CHAPTER XII

THE VEGETABLE BASES

We come, now, to the consideration of the characteristically nitrogenous compounds of plants. None of the groups of compounds which have been considered thus far have, as a group, contained the element nitrogen. This element is present in the chlorophylls and in certain other pigments, but not as the characteristic constituent of the molecular structure of the group of compounds, nor do these compounds serve as the source of supply of nitrogen for the plant's needs.

The characteristic nitrogen-containing compounds may all be regarded as derived from ammonia, or ammonium hydroxide, by the replacement of one or more hydrogen atoms with organic radicals of varying type and complexity. If the group, or groups, which be considered as having replaced a hydrogen atom in ammonia, in such compounds, is an alkyl group, the compound is strongly basic in character and is known as an _amine_; whereas if the replacing group is an acid radical, the resulting compound may be neutral (known as _acid amides_), or weakly acid (known as _amino-acids_) in type. Compounds of the first type constitute the _vegetable bases_; while those of the second type are the _proteins_.

The vegetable bases may be divided into three groups. These are (_a_) the _plant amines_, which are simple open-chain amines; (_b_) the _alkaloids_, which are comparatively simple closed-ring amines, containing only one nitrogen atom in any single ring; and (_c_) the _purine bases_, which are complex compounds containing a nucleus with four carbon atoms and four nitrogen atoms arranged alternately to form a double-ring group.

THE PLANT AMINES

The simple amines bear the relation to ammonia, or ammonium hydroxide, represented by the following formulas, in which the R indicates any simple alkyl radical:

H R R R R R H H / / / / \ / \ / N-H N-H N-H N-R N-R N-H \ \ \ \ / \ / \ H H R R R OH H OH

Ammonia Primary Secondary Tertiary Quaternary Ammonium amine amine amine amine hydroxide

The simple amines which occur in animal tissues are known as "ptomaines" and "leucomaines." The ptomaines are all decomposition products resulting from the putrefactive decay of proteins caused by moulds or bacteria. Some of these are highly toxic, producing the so-called "ptomaine-poisoning"; while others are wholly innocuous. They are all simple amines. Putrescine, di-amino butane, NH_{2}·CH_{2}·CH_{2}·CH_{2}·CH_{2}·NH_{2}, and cadaverine, di-amino pentane, HN_{2}·(CH_{2})_{5}·NH_{2}, are common non-toxic ptomaines, resulting from the decay of meat. Neurine, trimethyl-ethylene ammonium hydroxide, (CH_{3})_{3}(C_{2}H_{3})·NOH, is a violently poisonous ptomaine produced in the decay of fish. Amines of similar structure to these are occasionally found in living animal tissues. Such compounds are known as _leucomaines_, to distinguish them from the _ptomaines_, which are found only in dead material.

Corresponding in structure and properties to these amines of animal origin, there is a series of basic substances, found in many plants, known as the _plant amines_. The following are common examples:

=Trimethyl amine=, (CH_{3})_{3}N, is a very volatile compound, found in the flowers of several species of the Rose family, the leaves of certain weeds, etc. When crushed, these tissues give off a very fetid odor, which is due to this amine.

=Choline=, =muscarine=, and =betaine= are plant amines which are closely related to each other and to neurine (the toxic ptomaine) in composition and structure, as shown in the following formulas:

CH_{2}CH_{2}OH CH_{2}CHO / / (CH_{3})_{3}N (CH_{3})_{3}N \ \ OH OH

Choline Muscarine

CH_{2}CO CH=CH_{2} / / / (CH_{3})_{3}N / (CH_{3})_{3}N \ / \ O OH

Betaine Neurine

Choline and betaine are non-toxic; while muscarine and neurine are violent poisons.

Choline and muscarine occur in certain toadstools. Betaine and choline often occur together in the germs of many plants. Betaine is found in the beet root and the tubers of Jerusalem artichoke. Choline occurs alone in the seeds and fruits of many plants, sometimes as the free amine, but more often as a constituent of lecithin (see page 141).

Phenyl derivatives of simple amines are sometimes found in --- / \ plants. _Hydroxyphenylethyl amine_, HO-C CH_{2}·CH_{2}·NH_{2}, \ / --- --- / \ found in _ergot_, and _hordeine_, HO-C CH_{2}·CH_{2}·N·(CH_{3})_{2}, \ / --- found in barley, are examples. The former has marked medicinal properties.

There is no known physiological use for these simple amines in plants. By some investigators, they are regarded as intermediate products in the synthesis or decomposition of proteins; but it would seem that if this were a normal procedure, these amines would occur in varying proportions in all plants, under different conditions of metabolism, instead of in practically constant proportions in only a few species, as they do.

ALKALOIDS

These are a group of strong vegetable bases whose nitrogen atom is a part of a closed-ring arrangement.

As a rule, alkaloids are colorless, crystalline solids, although a few are liquids at ordinary temperatures. They are generally insoluble in water, but easily soluble in organic solvents. Being strong bases, they readily form salts with acids, and these salts are usually readily soluble in water.

Alkaloids are usually odorless; although nicotine, coniine, and a few others, have strong, characteristic odors. Most of them have a bitter taste, and many of them have marked physiological effects upon animal organisms, so that they are extensively used as narcotics, stimulants, or for other medicinal purposes.

Most of the alkaloids contain asymmetric carbon atoms and are, therefore, optically active, usually levorotatory, although a few are dextrorotatory.

The alkaloids are precipitated out of their solutions by various solutions of chemical compounds, known as the "alkaloidal reagents": iodine dissolved in potassium iodide solution gives a chocolate-brown precipitate; tannic acid, phosphotungstic acid, phosphomolybdic acid, and mercuric iodide solutions give colorless, amorphous precipitates; while gold chloride and platinic chloride solutions give crystalline precipitates, many of which have sharp melting points and can be used for the identification of individual alkaloids. There are a great many specific color reactions for individual alkaloids, which are important to toxicologists and pharmacists, but which it would not be desirable to consider in detail here.

The alkaloids are conveniently divided into groups, according to the characteristic closed-ring arrangements which they contain. The several closed-ring arrangements which are found in common alkaloids, and upon which their grouping is based, may be illustrated by the following formulas:

H H H H{2}_C---CH_{2} | \ / | | C C | | // \ / \ H{2}_C CH_{2} HC CH H_{2}C CH_{2} \ / | | | | N HC CH H_{2}C CH_{2} | \\ / \ / H N N | Pyrrolidine, C_{4}H_{9}N Pyrridine, C_{5}H_{5}N H

Piperidine, C_{5}H_{11}N

H H \ / H C | / \ H_{2}C-----C-----CH_{2} H_{2}C CH_{2} | | | | | | NH CH_{2} HC CH | | | |\ /| or H_{2}C-----C-----CH_{2} | N | | | /|\ | H |/ H \| H_{2}C-----CH_{2} Tropane, C_{7}H_{13}N

H H H H | | | | C C C C // \ / \\ // \ / \\ HC C CH HC C CH | ¦ | | ¦ | HC C CH HC C N \\ / \ // \\ / \ // C N C C | | | H H H

Quinoline, C_{9}H_{8}N Isoquinoline, C_{9}H_{8}N

The common alkaloids are distributed in the several groups as follows:

Pyrridine--piperidine group; piperine, coniine, nicotine. Pyrrolidine group; hygrine and stachydrine. Tropane group; atropine, hyoscine, cocaine, lupinine. Quinoline group; quinine, cinchonine, strychnine, brucine. Isoquinoline group; papaverine, hydrastine, morphine, codeine, berberine.

The composition and properties of the individual alkaloids have been extensively studied, because of their medicinal uses. As they have no known metabolic use to the plants which elaborate them, it will not be worth while to consider all of these investigations in detail here. The following facts with reference to certain typical members of each group will serve to illustrate the general constitution and properties of the alkaloids.

=Piperine=, C_{17}H_{19}O_{3}, is found in black peppers. Its constitution is represented by the following formula, the group which is united to the piperidine ring, in this case, being piperic acid:

H_{2} ¦ C / \ H_{2}C CH_{2} | | /\ --O H_{2}C CH_{2} | | \ \ / | | CH_{2} N----OC·CH=CH·CH=CH--| | / \/ --O

=Coniine=, C_{8}H_{17}N, is found in the umbelliferous plant, _Conium maculatum_. Structurally, it is a propyl-piperidine, represented by the following formula:

H_{2} ¦ C / \ H_{2}C CH_{2} | | H_{2}C CH-C_{3}H_{7} \ / N | H

=Nicotine=, C_{10}H_{14}N_{2}, is the alkaloid of tobacco leaves. It is an extremely poisonous, oily liquid, with a strong odor and a burning taste. Its structural formula shows it to contain both a pyrridine ring and a pyrrolidine ring, linked together thus

H | C H_{2}C---CH_{2} / \\ | | HC C------HC CH_{2} ¦ | \ / HC CH N \ // | N CH_{3}

=Hygrine=, C_{7}H_{13}NO, from coca leaves, is an acetic acid salt of pyrrolidine, represented by the following formula:

H_{2}C---CH--OC·CH_{3} | | H_{2}C CH_{2} \ / N | CH_{3}

=Atropine= and =hyoscyamine=, C_{17}H_{23}NO_{3}, are optical isomers. Atropine is an extremely poisonous, white crystalline compound, which is obtained from deadly nightshade and henbane, and used in medicine, in minute doses, as an agent for reducing temperature in acute cases of fevers. Structurally, it is a tropic acid ester of tropane, represented by the following formula:

H_{2}C---CH--------CH_{2} C_{6}H_{5} | | | | | N-CH_{3} CHOOC---CH | | | | H_{2}C---CH--------CH_{2} CH_{2}OH

=Cocaine=, C_{17}H_{21}NO_{4}, is found in coca leaves. It is a white crystalline solid, which is largely used as a local anæsthetic for minor surgical operations. Its structural formula is

H_{2}C---CH--------HC-OOC·CH_{3} | | | | N-CH_{3} HC-OOC·C_{6}H_{5} | | | H_{2}C---CH---------CH_{2}

It is, therefore, a di-ester of acetic and benzoic acids with tropane.

=Cinchonine=, C_{19}H_{22}N_{2}O, and =quinine=, C_{20}H_{24}N_{2}O_{2}, are alkaloids found in cinchona bark. They are white crystalline solids, which are extensively used in medicine. They have been shown to contain a quinoline group combined with modified piperidine groups, as represented in the following formulas:

H | N C / \ / \ /|\ | | | / | \ | | | H_{2}C HCH CH-CH=CH_{2} \ / \ / | | | CH-CHOH-HC HCH CH_{2} \ | / N

Cinchonine

H | N C / \ / \ / \ | | | / \ | | | H_{2}C CH-CH=CH_{2} \ / \ / | | CH-CHOH-HC CH_{2} \ / N

Quinine

=Strychnine=, C_{21}H_{22}N_{2}O_{2}, =brucine=, C_{21}H_{20}(OCH_{3})N_{2}O_{2}, and =curarine= are three alkaloids which are present in the seeds of several species of _Strychnos_. They are all highly poisonous. Beyond the fact that when they are hydrolyzed they yield quinoline and indole, their composition is unknown.

=Morphine=, C_{17}H_{19}NO_{3}, is the chief alkaloid of opium, which is the dried juice of young pods of the poppy. Both the alcoholic solution of opium (known as "laudanum") and morphine itself are extensively used in medicine as narcotics to deaden pain. Morphine has an exceedingly complex structure, being a combination of an isoquinoline and a phenanthrene nucleus, which is probably correctly represented by the following formula:

H H_{2} | ¦ C C // \ / \ HOC C CH_{2} | ¦ | C C N-CH_{3} / \\/ \ / / C CH O | | \ HC CH_{2} \ / \ / HC C | ¦ H_{2}C CH \ / C ¦ H_{2}

=Codeine=, C_{17}H_{18}(OCH_{3})NO_{2}, which is also found in opium, is a methyl derivative of morphine. =Papaverine=, =laudanosine=, =narcotine=, and =narceine= are four other alkaloids found in opium. They each contain an isoquinoline nucleus, combined by one bond to a benzene ring, with one or more methyl groups and three or more methoxy (OCH_{3}) groups attached at various points around the three characteristic rings. The following formula for laudanosine will illustrate their structure:

/ \ / \ CH_{3}O | | | | | OCH_{3} CH_{3}O | N-CH_{3} / \ \ / \ / | |OCH_{3} | | | | \ / H_{2}C----------------CH

The above discussions of the composition of typical alkaloids clearly indicate the extreme complexity of their molecular structure. It is generally supposed that they are formed by the decomposition of proteins. But they are developed in only a few particular species of plants and are always present in these plants in fairly constant quantities. Hence, it appears that, in these species, the production of alkaloids is in some way definitely connected with protein metabolism; but it is certain that this is not a common relationship, as it is manifested by such a limited number of species of plants, and there is absolutely no knowledge as to its character and functions. Some authorities prefer to regard the alkaloids as waste-products of protein metabolism; but here, again, it is difficult to understand why such products should result in certain species of plants and not in others.

THE PURINE BASES

This is a group of compounds, widely distributed in both plant and animal tissues, all of which are derivatives of the compound known as _purine_, C_{5}H_{4}N_{4}. All of the naturally occurring compounds of this group may be regarded as derived from purine, either by the addition of oxygen atoms, or by the replacing of one or more of its hydrogen atoms with a methyl (CH_{3}) group or an amino (NH_{2}) group. The following structural formula represents the arrangement of the purine nucleus, the numbers being used to designate the nitrogen or carbon atoms to which the additional atoms, or groups, are attached in the more complex compounds of the group. In purine itself, the four hydrogen atoms are attached in the 2, 6, 7, and 8 positions.

6 1N==C-- | | 7 --2C 5C---N-- ¦ ¦ \ ¦ ¦ 8C-- ¦ ¦ // 3N--4C--9N

The double bonds, in each case except those between the 4 and 5 carbon atoms, are easily broken apart and readjusted, so that other atoms or groups can be attached to any atom in the nucleus except the 4 and 5 carbon atoms. In all of the statements with reference to the structure of the purine bases, the term "oxy" is used to mean an oxygen atom attached by both its bonds to one of the carbons in the nucleus, instead of its customary use to mean the monovalent OH group replacing a hydrogen, as in the case of all other nomenclature of organic compounds. With this understanding, reference to the numbered nucleus formula above will make plain the structure of all of the purine bases which are included in the following list:

Hypoxanthine, C_{5}H_{4}N_{4}O, = 6-monoxypurine.

Xanthine, C_{5}H_{4}N_{4}O_{2}, = 2,6-dioxypurine.

Uric acid, C_{5}H_{4}N_{4}O_{3}, = 2,6,8-trioxypurine.

Adenine, C_{5}H_{3}N_{4}NH_{2}, = 6-aminopurine.

Guanine, C_{5}H_{3}N_{4}ONH_{2}, = 2-amino-6-oxypurine.

Theobromine, C_{5}H_{2}N_{4}O_{2}(CH_{3})_{2} = 3,7-dimethyl-2,6-dioxypurine, or dimethyl xanthine.

Theophylline, C_{5}H_{2}N_{4}O_{2}(CH_{3})_{2} = 1,3-dimethyl-2,6-dioxypurine.

Caffeine, C_{5}HN_{4}O_{2}(CH_{3})_{3} = 1,3,7-trimethyl-2,6-dioxypurine, or trimethyl xanthine.

In order to make these structural relationships quite clear, the following formulas for uric acid and for caffeine are presented as typical examples:

H N--C=O CH_{3}--N--C=O | | | | O=C C--N-H O=C C--N-CH_{3} | ¦ \ | ¦ \ | ¦ C=O | ¦ CH | ¦ / | ¦ // HN--C--N-H CH_{3}-N--C--N

Uric acid Caffeine

=Uric acid= is found in the excrement of all animals; in the urine of mammals, and in the solid excrement of birds and reptiles. It is not known to occur in plants.

=Xanthine= and =hypoxanthine= occur in animal urine, and also in the tissues of both plants and animals.

=Adenine= and =guanine= are constituents of all nucleic acids (see below) and, hence, are found in all plant and animal tissues. Guanine is the chief constituent of the excrement of spiders, and is found also in Peruvian guano. It is also a constituent of the scales of fishes.

=Caffeine=, =theophylline=, and =theobromine= are not found in animal tissues, but are fairly widely distributed in plants. Caffeine and theobromine are the active constituents of tea leaves and coffee seeds and are found also in cacao beans and kola nuts. The use of these three compounds in the metabolism of the plants which elaborate them is wholly unknown. They are not so directly related to protein metabolism as are the other purine bases.

The purine bases, other than the three mentioned in the preceding paragraph, are undoubtedly intermediate products in protein metabolism. In animals, they constitute a large proportion of the waste-products from the use of proteins in the body. It is not clear that there are similar waste-products in plant metabolism, however. In both plants and animals, the purine bases which are a part of the nucleic acids undoubtedly play an important and essential part in growth, since they form the major proportion of the nucleus, from which all cell-division proceeds.

THE PYRIMIDINE BASES

These compounds do not occur free in plants; but since they are constituent groups in the plant nucleic acids (see below), a brief explanation of their composition is desirable. They are nitrogenous bases, similar to, but somewhat simpler than, the purine bases. Their general composition and structural relationships are illustrated by the following typical formulas:

N==C-H H-N--C=O | | | | H-C C-H O=C C-H ¦ ¦ | ¦ N--C-H H-N--C-H

Pyrimidine Uracil C_{4}H_{4}N_{2} C_{4}H_{4}N_{2}O_{2} 2,6-dioxypyrimidine

N==C-NH_{2} H-N--C=O | | | | O=C C-H O=C C-CH_{3} | ¦ | ¦ H-N--C-H H-N--C-H

Cytosine Thymine C_{4}H_{3}N_{2}ONH_{2} C_ {4}H_{3}N_{2}O_{2}CH_{3} 2,oxy-6-amino-pyrimidine 2,6-dioxy-5-methyl-pyrimidine

THE NUCLEIC ACIDS

The nuclei of cells are composed almost wholly of complex organic salts, in which _proteins_ constitute the basic part and _nucleic acids_ the acid part. These salts, or esters, are known under the general name "nucleoproteins." The composition of the proteins is discussed in detail in the following chapter, and it seems desirable to present a brief discussion of the constitution of the nucleic acids here; although they are essentially acids rather than vegetable bases.

The nucleic acids are complex compounds consisting of a carbohydrate, phosphoric acid, two purine bases, and two pyrimidine bases. So far as is known, all animal nucleic acids are identical and all plant nucleic acids are identical; but those of plant origin differ from those found in animal cells in the character of the carbohydrate and that of one of the pyrimidine bases which are present in the molecule, as shown in the following tabulation of their composition:

Animal nucleic acid Plant nucleic acid Phosphoric acid Phosphoric acid Hexose (levulose) Pentose (_d_-ribose) Guanine Guanine Adenine Adenine Cytosine Cytosine Thymine Uracil

The structure of the plant nucleic acid may be represented by the following formula:

OH | O=P--O--carbohydrate-guanine group | O | O=P--O--carbohydrate-adenine group | O | O=P--O--carbohydrate-uracil group | O | O=P--O--carbohydrate-cytosine group | OH

That this is probably a correct representation of the general arrangement in this compound, is indicated by the fact that by different methods of hydrolysis it is possible to split off either the purine and pyrimidine bases, leaving a carbohydrate ester of phosphoric acid; or the phosphoric acid, leaving carbohydrate combinations with the nitrogenous bases.

Nucleic acid, prepared from animal glands which contain large proportions of it, is a white powder, which is insoluble in water, but when moistened forms a slimy mass. It is almost insoluble in alcohol, but dissolves readily in alkaline solutions, forming a colloidal solution which readily gelatinizes (see chapter on Colloids). Solutions of nucleic acids are optically active, probably because of the carbohydrate constituents.

From their structure and properties, it is apparent that nucleic acids are on the border line between carbohydrates, plant amines, and proteins. They undoubtedly play an important part, both in cell-growth and in the synthesis of proteins from carbohydrates and ammonium compounds.

References

BARGER, GEO.--"The Simpler Natural Bases," 215 pages, _Monographs_ on Biochemistry, London, 1914.

FISCHER, E.--"Untersuchungen in der Puringruppe, 1882-1906," 608 pages, Berlin, 1907.

HENRY, T. A.--"The Plant Alkaloids," 466 pages, Philadelphia, 1913.

JONES, W.--"The Nucleic Acids," 118 pages, _Monographs_ on Biochemistry, London, 1914.

PICTET, A.--"La Constitution Chimique des Alcaloides Vegetaux," 421 pages, Paris, 1897 (2d ed.).

VAUGHAN, V. C. and NOVY, F. G.--"Ptomaines, Leucomaines, Toxins and Antitoxins," 604 pages, Philadelphia, 1896, (3d ed.).

WINTERSTEIN, E. and TRIER, G.--"Die Alkaloide," 340 pages, Berlin, 1910.