A method is presented that attempts to exploit all the a priori available information in order to locate a fragment of known geometry in the unit cell. Whereas the orientation of the search model is determined by a conventional but highly automated real-space Patterson rotation search, its position in the cell is found by maximizing the weighted sum of the cosines of a small number of strong translation-sensitive triplephase invariants, starting from random positions. A Patterson minimum function based on intermolecular vectors is calculated only for those solutions that do not give rise to intermolecular contacts shorter than a preset minimum. This procedure avoids the timeconsuming refinement in Patterson space and should be especially efficient for large structures. Finally, the best solutions are sorted according to a figure of merit based upon the agreement with the Patterson function, the triple-phase consistency and an R index involving Eobs and Ecalc. Tests with about 30 known structures, using search fragments taken from other published structures or from f0rce-field calculations, have indicated that this novel combination of Patterson and direct methods is reliable and widely applicable. A few selected examples demonstrate the power of the computer program PATSEE, which is compatible with SHELX84 and will be distributed together with it. PATSEE is valid and efficient for all space groups and imposes no limits on the number of atoms or data. The orientation search for a single fragment allows one additional degree of torsional freedom, and up to two fragments may be translated simultaneously.0108-7673/85/030262-07501.50

No abstract

The antifungal drug 5-fluorocytosine (4-amino-5-fluoro-1,2-dihydropyrimidin-2-one) was cocrystallized with five complementary compounds in order to better understand its drug-receptor interaction. The first two compounds, 2-aminopyrimidine (2-amino-1,3-diazine) and N-acetylcreatinine (N-acetyl-2-amino-1-methyl-5H-imidazol-4-one), exhibit donor-acceptor sites for R(2)(2)(8) heterodimer formation with 5-fluorocytosine. Such a heterodimer is observed in the cocrystal with 2-aminopyrimidine (I); in contrast, 5-fluorocytosine and N-acetylcreatinine [which forms homodimers in its crystal structure (II)] are connected only by a single hydrogen bond in (III). The other three compounds 6-aminouracil (6-amino-2,4-pyrimidinediol), 6-aminoisocytosine (2,6-diamino-3H-pyrimidin-4-one) and acyclovir [acycloguanosine or 2-amino-9-[(2-hydroxyethoxy)methyl]-1,9-dihydro-6H-purin-6-one] possess donor-donor-acceptor sites; therefore, they can interact with 5-fluorocytosine to form a heterodimer linked by three hydrogen bonds. In the cocrystals with 6-aminoisocytosine (Va)-(Vd), as well as in the cocrystal with the antiviral drug acyclovir (VII), the desired heterodimers are observed. However, they are not formed in the cocrystal with 6-aminouracil (IV), where the components are connected by two hydrogen bonds. In addition, a solvent-free structure of acyclovir (VI) was obtained. A comparison of the calculated energies released during dimer formation helped to rationalize the preference for hydrogen-bonding interactions in the various cocrystal structures.

The determination of physically meaningful thermal ellipsoids for hydrogen from X‐ray diffraction data was achieved in the X‐ray structure analysis of N, N′‐dimethylindigo (1) by synchrotron radiation. Owing to the steric interactions of the CH3 groups with the carbonyl O atoms, the molecule is slightly twisted. This explains the bathochromic absorption of 1 in comparison to that of indigo and was also predicted from calculations.

The molecular structure of ammonium deoxycytidylyl-(3'-5')-deoxyguanosine, crystallized from aqueous acetone near pH 4, was determined for X-ray diffraction data. The crystals were tetragonal, space group P43212 with a = b = 11.078 (1) A and c = 45.826 (4) A. The structure was solved by tangent expansion of phases based on a derived phosphorus position and refined to R = 0.060 by full matrix least squares. Molecules related by a 2-fold symmetry axis are connected by hydrogen bonds between the bases and form parallel right-handed duplexes. Pairs of cytosines share a proton at N(3) and are joined by three hydrogen bonds: N(4)-H...O(2)...H-N(4), and N(3)-H...N(3). Guanines are joined by two hydrogen bonds: N(2)-H...N(3) and N(3)...H-N(2). Base-stacking interactions within the duplex are weak with the cytosine and guanine ring planes inclined at 24 degrees to each other in each monomer. Despite the unusual arrangement of the molecules, the sugar phosphate backbone has the g-g- conformation normally associated with right-handed double helical structures. Conformational parameters of the nucleosides are also typical with both sugars C(2')-endo and glycosidic torsion angles 55 degrees for cytidine and 94 degrees for guanosine. The bonding geometry of the bases is influenced by hydrogen bonding and charge-transfer networks in the crystal lattice. The solvent molecules interact with the dimer in three fused circular hydrogen bonding domains with a single disordered ammonium cation per d(CpG) dimer. Parallels with the formation of self base pairs and their implications in molecular biology are discussed.