A fluorenylidene-acridane that becomes dark in color upon grinding - ground state mechanochromism by conformational change.

We report mechanochromic color change controlled by conformational change (between folded and twisted conformers) of fluorenylidene-acridanes (FAs). FAs with four N-alkyl groups (methyl, ethyl, n-butyl and n-octyl) were synthesized via the Barton-Kellogg reaction of diazofluorene and electrophilic N-tert-butoxy carbonyl thioacridone, deprotection of the tert-butoxy carbonyl group gives fluorenylacridine, and alkylation on the nitrogen atom is done using alkyl tosylate or triflate. FAs were characterized by NMR, UV-vis absorption and photoluminescence spectroscopy, theoretical calculation, cyclic voltammetry, and powder and single-crystal X-ray analyses. The color and folded/twisted conformation of the FAs were changed by the choice of substituent on the nitrogen atom, physical state (solution or solid), and morphology (crystalline or amorphous). Grinding of N-methyl FA solids, using an agate mortar, caused the morphology to change from a crystalline to amorphous state, which induced a conformational change from the folded to the twisted conformer, and a mechanochromic color change from yellow to dark green. The reverse color change, along with a morphological and conformational change to the folded conformer, was performed by solvent vapor exposure (chloroform). The twisted and folded conformers showed ambipolar (hole/electron) and hole-only transport properties, respectively.

Behavior of intermolecular interactions in α-glycine under high pressure.

Pressure-response on the crystal structure of deuterated α-glycine was investigated at room temperature, using powder and single-crystal X-ray diffraction, and powder neutron diffraction measurements under high pressure. No phase change was observed up to 8.7 GPa, although anisotropy of the lattice compressibility was found. No significant changes in the compressibility and the intramolecular distance between non-deuterated α-glycine and deuterated α-glycine were observed. Neutron diffraction measurements indicated the distance of the intermolecular D⋯O bond along with the c-axis increased with compression up to 6.4 GPa. The distance of another D⋯O bond along with the a-axis decreased with increasing pressure and became the shortest intermolecular hydrogen bond above 3 GPa. In contrast, the lengths of the bifurcated N-D⋯O and C-D⋯O hydrogen bonds, which are formed between the layers of the α-glycine molecules along the b-axis, decreased significantly with increasing pressure. The decrease of the intermolecular distances resulted in the largest compressibility of the b-axis, compared to the other two axes. The Hirshfeld analysis suggested that the reduction of the void region size, rather than shrinkage of the strong N-D⋯O hydrogen bonds, occurred with compression.

Pressure-induced oligomerization of alanine at 25 °C.

Pressure-induced oligomerization was found from high-pressure experiments at 25 °C on alanine powder soaked in its saturated aqueous solution. The oligomerization to alanylalanine occurred at 5 GPa. The maximum yields of alanylalanine and trialanine were, respectively, 1.1 × 10(-3) and 1.3 × 10(-4) at 11 GPa.

Structure-activity relationships of IKM-159: Diverted synthesis and biological evaluation of a series of C5-oxy analogs.

Ligands for neuronal receptors are important for understanding the biological functions as well as for treatment of neuronal diseases associated with. Here, we report diverted synthesis and biological evaluation of four C-ring analogs of IKM-159, a subtype-selective inhibitor for (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA)-type ionotropic glutamate receptor. Starting from iodinated 7-oxanorbornene 7, those analogs 3-6 were successfully synthesized in 7.0-33% yields over 8-11 steps via a common intermediate 13. Intracerebroventricular injection of those analogs on mice showed that introduction of oxo group on the C-ring (analogs 4, 5) or cleavage of the C-ring (analog 6) caused significant loss of the activity, while the ether analog 3 still retain the suppressed motor activity, indicating the importance of the C-ring in the neuronal activity of IKM-159.

A novel role of group VIB calcium-independent phospholipase A2 (iPLA2gamma) in the inducible expression of group IIA secretory PLA2 in rat fibroblastic cells.

Group IIA secretory phospholipase A(2) (sPLA(2)-IIA) is a prototypic sPLA(2) enzyme that may play roles in modification of eicosanoid biosynthesis as well as antibacterial defense. In several cell types, inducible expression of sPLA(2) by pro-inflammatory stimuli is attenuated by group IVA cytosolic PLA(2) (cPLA(2)alpha) inhibitors such as arachidonyl trifluoromethyl ketone, leading to the proposal that prior activation of cPLA(2)alpha is required for de novo induction of sPLA(2). However, because of the broad specificity of several cPLA(2)alpha inhibitors used so far, a more comprehensive approach is needed to evaluate the relevance of this ambiguous pathway. Here, we provide evidence that the induction of sPLA(2)-IIA by pro-inflammatory stimuli requires group VIB calcium-independent PLA(2) (iPLA(2)gamma), rather than cPLA(2)alpha, in rat fibroblastic 3Y1 cells. Results with small interfering RNA unexpectedly showed that the cytokine induction of sPLA(2)-IIA in cPLA(2)alpha knockdown cells, in which cPLA(2)alpha protein was undetectable, was similar to that in replicate control cells. By contrast, knockdown of iPLA(2)gamma, another arachidonyl trifluoromethyl ketone-sensitive intracellular PLA(2), markedly reduced the cytokine-induced expression of sPLA(2)-IIA. Supporting this finding, the R-enantiomer of bromoenol lactone, an iPLA(2)gamma inhibitor, suppressed the cytokine-induced sPLA(2)-IIA expression, whereas (S)-bromoenol lactone, an iPLA(2)beta inhibitor, failed to do so. Moreover, lipopolysaccharide-stimulated sPLA(2)-IIA expression was also abolished by knockdown of iPLA(2)gamma. These findings open new insight into a novel regulatory role of iPLA(2)gamma in stimulus-coupled sPLA(2)-IIA expression.