A-]. The term Kw/[H+] becomes significant at pH greater than about 11.5 and the second term becomes significant at pH less than about 2. Both these terms are properties of water and are independent of the weak acid. Considering the third term, it follows that
1. Buffer capacity of a weak acid reaches its maximum value when pH = pKa
2. At pH = pKa ± 1 the buffer capacity falls to 33% of the maximum value. This is the approximate range within which buffering by a weak acid is effective. Note: at pH = pKa - 1, The Henderson-Hasselbalch equation shows that the ratio [HA]:[A-] is 10:1.
3. Buffer capacity is directly proportional to the analytical concentration of the acid.
Nowadays Applications of Buffer Solutions
Their resistance to changes in pH makes buffer solutions very useful for chemical manufacturing and essential for many biochemical processes. The ideal buffer for a particular pH has a pKa equal to that pH, since such a solution has maximum buffer capacity.
Buffer solutions are necessary to keep the correct pH for enzymes in many organisms to work. A buffer of carbonic acid (H2CO3) and bicarbonate (HCO3−) is present in blood plasma, to maintain a pH between 7.35 and 7.45.
Majority of biological samples that are used in research are made in buffers specially phosphate buffered saline (PBS) at pH 7.4
Buffered TCA are responsible of many dyschromies .
Useful buffer mixtures
Components pH range
Citric acid, Sodium citrate 2.5 - 5.6
Acetic acid, Sodium acetate
3.7 - 5.6
There is among physicians a big confusion between a buffered peel ( just see above) and a neutralized peel.
In chemistry, neutralisation is a chemical reaction whereby an acid and a base react to form water and a salt.
In an aqueous solution, solvated hydrogen ions (hydronium ions, H3O+) react with hydroxide ions (OH-) formed from the alkali to make two molecules of water. A salt is also formed. In non-aqueous reactions, water is not always formed; however, there is always a donation of protons (see Brønsted-Lowry acid-base theory).
Often, neutralization reactions are exothermic, giving out heat to the surroundings (the enthalpy of neutralization). An example of an endothermic neutralization is the reaction between sodium bicarbonate (baking soda) and any weak acid, for example acetic acid (vinegar)
Neutralization of the chemical peeling agent is an important step ,which is determined by either the frost or how much time has elapsed. Neutralization is achieved by a majority of peelers applying cold water or wet, cool towels to the face following the frost. According to physic chemistry ,using water just after the frost provokes an exothermic reaction which can provoke a ,, cold,, burn. Other neutralizing agents that can be used include bicarbonate spray or soapless cleanser. Peeling agents for which this neutralization step is less important include salicylic acid, Jessner solution, and phenol.
In partially neutralized AHA solutions, the acid and a lesser amount of base are combined in a reversible chemical reaction that yields unneutralized acid and a salt.
The resulting solution has less free acid and a higher pH than a solution that has not been
neutralized. In partially neutralized formulations, the salt functions as a reservoir of acid
that is available for second-phase penetration. This means that partially neutralized
formulas can deliver as much, if not more, alpha-hydroxy acid than free acid formulas,
but in a safer, "time-released" manner. Therefore, the use of partially neutralized glycolic acid solutions seems prudent, since they have a better safety profile than low-pH solutions containing only free glycolic acid (Becker and al., 1996).
Clinical studies have shown that a partially neutralized lactic acid preparation improves
the skin, both in appearance and histologically. Other studies using skin tissue cultures
showed that partially neutralized glycolic acid stimulates fibroblast proliferation -- an
index of tissue regeneration (Rubin, 1996). Looking at electrical conductance of the skin
(an indicator of water content or moisturization), higher pH products (those that have
been partially neutralized) are better moisturizers than lower pH preparations (Rubin,
Skin Basic Chemistry
The approximate skin composition is seen in Box 1.1.
Anatomy of the Skin
Like the whole human organism, the skin can be considered an aqueous solution into which are dissolved a certain number of molecules. These are molecules of proteins, lipids, and carbohydrates (sugars) in variable quantities and proportions.
There is more water in the dermis than in the epidermis. This is due to the presence of blood and lymph in the dermis, which both have a high water content, as well as the fact that the epidermis is in contact with a more or less dehydrated environment.
There are more proteins (keratin) in the epidermis than in the dermis whereas, on the other hand, more carbohydrates and lipids are to be found in the dermis, and there are even more in the subcutaneous layer than in the dermis.
The most important molecule in the epidermis is a fibrous and corneal protein, keratin, that protects and takes part, through its continuous production by the keratinocytes, in the complete replacement of the epidermis every 27 days.
The most important molecules of the dermis are collagen, elastin, glycosaminoglycans (GAGs) and the proteoglycans. Collagen and elastin are proteins, while GAGs (e.g., hyaluronic acid) and the proteoglycans are biological polymers formed mainly by sugars that retain water.
Collagen constitutes the skin's structural resource and is the most abundant protein in the human body. It is formed mainly by glycine, proline, and hydroxyproline. It is one of the most resistant natural proteins and helps to give the skin structural support. Elastin is similar to collagen but it is an extensible protein responsible for elasticity; hence its name. It has two unique amino acids, desmosine and isodesmosine.
The GAGs contain specific sugars such as glucosamine sulfate,
N-acetylglucosamine and glucosamine hydrochloride, all very able of attracting water. They form long chains of molecules that retain water, such as hyaluronic acid, keratin sulfate, heparin, dermatin, and chondroitin.
The hypodermis or subcutaneous tissue consists mainly of fat, although this tissue accounts for a completely different chemical interaction with peeling solutions. Chemical peeling is not meant to extend down into the subcutaneous layer so we will not discuss this.
The different molecular composition of the different levels of the skin may explain the variability of the interactions and the results obtained according to the penetration level when using a given aqueous solution, such as while undertaking a chemical peel.
It is likewise for the pH. While the pH of the epidermis is a well-established notion, the pH of the dermis is not an exact value and has been difficult to measure precisely.
The epidermal acid layer or mantel is the result of serum secretion and sweat. It protects the skin and makes it less vulnerable from attacks of microorganisms such as bacteria and fungi. The normal epidermis has a slightly acidic pH with a range between 4.2 and 5.6. It varies from one part of the skin to another and, in general, it is more acidic in men than in women.
The pH of the epidermis also varies depending on its different layers. For a "skin" pH of around 5 we will find a pH near 5.6 in the corneal layer and one of 4.8 in the deep layers of the epidermis which are rich in corneocytes and melanocytes. Finally, dry skin is more acidic than oily skin, which can reach pH 6.
Since the dermis contains a significant amount of fluid and blood, we can presume the pH to be 6 to 6.5 and it is slightly less acidic than the epidermis, with a pH of 6 for the papillary dermis and 7 for the reticular dermis rich in blood vessels.
Acids and Cell Membranes
Cell membranes contain fatty acid esters such as phospholipids. Fatty acids and fatty acid derivatives are another group of carboxylic acids that play a significant role in biology. These contain long hydrocarbon chains and a carboxylic acid group on one end. The cell membrane of nearly all organisms is primarily made up of a phospholipid bilayer, a micelle of hydrophobic fatty acid esters with polar, hydrophilic phosphate "head" groups. Membranes contain additional components, some of which can participate in acid-base reactions. Cell membranes are generally impermeable to charged or large, polar molecules because of the lipophilic fatty acyl chains comprising their interior. Many biologically important molecules, including a number of pharmaceutical agents, are organic weak acids which can cross the membrane in their protonated, uncharged form but not in their charged form (i.e. as the conjugate base). . The charged form, however, is often more soluble in blood and cytosol, both aqueous environments. When the extracellular environment is more acidic than the neutral pH within the cell, certain acids will exist in their neutral form and will be membrane soluble, allowing them to cross the phospholipid bilayer. Acids that lose a proton at the intracellular pH will exist in their soluble, charged form and are thus able to diffuse through the cytosol to their target.
Basic Chemistry of the Most Used Molecules in Solutions for Chemical Peelings
It is interesting to consider the chemical nature of the molecules most commonly found in chemical peels. . In the case of the alpha-hydroxy acids (AHAs), the acid carboxyl group is on the first carbon (C1) and the hydroxyl is on the alpha carbon (C2). Salicylic acid is a beta-hydroxy acid with the hydroxyl group on C3.
How the Most Commonly Used Substances in Chemical Peel Solutions Work – a Hypothesis
Based on their different properties and the ways in which they work, L.Dewandre divides the substances most used for chemical peels into three categories: metabolic, caustic, and toxic.
Substances with mainly metabolic activity
Except for glycolic and lactic acid, the metabolic substances described below are not used, properly speaking, in the solutions involved in chemical peels. However, owing to their well-known use in medical cosmetology and in the "in office" procedure of chemical peeling, they have gained an interesting and promising place in strong concentration and in immediate post peeling.
Classification of chemical peels ( A.Tenenbaum)
Acids category Acids subcategory pKa >3
from lower to higher pKa =3 pKa <3 pKa1
pKa2 pKa3 Classification
Of L.Dewandre Number of reactions
Alpha hydroxy aliphatic tartaric 3.04 4.37 metabolic diprotic
citric 3.15 4.77 6.40 metabolic triprotic
malic 3.40 5.13 metabolic diprotic
glycolic 3.83 metabolic monoprotic
lactic 3.86 metabolic monoprotic
Aromatic mandelic 3.37 metabolic monoprotic
Alpha keto pyruvic 2.49 Not available monoprotic
Bicarboxylic azelaic 4.55 5.59 metabolic diprotic
Beta Hydroxy salicylic 2.97 toxic monoprotic
TCA TCA 0.53 caustic monoprotic
Phenol Aromatic Phenol 9.95 toxic Alcohol > acid
Alpha hydroxy acids
Alpha hydroxy acid peels include aliphatic (lactic acid, glycolic acid, tartaric acid, and malic acid ) and aromatic ( mandelic) acids ,that are synthesized chemically for use in peels. Various concentrations can be purchased, with 10-70% concentration used for facial peels, most commonly 50% or 70%. Alpha hydroxy acids are weak acids that induce their rejuvenation activity by either metabolic or caustic effect. At low concentration (<30%), they reduce sulfate and phosphate groups from the surface of corneocytes. By decreasing corneocyte cohesion, they induce exfoliation of the epidermis. At higher concentration, their effect is mainly destructive. Because of the low acidity of alpha hydroxy acids, they do not induce enough coagulation of the skin proteins and therefore cannot neutralize themselves and must to be neutralized using a weak buffer.
α-hydroxy acids, or alpha hydroxy acids (AHAs), are a class of chemical compounds that consist of a carboxylic acid with a hydroxy group on the adjacent carbon. They may be either naturally occurring or synthetic. AHAs are well-known for their use in the cosmetics industry. They are often found in products claiming to reduce wrinkles or the signs of aging, and improve the overall look and feel of the skin. They are also used as chemical peels available in a dermatologist's office, beauty and health spas and home kits, which usually contain a lower concentration. Although their effectiveness is documented numerous cosmetic products have appeared on the market with unfounded claims of performance. Many well-known α-hydroxy acids are useful building blocks in organic synthesis: the most common and simple are glycolic acid, lactic acid, citric acid, mandelic acid.
Knowing well the skin structure as the cutaneous aging is helpful to understand the topical action of AHAs. Human skin has two principal components, the avascular epidermis and the underlying vascular dermis. Cutaneous aging, while having epidermal concomitants, seems to involve primarily the dermis and is caused by intrinsic and extrinsic aging factors.
AHAs most commonly used in cosmetic applications are typically derived from fruit products including glycolic acid (from sugar cane), lactic acid (from sour milk), malic acid (from apples), citric acid (from citrus fruits) and tartaric acid (from grape wine). For any topical compound, including AHA, it must penetrate into the skin where it can act on living cells. Bioavailability (influenced primarily by small molecular size) is one characteristic that is important in determining compound's ability to penetrate the top layer of the skin. Glycolic acid having the smallest molecular size is the AHA with greatest bioavailability and penetrates the skin most easily; this largely accounts for the popularity of this product in cosmetic applications.
Epidermal effect: AHA's have a profound effect on keratinization; which is clinically detectable by the formation of a new stratum corneum. It appears that AHAs modulate this formation through diminished cellular cohesion between corneocytes at the lowest levels of the stratum corneum.
Dermal effects: AHAs with greater bioavailability appear to have deeper dermal effects. Glycolic acid, lactic acid and citric acid, on topical application to photodamaged skin, have been shown to produce increased amounts of mucopolysaccharides and collagen and increased skin thickness without detectable inflammation, as monitored by skin biopsies
AHAs are generally safe when used on the skin as a cosmetic agent using the recommended dosage. The most common side-effects are mild skin irritations, redness and flaking. The severity usually depends on the pH and the concentration of the acid used.
The FDA has also warned consumers that care should be taken when using AHAs after an industry-sponsored study found that they can increase photosensitivity to the sun.
Also making a comparaison of their pH to their pKa , the cosmetic actions of the AHA are interesting :
- For a pH superior to the pKa , the AHA are essentially moisturizers.
The main differences between the moisturizing and caustic effects are due to the amount of neutralization of the alpha-hydroxy acid molecule which has taken place. Neutralizing the AHA with sodium or ammonium creates a salt with more moisturizing and less caustic effect.
- For a pH equal or inferior to the pKa, the AHA are keratoregulators that increase skin flaking and cell replacement.
In such case , the acid form is preponderant, which is more absorbent and facilitates penetration.
Their antiaging action can be compared to retinoids but their mechanism of action is different. They interfere with certain kinds of enzymes (sulfotransferases, phosphotransferases, kinases) whose function is to fix the sulfate and phosphate groups to the surface of the corneocytes. The reduction of these groups involves a decrease in electronegativity and corneocyte cohesion, which leads to a breaking away of the cells from each other, creating exfoliation and flaking. This activity can be characterized as a metabolic action. ( L.Dewandre). However, when used in strong concentrations of 30 to 70% free acid in aqueous solution for peeling, their effect is based on their acidity and results in destruction.
Aliphatic alpha hydroxy acids ( glycolic,lactic, malic, tartaric, citric) with pKa >3
Glycolic acid ( pKa = 3.83) and its different concentrations
Abbreviation : GA
Molecular formula C2H4O3
Molar mass 76.05 g/mol
Appearance white, powdery solid
Density 1.27 g/cm³
Solubility in water 70% solution
Solubility in other solvents alcohols, acetone,acetic acid and ethyl acetate
Acidity (pKa) 3.83
Glycolic acid (or hydroxyacetic acid) is the smallest α-hydroxy acid (AHA). This colorless, odorless, and hygroscopic crystalline solid is highly soluble in water. It is used in various skin-care products
Glycolic Acid: Formulated from sugar cane, this acid creates a mild exfoliating action. Glycolic acid peels work by loosening up the horny layer and exfoliating the superficial top layer. This peel also stimulates collagen growth.
Once applied, glycolic acid reacts with the upper layer of the epidermis, weakening the binding properties of the lipids that hold the dead skin cells together. This allows the outer skin to "dissolve" revealing the underlying skin
In low concentrations, 5 - 10% , glycolic acid reduces cell adhesion in the top layer of the skin. This action promotes exfoliation of the outermost layer of the skin accounting for smoother texture following regular use of topical GA. This relatively low concentration of glycolic acid lends itself to daily use as a monotherapy or a part of a broader skin care management for such conditions as acne, photo-damage, wrinkling . Care needs to be taken to avoid irritation as this may result in worsening of any pigmentary problems. Newer formulations combine glycolic acid with an amino acid such as arginine and form a time-release system that reduces the risk of irritation without affecting glycolic acid efficacy. The use of an anti-irritant like allantoin is also helpful. Because of its safety, glycolic acid at the concentrations below 10% can be used daily by most people except those with very sensitive skin.
In medium concentrations, between 10 and 50%, its benefits are more pronounced but are limited to temporary skin smoothing without much long lasting results. This is still a useful concentration to use as it can prepare the skin for more efficacious glycolic acid at higher concentrations (50 - 70%) as well as prime the skin for deeper chemical peels such as TCA peel (trichloroacetic acid).
At higher concentrations ( called here high concentrations), 50 - 70% applied for 3 to 8 minutes ( has to be done by a physician ) , glycolic acid promotes slitting between the cells and can be used to treat acne or photo-damage (such as mottled dyspigmentation, or fine wrinkles). The benefits from such short contact application (chemical peels) depend on the pH of the solution (the more acidic the product, or lower pH, the more pronounced the results), the concentration of GA (higher concentrations produce more vigorous response), the length of application and prior skin conditioning such as prior use of topical vitamin A products. Although single application of 50 - 70% GA will produce beneficial results, multiple treatments every 2 to 4 weeks are required for optimal results. It is important to understand that glycolic acid peels are chemical peels with similar risks and side effects as other peels.
Lactic acid ( pKa = 3.86)
This acid is derived from either sour milk or bilberries. This peel will remove dead skin cells, and promote healthier, softer and more radiant skin.
Molecular formula C3H6O3
Molar mass 90.08 g/mol
Acidity (pKa) 3.86 at 25 °C
In our opinion, glycolic and lactic peel solutions must have a pH of between 1.5 and 2.5 in order to combine a source of inflammation and stimulation, with their metabolic effects being, essentially, the replacement of corneocytes.
Malic acid ( pKa1 = 3.4, pKa2 = 5.13)
This peel is the same type of mildly invasive peel derived from the extracts of apples. It can open up the pores, allow the pores to expel their sebum and reduce acne
Tartaric acid (pKa1=3,04, pKa2 =4,37)
This is derived from grape extract and is able of delivering the same benefits as the above peels
Citric acid ( pKa1=3.15 ,pKa2=4.77,pKa3=6.40 )
Usually derived from lemons, oranges, limes and pineapples. These peels are simple and effective, although not incredibly invasive or capable of significant improvement with one treatment.
The citric acid is triprotic , having 3 pKa. It is quite interesting because its 1 st pKa is lower than the pKa of the monoprotic glycolic acid on one side and the 3 reactions are made of 2 peelings (pKa1=3.15 ,pKa2=4.77) which end by a buffer ( 3 rd reaction ) with pKa3=6.40.
We can easily understand that citric acid used for peelings do not need any neutralization nor a buffer.
Aromatic Alpha hydroxy acid with pKa >3
Mandelic acid : an aromatic alpha hydroxy acid ( pKa= 3.37)
Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C8H8O3. It is a white crystalline solid that is soluble in water and most common organic solvents.
Mandelic acid has a long history of use in the medical community as an antibacterial, particularly in the treatment of urinary tract infections. It has also been used as an oral antibiotic. Lately, Mandelic acid has gained popularity as a topical skin care treatment for adult acne. It is also used as an alternative to glycolic acid in skin care products. Mandelic acid is a larger molecule than glycolic acid which makes it better tolerated on the skin. Mandelic acid is also advantageous in that it possesses antibacterial properties, whereas glycolic acid does not.
Its use as a skincare modality was pioneered by James E. Fulton, who developed vitamin A acid (tretinoin, Retin A) in 1969. On the basis of this research, dermatologists now suggest mandelic acid as an appropriate treatment for a wide variety of skin pathologies, from acne to wrinkles; it is especially good in the treatment of adult acne as it addresses both of these concerns. Mandelic acid is also recommended is a pre- and post-laser resurfacing treatment, reducing the amount and length of irritation
Mandelic acid peels are commercialized nowadays as gels with a specific viscosity which make easier their use for beginners...
Alpha keto acids with pKa<3
Pyruvic acid : an alpha keto acid ( pKa= 2.49 )
40% -50% pyruvic acid in ethanol is the most used pyruvate nowadays.
Pyruvic acid is a ketone as well as the simplest alpha-keto acid. The carboxylate (COOH) ion (anion) of pyruvic acid, CH3COCOO-, is known as pyruvate, and is a key intersection in several metabolic pathways.
It is often used by to treat mild to moderate papulo-pustular acne with concentrations between 40–50% every 2 weeks for a total of 3–4 months ,It reduces the sebum levels and has does not affect the cutaneous hydratation.
Bi carboxylic acid with pKa>3
Azelaic Acid (pKa1= 4.550, pKa2 = 5.598)
Azelaic acid or 1,7-heptanedicarboxylic acid is a saturated dicarboxylic acid naturally found in wheat, barley, and rye. It is active in a concentration of 20% in topical products used in a number of skin conditions, mainly acne .Azelaic acid is used to treat mild to moderate acne; i.e. both comedonal acne and inflammatory acne. It works in part by stopping the growth of skin bacteria that cause acne, and by keeping skin pores clear
It has some interesting properties :
• Antibacterial: it reduces the growth of bacteria in the follicle (Propionibacterium acnes,Staphylococcus epidermis)
• Keratolytic and comedolytic: it returns to normal the disordered growth of the skin cells, lining the follicle.
• Scavenger of free radicals and reduces inflammation
• Reduces pigmentation
• Non-toxic, and is well tolerated by most patients.
Azelaic acid does not result in bacterial resistance to antibiotics, reduction in sebum production, photosensitivity (easy sunburn), staining of skin or clothing, or bleaching of normal skin or clothing.
20% azelaic acid can be a skin irritant
The azelaic acid is diprotic , having 2 pKa. It is quite interesting because its 2 nd pKa is almost equal to the pH of the skin ( 5.5)
We can easily understand that azelaic acid used for peelings may need to be neutralized but does not need any buffer. For S.DiBlasi, azelaic acid is not buffered, nor neutralized.
In vitro, the azelaic acid works as a scavenger (captor) of free radicals and inhibits a number of oxidoreductase enzymes including 5-alpha reductase, the enzyme responsible of turning testosterone into dihydrotestosterone. It normalizes keratinization and leads to a reduction in the content of free oily acids in lipids on the skin surface.
Apart from that, azelaic acid has antiviral and antimitotic properties. Finally, it can also act as an antiproliferant and a cytotoxin via the blockage of mitochondrial respiration and DNA synthesis.
Beta hydroxy acid peels with pKa around 3
It is becoming common for beta hydroxy acid (BHA) peels to be used instead of the stronger alpha hydroxy acid (AHA) peels due to BHA's ability to get deeper into the pore than AHA. Studies show that BHA peels control oil, acne as well as remove dead skin cells to a certain extent better than AHAs due to AHAs only working on the surface of the skin.
Salicylic acid (from the Latin Salix meaning: willow tree) is a biosynthesized, organic, beta hydroxy acid that is often used. Sodium salicylate is converted by treating sodium phenolate (the sodium salt of phenol) with carbon dioxide at high pressure and temperature. Acidification of the product with sulfuric acid gives salicylic acid. Alternatively, it can be prepared by the hydrolysis of Aspirin (acetylsalicylic acid) or Oil of Wintergreen (methyl salicylate) with a strong acid or base.
Salicylic acid (pKa = 2.97)
30% salicylic acid in ethanol is the most used peeling nowadays
Salicylic acid is lipid soluble; therefore, it is a good peeling agent for comedonal acne. The salicylic acid is able to penetrate the comedones better than other acids. The anti-inflammatory and anesthetic effects of the salicylate result in a decrease in the amount of erythema and discomfort that generally is associated with chemical peels
Salicylic acid is a key ingredient in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts. It works as both a keratolytic and comedolytic agent by causing the cells of the epidermis to shed more readily, opening clogged pores and neutralizing bacteria within, preventing pores from clogging up again by constricting pore diameter, and allowing room for new cell growth.Because of its effect on skin cells, salicylic acid is used in several shampoos used to treat dandruff. Use of concentrated solutions of salicylic acid may cause hyperpigmentation on unpretreated skin for those with darker skin types (Fitzpatrick phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock.
Also known as 2-hydroxybenzoic acid, it is a crystalline carboxylic acid and classified as a beta-hydroxy acid.
Salicylic acid is slightly soluble in water but very soluble in ethanol and ether (like phenol and resorcinol). It is made from sodium phenolate and this explains its direct relationship with phenol with which it shares certain toxic properties that become apparent when used in great quantity and on large surface areas (Table 2).
Salicylic acid is found naturally in certain plants (Spiraea ulmaria, Andromeda leschenaultii), particularly fruits.
Jessner's peel solution, formerly known as the Coombe's formula,was pioneered by Max Jessner, a dermatologist. Jessner combined 14% salicylic acid, 14% lactic acid, and 14% resorcinol in an ethanol base. It is thought to break intracellular bridges between keratinocytes.
Retinoic acid peel
Retinoic Acid or Vitamin A acid is not soluble in water and soluble in fat.
Therefore retinyl palmitate or Vitamin A palmitate is the elected retinoic agent for chemical peels.
Retinyl palmitate, or vitamin A palmitate is the ester of retinol and palmitic acid.
Tretinoin is the acid form of vitamin A and so also known as all-trans retinoic acid or ATRA. It is a drug commonly used to treat acne vulgaris and keratosis pilaris.
Tretinoin is the best studied retinoid in the treatment of photoaging. It is used as a component of many commercial products that are advertised as being able to slow skin aging or remove wrinkles
The terpene family, to which retinoic acid belongs, includes numerous compounds whose common feature is that they are formed by a chain of isoprene units CH2=C(CH3)–CH=CH2 Terpenes have a raw formula type (C5Hx)n, x being dependant on the amount of insaturation. Their names depend on n:
• n=2 Æ C10 : monoterpenes
• n=3 Æ C15 : sesquiterpenes
• n=4 Æ C20 : diterpenes
• n~1000: polyterpenes (rubber)
The main representative of the family of diterpines is vitamin A or retinol. Retinol is present in food (beta carotene) and converts completely in the skin into retinaldehyde (retinal). Subsequently, 95% of this is converted into retinyl ester and 5% into all-trans and 9-cis retinoic acids
Retinoids have multiple properties in embriogenesis, growth control and differentiation of adult tissues, reproduction, and sight. In dermatology their use is well established for psoriasis, hereditary disorders of keratinization, acne, and skin aging. The most commonly used retinoids are all-trans retinoic acid (tretinoin; used topically), 13-cis retinoic acid (isotretinoin; used both orally and topically), retinaldehyde/retinal and retinol (both of which are used topically). In addition there are the synthetic retinoids: etretinate, acitretin, adapalene, tazarotene, etc.
When considering chemical peelings we are only interested in the natural retinoids––retinol, all-trans retinal and retinoic acid––the last two of which are useful in strong concentrations as peeling agents used under medical supervision.
Trichloroacetic acid peels
Substance with mainly caustic activity
Trichloroacetic acid (TCA) (pKa = 0.54)
UN 1839 is required to transport it because of its corrosive activity.
TCA is also called trichloroethanoic acid. It is obtained through distillation of the product from nitric acid steam on chloral acid. It is found as anhydrous (very hygroscopic), white crystals.
TCA is used as a herbicide (as sodium salt) and because of that it can be found directly in the environment and indirectly as metabolite derived from chlorination reactions for water treatment. At the same time, it is a major metabolite of perchlorethylene (PCE), which is used mainly in the field of dry cleaning. Its general toxicity when taken in low dose is almost nonexistent. Its molecular structure is very close to glycolic acid. The carbon in the alpha position has a hydroxyl group and two hydrogens in the case of glycolic acid, as opposed to three chlorines in TCA. TCA is much stronger acid than any other current acids used for peelings ; its pKa is the lowest of any current acids used for chemical peels.. Like glycolic acid, TCA does not have general toxicity, even when applied in concentrated form on the skin. When applied to the skin, it is not transported in the capillary dermic vessels, nor into the blood circulation. TCA's destructive activity is a consequence of its acidity in aqueous solutions, but in peels the acid is rapidly ,,neutralized,, as it progresses through the different skin layers, leading to a coagulation of skin proteins.
The more concentrated the TCA in the solution the more acidic it is and, in addition, it will penetrate deeper looking . The greater the amount of solution placed on the skin
the more intense the destructive effect. TCA action is simple, reproducible, proportional to the concentration and to the amount applied and, finally, as with any solution chemically aggressive to the skin, able to be visually controlled through the color change (frost or coagulation) brought about by transformation of protein molecules (Table 1.1).
Trichloroacetic acid (TCA) is used as an intermediate to deep peeling agent in concentrations ranging from 20-50%. Depth of penetration is increased as concentration increases, with 50% TCA penetrating into the reticular dermis.
The quality of manufacture of a particular TCA depends of 14 parameters linked to the raw material itself and one parameter linked to the manufacturer ( material of protection if necessary like dustmask, eyeshield,faceshield,, full face particle respirator, gloves,respirator cartridge, respirator filter).
These 14 parameters are the following ones :
1 the density of the vapor , Ex Relative vapour density (air = 1): 5.6
2 the grade of purity
3 the quality ( analytical specification of the pH )
4 the index of refraction
5 the temperature of ebullition per liter
6 the density in g/ml at 25C
7 the residual traces of anions and/or cations if they still exist , which may cause tattoos ( differential diagnosis with dyschromies) in case of the penetrations depth linked to the pH .That is why it is not recommend to use buffered TCA nor neutralization with ,, normal,, water containing metallic ions.
8 other residual chemical elements : if they should be considered as ignored or not like SO4
9 the flash point (High flash point offers greater safety)
10 the impurities if they exist, for example not soluble material and so on
11 the solubility in water in mole at 20C, with the clearness or colourness ( without any colour) of the obtained solution
12 the turbidity
13 the pressure of the vapor (For low vapor pressure sealing and lubrication in high vacuum applications.) Ex Vapour pressure, Pa at 51°C: 133
14 the suitability to fix eventually a solution ( gels )
The storage of TCA peel has to be separated from food and feedstuffs. in a cool.dry.place, well closed. and kept in a well-ventilated room.
The packaging has to be unbreakable , if breakable put into closed unbreakable container.
It is preferable to keep the TCA peels solutions in opaque glass bottles.
In addition to the detailed chemistry datas up, we allow us to introduce some clinical datas just to highlight the mysteries of the action of the TCA onto the skin. TCA is the most aggressive acid ( lowest pKa of all acids used for peels) and the depth of penetration is correlated with its pH .
The TCA application is linked to the pressure of application, the time, the number of coats, the total quantity used and the neutralization.
We do prefer special creams called ,, frosting stoppers,, instead of water to neutralize the TCA , avoiding then an exothermic reaction , which would provoke a ,, cold,, burn.
For our own point of view , the not buffered TCA prepared with pure crystals and completed with bidistilled water added with rose oil mosqueta will never provoke long term any pigmentary rebounds or hyperchromies vs the buffered TCA .
The following scheme shows the difference of skin reactivity to the coating with TCA
The darker the area ,the higher the number of coats to be applied at the same concentration to get the same frosting.
It is recommended not to use water or primary or secondary alcohols before and after the application of an unbuffered TCA to avoid any exothermic reaction as a reversible reaction of esterification
Substances with mainly toxic activity
Phenol ((pKaPhOH2+/PhOH) - 6.4 (pKaPhOH/PhO-) 9.95 )
Phenol is also named phenic acid, or hydroxybenzene. It is a colorless, crystalline solid that melts at 41° and boils at 182°, is soluble in ethanol and ether and sometimes soluble in water.
Alcohols are organic compounds that have a functional hydroxyl group attached to a carbon atom of an alkyl chain. Benzene hydroxyl derivatives and aromatic hydrocarbons are called phenols, and the hydroxyl group is directly attached to a carbon atom in the benzene ring. In this case, phenol is an alcohol but not an alkyl alcohol: the group C6H5– is named phenyl but the C6H5OH compound is called phenol and not phenylic alcohol.
Properties of phenols
Phenol is an aromatic alcohol with the properties of a weak acid (it has a labile H, which accounts for its acid character). Its three-dimensional structure tends to retain the H+ ion from the hydroxyl group through a so-called mesomeric effect. It is sometimes called carbolic acid when in water solution. It reacts with strong bases to form the salts called phenolates. Its pKa is high, at 9.95. Phenol has antiseptic, antifungal, and anesthetic pharmacological properties.
Carbolic acid is more acidic than phenol and it exists 3 differences between phenol and carbolic acid
1.First explanation for the increased acidity over alcohols ( Phenol) is resonance stabilization of the phenoxide anion by the aromatic ring. In this way, the negative charge on oxygen is shared by the ortho and para carbon atoms.That is why carbolic acid is used instead of phenol for endopeel techniques .
2. In a second explanation, increased acidity is the result of orbital overlap between the oxygen's lone pairs and the aromatic system.
3. In a third explanation, the dominant effect is the induction from the sp2hybridised carbons; the comparatively more powerful inductive withdrawal of electron density that is provided by the sp2 system compared to an sp3 system allows for great stabilization of the oxyanion
Resorcinol (pKa =11.27)
Resorcinol is a phenol substitued by an hydroxyl in position meta
( Also hydroquinone is a phenol substituted by an hydroxyl in position para)
( Also pyrocatechol is a phenol substituted by an hydroxyl in position otho)
Resorcinol is also named resorcin, m-dihydroxybenzene, 1,3-dihydroxybenzene or benzenediol-1,3 . It is a crystalline powder that melts at 111 °C, boils at 281 °C, and is soluble.
Mechanism of action of phenol and resorcinol
Like resorcinol, phenol is a protoplasmatic poison that works through enzymatic inactivation and proteic denaturation with production of insoluble proteinates. Apart from that, both phenol and resorcinol
act on the cellular membrane, modifying its selective permeability by changing its physical properties. This change in permeability then leads to cell death.
Phenol alone is a more powerful poison, with an anesthetic secondary action of paralysis of sensory nerve endings.
Phenol and (to a lesser extent) resorcinol are cardiac, renal, and hepatic toxins that are eliminated from the body at 80% concentration either unchanged or conjugated with glucuronic or sulfuric acid.
How the Most Commonly Used Substances in Chemical Peels Work – a Proposal for Classification
When making reference, even superficially as we do, to the chemical and pharmacological properties of these diverse molecules, we realize that acidity is far from being the only mechanism of action that causes the previously documented peel-induced modifications of the skin. The pH alone is only destructive in the case of trichloroacetic acid. The other substances act mainly through toxic effects (phenol, resorcinol and, at a lower level, salicylic acid) or through metabolic effects in the case of AHAs, azelaic and retinoic acids, and interfering with cell structure and synthesis without destroying them, merely modifying them or stimulating them.
Thus we can propose to classify the substances used in the peels
in three categories: caustic, metabolic and toxic. Keep in mind that caustic effects are localized only to the areas the chemical touches, while toxic effects, although mainly localized in nature, can also affect cells some distance from where the chemical has been applied.
Classification of substances used for chemical peels ( L.Dewandre)
• Caustic: trichloracetic acid
• Metabolic: AHAs, azelaic acid, retinoic acid
• Toxic: phenol, resorcinol, salicylic acid
When acidity is not the main mechanism of action, the pH seems to be the factor that allows certain other substances present in the solution (that have mainly metabolic effects) to penetrate the skin. The skin and its constituent molecules, and water, act as a kind of buffer for the solution that makes contact and penetrates until it reaches the depth necessary for its relative neutralization. It acts as a blotter of the solution applied, which is more or less avid depending on the pH and, most of all, on the pH gradient between this solution and the depth of the skin involved.
Toxins, particularly phenol, have little if any caustic action; phenol solutions have a pH of 5 or 6.
We understand well the interest in using peeling mixtures of different substances so as to combine caustic, toxic, and metabolic effects. This explains the interest in Jessner's solution (a mixture of resorcinol, lactic acid, and salicylic acid) and Monheit's formula, which is a version of a modified Jessner's solution with the resorcinol replaced with citric acid and undoubtedly secret phenol formulas and others ( Fintsi,Kakowicz,De Rossi Fattaccioli , etc.).
From the classification of A.Tenenbaum , it is easy to understand that even some acids with pKa >3 cannot be used by not specialists as for example ( tartaric, mandelic, salicylic and of course phenol) .
Therefore it is recommended that beginners or not specialists have to be limited to use at low concentrations the non aromatic alpha hydroxyl acids with pKa >3.
If we look at the history and the evolution of chemical peels it is possible to distinguish two great developmental periods. The period during which great substances were discovered, classical formulas and mixtures created, and their histological and clinical effects studied, lasted from the 19th century to the end of the 1980s. The second period includes the development and improved understanding of modified TCA, mainly influenced by Z. Obagi, and the development of AHAs. The AHAs (rediscovered by Van Scott et al.), notably glycolic acid, popularized mild chemical peels for a large part of the population.
In spite of this important progress, the science of chemical peels is still mainly empiric and its applications are often intuitive. We believe that we might be entering a third period, characterized by a better understanding of the mechanism of action of peels, as discussed above. Hopefully we will emerge from this period with the appearance of new, more scientific methods and products for use in chemical peeling.
Although some have predicted the disappearance of chemical peels in favor of physical peeling using lasers, quite the opposite has occurred and we are witnessing a rekindled interest. This development in this field will be completely achieved when the application of chemical peels stops being empiric and becomes scientific.
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Box 1.1 Approximate skin composition
• Water 70%
• Proteins 25.5%
• Lipids 2.0%
• Oligo mineral elements 0.5% (e.g., zinc, copper, selenium)
• Carbon hydrates 2.0% (mucopolysaccharides)