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any appreciable effect upon the indications of the instrument itself, I proceeded to the determination of the rotation power of the purest sample of quinine I could procure.
Bearing in mind the statement quoted above, that the concentration, solvent and chemical combination have their influence on the amount of rotation, I assumed specific conditions for the preparation of the experimental solutions which might be easily reproduced. They were, 1st, the use of the uncombined alkaloid quinine, carefully dried over strong sulphuric acid, 2d, ninety-seven per cent alcohol as the solvent and a concentration proportion of one gram of quinine, to fifty cubic centimeters of the alcoholic solution. For the sake of convenience the factors required in calculating the results are presented in the following tabular arrangement, viz:
v. volume of 97 p. c. alcoholic solution=50 cubic centimeters. p. weight of quinine
= 1 gram. a. length of tube
= 220 millimeters. a=angle of rotation observed with sodium flame. The formula being [w];="xx 100 and the average of 200 observations on four solutions at a temperature of 25° C. being a= -6.789o we have
- 6.789°x 50
x 100 or (1)
[a]j=-154:30° at 25° C. Raising the temperature to 47° C. the average of 200 observations on the same solutions as before was a=-6245° from which by the formula we bave
[a];=-141.93° at 47° C. The difference of temperature in (1) and (2) being 22° C. and the difference in the angle of rotation 12 37°, it follows that 1° C.= .562° difference.
That is, in a solution of quinine of the strength in question, viz: 20 milligrams of alkaloid to one cubic centimeter of alcoholic solution, for each additional degree Centigrade of temperature the angle of rotation diminishes '562 of a degree.
To ensure the correctness of these figures I caused my assistant, Mr. Ivan Sickels, also to carry out a series of experiments, and the result of seven hundred observations at temperatures between 25° C. and 47° C. gave figures which only differed in the third decimal place. We are therefore justified in employing the correction in question for values in the vicinity of 25°
C. which closely approaches the temperature at which such observations are made in actual practical work.
Effect of variation in the Proportion of Alcohol in the Solution.Hesse having shown that the strength of the alcobol has a marked effect on the rotating power of quinine, it followed that perhaps variation in the proportion of quinine dissolved in a given specimen of alcohol would also give variation in the power of rotation. In the examination of this problem I employed a freshly prepared solution of one gram of undried quinine in 50 cubic centimeters of 97 per cent alcohol. The average of 100 readings of the angle of rotation at various temperatures from 20° Č. to 50° C. was
(3) a=-6:05° at 35° C. To the above 50 cubic centimeter solution 50 cubic centimeters of the same alcohol were added, forming a solution of half the strength of the first solution. The average of 100 readings at similar temperatures was
(4) a=-2:61° at 36° C. To this second solution an equal volume of alcohol viz: 100 C. C. was added, giving a solution of one quarter the strength of the first. The average of 100 similar readings was
(5) a=-1.27° at 36° C.
In the third solution (5) p=l and v=200
-2.61°x100 For (4) [a];=-990971x100=-118-64° at 36° C.
:-1270x200 For (5) [a]j=-99061-X100=-115.45° at 36° C.
From the above experiments we perceive that the effect of a dilution by alcohol of the solution of quinine is to lessen its power of rotation, and as far as the experiments have been conducted this effect is more marked in the first degree of dilution than in the second.
The repetition of these experiments by Dr. R. A. Witthaus and Mr. Sickels, on a similar series of solutions made with the same alcohol and an undried specimen of quinine, gave the following averages of many hundred readings.
By the formula [a];=4*4x100 we have
-5.58° x 50 For (6) [a]j =-290 4 x 100=-126.82° at 29° C.
–2:40°x100 For (7) [a]j= 1900 x 100=-109.09o at 31° C.
-1.17° x 200 For (8) [a]j= 5900 x 100=-106.36° at 35° C.
Here again we perceive that the effect of dilution is to diminish the power of rotation, and to about the same extent and in the same manner as in my series of observations. It is therefore evident, that to secure results suitable for a reliable comparison, the solutions of quinine employed should be as nearly as possible of the same strength. The proportion which according to my experience it is most desirable to use is that of about one gram of alkaloid to 50 cubic centimeters of alcoholic solution. While a greater strength than this does not present any advantage in a tube of 220 millimeters, it is objectionable on account of its obstructing the passage of the light.
Quinine combined with Sulphuric Acid.—For the examination of this compound of quinine I prepared a solution which held the same proportion of quinine alkaloid in a given portion of the solution as that contained in the alcoholic solution. The solution was made by taking one gram of dried quinine, dropping it into about 30 cubic centimeters of distilled water, and adding just sufficient sulphuric acid to dissolve it.* The quantity was then made up to 50 centimeters with distilled water, and the 220 millimeter tube filled therewith.
At a temperature of 21° C. the average rotation as determined by 100 observations was – 11:36o. By the formula
αXυ, [a]] =1xp
20x100 we have
-11:36°x 50 (9) [a]j=-2000 1 x100=-258.18° at 21° C. The temperature of the solution in the tube was then raised by means of the water jacket, and the average of 100 observations was a=-10-73° at 43° C. By the formula
-10-73°x 50 (10) [a]j= 5900 1 x100=-243.86° at 43° C.
* This solution was employed as being similar to that used by physicians.
The difference in temperature being 22° C. and the difference in rotation 14:32°, we have
1° C.=.650° difference in rotation. That is, for every rise of one degree Centigrade the rotation diminishes 650 or nearly two thirds of a degree in a solution of sulphate of quinine in which there is one gram of alkaloid to 50 cubic centimeters of solution.
Effect of variation in the proportion of water.—A solution of sulphate in water prepared as before and containing one gram of alkaloid to 50 c. c. of solution when examined under a variety of temperatures, gave as the average result
(11) a=-11:03° at 311° C. This solution diluted by an addition of 50 c. c. of distilled water by which v was raised from 50 to 100 gave under a similar variety of temperatures the average
(12) a=-5:18' at 32° C. Adding 100 c. c. of water to the last solution and thereby raising v to 200, gave under the same conditions
(13) a=-2.58° at 31;° C. Arranging these in a tabular form we have
For (11) p=1..v=50..a=-11.03°
For (13) p=1..v=200.•a= -2:58°
. - 11.03°x 50 For (11) [a]j= 590090x100=-250-70° at 311° C.
._-5.18°x100 For (12) [a]j= 5900 x 100=-235.45° at 32° C.
–2:58° x 200
140x100=-234:54 at 31;° C.
hers, there id by its are: for one 154-30
Conclusions. (a.) In the case of the sulphate, as has also been shown by Hesse and others, there is a greatly increased rotation power imparted to the alkaloid by its union with the acid. In the experiments presented the values are: for one gram of alkaloid to 50 cubic centimeters of solution [a] j =-154:30° at 25° C. for the alkaloid : for one gram of alkaloid + sulphuric acid to 50 c. c. of solution in water [a];=-258.18° at 21° C., which applying the correction of 650° for each degree Centigrade becomes saj =-255.48° at 25° C. for the sulphate.
(6.) The aqueous solution of sulphate shows the same changes under the influence of temperature as the alcoholic solution of the alkaloid, the difference being in the case of the alkaloid 1° C.=-562 and in the case of the sulphate 1° C.=-650°.
(c.) In both the sulphate aqueous solution and the alcoholic alkaloid solution, there is the same diminished rotation under dilution, and this occurs chiefly in the first dilution as is shown in the following table: Alkaloid Solution.
Sulphate Solution. 1st dilution [alj=-137-50° at 35° C. salj=-250•70° at 311°C. 2d dilution li=-118.64° at 36° C. salj=-235.45° at 32° C. 3d dilution (alj=-115-45° at 36° C. [a];=~234:54° at 314° C.
In closing, I would direct attention to the results indicated in conclusion (a), wherein we find that the presence of sulphuric acid bas changed the rotation power of a given weight of the alkaloid from – 154:30° to - 255.48°; and I ask, is it not possible, day, even probable, that the physiological action of the drug may undergo a similar or perhaps even greater increase? In past times it was the custom to administer quinine in the form of a sulphuric acid solution, and the results were certain and prompt even with minute doses. In recent times, on the contrary, the fancy of patients demands that quinine should be given in pill or some allied form ; and though greatly increased doses are used, the practitioner finds it is less certain in its effect. The cause of the difference is doubtless the change in molecular arrangement that produces the marked difference in the action of the alkaloid and sulphate solutions on polarized light; and since the action of the sulphate solution is so much greater than that of the alkaloid solution it is evidently the proper form for the administration of Quinine as a Medicine.
College of the City of New York, Oct. 29, 1875.
ART. V.—Description of some remains of an Estinct Species of
Wolf and an Extinct Species of Deer from the Lead Region of the Upper Mississippi ; by J. A. ALLEN.
The remains described in the present paper form part of the collection of mammalian fossils made many years since by Professor J. D. Whitney, from the lead-crevices and superficial strata of the lead region of Wisconsin, Iowa, and Illinois, being a part of those enumerated by the late Professor Jeffries Wyman in Whitney's Geological Report of the Lead Region of the Upper Mississippi (pp. 421-423), published in 1862.
The collection originally contained, besides those now described, other remains belonging to the genera Mastodon, Megalonyx and Platygonus, and an extinct species of Bison. In