Structure of a 1:1 complex between L-Asp-L-Phe and L-His-Gly.

Both molecules occur in slightly folded conformations, characterized by phi 2 = -93.7 degrees in L-His-Gly and an unusual phi 2 = 60.2 degrees in L-Asp-L-Phe. The peptide linkage of L-His-Gly displays a substantial deviation from planarity with omega 1 = -163.5 degrees. The crystal packing is arranged in thick hydrophilic layers separated by hydrophobic sheets composed of L-Phe aromatic side chains. There are numerous hydrogen bonds, including an extremely short contact [O...N = 2.532 (6) A] between the ionized L-Asp and L-His side chains.

Structure of L-phenylalanine L-phenylalaninium formate.

C9H11NO2.C9H12NO2+.CHO2-, M(r) = 376.41, monoclinic, P2(1), a = 11.507 (6), b = 5.638 (3), c = 14.610 (5) A, beta = 100.65 (4) degrees, V = 932 (1) A3, Z = 2, Dx = 1.342 g cm-3, lambda(Mo K alpha) = 0.7107 A, mu = 0.94 cm-1, F(000) = 400, T = 295 K, final R = 0.047 for 2693 observed reflections. The phenylalanine zwitterion and the phenylalanine cation form a Speakman-salt-type hydrogen bond [O ... O = 2.496 (3) A]. Aromatic side chains constitute a thick hydrophobic layer with edge-to-face interactions between the phenyl rings.

Hydrogen bond connectivity patterns and hydrophobic interactions in crystal structures of small, acyclic peptides.

Crystal structures of all available unblocked linear peptides with two to five residues were retrieved from the Cambridge Structural Database and their intermolecular contacts and packing modes studied using molecular graphics. This survey reveals that interactions between hydrophobic portions of the molecules are critically important in determining the overall features of their crystal packing patterns. Distinct hydrophobic columns or layers are observed in almost all crystal structures. Analyses of the relationships between these interactions and crystal growth properties of small peptides are given. It is suggested that needle growth is promoted by hydrophobic packing, usually along a short crystallographic axis (4.6-6.0 angstroms). Also contributing to these morphologic characteristics are entropic factors associated with hydrophobic aggregation as well as tightly bound water molecules on hydrophobic faces. The paper also provides a comprehensive overview of hydrogen bond patterns in acyclic peptide crystals. It is demonstrated that one of their primary roles is to provide a scaffolding within which hydrophobic groups can aggregate. Even though there is a high density of hydrogen bonds in the crystals, often with complex patterns and networks, certain motifs are found to recur in a number of structures indicating specific hydrogen bond preferences. Water, for example, is an integral part of the hydrogen bond networks in these crystals, usually acting as the primary donor for main-chain carboxylate groups in peptide hydrates.

Structures of N-acetylbenzamide, N-propionylbenzamide and N-butyrylbenzamide and analysis of imide hydrogen-bond patterns.

N-Acetylbenzamide, C9H9NO2 (I) Mr = 163.18, orthorhombic, Pbca, a = 8.990 (2), b = 9.208 (3), c = 19.619 (3) A, V = 1624 (1) A3, Z = 8, Dx = 1.335 (1) g cm-3, lambda(Mo K alpha) = 0.710569 A, mu = 0.89 cm-1, F(000) = 688, T = 295 K, R = 0.031 for 865 observed reflections. N-Propionylbenzamide, C10H11NO2 (II), Mr = 177.20, monoclinic, P2(1)/c, a = 10.485 (2), b = 23.236 (4), c = 8.132 (2) A, beta = 108.43 (2) degrees, V = 1880 (1) A3, Z = 8, Dx = 1.252 (1) g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.82 cm-1, F(000) = 752, T = 297 K, R = 0.044 for 1407 observed reflections. N-Butyrylbenzamide, C11H13NO2 (III), Mr = 191.23, monoclinic, P2(1)/n, a = 8.270 (4), b = 12.600 (3), c = 10.459 (3) A, beta = 108.16 (3) degrees, V = 1040 (1) A3, Z = 4, Dx = 1.221 (1) g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.79 cm-1, F(000) = 408, T = 298 K, R = 0.038 for 1060 observed reflections. Compound (I) crystallizes in the Z,Z(trans-trans) conformation in chains linked by N-H...O hydrogen bonds. (I): N...O = 2.910 (2) A, NH...O = 170 (3) degrees. Compounds (II) and (III) crystallize in the E,Z(cis-trans) conformation and are linked by N-H...O hydrogen bonds forming eight-membered ring dimers. (II): N...O = 3.019 (4) A, NH...O = 167 (3) degrees and N...O = 2.982 (4) A, NH...O = 170 (3) degrees; (III): N...O = 2.990 (2) A, NH...O = 165 (2) degrees.

Graph-set analysis of hydrogen-bond patterns in organic crystals.

A method is presented based on graph theory for categorizing hydrogen-bond motifs in such a way that complex hydrogen-bond patterns can be disentangled, or decoded, systematically and consistently. This method is based on viewing hydrogen-bond patterns topologically as if they were intertwined nets with molecules as the nodes and hydrogen bonds as the lines. Surprisingly, very few parameters are needed to define the hydrogen-bond motifs comprising these networks. The methods for making these assignments, and examples of their chemical utility are given.

X-ray crystal structure of the opioid ligand naltrexonazine.

The anti-anti isomer of naltrexonazine (1) was synthesized, and its configuration was confirmed by X-ray crystallography. The syn-anti isomer is readily converted to 1 under acidic conditions. The apparent equal receptor binding of 1 and syn-anti isomer indicates that isomerization of the azine moiety may take place under the conditions of biological evaluation. Two possible explanations for wash-resistant binding of 1 to opioid receptors are presented. The first possibility involves a noncovalent interaction of the ligand with the opioid receptor, and the second considers covalent binding by a receptor-based sulfhydryl group.