No abstract

The design, synthesis, and characterization of amino acid-based cyclic bisureas, a new class of macrocyclic peptides, are described. These cystine-based macrocycles are constructed by a single-step procedure involving condensation of 1,ω-alkane diisocyanate[(CH2) n (NCO)2; n = 4, 6, 12] with either the simple l-cystine dimethyl ester to provide simple cyclic bisureas of 16-, 18-, and 24-membered rings through 1 + 1 cyclization or with extended cystine bispeptides leading to a variety of cystine-based macrocyclic peptide bisureas. The potential of cyclic bisureas to serve as artificial receptors for 1,ω-alkane dicarboxylic acids has been demonstrated with 18- and 24-membered macrocycles which show specific binding with dianions of oxalic and succinic acid, respectively. Single-crystal X-ray studies have shown these cyclic bisureas to possess an inherent property of self-assembling into vertical stacks of tube-like structures. The hollow, open-ended tubes offer enormous scope as models for studying biological phenomena or for designing materials with novel electronic and optical properties.

A variety of 18-membered cyclodepsipeptides with alternating repeats of aromatic (phenyl or pyridyl) and Ser units in the ring have been synthesized and studied by X-ray crystallography for self-assembly patterns. Single-crystal structures of the macrocycles showed similar, relatively flat-ring structures. Those molecules containing one or two pyridine units showed self-assembly by stacking one over the other, thus creating tubular structures using aromatic π-π interactions between Ph/Pyr or Pyr/Pyr as the main organizing force. The cylindrical stacks are further stabilized by water molecules acting as bridges in intermolecular hydrogen bonding. In both the macrocycle 4b, a hybrid of benzene and pyridine units connected through ester and amide bonds, respectively, and the macrocycle 4d with two pyridine units, the molecules form parallel cylindrical stacks wherein the aromatic rings interdigitate from one column to a neighboring one with a ∼3.5-Å separation between the planes of the rings. Macrocycle 4a, with two phenyl rings, packs in a herringbone fashion and does not form any tubes. Macrocycle 4a does not exhibit any internal hydrogen bonds. Only 4d forms a tube with an inner space large enough to accommodate a water molecule.

The synthesis and single-crystal X-ray structures of hydrogen squarates of imidazole (1), histidine (2), and 2-aminopyridine (4) and squarates of histidine (3) and 4-aminopyridine (5) are reported. Both hydrogen squarate [HSQ] 1and squarate [SQ] 2ions participate in complementary hydrogen bonding [X-H‚‚‚O; X ) N, O, or C] networks. While the [HSQ] 1ion acts both as a donor and as an acceptor of hydrogen bonds in salts 1, 2, and 4 and creates head-to-tail infinite chains of anions in 1 and head-to-head ten-membered cyclic dimers in 4, the [SQ] 2ion participates as a powerful acceptor of as many as six hydrogen bonds in 3 and 5. In all cases, extensive hydrogen bonding and ionic interactions between the components lead to layered assemblies. In 1, the cross-linking of the [HSQ] 1chains by protonated imidazolium ions through N-H‚‚‚O bonds creates a two-dimensional ionic sheet which is further stabilized by the presence of C-H‚‚‚O bonds resulting from the participation of the imidazolium C-H groups. In 2 and 3, the layered structures are formed by cross-linking of the cationic self-assemblies (His-His infinite helices in 2 and His-His zigzag ribbons in 3) by [HSQ] 1and [SQ] 2-, respectively. A novel feature in 3 is the presence of two C-H‚‚‚O bonds between the more acidic CH group and the O1 in [SQ] 2-. In 4, the cyclic dimers of [HSQ] 1are interwoven into a two-dimensional sheet with a checker-board motif by the participation of 2-aminopyridinium cation in horizontal and vertical N-H‚‚‚O bonds. The two-dimensional layered assembly in 5 arises by extensive participation of water molecules in cross-linking of the alternating anion-cation conjugates both in horizontal and vertical directions. Irrespective of the presence of different types of hydrogen-bonding patterns in the structures of 1-5, the persistent formation of a two-dimensional layered assembly is significant and may be a characteristic of squaric acid salts.