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The IR-X-ray method for determining solution conformation was used to compare the conformations of the antitumor agents hydroxyurea and its 3-ethyl analog in solutions with conformations in the solid state. X-ray crystal analysis data for hydroxyurea obtained from the literature and the 3-ethyl analog data determined experimentally indicated that similar conformations are present in both compounds, with a car bony1 bond of mostly double bond character and intermolecular hydrogen bonding. The ethyl analog also possessed inter- and intramolecular hydrogen bonding involving the I- and 3-hydrogens and the carbonyl and hydroxyl oxygens. Comparison of IR spectra (1780-1550cm−1) of the solid state (mineral oil mulls) with solution spectra (taken in dry octanol, in octanol equilibrated with water and dried, and in wet and dry acetonitrile) indicated that only in dry acetonitrile did the spectrum of hydroxyurea resemble that of the solid. The ethyl analog possessed absorptions similar to the solid only in dry octanol, while spectra of all other solutions for both compounds had strong C=N character and diminished C=O double bond character. The IR solution data were rationalized according to the conformational system of hydroxyureas, which is represented by canonical forms possessing a C=O bond or strong C=N bonds and a CO bond. Hydroxyurea appears to prefer hydrogen bonding to a solvent (water) to bonding with itself, while the ethyl analog possesses internal hydrogen bonding which changes the conformational preferences and conformational equilibrium. In solvents where this inter- or intramolecular hydrogen bonding competes with bonding with the solvent, interconversion of conformers takes place; but this interconversion cannot occur when strong hydrogen bonding (with solvate formation) exists with water. Hydroxyurea tends to exhibit this behavior only when hydrogen bonding to solvent or water is not possible, allowing interconversion through a form possessing a C=O bond. Hydroxyurea and its 3-ethyl analog thus have different solution conformational equilibria depending on the solvent.

The X-ray crystal structure and absolute configuration of 3,6-epidithio-l-prolyl-l-proline-anhydride (C10H12O2N2S2) have been determined from single-crystal diffraction data. The compound crystallizes in the orthorhombic space groupP21212 with two molecules in a unit cell having dimensionsa=9.573(3),b=10.143(2), andc=5.761(2) Å. The structure was solved by the Patterson method and refined to a finalR value of 6.7%. The Bijvoet test, performed using CuKa radiation, shows that the configuration at both chiral carbons is (R) for the diastereoisomer having a specific rotation [a]D25=-54.5°. The torsion angle of the C-S-S-C fragment is -8.5°, giving helical sense (M), and the CD spectrum shows four major chiro-optical regions: 366(+), 336.5(-), 262(+), and 235(-) nm. The S-S bond length of 2.078 Å is intermediate between the values found in aliphatic disulfides having torsion angles near 0° and those with angles near 90°. The C-S distance of 1.899 Å is unusually long for disulfides, but seems to be characteristic of the small number of epidithiodiketopiperazines which have been studied.

The crystal structure of 2,4-dinitrophenyl phenylsulfide, C12H8N2O4S, has been determined by single crystal X-ray diffraction. The crystals are monoclinic, space groupP21/n, Z = 8, witha = 10.670(2),b = 8.381(4),c = 27.998(18) Å, and ß = 100.44(4) °. There are two crystallographically independent molecules per asymmetric unit. All intensity measurements were made at room temperature on an Enraf-Nonius CAD-4 automatic diffractometer using monochromatized MoKa radiation. The structure was solved by direct methods and refined to a finalR value of 0.032. The two independent molecules have nearly identical geometries, with the most notable difference being the torsion angles involving the sulfur atoms. Thepara-nitro groups are more nearly in the planes of the central phenyl rings than are theortho-nitro groups although there may be nonbonded attractions between the latter. The two phenyls of each molecule are nearly at right angles to each other, as necessitated by steric forces involvingortho hydrogens. The characteristic distortions of the central phenyl rings caused by differing substituent electronegativities and degrees of conjugation are noted. The13C-NMR spectrum of the compound was assigned by comparison of calculated with observed chemical shift data. Calculated chemical shifts were obtained by incrementation of the chemical shifts of diphenylsulfide with standard nitro group additivities which were adjusted for the sulfur-nitro group interaction. Where necessary, assignments were confirmed with selective excitation spin-coupled subspectra. Solution behavior of the molecule was determined from spin-lattice (T1) relaxation measurements which showed the unsubstituted ring to reorient anisotropically about the C(21)-C(24) bond axis while the substituted ring appears to be governed by the overall isotropic reorientation of the molecular framework, indicating that the sulfur-nitro group interaction restricts anisotropic reorientation about the C(11)-C(14) bond axis.