Microporous Molecular Materials from Dipeptides Containing Non-proteinogenic Residues.

Dipeptides with two hydrophobic side chains have proved to be an exceptional source of microporous organic materials, but since previous structures were limited to the incorporation of only proteinogenic residues, their full potential as adsorbents has remained unexplored. Single-crystal XRD data for ten new compounds with non-proteinogenic L-2-aminobutanoic acid and/or L-2-amino-pentanoic acid are presented. The gas-phase accessibility of their crystal pores, with cross-sections of 2.3 to 5.1 Å, was monitored by CO2 and CH4 adsorption isotherms. Included CO2 was also detected spectroscopically by 2D MAS NMR. An extensive conformational analysis reveals that the use of linear rather than branched side chains (such as L-valine and L-isoleucine) affords peptides with a greater degree of conformational freedom and yields more-flexible channel surfaces that may easily adapt to a series of potential guest molecules.

N-(L-2-aminopentanoyl)-L-phenylalanine dihydrate, a hydrophobic dipeptide with a nonproteinogenic residue.

The title dipeptide, better known as L-norvalyl-L-phenylalanine {systematic name: (S)-2-[(S)-2-aminopentanamido]-3-phenylpropanoic acid dihydrate}, C14H20N2O3·2H2O, has a nonproteinogenic N-terminal residue. In the solid state, it takes on a molecular conformation typical for one of the three classes of nanoporous dipeptides, but like two related compounds with a hydrophobic N-terminal residue and a C-terminal L-phenylalanine, it fails to form channels or pores. Instead, the crystal structure is divided into distinct hydrophobic and hydrophilic layers, the latter encompassing cocrystallized water molecules connecting the charged N- and C-terminal groups.

An unexpected tetragonal unit cell for N-(L-2-aminobutyryl)-L-serine.

The title dipeptide {systematic name: (S)-2-[(S)-2-azaniumylbutanamido]-3-hydroxypropanoate}, C7H14N2O4, was synthesized in the anticipation that it would form nanoporous crystals with hexagonal symmetry. Single-crystal X-ray diffraction analysis showed that it had instead adopted a unit cell in the space group I4, similar to L-alanyl-L-alanine [Fletterick, Tsai & Hughes (1970). J. Phys. Chem. 75, 918-922]. The resulting packing arrangement has a high density for a peptide (1.462 Mg m⁻³), which is rendered possible by extensive disorder over two positions for the ethyl side chain of the 2-aminobutyric acid fragment and over three positions for the serine side chain.

A water wire in L-prolyl-L-serine monohydrate.

Despite the extra functional group in the serine side chain, the crystal packing arrangement of the title compound {systematic name: (S)-3-hydroxy-2-[(S)-pyrrolidine-2-carboxamido]propanoic acid monohydrate}, C8H14N2O4·H2O, is essentially the same as observed for a series of L-Pro-L-Nop peptide hydrates, where Nop is a strictly nonpolar residue. This is rendered possible by a monoclinic P2(1) packing arrangement with Z' = 2 that deviates from orthorhombic P2(1)2(1)2(1) symmetry only for the seryl hydroxy groups, which form infinite O-H···O-H hydrogen-bonded chains along the 5.3 Ša axis. At the same time, cocrystallized water molecules form parallel water wires.

Synthesis and biological activity of novel MIF antagonists.

Two series of novel furan and indole compounds were synthesized and probed for inhibition of macrophage migration inhibitory factor (MIF) activity. Several compounds from both series inhibited the enzymatic activity of MIF at levels equal to or significantly better than ISO-1 (an early MIF inhibitor). The majority of the compounds that robustly inhibited the spontaneous secretion/release/recognition of MIF from freshly isolated human peripheral blood mononuclear cells were from the furan series (compounds 5, 9, 13, 15, and 16). In contrast, compounds that markedly inhibited the MIF-induced production of pro-inflammatory cytokines were predominantly from the indole series (compounds 26, 29, and 32).

1,1'-(4,4'-Bipiperidine-1,1'-di-yl)bis-(2,2,2-trifluoro-ethanone).

The title compound, C(14)H(18)F(6)N(2)O(2), has a central center of symmetry with both piperidine rings occurring in regular chair conformations. Even though the structure is fairly compact with no sizable voids, the shortest H⋯O distance is as long as 2.58 Å.

Novel derivatives of ISO-1 as potent inhibitors of MIF biological function.

A series of novel 1,2,4-oxadiazole, phthalimide, amide and other derivatives of ISO-1 were synthesized and probed for inhibition of macrophage migration inhibitory factor (MIF) activity. Several compounds inhibited MIF enzymatic activity at levels better than ISO-1. Of note, compounds 7, 22, 23, 24, 25 and 27 inhibited the spontaneous secretion/release/recognition of MIF from freshly isolated human peripheral blood mononuclear cells and, more importantly, inhibited the MIF-induced production of interleukin-6 (IL-6) and/or interleukin-1beta (IL-1beta) significantly better than ISO-1.

A supramolecular ladder-like network from trimesic acid and pyrazine N,N'-dioxide.

In the title complex, benzene-1,3,5-tricarboxylic acid-pyrazine N,N'-dioxide (2/1), C9H6O6·0.5C4H4N2O2, cocrystallized trimesic acid (TMA) and pyrazine N,N'-dioxide (PNO) molecules form strong O-H...O hydrogen bonds, but also important weak C-H...O and dipole-dipole intermolecular interactions, to generate a densely packed three-dimensional network. PNO molecules lie on inversion centres where they connect pairs of TMA sheets into distinct two-dimensional hydrogen-bonded layers perpendicular to the crystallographic ab diagonal.