Cocrystals of 6-methyl-2-thiouracil: presence of the acceptor-donor-acceptor/donor-acceptor-donor synthon

The results of seven cocrystallization experiments of the antithyroid drug 6-methyl-2-thiouracil (MTU), C5H6N2OS, with 2,4-diaminopyrimidine, 2,4,6-triaminopyrimidine and 6-amino-3H-isocytosine (viz. 2,6-diamino-3H-pyrimidin-4-one) are reported. MTU features an ADA (A = acceptor and D = donor) hydrogen-bonding site, while the three coformers show complementary DAD hydrogen-bonding sites and therefore should be capable of forming an ADA/DAD NH...O/NH...N/NH...S synthon with MTU. The experiments yielded one cocrystal and six cocrystal solvates, namely 6-methyl-2-thiouracil-2,4-diaminopyrimidine-1-methylpyrrolidin-2-one (1/1/2), C(5)H(6)N(2)OSC(4)H(6)N(4)2C(5)H(9)NO, (I), 6-methyl-2-thiouracil-2,4-diaminopyrimidine (1/1), C5H6N2OSC4H6N4, (II), 6-methyl-2-thiouracil-2,4-diaminopyrimidine-N,N-dimethylacetamide (2/1/2), 2C(5)H(6)N(2)OSC(4)H(6)N(4)2C(4)H(9)NO, (III), 6-methyl-2-thiouracil-2,4-diaminopyrimidine-N,N-dimethylformamide (2/1/2), C(5)H(6)N(2)OS0.5C(4)H(6)N(4)C(3)H(7)NO, (IV), 2,4,6-triaminopyrimidinium 6-methyl-2-thiouracilate-6-methyl-2-thiouracil-N,N-dimethylformamide (1/1/2), C(4)H(8)N(5)(+)C(5)H(5)N(2)OS(-)C(5)H(6)N(2)OS2C(3)H(7)NO, (V), 6-methyl-2-thiouracil-6-amino-3H-isocytosine-N,N-dimethylformamide (1/1/1), C5H6N2OSC4H6N4OC3H7NO, (VI), and 6-methyl-2-thiouracil-6-amino-3H-isocytosine-dimethyl sulfoxide (1/1/1), C5H6N2OSC4H6N4OC2H6OS, (VII). Whereas in cocrystal (I) an R-2(2)(8) interaction similar to the Watson-Crick adenine/uracil base pair is formed and a two-dimensional hydrogen-bonding network is observed, the cocrystals (II)-(VII) contain the triply hydrogen-bonded ADA/DAD NH...O/NH...N/NH...S synthon and show a one-dimensional hydrogen-bonding network. Although 2,4-diaminopyrimidine possesses only one DAD hydrogen-bonding site, it is, due to orientational disorder, triply connected to two MTU molecules in (III) and (IV).