54 ADSORPTION AND SOME CONSTITUTIONAL AND STERIC PROPERTIES BY L. ZECHMEISTER discussed. Received 15th July 1949 The concept " anchoring group " is proposed and some pertinent experimental approaches are indicated. A report is submitted on the separation of cistrcrns stereo- isomers and the dependence of the adsorption affinity on molecular morphology is Although it is not assumed that a single correct picture can be given for the adsorption and geometrical orientation of organic molecules on a solid surface the following concept may serve as a basis of discussion. Two essential features can be postulated for the simple and stable fixation of an organic solute on an adsorbent first its molecules should fit into the cavities of a certain size located on the active surface; and second adequately oriented forces should be operative between the adsorbent and the adsorbed molecule.These two postulates are of course closely interrelated. Very little is known about the geometrical orientation of adsorbed mole- cules but one may speculate that the manner of orientation would influence among others the relative behaviour of closely related compounds. If the L. ZECHMEISTER 55 orientation be roughly parallel to the surface it could be perhaps expected that within a homologous series a maximum of the adsorption affinity would be reached at a certain chain length. On the other hand it may be considered that in the case of a roughly vertical orientation of the adsorbed molecules with reference to the surface a continuous increase or decrease in the adsorption affinities would be observed by passing stepwise from lower members of the series to some higher ones.Whatever the orientation may be in a given system it seems reasonable to assume that not each section of the adsorbed molecule will be equally responsible for the fixation process. On the contrary we propose that a decisive part will be played by certain atomic groups which are conveniently designated as “ anchoring groups.” This concept is similar to that in which it is presumed that the fixation of a drug to bacteria takes place by the intermediary of a haptene group (or groups). In favourable instances an anchoring group could be located experimentally by showing that a modi- fication of that particular section of the molecule causes an unusually sharp change in the adsorption affinity.Perhaps a single example will demonstrate the general lines along which we think that laboratory work may help in collecting material for a more satisfactory discussion of such problems. It was found that the introduction of a methyl group in the a-position to the sulphur atom of cc-terthienyl markedly increased the adsorption affinity; and that upon dimethylation this effect was about doubled. On the other hand Kofler reported that the adsorbability of some tocol derivatives decreased upon methylation near the phenolic OH group although this substitution had but little effect in a more remote position to the hydroxyl mentioned. In the case of thiophene rings the introduced methyl group seems to have been involved in the fixation process but the anchoring group of the tocol derivative was probably the phenolic hydroxyl whose function is sterically hindered by the presence of adjacent methyl groups.While manifold possibilities are open for experimentation in the direction just outlined our problem changes its character entirely when we pass from chemical to stereochemical considerations. Then in a way the situation appears to be simplified since in stereochemistry the dependence of the adsorption affinity on the overall shape of the molecules is to be considered and not the presence or absence of certain functional groups. The compounds which are suitable for such investigations should possess numerous stereo-isomeric forms whose respective morphological types should vary as widely as possible.This postulate is unequally fulfilled in various stereo-isomeric sets ; for example the epimerization of a sugar would not essentially alter the overall shape of its molecules. The conditions for studies of this kind are especially favourable in the field of the natural and synthetic polyenes which compounds possess a long conjugated carbon-carbon double-bond system in an open chain. Their structure is “ morphologically sensitive ’’ to spatial variations. Although the ordinary or all-tram form (Fig. I) which shows a rod-like general shape is not greatly modified by a single trans+& rotation which occurs near an end of the system it undergoes a radical change and is converted into a V-like pattern when such a spatial re-arrangement takes place at or near the centre (11).On the other hand in the course of continued tralzs+cis rotations after having passed through several bent forms a straightening-out takes place. Thus the molecules of the resulting poly-cis compound show a rod- like overall shape (111) which is morphologically similar to that of the all- a-carotene p-carotene y-carotene and lycopene can trans molecules (I). As is well known the respective all-trans forms of the polyene hydro- carbons (C ,H 5 CONSTITUTIONAL AND STERIC PROPERTIES 56 be easily converted into a mixture of stereo-isomers containing mainly compounds with mono-cis and di-cis configurations. Such a mixture is resolved chromatographically whereupon some insight into the respective configurations can be gained by means of appropriate spectroscopic methods.Whereas any manner of bending of an all-trans carotene molecule causes a displacement of the main extinction maxima towards shorter wavelengths in the visible spectral region the simultaneously occurring alteration in the adsorption affinity does not follow such a simple rule. It was found for each of the three carotenes for example that a stereo-isomer which very probably contains a single peripherally-located cis double bond is adsorbed above the corresponding all-tram compound in the Tswett column. In contrast those spatial forms of the carotenes which possess a centrally-located cis double bond (and in some instances another cis bond) show considerably weaker adsorbability than the all-trans isomer.Thus we have the following chromatographic sequence (Top) Peripheral mono-cis carotene } essentially straight types. All-trans carotene (Bottom) Central mono-cis carotene etc. essentially bent type. I. II. 111. Fig. I . Typical spatial forms of a long conjugated double bond system in an open chain I all-trans ; 11 central mono-cis; and 111 poly-cis (penta-cis). I t should be noted in this connection that the adsorption affinity of a monohydroxy-P-carotene viz. all-trans cryptoxanthin (C ,H 6.0H) undergoes the changes just described when stereo-isomerized in vitro ; hence in this instance the presence of a single hydroxyl group has no decisive influence on the relative adsorbabilities of the respective spatial forms.In contrast each cis isomer so far observed of the analogous dihydroxy compounds viz. zeaxanthin and lutein (H0.C 4oH 6,.0H) is located in chromatograms above the corresponding all-trans zone. Thus the outstanding features of this Irans+cis isomerization are weakening of the colour and an L. ZECHMEISTER 57 increase in the adsorption affinity. One could suppose that in these stereo- chemical sets both hydroxyl groups would participate in the anchoring process and that the decrease of the distance between them as caused by bending of the molecule would promote fixation. However it is also possible that such spatial forms of the dihydroxycarotenes do exist which show decreased adsorption affinities as compared with the all-trans form ; but for some reason they do not appear in appreciable quantities in the stereo- isomeric mixtures which can be obtained by current methods.Some representatives of a different type of stereo-isomeric hydrocarbons viz. poly-cis y-carotenes and poly-cis lycopenes which so far we were unable to prepare in the laboratory could be isolated from some plant materials. They contain four to seven of their double bonds in cis configura- tion. If we pass from an all-trans compound to either of its poly-cis forms then the remarkable weakening in the colour runs parallel with a substantial decrease in the adsorption affinity. A similar parallelism is also observed within the subclass of the poly-cis lycopenes whose chromatographic sequence and spectral sequence are identical.With reference to both of these physical characteristics the individual differences are much smaller within the class of the poly-cis isomers than between either poly-cis form and all-trans lycopene. Before closing these considerations we should stress that the described variations in the adsorption affinity which are a function of morphological changes are of the same order of magnitude as analogous effects caused by reasonably-chosen structural conversions. For example a solution containing several spatial forms of both a-carotene and p-carotene gave the following chromatographic sequence on calcium hydroxide when developed with petroleum ether (Top) Neo-P-carotene V Neo-a-carotene U All-trans p-carotene Neo-a-carotene V Neo-P-carotene B Neo-(3-carotene E Neo-a-carotene W Neo-P-carotene F All-trans a-carotene (Bottom) Neo-a-carotene B Evidently the weaker adsorption affinity of all-trans a-carotene (con- taining 10 conjugated double bonds) as compared with that of all-trans ?- carotene (11 such bonds) can be compensated and even overruled by a suitable adjustment of the molecular form.Furthermore an increase of the adsorption affinity several times stronger than that caused by the reaction a-carotene +p-carotene is obtained when we convert a poly-cis compound into the corresponding all-trans form. Finally the author wishes to express his appreciation to his colleagues (Mrs.) A. Chatterjee R. B. Escue F. Haxo R. M. Lemmon A.L. LeRosen W. H. McNeely J. H. Pinckard A. Polgh- A. Sandoval W. A. Schroeder J. W. Sease and B. Wille. California Institute of Technology Pasadena. 54 ADSORPTION AND SOME CONSTITUTIONAL AND STERIC PROPERTIES BY L. ZECHMEISTER Received 15th July 1949 The concept " anchoring group " is proposed and some pertinent experimental approaches are indicated. A report is submitted on the separation of cistrcrns stereo-isomers and the dependence of the adsorption affinity on molecular morphology is discussed. Although it is not assumed that a single correct picture can be given for the adsorption and geometrical orientation of organic molecules on a solid surface the following concept may serve as a basis of discussion. Two essential features can be postulated for the simple and stable fixation of an organic solute on an adsorbent first its molecules should fit into the cavities of a certain size located on the active surface; and second adequately oriented forces should be operative between the adsorbent and the adsorbed molecule.These two postulates are of course closely interrelated. Very little is known about the geometrical orientation of adsorbed mole-cules but one may speculate that the manner of orientation would influence, among others the relative behaviour of closely related compounds. If th L. ZECHMEISTER 55 orientation be roughly parallel to the surface it could be perhaps expected that within a homologous series a maximum of the adsorption affinity would be reached at a certain chain length.On the other hand it may be considered that in the case of a roughly vertical orientation of the adsorbed molecules with reference to the surface a continuous increase or decrease in the adsorption affinities would be observed by passing stepwise from lower members of the series to some higher ones. Whatever the orientation may be in a given system it seems reasonable to assume that not each section of the adsorbed molecule will be equally responsible for the fixation process. On the contrary we propose that a decisive part will be played by certain atomic groups which are conveniently designated as “ anchoring groups.” This concept is similar to that in which it is presumed that the fixation of a drug to bacteria takes place by the intermediary of a haptene group (or groups).In favourable instances an anchoring group could be located experimentally by showing that a modi-fication of that particular section of the molecule causes an unusually sharp change in the adsorption affinity. Perhaps a single example will demonstrate the general lines along which we think that laboratory work may help in collecting material for a more satisfactory discussion of such problems. It was found that the introduction of a methyl group in the a-position to the sulphur atom of cc-terthienyl markedly increased the adsorption affinity; and that upon dimethylation, this effect was about doubled. On the other hand Kofler reported that the adsorbability of some tocol derivatives decreased upon methylation near the phenolic OH group although this substitution had but little effect in a more remote position to the hydroxyl mentioned.In the case of thiophene rings the introduced methyl group seems to have been involved in the fixation process but the anchoring group of the tocol derivative was probably the phenolic hydroxyl whose function is sterically hindered by the presence of adjacent methyl groups. While manifold possibilities are open for experimentation in the direction just outlined our problem changes its character entirely when we pass from chemical to stereochemical considerations. Then in a way the situation appears to be simplified since in stereochemistry the dependence of the adsorption affinity on the overall shape of the molecules is to be considered and not the presence or absence of certain functional groups.The compounds which are suitable for such investigations should possess numerous stereo-isomeric forms whose respective morphological types should vary as widely as possible. This postulate is unequally fulfilled in various stereo-isomeric sets ; for example the epimerization of a sugar would not essentially alter the overall shape of its molecules. The conditions for studies of this kind are especially favourable in the field of the natural and synthetic polyenes which compounds possess a long, conjugated carbon-carbon double-bond system in an open chain. Their structure is “ morphologically sensitive ’’ to spatial variations. Although the ordinary or all-tram form (Fig. I) which shows a rod-like general shape is not greatly modified by a single trans+& rotation which occurs near an end of the system it undergoes a radical change and is converted into a V-like pattern when such a spatial re-arrangement takes place at or near the centre (11).On the other hand in the course of continued tralzs+cis rotations, after having passed through several bent forms a straightening-out takes place. Thus the molecules of the resulting poly-cis compound show a rod-like overall shape (111) which is morphologically similar to that of the all-trans molecules (I). As is well known the respective all-trans forms of the polyene hydro-carbons (C ,H 5 a-carotene p-carotene y-carotene and lycopene ca 56 CONSTITUTIONAL AND STERIC PROPERTIES be easily converted into a mixture of stereo-isomers containing mainly compounds with mono-cis and di-cis configurations.Such a mixture is resolved chromatographically whereupon some insight into the respective configurations can be gained by means of appropriate spectroscopic methods. Whereas any manner of bending of an all-trans carotene molecule causes a displacement of the main extinction maxima towards shorter wavelengths in the visible spectral region the simultaneously occurring alteration in the adsorption affinity does not follow such a simple rule. It was found for each of the three carotenes for example that a stereo-isomer which very probably contains a single peripherally-located cis double bond is adsorbed above the corresponding all-tram compound in the Tswett column. In contrast, those spatial forms of the carotenes which possess a centrally-located cis double bond (and in some instances another cis bond) show considerably weaker adsorbability than the all-trans isomer.Thus we have the following chromatographic sequence: (Top) Peripheral mono-cis carotene All-trans carotene (Bottom) Central mono-cis carotene etc. essentially bent type. } essentially straight types. I. II. 111. Fig. I . Typical spatial forms of a long conjugated double bond system in an open chain : I all-trans ; 11 central mono-cis; and 111 poly-cis (penta-cis). I t should be noted in this connection that the adsorption affinity of a monohydroxy-P-carotene viz. all-trans cryptoxanthin (C ,H 6.0H), undergoes the changes just described when stereo-isomerized in vitro ; hence, in this instance the presence of a single hydroxyl group has no decisive influence on the relative adsorbabilities of the respective spatial forms.In contrast each cis isomer so far observed of the analogous dihydroxy compounds viz. zeaxanthin and lutein (H0.C 4oH 6,.0H) is located in chromatograms above the corresponding all-trans zone. Thus the outstanding features of this Irans+cis isomerization are weakening of the colour and a L. ZECHMEISTER 57 increase in the adsorption affinity. One could suppose that in these stereo-chemical sets both hydroxyl groups would participate in the anchoring process and that the decrease of the distance between them as caused by bending of the molecule would promote fixation. However it is also possible that such spatial forms of the dihydroxycarotenes do exist which show decreased adsorption affinities as compared with the all-trans form ; but for some reason they do not appear in appreciable quantities in the stereo-isomeric mixtures which can be obtained by current methods.Some representatives of a different type of stereo-isomeric hydrocarbons, viz. poly-cis y-carotenes and poly-cis lycopenes which so far we were unable to prepare in the laboratory could be isolated from some plant materials. They contain four to seven of their double bonds in cis configura-tion. If we pass from an all-trans compound to either of its poly-cis forms, then the remarkable weakening in the colour runs parallel with a substantial decrease in the adsorption affinity. A similar parallelism is also observed within the subclass of the poly-cis lycopenes whose chromatographic sequence and spectral sequence are identical.With reference to both of these physical characteristics the individual differences are much smaller within the class of the poly-cis isomers than between either poly-cis form and all-trans lycopene. Before closing these considerations we should stress that the described variations in the adsorption affinity which are a function of morphological changes are of the same order of magnitude as analogous effects caused by reasonably-chosen structural conversions. For example a solution containing several spatial forms of both a-carotene and p-carotene gave the following chromatographic sequence on calcium hydroxide when developed with petroleum ether: (Top) Neo-P-carotene V Neo-a-carotene U All-trans p-carotene Neo-a-carotene V Neo-P-carotene B Neo-(3-carotene E Neo-a-carotene W Neo-P-carotene F All-trans a-carotene (Bottom) Neo-a-carotene B Evidently the weaker adsorption affinity of all-trans a-carotene (con-taining 10 conjugated double bonds) as compared with that of all-trans ?-carotene (11 such bonds) can be compensated and even overruled by a suitable adjustment of the molecular form. Furthermore an increase of the adsorption affinity several times stronger than that caused by the reaction a-carotene +p-carotene is obtained when we convert a poly-cis compound into the corresponding all-trans form. Finally the author wishes to express his appreciation to his colleagues, (Mrs.) A. Chatterjee R. B. Escue F. Haxo R. M. Lemmon A. L. LeRosen, W. H. McNeely J. H. Pinckard A. Polgh- A. Sandoval W. A. Schroeder, J. W. Sease and B. Wille. California Institute of Technology, Pasadena