REVERSIBLE POLYMERIZATIOS h X D MOLECULAR ~IGGREGATIOS‘ L. JIICHAELIS T h e Laboratories of T h e Rockefdler Institirte for Medical Research, Seu York, S e w York Received .4ugiist 8 8 , 1949
I n addition to the irreversible polymerizations encountered in the field of rubber and plastics chemistry, reversible polymerizations have been known for a long time. Special emphasis will be put upon those cases where the forces of molecular aggregations are obviously not of the nature of a regular covalent bond. From the large field of “molecular compounds,” a few ivill be discussed here in the form of a revieiv of several previous papers (1 to 8) augmented by additional recent unpublished material. This paper should be considered as a contribution to the problem rather than as an exhaustive review of it. I. T H E REVERSIBLE MOLECULAR AGGREGATIOX O F DYESTCFFS
I t has been known for a long time (10, 15, I B , 17) that the absorption spectra of the majority of organic dyestuffs in aqueous solution do not obey Beer’s Ian; rather does the molar absorption curve in most cases depend on the concentration. This is the case in aqueous solution, whereas in alcoholic solution (not necessarily quite water-free) Beer’s law is obeyed. I n some cases Beer’s law is valid even in aqueous solution: namely, (1) for such dyes as phenosafranine and related ones; the acridine dyes; several dyestuffs of the indamine and indophenol group, e.g., Bindschedler’s Green; (a) even for those cationic dyes which, in the form of their ordinary, singly charged cation, strongly deviate from Beer’s law (such as the thiazines, the oxazines, triphenylmethane dyes, etc.), Beer’s law is strictly obeyed for the doubly charged cations which exist in sufficiently acid solutions; (3) methyl green, which is a doubly charged cation even in approsimately neutral solution (pH i to 5, say), also obeys Beer’s law in aqueous solution. The deviation from Beer’s law is accounted for by the hypothesis of a reversible dimerization and polymerization. The energy of the bond is of the order of the thermal energy at room temperature, since the effect of concentration on the deviation from Beer’s law depends strongly and reversibly on temperature. This bonding energy in the dissolved state is in fact the difference between the affinities of the dye molecule for another molecule of its kind and for water . I t is understandable that a doubly charged cation should resist polymerization for electrostatic reasons. However, no clear understanding has been reached as yet as to the manner in which the structure of a single charged dye ion is cor1 Presented a t the Twenty-third Sationsl Colloid Symposium, which was held under the auspices of the Division of Colloid Chemistry of the American Chemical Society a t Minneapolis, Minnesota, June 6-8, 1949.
J
2
L. YICH.kELIS
related with its tendency toward molecular association. One remarkable example is this. Whereas thionine in aqueous solution shows very strong association, oxonine (which differs from it only by having an oxygen bridge instead of a sulfur bridge) deviates from Beer's law only very slightly. The evidence for polymerization in aqueous solution is derived from the absorption spectrum. Taking methylene blue as an example (figure 1) the absorption spectrum in alcoholic solution shows a sharp and high maximum at 650 mp,
nP FIG
1
which \vi11 be referred to as the a-band, and a very slight secondary hump at 590 mp, Jyhich will be referred to as the 8-band. There is, furthermore, a rather high band in the ultraviolet a t 295 mp and a smaller one at 250 mp. First of all it should be stated that modifications of this spectrum to be discussed in what follo\vs are concerned only with the bands in the visible spectrum. The ultraviolet bands are, for all practical purposes, unaffected by all those circumstances which so strongly influence the absorption in the visible spectrum ( G ) . In aqueous solution of high dilution (lo-' t o -11)the absorption spectrum resembles very
REVERSIBLE POLY3fEHIZATIOS
3
much that in alcohol, although the peak is slightly displaced (660 mp instead of 650). As the concentration increases in aqueous solution, the a-band decreases and the p-band increases considerably, a t the expense of the a-band, soon to such a degree that the p-band almost suppresses the a-band. This effect is reversibly abolished by raising the temperature. The following interpretation has been suggested: The a-band is characteristic of the monomeric cation and corresponds to an electric oscillator along the z-axis of the molecule (the long axis). The B-band, whenever it increases in height beyond that prevailing in alcohol, is characteristic of the dimer. I t has been interpreted as due to an oscillator in the y-direction (the shorter axis in the plane of the molecule). An alternate explanation is that it is due to higher vibrational energy levels of the dye. When the dye solution of loiv concentration is mixed with a neutral salt, there may be, previous to distinct crystallization of the dye, a transitional colloidal or quasi-colloidal state, an “incipient saltingout” effect, which shows a molar absorption spectrum resembling that for a much higher dye concentration without salt. This fact is fair evidence that the change of spectrum with concentration is correlated Lvith molecular aggregation. I n the presence of very much ammonium sulfate in very dilute methylene blue solution (figure 1) the p-band is not only very high but even slightly displaced toward still shorter wave lengths. When the dye is adsorbed on a stainable substrate the absorption spectrum may depend both on the relative amount of dye with respect to that of the substrate and on the chemical nature of the stainable substrate. The behavior of various stainable substrates varies between two extremes, with all transitions occurring. I may restrict myself essentially to two substrates of extremely different behavior and discuss later on, more briefly, some substrates of intermediate behavior. Those two extreme types are represented by solutions of nucleic acid (of pH about 4 to i ) (usually using yeast nucleic acid, which in this respect does not differ essentially from thymonucleic acid), and on the other hand agar (a half-ester of sulfuric acid with high-polymeric hexosan). All experiments with those t\vo substrates can be carried out in a macrohomogeneous system and lend themselves readily to quantitative spectrophotometry in transmitted light. The characteristic of nucleic acid is this: When a dye showing no deviation from Beer’s law, such as phenosafranine, is adsorbed by nucleic acid, the peak of absorption is usually slightly shifted toward longer wave lengths. Kothing else happens. On the other hand, when a dyestuff capable of polymerization is adsorbed by nucleic acid, the situation is very different. There may be a slight displacement of the peak of the a-band too, but what is much more striking is the following phenomenon: When a solution of nucleic acid is mixed with the dye of such a concentration that in aqueous solution there mould be a strong @-band and a distinctly depressed a-band, nucleic acid makes the &band disappear and causes the a-band to increase (see figure 2). With the unaided eye, toluidine blue, for instance, at a concentration a t which it appears blue-violet
4
L. MICHAELIS
in water, shows a pure blue even with greenish tint in nucleic acid. The effect of nucleic acid is as though it had "depolymerized" the dye. This interpretation is compatible with the following picture: The negatively charged groups of nucleic acid (phosphate side chains) are present in large excess over the dye cat-
REVERSIBLE POLYMERIZ.4TIOS
3
ions, so the dye cations v-ill be singly distributed over the phosphate groups of nucleic acid, and the p-band characteristic of the dimer will disappear at the expense of the increased a-band. When nucleic acid solution of much lower concentration (figure 3) is mixed with the same amount of dye, a B-band may reappear. However, never does any other band at $till shorter wave length appear, in contrast to what will be shown presently. An especially interesting phenomenon is this: When a fixed tissue slice (say of liver) is stained v i t h a solution of such a dye (methylene blue, toluidine blue, crystal violet), the over-stained slice may be washed first with \rater and then with alcohol to such an extent that the dye can no longer be extracted. We may consider that all the dye permanently adsorbed is adsorbed by some cationic ion exchange : some cations previously held by the phosphate groups of nucleic acid (alkali ions, or even anions of proteins) hare been replaced by dyestuff cations. Such a stained section, when viewed in the microscope, embedded in water, shoivs always n distinct P-band and some a-band. The same slice, viewed in alcohol, s h o w only a very strong a-band and no p-band. This change of spectrum, on changing from water to alcohol, is perfectly reversible and can be, in fact, reversed any number of times. The spectrum as it appears in alcohol is not essentially changed on following the customary procedure of histologic technic, passing from alcohol through xylene to balsam. The other extreme representative of a stainable substrate is agar. Many other sulfuric esters, provided they are derived from highly colloidal carbohydrates, show the same behavior, as Lison (12, 13) first emphasized, such as mucin, chondroitinsulfuric acid, heparin, and others. Agar is the most convenient one and besides shoivs the specific effect to an especially high degree. The staining of substrates of this type with certain basic dyestuffs is characterized by the fact that the color of the adsorbed dye is quite different from the color of the dye solution itself, even as seen with the unaided eye. This effect has been known under the name of metachromasy (Paul Ehrlich). Good examples of metachromatic dyes are thionine and toluidine blue, which stain most stainable substrates blue, especially cellular nuclei, nhereas agar is stained pink to purple. All those dyestuffs Ivhich exhibit polymerization in aqueous solution shoiv the metachromatic effect, as has h e n pointed out by Kelley (11) and the speaker (6, i ) . The absorption spectrum of the metachromatically adsorbed dye s h o w a very characteristic property: The a- and p-bands are almost or even entirely annihilated, and a new band at longer wave length appears, which is rather diffuse; e.g., in toluidine blue where the CY- and P-bands are a t 630 and 590 mp, respectively, this new band has its peak at 540 mp, varying slightly according to conditions (figures 4 and 5 ) . The diffuseness and variability of the peak of the band obviously indicate that the curve is just the envelope of a series of overlapping bands. This complex band \rill be referred to as the metachromatic or p-band. (The name “?-band” will be reserved for something else to be discussed presently.) The absorption spectrum is reversibly shifted to the ordinary one, with a- and &bnnds, in a perfectly reversible manner by mwming (figure 5).
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L. MICHAELIS
This phenomenon will become especially clear in some polymethine dyes; e.g., it has been known that pinacyanol shows a high a-band and, even in alcohol, a very distinct, although lower @-band (figures 6 and 7 ) . I n aqueous solution with increasing dye concentration the a-band is lowered and the @-bandincreased. At still higher concentration, another “7-band” at still shorter wave length appears. (Furthermore, in very highly concentrated solution, where the solution becomes very viscous and s h o m the property of a liquid crystal, a new, very sharp band (at the red end of the spectrum) and resonance fluorescence appear, as first shown by Scheibe (16). (This interesting band is no concern of ours for the present problem.*) The dye is adsorbed by nucleic acid again in such a n a y
460
500
540
580 mP
620
660
’IC0
FIG.4
that the @-bandalmost disappears and the a-band strongly increases, the absorption spectrum approaching that in alcohol solution: the dye is seemingly depolymerized by nucleic acid: I n agar, however, a new very diffuse band appears, the peak of which lies at very much shorter wave length than the 7-band previously described by other authors. It will be referred to as the p-band or metachromatic band. The color of the dyestuff is blue with nucleic acid but pink with agar. M y previous interpretation of the @-bandwas to the effect that it represents a state of high molecular aggregation of the dye. This interpretation was favored by two facts: ( 1 ) the metachromatic color returns to the normal color a t higher temperature (70-80” C.), in a perfectly reversible manner, seemingly indicating a reversible dissociation of the polymer, the bond energy being of the same order as the thermal energy around room temperature; ( 2 ) the p-band arises also when 1 However, it is worth while mentioning that the little hump a t about 640 mu in the “metachromatic” band of very dilute pinacyanol shown in figures 6 and 7, as obtained in agar, appears at the same wave length as the band which in a pure aqueous solution of the dye is established only in very concentrated solutions.
REVERSIBLE POLTMERIZATIOS
7
8
L. MICH.IELIJ
a suitable dyestuff' a t a very low concentration in aqueous solution is being salted out, as Tvith ammonium sulfate, in such a n-ay that as a primary reaction a colloidal solution arises which only gradually undergoes distinct crystallization. It must be added, however, that the cy- and 8-hands lie each a t a very definite Jvave length, which may depend slightly on the solvent (water or alcohol). Only in extremely high concentrations of the dye is the p-band perhaps slightly displaced toward shorter wave length, as can be seen from spectrophotometric graphs of methylene blue (figure 1). In contrast, the p-band may have its peak within a certain, larger range of wave lengths, according to conditions. So, in
m/-L
FIQ.7
toluidine blue, the peak of the p-band in agar mag vary from 560 to 540 m p with increasing dye concentration. However, the interpretation of the p-band as that of a high, reversible polymer of the dye has become doubtful as to its generality. S o doubt a hand resembling the p-band can be produced by incipient salting out of the dye. I n this case it is certainly the polymolecular micelle mhich exhibits the @-hand.However, when a 1-3 per cent agar gel is stained with pinacyanol or toluidine blue, a t such a low concentration of the dye that the color is distinct only on looking through the whole length of a test tube, the color is still a t room temperature very decidedly the pink, metachromatic color, shoxving the p-band only. I n this case it is unlikely that the dye should have been adsorbed in the form of polymolecular dye micelles, rather is a monomolecular distribution of the dye over the negatively charged sites of the colloid the only reasonable assumption.
9
REVERSIBLE POLYMERIZATION
If so, the result is this: The “metachromatic” dyes are characterized by the fact that their absorption spectra, especially the number of different absorption maxima and their relative height, are very sensitive to external fields. Di- and polymerization are just two of the factors influencing the type of spectrum; the nature of the substrate by which they may be adsorbed is another factor. The t ~ v oextreme types of stainable substrates in this respect are represented by nucleic acid, which influences the spectrum in the direction as though it were depolymerized, and agar, vhich influences the spectrum always in the direction as though it Tvere highly polymerized. Among other stainable subst,rates there are some high-molecular-weight metaphosphates encountered in
i
Toluidine blue 1.45~10-~n
~
1
FIG.8
living cells (18) and some silicates (11) vhich approach the staining qualities of agar. We shall now discuss a fen- examples of stainable substrates x i t h an intermediate behavior. Many of the long-carbon-chain “detergents” helong here. The simplest example is sodium oleate. When the concentration of the soap is very high, soap behaves as nucleic acid. I t seemingly depolymerizes the dye, and only the a-band is developed. As the concentration becomes lower (figure 8) the a-band decreases and a @-band develops; on further increase a p-band develops. Thus, toluidine blue in a soap solution may appear blue, violet, or pink according to the concentration of the soap. Other detergents behave similarly. Figure 9 shows -%emsol22 as one example of many. Here, according to the concentration of the colloid, 71-e have for toluidine blue either a strong a-band almost exclusively, or a strong /3-band, or even a u-hand.
L. MICHAELIS
10
.......
-
Aerosol 22 10
7
'1 0010 u 't 00010 '0 near1 rndistingurshable from p u r e w t e r (nozplotted) in puoe wattel.
- in pure w a t e r
mP
FIG.10
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11
The behavior of cellulose esters is somewhat different, approaching that characteristic of agar in some degree. So, sodium carboxymethylcellulose, stained with toluidine blue, never shows a strong a-band. With increasing dye concentration it develops a p-band, like agar. Corrin and Harkins (9) claim that the change in the color of pinacyanol in soap solutions, from blue t o pink, occurs at a very definite concentration of the soap and is indicatiw of the “critical concentration” of the soap solution when a true molecular dispersion begins to form molecular aggregates or micelles. The final interpretation of the color change is still open to discussion. It seems that the sensitivity of the absorption spectrum of some dyestuffs with respect to the nature of the substrate by which they are adsorbed may serve as a powerful tool for the elucidation of the structure and the chemical nature of the colloidal micelle. The final solution of the problem, however, is still far remote. I wish not to enter into a premature speculation but merely to draw your attention to an as yet unexhausted source of future information about the structure of colloidal micelles. 11. QCI.?“YDRONE-LIKE
MOLECULAR COMPOUNDS
The molecular compounds of the quinhydrone type may be considered as dimers composed of two molecular species of the same kind, just as the dimers discussed before. To wit, quinhydrones may be considered as dimerized semiquinone radicals. On the other hand, a quinhydrone may also be conceived of as a molecular compound of a quinone and a hydroquinone, that is to say, as a compound of two molecules of different though related structures differing in their level of oxidation. Thus, quinhydrones represent a transition of the cases of the reversible polymers (to be discussed later on) which are composed of two essentially different molecular species. The quinhydrone-like compounds may be divided into two classes, each with a somewhat different behavior: yuinhydrones formed from a hydroquinone and a quinone, and quinhydrones formed from an aromatic p-diamine and a corresponding diimine. They all are quite stable in the crystalline solid state and dissociate very strongly in the dissolved state, the dissociation depending strongly and reversibly on temperature. They are all strongly colored compounds, very much more so than the corresponding quinones. The justification for considering them as dimers of the semiquinone radical is based on the following consideration. If Q designates the compound of quinonoid structure, B that of t,he corresponding benzenoid structure, S the free, paramagnetic semiquinone radical, and D the dimeric, diamagnetic, quinhydrone-like compound, the following equilibria must be considered, each characterized by an equilibrium constant K : KI
Q+B$2S
’, 1)
12
L. MICHAELIS
Kz
2s e D K3
Q+B$D with
K ) Ki X K1 Let u s consider especially KP, the constant involved in the dimerization oi the free radical. Two general rules can be stated concerning this constant: (1) If the resonance energy of the free radical is strong, the radical may be so stable a compound as to counteract dimerization. For instance, in duroquinone in alkaline solution the two limiting structures of the semiquinone may be in some loose way symbolized as in formula I. These tTyo structures are perfectly 0 0-
equivalent and so bring about strong resonance and high stat)ility, strongly counteracting dimerization. In fact, until recently it has been assumed that no real diamagnetic quinhydrone could be obtained from duroquinone. Recently its existence-at least in the solid crystalline state-has been shown (4). It is, practically speaking, completely dissociated in the dissolved state. In the same manner, phenanthrenequinonesulfonate (11) can be reduced to a semiquinone which, in alkaline solution, can be symbolized as in formula 111, ivith two equiv-
13
REVERSIBLE POLYMERIZATIOK
0
0-
I
IVb alent resonating limiting structures, bringing about high stability, with little, although not entirely lacking, tendency of the free radical toward dimerization; whereas in acid solution the structure may be represented as in formulas IVa and IVb, IVb being much more improbable than IVa. Here the resonance energy is small, the stability is low, and the tendency toward dimerization is high. In fact, with this compound, in alkaline solution, a large amount of the paramagnetic free radical is formed, together with a small amount of the dimer, the diamagnetic quinhydrone, whereas in acid solution only the diamagnetic quinhydrone can be observed. ( 2 ) Another factor, important for the formation of the dimer of the free radical, is the nature of the solvent,. In several cases (duroquinone and phenanthrenequinonesulfonate) the dimerization of the free radical takes place only in aqueous solution. In alcohol and pyridine (even in the presence of relatively large amounts of water) the dimerization of the free radical is ent,irely prevented. Yo satisfactory explanation for this remarkable fact can be presented. It recalls vividly the fact that also the polymerization of organic dyestuffs takes place only in aqueous solution. It does not seem likely that the dielectric constant of the solvent should be the essential factor responsible for this difference. The difference between the quinhydrones proper and the analogous compounds derived from aromatic diamines is as follows (3, 4): Benzoquinone and hydroquinone, when mixed in solution, form immediately the sparingly soluble, dark-colored, crystalline, diamagnetic quinhydrone, which in solution strongly, although not entirely, dissociates into its components. The affinity for the formation of the quinhydrone is diminished to an enormous extent if the four hydrogen atoms of the ring are methylated. As said before, the quinhydrone of duroquinone is much more difficult to obtain than ordinary quinhydrone, although the free monomeric semiquinone of duroquinone can be obtained with great ease in an alkaline solution. The methyl groups of duroquinone obviously represent steric hindrance for the formation of the dimeric quinhydrone. It may be inferred therefrom that the dimerization takes place by packing the two rings upon each other. I n contrast, the dimerization of the free radical derived from p-phenylenediamine is not at all inhibited, rather even a little favored, by methyl groups in the aromatic ring. On t'he other hand, if all hydrogen atoms of the amino groups of the diamine are methylated, the formation of the diamagnetic quinhydrone is entirely prevented, and this is the case even in thk
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L. MICHAELIS
solid crystalline state; the crystals are paramagnetic, with a permanent dipole moment corresponding precisely t o one unpaired electron. ( 4 ) This compound (the univalent oxidation product of N ,N’-tetramethyl-p-phenylenediamine,or “Wurster’s blue,” as a perchlorate) is perhaps the free radical easiest to prepare in the crystalline state and perhaps the most stable solid radical. If not all of the amino groups of the diamine are methylated, the crystalline compound is always entirely represented by the diamagnetic quinhydrone-like compounds which in the solid state may be considered as high polymers, although in solution they are certainly dimers to the extent to which they do exist a t all in the dissolved state. These facts are compatible only with the assumption that in this case the two rings of the quinhydrone are not stacked upon each other but lie in one plane, and for this reason the substitution of all the amino hydrogen atoms prevents steric hindrance for dimerization (4). As regards the nature of the bond which holds together the two moieties of a quinhydrone-like dimer, it may be considered first of all as a double hydrogen bond, as symbolized in formula T’. However, in addition, there is a perfectly
H
...”
0”
\ 0
v equivalent resonance. Formula V is one limiting structure, and its mirror image is the other. I t is uncertain which of the two moieties has the quinonoid structure and which has the benzenoid structure. The unsubstituted hydrogen atom is necessary for the structure. This fact, although appearing self-evident, is emphasized here in contrast to a phenomenon to be described in the following section. 111. MOLECUL 4R COMPOUSDS COMPOSED O F T W O D I F F E R E S T MOLECULAR S P E C I E S
There are a great number of molecular compounds which resemble quinhydrone in so far as the one component is on a higher oxidation level than the other, but differ from true quinhydrones in so far as the two components are not components of one single redox system. The component of “higher oxidation level” may be a quinone or a nitro compound; the component of lower oxidation level may be a phenol, or an aromatic amine, or even an aromatic hydrocarbon. Among such compounds I wish to mention only a few typical representatives which show the various kinds of behavior. It is important to emphasize that such compounds
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15
must be dealt with on a different footing according to whether they are in the crystalline, the dissolved, or the melted state (5). To begin with the solid state, typical representatives are the strongly colored molecular compounds of quinone with phenols. Designating the quinonoid component as Q and the other component (of benzenoid structure) as B, the molecular compound may have, according t o the particular compound, the composition QB, or QB2, or in rare cases also Q2B.However, from each given pair of components, always only one of the three possibilities is materialized. rhus, the intensely blue compound of chloranil with hexamethylbenzene IS QB; the compound of quinone and phenol is always QB,, independent of the ratio in which Q and B may be mixed when the compound is being prepared. Some compounds of the type QZB have been reported, but most of them are doubtful because of their instability. The only case (not previously described and rather unexpected) in which a compound of the composition Q?B and sufficiently stable for a reliable analysis can be prepared is a compound of quinone and phloroglucinol. The case of quinone plus two phenols is understandable from the followng picture (formula VI), with the suggestion that this structure is in resonance with another, in which the hydrogen atoms are 0
11
H - 0 \- 9
VI covalently bound to the left-hand moiety, i. e., now hydroquinone, and bound by hydrogen bonds to two phenol radicals (phenol minus hydrogen). The same situation prevails for the compound of phenol with hydroquinone monomethyl ether. After this very brief rei.ien of the solid compounds we should discuss those compounds in the dissolved state. First of all, they are all very strongly dissociated into their components in any solvent; secondly, a remarkable feature is the fact that in any compound in the dissolved state there could be shown to exist only a compound of the composition QB, even in those cases where in the solid state the composition is QB, or Q?B. Furthermore, whereas solid compounds are formed only if hydrogen atoms are present to form hydrogen bonds, compounds of the composition QB are formed in solution and also in the melted state, even if all hydrogen atoms of the hydroxyl groups are substituted by methyl. For instance, quinone and hydroquinone dimethyl ether when melted together form an intesnsely red compound of composition QB, which exists also, to a small extent, in alcoholic solution. Hydrogen bonds are obviously not necessary for the formation of such compounds. -1most interesting phenomenon
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L. MICHAELIS
can be observed in the latter case: When the melted, red compound is cooled and crystallization sets in, the color fades and separate crystals of the colorless hydroquinone dimethyl ether and of the pale yellow quinone are formed. The crystal-lattice energy of each is greater than the affinity for the tIvo for the formation of the compound. The formation of the polymer and its complete dissociation according to the change of the solid and melted states is perfectly reversible, The analysis of the composition of those compounds in the dissolved state can be carried out by spectrophotometry, owing to the intense color of the compound. The concentration of the compound is assumed to be proportional to its
extinction coefficient a t a suitable nave length. Then, a variation of the concentration of any one component shoived that the extinction is proportional to the concentration of each component, and never to its square or t o its square root.. An example of such an experiment is shown in figure 11. It is thus shown that a molecular compound formed of two molecular species may be of quite different nature in the solid state from that formed in solution. I n the solid state the composition may vary according to the individual compound betiveen QB, QB,, and Q2B, but it cannot be varied for one given pair of Q and €3. S o solid compound is formed when the hydrogen of the phenolic hydroxyl group, or all hydrogen atoms of a polyphenol, are alkylated. Obviously hydrogen tionds are necessary. I n the dissolved state, however, only compounds
REVERSIBLE POLYMERIZ.%TIOS
17
of the composition QB exist, even if t,he composition of the crystals is QB2 or Q2R, and molecular compounds exist even n-ith alkylated phenols, in which case no hydrogen bonds can be formed. I n the melted state a molecular compound may he formed, which, on crystallization, entirely dissociates into its components. REFERENCES Papers froin the author's laboratory, arranged i n chronological order (11 XICHAELIS, L., A N D FETCHER, B. S.: J. Am. Chem. SOC.69, 2460 (1937).
(21 hlrcHaELrs. L . , AOEKER, G. F . , .AX R E B E RR. , K.: J. Am. Chem. Sac. 60,202 (1938); 60, 214 (1938). (31 MICHAELIS, L . , SCHL-BERT. XI. P.. A N D GR.ANICK, S.: J. Am. Chem. SOC. 61, 1987 11939). ( 4 J MICHAELIS. L.:. ~ S D GRANICK.5.: J. Am. Chem. SOC.66, 1747 (1943). ( 5 ) \IICH.AELIS, L . , A N D GRANICK, S.: J. Am. Chem. SOC. 66, 1023 (19441. (6) MICHAELIS, L., A N D GRANICK. 6 . : J. .4m. Chem. SOC.67, 1212 (1945). (7) ~ I I C H A E LL.: I S . Cold Spring Harbor Symposia Quant. Biol. 12, 131-42 (Y94i). (8) MICHAELIS, L.. A Y D GR.ASICK,S.:J. Am. Chem. Sac. 70, 624 (1918).
General references
w.
(9) CORRIS..\I. L..A N D H.ARKIN's, D.: J. A m Chem. sot. 60, 679-83 (1947). (10) HOLMES. W. C.: Tnd. Eng. Chem. 16, 35 (1924). (111 KELLEY. E. G., ASD MILLER.E. G . , JR.: J. B i o l . Chem. 110, 113, 119 (1935). (12) LISON,L.: Histochimie animale. Gauthier, Paris (19361. (13) LISOS. L.: Arch. biol. 46, 599-606 (1935). (14) h f E R R I L L , R. A S D SPENCER, R. J. Am. Chem. SOC. 70, 3683-9 (1948). (15) RABIBOWITSCH, E., A N D EPSTEIX,L. F.: J. Am. Chem. SOC.63, 69-78 (1941). (16) SCHEIBE, G.: K o l l o i d - 2 . 82, 1-14 (1938). (17) SHEPPARD, s. E.: Rev. Modern Phys. 14, 303-40 (1942). (18) WIAME,J. 51.:J. .4m. Chem. Sac. 69, 3146 (194i).
c.,
w.:
