Principles of General Physiology

Solubility. — As to what happens in the actual process of solution, we are, as yet, very much in the dark. Why, for example, sodium salts are nearly all soluble in water, whereas certain corresponding potassium salts are insoluble, and why the nitrates of practically all metals are freely soluble, but only the chlorides of some of them, is not explained. The fact itself is of great importance in the production of osmotic pressure. When dissolved, the molecules of a substance are free to manifest the effects of the energy due to their movement. The process is, in fact, a " dispersion " of the same kind as that more or less visible and obvious in the case of colloidal solutions, differing only in the degree of subdivision.

The history of the various theories proposed is of much interest and may be read in the account given by Walden (1910). We note that there has been much argument between the adherents of physical and of chemical theories. The question has, from the first, been closely connected with that of the nature of chemical affinity, so that as molecular physics made further and further strides, attempts were made repeatedly at physical explanations of chemical affinity. In the case of solution, as we shall see presently, there is undoubted evidence of combination of some kind between solvent and solute, " hydration " or " solvation " ; but, since the chemical properties of a substance suffer little or no change in the process, it seems rather a matter of words whether we choose to consider the process as one of satisfaction of "residual affinities" or prefer to speak of attractive forces between molecules ; neither, in fact, goes far towards an explanation and the different modes of expression serve equally well at present and will probably appeal differently to investigators according to whether they are chiefly occupied with the physical or chemical aspects of the phenomena. In the distant future they will, no doubt, be reconciled ; although, presumably, it must be admitted that the explanation will most likely be in a better knowledge of the physics of the atom.

As dilute solutions are of frequent use in physiological work, and changes in their concentration require to be known, it may be useful to refer to the delicate method of measuring these changes by the principle of interference of light waves. A method has long been in use for many purposes, in which the refractive index of a liquid is determined directly, by the amount of deviation through a prism ; but the method by which changes in the refractive index are caused to produce interference bands is far more delicate. Suppose that we have a train of light waves, of a particular wave length, and that part of this passes through a column of water, on the one hand, and another part through a solution of a substance which slows the rate of transmission of light through it. The wave length will not be the same in the two beams, so that, if they are combined together, the direction of vibration, if coincident at one point, will be opposite at a certain number of waves distant, where there is half a wave length difference between them. When there is again a whole wave length difference, the directions are again coincident. The result is a series of alternate dark and light bands. This brief description is only intended to illustrate the principle on which the method is based. Details of the construction of the instrument will be found in Lowe's papers (1910 and 1912). It will be clear that the changes in concentration to be measured must affect one constituent of the solution only, unless those of other constituents are related to this in a known way. The method can also be used, as originally by Rayleigh, for the analysis of mixtures of gases, if the tension of one only varies independently. The instrument, as made by Zeiss, determines the concentration of solutions up to 8 per cent, sodium chloride with an error of 0'003 per cent, of the solute, or, with a longer chamber, solutions between 0 and 1 per cent, with an error of O0004 per cent, in the salt.

Hydration of Solute. — As just mentioned, there is, at all events in a large number of cases, combination of some kind or association between the molecules of the solvent and those of the solute. Leaving out for the present the hydration of ions, it must be admitted that the evidence for such hydration is mainly indirect, and, in fact, Nernst (1911, pp. 271 and 537) appears to regard the hypothesis as by no means proven. The meaning of the name "hydration" must be distinguished from that of hydrolytic dissociation. The former refers to the combination of the molecules or ions of the solute with the molecules of water as such. The latter, as already explained, is a decomposition of a salt into free acid and base by interaction with the hydrogen and hydroxyl ions of electrolytically dissociated water.

The solubility of gases in water is diminished, not only by electrolytes, but also by some non-electrolytes, and the most satisfactory way of accounting for the fact is that the solute has in some way taken up a number of the molecules of the water, leaving fewer to dissolve the gas. One molecule of saccharose, for example, takes up six molecules of water (Philip, 1907). Carl Miiller (1912, p. 502) finds that the diminution of solubility of a gas by a given solute is independent of the chemical nature of the gas. This can only be explained by an influence of the solute on the solvent, and most readily by the formation of " hydrates." This phenomenon of hydration may possibly play a part in the effect of neutral salts on the activity of an acid in the inversion of cane-sugar. It is clear that, if the neutral salt takes up a number of the molecules of the disposable water, the acid present will be in higher concentration in the remainder. It seems, however, doubtful whether this effect is capable of accounting for the whole of the apparent increase in the concentration of H' ions (see also page 195 above).

Considerable evidence has been brought by Jones (1907) and by Jones and Anderson (1909) in favour of the hydration of salts in solution. If this takes place, it is generally supposed to be an equilibrium of such a kind that the more water present, relatively to the solute, the more molecules of it are associated with each molecule of the latter. Now, the absorption of light by solutions of substances is, by Beer's law (see Chapter XIX.), proportional to the number of molecules through which the rays pass. Further, if water molecules are taken up, it is to be expected that the vibration period and other properties of the molecules of the solute will be found to be different according to the dilution. Fig. 67 shows four series of photographs of absorption spectra of solutions of

copper chloride in water. In A, the concentration increases from 0'562 molar to 4'5 molar, from above downwards, and the depth of the solution is varied inversely with the concentration, so that the same total amount of solute lies in the path of the light. It is seen that the more dilute the solution, the It •>> ultra-violet is absorbed. In B, we have a similar series with more dilute solutions. In C and D, the concentrations are chosen so as to compensate for increa>rd dissociation on dilution, so that the number of undissociated molecules in the path of the light should be constant. A similar effect is seen. There are two ways of accounting for the increase in absorption with concentration, when the number of molecules is kept constant. Aggregates may be formed and the absorbing power increased thereby ; or solvates may be formed, in proportion to dilution, and the absorbing power decreased with increase in number of molecules of water taken up. To decide between the two views, we can test the effect of rise of temperature, which breaks up aggregates. The effect is the same as that of increasing concentration ; hence it is to be concluded that the action of increased concentration on the absorption of light is not due to aggregation of solute, which would have the opposite effect. The concentration of water, in the experiments in question, was also varied by the addition of calcium chloride or alcohol, and the salts of several different metals were investigated, with results similar to those mentioned.

An important case for the physiologist is the state of amino-acids in water. Winkelblech (1901, p. 590) points out that taurine (amino-ethyl sulphonic acid) forms no salt with hydrochloric acid, and that it is usually supposed to form a ring compound, internal anhydride, or internal salt, in water. Might it not also be that the sulphonic acid group makes it too strong an acid, even when partially counteracted by the NH., ? In the case of the ordinary carboxylic aminoacids, even supposing that such internal salts are formed by combination of the NH., and COOH groups with one another, as salts of very weak acids and bases, they will be greatly dissociated hydrolytically in water, according to the laws given on page 198 above. In fact, as Winkelblech shows (1901, p. 592), glycine, according to the equation of Arrhenius, must be hydrolytically dissociated to the extent of 99*967 per cent. ; this proportion is present as hydrated glycine, the smaller remainder as internal salt together with a few ions. It is therefore present in solution practically entirely as —

The fact that taurine and the corresponding carboxylic acid, alanine, have the same very small electrical conductivity shows that electrolytic dissociation is extremely low ; one would expect that the presence of the strongly acid sulphonic acid group would give rise to considerably more H' ions than the carboxyl group. This is one of the numerous cases that show that the chemical properties of a particular group are not fixed, but depend on other constituents of the whole molecule.

The relation of lyophile colloids to the solvent has been treated of above (page 97), so that it is unnecessary to do more than remind the reader of the facts, in connection with the properties of water. In the previous chapter the relation of the dielectric constant to electrolytic dissociation has been discussed and the fact pointed out that water has a higher dielectric constant than any other solvent, with the exception of prussic acid and hydrogen peroxide. Even where electrolytic dissociation is produced by other solvents, the process appears to be a very complex one compared to the simple splitting of the majority of salts in water. Association of solvent and solute seems to occur to a large extent, as well as between the molecules of the solute itself. This latter fact reminds us of the state of affairs in electrolytically dissociated colloids in water, as described on page 160 above.

Although water does not chemically decompose salts dissolved in it, yet by causing their dissociation into ions, it enables all kinds of reactions to take place which do not occur between the solutes in their molecular state. It was shown by Yeley (1910, p. 49) that pure nitric acid does not react with calcium carbonate. The importance of ions in physiological processes has been abundantly illustrated in the previous chapter and need not be further insisted on here.

If now we look at a series of substances arranged in order of dielectric constants, heats of vaporisation and conductivity for heat, we notice that there is an unmistakable connection between these properties. It will also be found that these properties are related to the critical pressures and to both the constants of van der Waals. So that, after all, some of the wonderful properties of water are mutually dependent. The actual percentage composition of water, as formed by two volumes of hydrogen to one of oxygen, was proved by Cavendish (1781), although the true explanation of the results obtained was not known until the experiments of Lavoisier in 1783, as Cavendish held to the doctrine of phlogiston.

It is only of recent years, however, and owing greatly to the influence of Armstrong, that it has been realised that water cannot be correctly represented by the symbol H9O, with the molecular weight of only 18, or rather it is only under limited conditions that this can be done. In the first place, the freezing and boiling points are not at all where they would be expected to be in a simple compound containing three molecules only of gases with extremely low freezing and boiling points. In fact, comparing it with similar compounds, as Jacques Duclaux points out (1912), the freezing point should be about -150° and the boiling point —100°. It appears then that the molecular weight of water must be greater than 18; in other words, it must be a polymerised or associated liquid, in which a number of molecules are united together. Comparing formaldehyde, which is liquid at - 20°, with its polymer trioxymethylene, composed of three molecules of formaldehyde, we notice that the latter is solid even at 150° ; so that considerable changes of properties occur even when only three molecules are combined together, and although H2O ought to boil at - 100°, H6O3 might well boil at + 100°.

We must suppose that chemical combination takes place between the simple molecules when polymerisation takes place. Thus, although formaldehyde and glucose have the same percentage composition, no one would regard them as the same chemical substances. Also, at any given temperature, there is an equilibrium between the polymers of water, which are mutually convertible, so that the different chemical individuals are easily changed into one another, and the chemical change is by no means so marked as in the example given above.

We may now at once proceed to make use of the names proposed by Sutherland (1900). The substance composed of single molecules, which does not appear to exist as a liquid, is hydrol, that of two molecules is dihydrol, that of three molecules is trihydrol, and so on. So far the theory is simple, but already several of the peculiar properties of water can be explained by it. The degree of polymerisation, as a general rule, increases as the temperature falls, so that cold water is not the same liquid chemically as warm water and is less volatile; hence its vapour pressure falls more rapidly than that of a simple liquid would. This is a favourable circumstance in regard to the properties of water as a regulator of animal temperature, since the cooling produced by its evaporation is greater the higher the temperature is.

We saw that the specific heat of water is unusually high. Now when heat is applied to water, it has to do three things : a part serves to heat the complex molecules, another part to heat the simple molecules, and a third part to decompose a certain number of complex molecules into simple ones. The specific heat of water, furthermore, presents a minimum at about 30°. The two first-mentioned fractions of the heat probably increase regularly with the temperature, as is usual, but the third rapidly decreases, being proportional to the concentration of complex

molecules present, which diminishes considerably between 0° and 100° ; a minimum would therefore be expected. There are, however, certain properties left unexplained by the hypothesis in this simple form. Rontgen (1892), considering what might be the nature of the polymer formed at low temperatures, was struck with the idea that it ought to show itself when the whole of the water was transformed into the polymer. But when water is cooled it turns into ice. How then do the properties of ice coincide with the requirements of the case 1 Take the density ; ice is more bulky than water at 0°, so that if we assume that ice molecules exist in liquid water, we can explain the existence of a point of maximum density at 4°. Thus : the change of volume when water is warmed from 0° to 1° is the result of two opposite effects — dilatation of the simple molecules, according to rule, and contraction, due to change of ice into water. The latter process is preponderant at the lower temperatures, -but nearly absent at the higher, and a point will exist where the difference between the two is the least. It will probably occur to the reader that water, according to this view, is a colloidal solution of ice. We shall see presently that a third component has to be added, namely steam.

Since the presence of the large molecules of ice increases viscosity, we see why this property of water increases unusually rapidly when the temperature falls. The compressibility behaves similarly, on account of the effect of pressure in causing depolymerisation. This would of itself result in a diminution of volume and be added on to the compressibility of the pure hydrol. There still remain some questions unanswered. Although the compressibility of water is greater than that of hydrol, it is unusually small. Again, we have not yet an explanation for the high dielectric constant, nor why ice is lighter than water.

There is an interesting fact in connection with water which throws some light on all of these problems. Water of all known liquids (except fused metals) contains the largest number of molecules per unit volume. Thus, in gram-molecules per cubic centimetre : — This means that there is less space between the molecules of water than of other liquids. The low compressibility is doubtless explained by this. The dielectric constant also increases rapidly as the molecular condensation of a substance increases. Finally, it is to be supposed that the molecular forces, which permit the molecules of hydrol to press unusually closely together, disappear when the new group constituting ice is formed, so that the latter occupies the greater volume corresponding to that which might be called the normal volume of water. It is to be admitted, nevertheless, that the reason why water is such a closely packed liquid has not been explained.

As to the actual number of molecules existing in the various polymers, opinion is still divided. The balance of evidence appears to be that ice is trihydrol, steam is monohydrol, liquid water is mostly dihydrol with varying amounts of the other two polymers according to the temperature. A curious fact is that, according to Nernst and Levy (1909), there are still some polymerised molecules in water vapour, so that, if these are identical with ice, it seems that we must admit the presence of ice in steam !

There is also difference of opinion as to the relative number of molecules of ice present in liquid water at various temperatures. As J. Duclaux (1912) points out, it might be possible to attack the problem by the determination of the absorption of light of different wave lengths by water and by ice. It appears that ice is much bluer in colour (than water, which is stated to have, as dihydrol, a very pale green colour. The reader will probably have noticed that the ice of glaciers is of a deeper olue than that of the same depth of water.

It was incidentally mentioned above that it is necessary to introduce steam, as a third component, into the water system, so that water in its ordinary liquid state is a ternary mixture. This has been shown by Bousfield and Lowry (1910) by comparison of the properties of water with a series of aqueous solutions of which it may be regarded as the limit of dilution. The careful study of " solution volumes " of caustic soda at different concentrations and temperatures showed that, in addition to the abnormality of water near the freezing point, there is a second in the neighbourhood of 60° and that the factor responsible for this effect becomes more and more obvious as the boiling point is approached. The complete evidence

for the view that the phenomenon is due to the existence of a third compound, steam or monohydrol, is too long for the present work. One or two main facts should be given on account of their importance. The "Solution Volume" of a given solute is the increase in volume of the solvent when 1 g. of the solute is dissolved in 100 c.c. of the liquid. Thus, when -1 g. of sodium chloride is dissolved in 100 c.c. of water, the volume of the solution is 100'2. c.c., so that 0"2 c.c. is the solution volume of 1 g. of sodium chloride. It might be supposed that this would be the volume of the salt in the liquid state, but this cannot be so, since the volume changes with concentration. Moreover, sodium hydroxide has a negative solution volume at certain temperatures and concentrations, so that 140 g. of the solid can be added to a litre of water at 0° without increasing the volume at all, keeping the temperature at 0°, of course. It is evident that changes take place in the solvent itself.

The contraction produced on dissolving is greatest in presence of large excess of the solvent, just as the number of molecules of water in the hydra ted solute is greater the more dilute the solution. The most reasonable explanation of the contraction is, then, that the combined water has a greater density than normal water ; a view indeed supported by other evidence. Further, the degree of contraction with the same volume of solvent varies with the temperature, but in such a manner as to show a maximum at a particular temperature, which itself naturally varies with the degree of hydration -of the solute used. In most cases investigated by Bousfield and Lowry, the temperature at which this maximum occurs is about 60°. On passing from solutes with a small affinity for water to those with a strong one, the maximum is reached at lower and lower temperatures ; in the case of lithium chloride at 35°. The deviations thus have their origin at the higher temperatures and extend gradually downwards.

Now, in the case of the point of maximum density of water at 4°, we have seen that the most satisfactory explanation rests on the presence in liquid water of a polymer, identical with ice, which diminishes in concentration as the temperature rises. Similarly, to explain the changes in the volume of the water taken up in hydration of solutes, it is in accord with all facts to assume that, as the temperature rises, there is an increasing formation of a third component of low density, and a partial destruction of this when a hydrate-forming salt is added. It is natural to regard this third component as being identical with steam, that is, monohydrol, and, if this is so, the component intermediate between steam and ice must be dihydrol.

To sum up, we arrive at the conclusion that liquid water is a system of three components — ice, or trihydrol, which is present in greatest concentration at the freezing point; dihydrol, the main component at ordinary temperatures; and monohydrol, or steam, increasing ' as the temperature rises to the boiling point. It is to be remembered that, at any temperature, there will be a certain definite relative proportion of all three of these substances, although at the freezing point monohydrol is probably nearly absent, while trihydrol is nearly absent at the boiling point.

It is probable, as already remarked, that these three constituents must be looked upon as distinct chemical individuals, although easily converted into one another by small changes of conditions. Thus, regarding the quadrivalence of oxygen as an established fact, trihydrol may be represented : — and in monohydrol, H2O, two of the affinities of oxygen must mutually satisfy one another. Armstrong (1908) prefers the name "hydrone" instead of "hydrol" to express the simple molecule and dihydrone, etc. , for the polymers. The reason is that water belongs not to the class of alcohols, but rather to that of the ketones. Strictly speaking, this is no doubt correct, but, on the other hand, water may conveniently be regarded as the simplest of the alcohols, if we consider OH as the characteristic group of the class.

Armstrong assumes further that there is present in water an isomeric form of dihydrone, in which one of the molecules is resolved into H and OH, with increased chemical activity. Thus, dihydrone being and, in this latter compound, we may consistently use the termination — ol. The activity <>t •• Imlnmul" corresponds, on the "association" theory of chemical change, to the H> and Oil ions of water on the electrolytic dissociation theory. In the former view, which cannot be discussed further in this place, the electrical conductivity of concentrated solutions, say

of hydrochloric acid, is conditioned mainly by hydrolyxed solute, H2O , and in dilute •Cl solution by hydrolated solute, HClC ; so that, in strong solutions, it is chiefly the solute which is active, in \veak solutions, the solvent. It follows further that "hydration" may be of two types, " hydrolation " and " hydronation. " For more details the reader is referred to the paper qu"oted. With regard to the actual existence of these two isomeric forms of the associated molecules of water, it is clear that they can be represented by structural formulae ; but, as previously remarked, this does not in itself prove their existence. I cannot pretend to be able to give an opinion on the evidence for this, about which there is much contention. I would merely point out that the phenomena whose explanation requires their assumption can, apparently, be explained as satisfactorily on the electrolytic dissociation theory.

In any case, the arguments of Bousfield. and Lowry (1910, p. 18) are not affected, since, as they indicate, dihydrol, and perhaps trihydrol, would only have to be thought of as mixtures of hydrone and hydronol with a given average density, instead of simple substances. It is important to note that Philippe A. Guye (1910), approaching the problem from the chemical point of view, also comes to the same conclusion as Bousfield and Lowry do, with regard to the ternary nature of water.