Nov., 1946
ULTRAVIOLET ABSORPTION SPECTRA OF THIOURACILS
2137
Data obtained from oxidation of these esters in 0.376 N hydrochloric acid at 36' and also their with sodium periodate show that the maltose ester dissociation constants were determined. is glucopyranosido-4-glucopyranose-1-phosphate Maltose-1-phosphate and D-xylose-1-phosphate and that the xylose ester is D-xylopyranose-1-phos- are not converted t o polysaccharide by potato phate. Both esters probably exist in the a-form. phosphorylase. The rate constants for hydrolysis of these esters BERKELEY, CALIFORNIA RECEIVED JUNE 5, 1946
[CONTRIBUTION FROM THE WELLCOME
RESEARCH LABORATORIES]
The Ultraviolet Absorption Spectra of Thiouracils1 BY GERTRUDE B. ELION, WALTERS. IDEAND GEORGEH. HITCHINGS The ultraviolet absorption spectra of pyriniidines have received a good deal of attention in recent years. However, except for the recent paper of Miller, Roblin and Astwood2 on 2thiouracil and its oxidation product, no thiopyrimidine spectra have been reported in the literature. During the present investigation of the absorption spectra of the mono- and dimercaptoanalogs of uracil (2,4dihydroxypyrimidine) and thymine (2,4-dihydroxy-5-methylpyrimidine)it was found that 2-hydroxy--Linercaptopyrimidine (4-thiouracil) and 2-hydroxy-4-mercapto-Zmethylpyrimidine (4-thiathymine) possess absorption bands so far removed from the usual absorption range of pyrimidines as t o be unrecognizable as members of that group. It is interesting that the anomalous spectra of these +thioderivatives are paralleled by their lack of antithyroid activity. Thus, Astwood3 has reported that whereas 2-thiouracil and 2,4-dithiouracil have approximately the same antithyroid activity, 4thiouracil is practically inactive. Results and Discussion The ultraviolet absorption spectra of 2-thiouracil , 2,4-dithiouracil, 4-thiouracil, 2-thiot hymine, 2,4-dithiothymine and 4-thiothymine a t pH values of 1.0, 7.0 and 11.0 are reported here. A comparison of the spectra of these thiocompounds with the corresponding hydroxycompounds reveals soiiie expected as well as some unexpected differences. According to the data of Loofbourow, Stinison and Hart,4 uracil ;kt pH 7 shows an absorption maximum a t 25S0 A. with a mo:lecular extinction coeficient ( e ) of 10,600. As might be anticipated from the increased niass of sulftir, the spectrum of ?-thiouracil a t 1)H 7.0 (Fig. l ) shows ~i shift i i i the wave length of maximurn absorption to 2740 A., with a n E. value only slightly higher than for uracil. The replacement of both oxygens by sulfur, as in (1) Presented before the Division of Organic C.hetnistry a t the 109th meeting of the American Chemical Society, Atlantic City, S . J., April, 1946. (7) Miller, Koblin and Astwooil, THISJ U U R N A L , 67, 2201 (1'345). (3) Astwood, 13issell and Hughes, E i z d o c r i ~ i o l o g y37, , 456 (1945). (4) Loofbourow Stimson and Hart, Txrs J O U R X A I . , 65, 148 (10431.
2,4-dithiouracil (Fig. 2) results in a shift of the wave length of maximum absorption still further toward the visible range, and also the introduction of a second, weaker band a t 3600 8. The molecular extinction coefficient of this compound for the main band is much higher than for 2thiouracil. In contrast t o these two compounds,
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2500 2900 3.730 \yaw leligtti i l l A. Fig. l.-.kbsorption spectra of %thiouracil: __ at pH 1.0; - - - a t p H 7 . 0 ; - . - . - a t p H 11.0.
the spectrum of 4-thiouracil (Fig. 3) is quite unusual. The pyrimidine band has been shifted so far toward the visible that in the usual range of pyrimidine absorption (2GOO-2800 A.) there occurs a minimum rather than a maximum in the spectral distribution curve. The peak occurs a t
GERTRUDE B. ELION,WALTER S. IDEAND GEORGE H. HITCHINCS
2138
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2000 2500 2900 3300 3700 Wave length in A. Fig. 2 -Absorption spectra of 2,4-dithiouracil: - a t PH 1.0; - - - a t p H 7 0 ; - - - a t p H 1 1 0 .
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2500 2900 3300 Wave length in A. Fig. 4.-Absorption spectra of 2-thiothymine: - a t pH 1.0; - - - a t p H 7.0; a t pH 11.0.
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260U 2900 8300 3700 Wave length iii A. Fig. B.--Absorptioii spectra of 2,4-~lithiothymiiie:-- a t pH 1 . 0 ; - - - a t p H 7.0; a t p1-I 11.0.
the spectruni of t!l;;.-itce, as can be seen by a comparison of Figs. 4, .? and ti with the data for thymine repor$ed I>?- (stimson arid R e ~ t e r , ~ The absorption spectra of the three thiothv- . , , ,X = 2WO A , E = TSOO. It will be noted, mines show very tniich the sxme relationship to ’ 5 ) Stirnwn and Keuter, THISJ O U R W A I . , 67, 817 (1
