CHELATING AND SEQUESTERING AGENTS IN COSMETICS 97 to analyze a complete bottle, the amount of metal therein would seem insignificant. Nevertheless, what is there, is on the surface of the bottle, where it can most readily get into the product and its effect may be many times greater than would appear from the analytical figures. Actually, the question in my mind is: How many milligrams of active perfume are present in a 1-oz. jar of cold cream and what proportion of that small amount of perfume can be catalytically oxidized before an undesirable or off odor is noticeable? The most obvious method of preventing trouble from metallic ion contamination is to see that all of them are removed or that only raw materials are bought which have none of them present. This is impossible. The most satisfactory answer at present is to inacti- vate residual metallic ions insitu during the course of manufacture. This can be done by sequestering and chelating agents. There are numerous examples of sequestering and chelating agents in nature. For instance, chlorophyll has a complex, organic structure with which magnesium is chelated. Many synthetic organic chemicals have chelating power. Thus 8-hydroxyquinoline will chelate copper to form a 8-quinolinolate which is widely used in the textile industry as a mildew- proofing agent. There are numerous other organic products offered for special uses. Anyone interested in others having chelating properties can find many examples in the book "Chemistry of the Metal Chelating Compounds" by Martell and Calvin. There are two types of commer- cially available materials for the purpose of inactivating metallic ions. The first of these, probably more familiar because they have been generally available for a longer period of time, are the complex phosphates. These have many desirable properties but they have other characteristics which limit their applications in the cosmetic field. The organic chelating agents of the ethylenediamine tetraacetic acid (EDTA) type and its salts are among the most effective of all the chelating agents, and at the same time they can be marketed at a price low enough to be economically useful. I shall compare the properties of the EDTA type of compounds with that of the complex phosphates a little later so that the field of usefulness cov- ered by each of them will be understood. The structure of ethylene diamine tetraacetic acid is as follows: HOOCCH2--N CH2C--O CH2 OH I CH2 OH I HOOCCHg--N--CH2C=O Note that it resembles a lobster's claw ready to grab any calcium ion which may be present. The word "chelate" comes from the Greek word "kelos" which refers to the great claw of the lobster. Chelating (Kelating) is

98 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS the correct pronunciation of this term. Now, generally it is the di- sodium salt of ethylene diamine tetraacetic acid which would tie up the calcium. After the usual type of a salt reaction, there is a further sharing of electrons between the divalent metal, like calcium, and the two nitro- gens. This results in an inner ring complex which is so stable it is very slightly, if at all, ionized. I believe some definitions are in order so that we may be more specific in our thinking: 1. A chelating agent is one which can inactivate a multivalent ion by making it an integral part of an inner ring structure. 2. A sequestering agent is one which inactivates a metallic ion by form- ing a water-soluble complex in which the metal is held in non-ionizable form. 3. A complexing agent is one which can inactivate a metallic ion. If the resulting complex is soluble, then it is also a sequestering agent. Ethylenediamine tetraacetic acid and its salts are both chelating and sequestering agents and, of course, complexing agents. I shall indicate the reaction between the di-sodium ethylenediamine tetraacetic acid ion and a divalent metal ion such as calcium by the following: Na2Te q- Me + + • MeNa.e Note that no change in valence occurred so that there is no oxidation or reduction reaction here. In fact, this most closely resembles a simple, acid base titration which is represented by: H * q- OH- --• H•O In each case, ions have come together to form a product having slight, if any, ionization and therefore causing the reaction to go to an end. As a matter of fact, this reaction between EDTA and metals is gaining ever increasing analytical usage for purposes of quantitative determination and is readily accomplished by titration methods. The higher valence metallic ions are most strongly chelated and then those of lower valence, for instance, ferric iron is more strongly chelated than is ferrous iron. In fact, iron is one of the most strongly chelated of all the metals. At- tempts have been made to set up a series similar to the electromotive series which will show the order of chelation. This has met with indifferent success since a series arranged under one specific set of conditions may be found to have an altogether different order under another set of conditions. Some of the factors affecting the order of such a series are: (a) Concentration of the metallic ion. (b) pH. (c) Temperature. (d) Other electrolytes present and their concentration. (e) Other complexing agents present. (f) Precipitating anions and their concentrations, etc.