s-Indacene Revisited: Modular Synthesis and Modulation of Structures and Molecular Orbitals of Hexaaryl Derivatives.

Though s-indacene is an intriguing antiaromatic hydrocarbon of 12 π-electrons, it has been underrepresented due to the lack of efficient and versatile methods to prepare stable derivatives. Herein we report a concise and modular synthetic method for hexaaryl-s-indacene derivatives bearing electron-donating/-accepting groups at specific positions to furnish C2h-, D2h-, and C2v-symmetric substitution patterns. We also report the effects of substituents on their molecular structures, frontier molecular orbital (MO) levels, and magnetically induced ring current tropicities. Both theoretical calculations and X-ray structure analyses indicate that the derivatives of the C2h-substitution pattern adopt different C2h structures with significant bond length alternation depending on the electronic property of the substituents. Due to the nonuniform distribution of the frontier MOs, their energy levels are selectively modulated by the electron-donating substituents. This leads to the inversion of the HOMO and HOMO-1 sequences with respect to those of the intrinsic s-indacene as theoretically predicted and experimentally proven by the absorption spectra at visible and near-infrared regions. The NICS values and the 1H NMR chemical shifts of the s-indacene derivatives indicate their weak antiaromaticity. The different tropicities are explained by the modulation of the HOMO and HOMO-1 levels. In addition, for the hexaxylyl derivative, weak fluorescence from the S2 excited state was detected due to the large energy gap between the S1 and S2 states. Notably, an organic field-effect transistor (OFET) fabricated using the hexaxylyl derivative exhibited moderate hole carrier mobility, a result which opens the door for optoelectronic applications of s-indacene derivatives.

Fluoreno[2,3-b]fluorene vs Indeno[2,1-b]fluorene: Unusual Relationship between the Number of π Electrons and Excitation Energy in m-Quinodimethane-Type Singlet Diradicaloids.

The dimesityl derivative of fluoreno[2,3-b]fluorene (6b) was synthesized and its structure and physical properties were investigated to elucidate the effects of its enhanced open-shell character, which was predicted theoretically in comparison with the smaller congener indeno[2,1-b]fluorene (5b). All structural and physical properties are in accordance with the theoretical predictions and can be interpreted in terms of the resonance contributors. The most remarkable spectroscopic property is the larger excitation energy of 24π-electron hydrocarbon 6b than that of 20π-electron system 5b in their lowest energy absorption bands of electronic spectra, a trend that is contrary to the well-known feature for common, alternant aromatic hydrocarbons. The theoretical basis of this unusual behavior was elucidated on the basis of the balance between the diradical character, exchange integral, and HOMO-LUMO gap and was confirmed by a complete-active-space configuration-interaction method with two electrons in two orbitals for the corresponding parent hydrocarbons 5a and 6a.

G(olf) protein levels in rat striatum are increased by chronic antidepressant administration and decreased by olfactory bulbectomy.

There are many studies of the mechanisms of antidepressants; however, most of these studies were conducted on the hippocampus or frontal cortex. In the present study, we hypothesized that the nucleus accumbens and caudate/putamen might be major targets for antidepressant effects. Thus, we focused on G(olf) protein, a stimulant alpha-subunit of G protein that is coupled with the dopamine D1 receptor and specifically expressed in the striatum (nucleus accumbens, caudate/putamen and olfactory tubercle) in the rat brain. We examined the effects of chronic administration of imipramine, fluvoxamine, maprotiline and, as a negative control, cocaine on the level of G(olf) protein in the rat striatum. We also examined the effect of olfactory bulbectomy. Chronic imipramine treatment (10 mg/kg for 2 or 4 weeks) significantly increased the level of G(olf) in the striatum (by 17% or 18%, respectively), although this increase was not apparent after only 1 week of treatment. The time course of these changes corresponded well to that of the clinical efficacy of imipramine. Chronic fluvoxamine and maprotiline treatment (20 mg/kg for 2 weeks) also significantly increased the level of G(olf) (by 9% and 25%, respectively), but cocaine did not alter it significantly. Bulbectomy decreased the G(olf) protein level by 9%. The increases in G(olf) protein after chronic administration of these three different classes of antidepressants and the decrease after bulbectomy suggest that G(olf) protein may play an important role in the antidepressant effect.

Contrasting Fos expression induced by acute reboxetine and fluoxetine in the rat forebrain: neuroanatomical substrates for the antidepressant effect.

RATIONALE: Antidepressants preferentially facilitating serotonin seem to be particularly effective for treating the anxiety and aggressive component of the depressive syndrome, whereas those with a noradrenergic profile seem to be more effective in reducing psychomotor retardation, although their overall antidepressant effects are about the same. However, the mechanism of this difference remains unknown. OBJECTIVES: To investigate the neural substrate for the different therapeutic efficacies of fluoxetine and reboxetine, we examined the regional Fos immunoreactivity (Fos-ir) induced by the two agents. METHODS: Male Wistar rats (290-330 g) were given a subcutaneous injection of fluoxetine (5 or 10 mg/kg), reboxetine (5 or 10 mg/kg) or saline. Two hours later, rats were perfused through the ascending aorta and their brains were processed for Fos immunohistochemistry. Fos-ir was quantified by counting the number of Fos-ir-positive nuclei in six areas of the forebrain. RESULTS: The shell of the nucleus accumbens was the only region in which both fluoxetine and reboxetine equally increased Fos-ir expression. Fluoxetine particularly induced Fos-ir in the central nucleus of the amygdala. In contrast, reboxetine induced Fos-ir in the cingulate cortex area 3 and the lateral orbital cortex. CONCLUSIONS: These results suggest that the shell region may be one possible target for the antidepressant effects of fluoxetine and reboxetine. Furthermore, the difference in their clinical effects may depend on their different target sites of action.