Twist of CC Bond Plays a Crucial Role in the Quenching of AIE-Active Tetraphenylethene Derivatives in Solution

Aggregation-induced emission (AIE) has emerged as a new class of attractive photoluminescence behavior. Understanding the precise mechanism of the AIE phenomenon will lead to the rational molecular design of novel molecules with AIE properties (AIEgens). In this work, we selected disubstituted derivatives of tetraphenylethene (TPE), a well-known archetypal AIEgen, as the model compounds to elucidate the AIE mechanism. As the result of photochemical experiments and quantum chemical computations, π-bond twist (π twist), including <i>E</i>–<i>Z</i> isomerization (EZI), was found to be the major factor for quenching the photoexcited state of TPE derivatives in the solution state, differently from the well-accepted propeller-like rotation of the side phenyl groups in earlier research. In photochemical experiments, the prepared TPE derivatives exhibited EZI in the solution state upon photoirradiation, and a negative correlation was observed between this isomerization and the AIE phenomenon. The theoretical computations verified the crucial role of π twist triggered by photoirradiation in the solution state, rather than intramolecular rotation. In the crystal state, π twist was efficiently suppressed by the surrounding molecules. Our results will support the realization of novel smart AIEgens that can respond to various external stimuli

Transport of ¹²⁵I-thrombin across the BBB in normal mice.

<p>(A) Multiple time regression analyses of ¹²⁵I-thrombin and ¹²⁵I-albumin versus time after i.v. injection in normal mice. The unidirectional influx rate (K_in) of ¹²⁵I-thrombin was 0.0278 ± 0.0037 μL/g brain-min. The inset shows brain/serum ratios from 0 to 15 min. Each point represents data from one mouse. (B) Time courses of the brain/perfusate ratios of ¹²⁵I-thrombin (left panel) and ¹²⁵I-albumin (right panel), with or without an excess amount of unlabeled thrombin (50 μg/mL), obtained in normal mice by transcardiac brain perfusion. Data are means ± SEM (n = 3–4 mice per point).</p

Blood chemistry in ND- and HFD-fed mice.

<p>Blood chemistry in ND- and HFD-fed mice.</p

Prothrombin/thrombin levels in brain (A, C) and plasma (B, D) of mice fed ND or HFD for 2W or 8W.

<p>Measured using ELISA. Circles represent individual ND mice and triangles HFD mice. Dotted lines represent means and solid lines SEMs (n = 9–10). *p<0.05 vs ND-fed mice.</p

mRNA expression levels of proinflammatory cytokines in brain pericytes exposed to thrombin for 24 h.

<p>(A) interleukin-1β (IL-1β), (B) interleukin-6 (IL-6) and (C) tumor necrosis factor-α (TNF-α). Total mRNA of brain pericytes was used for quantitative real-time RT-PCR analysis. Data are mean ± SEM (n = 8). *p<0.05, ***p<0.001 vs vehicle-treated pericytes.</p

Western blot analysis of tight junction protein expression by rat brain microvascular endothelial cells (RBECs) in RBEC monolayers and RBEC/pericyte co-cultures.

<p>RBEC monolayers or RBEC/pericyte co-cultures were treated by addition of thrombin (3 U/mL) to abluminal chambers for 24 h. (A) Representative immunoblots of tight junction proteins (ZO-1, occludin and claudin-5). (B-D) Quantitative analysis of the immunoblots using densitometry. Data are mean ± SEM (n = 3) *p<0.05 vs. each vehicle-treated group.</p

Brain uptake of sodium fluorescein in mice fed ND or HFD for two (2W) or eight (8W) weeks.

<p>Mice were injected with 200 μL of physiological buffer containing Na-F (6 mg/mL) i.v. and killed 5, 10, 15 and 20 min later. Each point represents data from one mouse.</p

Obesity and glucose tolerance in ND- and HFD-fed mice.

<p>Obesity and glucose tolerance in ND- and HFD-fed mice.</p

Effects of thrombin on brain endothelial barrier function in the absence or presence of pericytes.

<p>Two types of blood–brain barrier models, rat brain microvascular endothelial cell (RBEC) monolayers and RBEC/pericyte co-cultures, were treated by thrombin (1 or 3 U/mL) addition to abluminal (A) or luminal (B) chambers for 24 h. Barrier function was then evaluated by Na-F permeability. (C) Effect of thrombin (3 U/mL) added to abluminal chambers on viability of RBECs in RBEC monolayers and RBEC/pericyte co-cultures. Cell viability of RBECs was assessed using a WST-8 assay. Data are expressed as a percentage of the vehicle control group. *p<0.05, **p<0.01, ***p<0.001 vs. vehicle, ##p<0.01, ###p<0.001 vs each thrombin-treated group (A: n = 14–16, B: n = 8–12, C: n = 7).</p

Immunofluorescence staining for tight junction proteins expressed by rat brain microvascular endothelial cells (RBECs) in RBEC monolayers and RBEC/pericyte co-cultures.

<p>RBEC monolayers and RBEC/pericyte co-cultures were treated by addition of thrombin (3 U/mL) to abluminal chambers for 24 h. RBECs on trans-well membranes were immunostained (green: ZO-1 (A), red: claudin-5 (B)). Arrows indicate areas of altered localization of ZO-1. Scale bar: 20 μm.</p