Hydrogen-Bonded Thiol Undergoes Unconventional Excited-State Intramolecular Proton-Transfer Reactions.

The chapter on the thiol-related hydrogen bond (H-bond) and its excited-state intramolecular proton-transfer (ESIPT) reaction was recently opened where compound 4'-diethylamino-3-mercaptoflavone (3NTF) undergoes ESIPT in both cyclohexane solution and solid, giving a 710 nm tautomer emission with an anomalously large Stokes shift of 12,230 cm-1. Considering the thiol H-bond to be unconventional compared to the conventional Pauling-type -OH or -NH H-bond, it is thus essential and timely to probe its fundamental difference between their ESIPT. However, thiol-associated ESIPT tends to be nonemissive due to the dominant nπ* character of the tautomeric lowest excited state. Herein, based on the 3-mercaptoflavone scaffold and π-elongation concept, a new series of 4'-substituted-7-diethylamino-3-mercaptoflavones, NTFs, was designed and synthesized with varied H-bond strength and 690-720 nm tautomeric emission upon ultraviolet (UV) excitation in cyclohexane. The order of their H-bonding strength was experimentally determined to be N-NTF < O-NTF < H-NTF < F-NTF, while the rate of -SH ESIPT measured by fluorescence upconversion was F-NTF (398 fs)-1 < H-NTF (232 fs)-1 < O-NTF (123 fs)-1 < N-NTF (101 fs)-1 in toluene. Unexpectedly, the strongest H-bonded F-NTF gives the slowest ESIPT, which does not conform to the traditional ESIPT model. The results are rationalized by the trend of carbonyl oxygen basicity rather than -SH acidity. Namely, the thiol acidity relevant to the H-bond strength plays a minor role in the driving force of ESIPT. Instead, the proton-accepting strength governs ESIPT. That is to say, the noncanonical thiol H-bonding system undergoes an unconventional type of ESIPT.

Pentaleno[1,2-c]pyrroles: Tricyclic 5/5/5 Fused Rings.

A novel method for the preparation of tetrahydropentaleno[1,2-c]pyrroles (8) is described via the reaction of anilines with 1-en-4-yn-3-ols in the presence of Lewis acid. Oxidation of 8 with Br2 gave pentaleno[1,2-c]pyrroles (10), which is the first reported tricyclic 5/5/5 ring with a fully conjugated system. Structures of these obtained compounds were characterized by spectroscopic methods, and compounds 8a,b and 10c were further confirmed by X-ray crystallographic determination.

Highly Efficient Singlet Oxygen Generation by BODIPY-Ruthenium(II) Complexes for Promoting Neurite Outgrowth and Suppressing Tau Protein Aggregation.

Singlet oxygen (1O2) has been recently identified as a key molecule against toxic Aß aggregation, which is associated with the currently incurable Alzheimer's disease (AD). However, limited research has studied its efficiency against tau protein aggregation, the other major hallmark of AD. Herein, we designed and synthesized boron-dipyrromethene (BODIPY)-ruthenium conjugates and isolated three isomers. Under visible-light irradiation, the ε isomer can be photoactivated and efficiently generate singlet oxygen. Particularly, the complex demonstrated successful results in attenuating tauopathy─an appreciable decrease to 43 ± 2% at 100 nM. The photosensitizer was further found to remarkably promote neurite outgrowth and significantly increased the length and number of neurites in nerve cells. As a result of effective photoinduced singlet oxygen generation and proactive neurite outgrowth, the hybrid design has great potential for therapeutics for Alzheimer's disease.

Briavioids E-G, Newly Isolated Briarane-Diterpenoids from a Cultured Octocoral Briareum violaceum.

The chemical screening of a cultured soft coral, Briareum violaceum, led to the isolation of eight natural, briarane-related diterpenoids, including three unreported metabolites, briavioids E-G (1-3), and five known briaranes, briacavatolides B (4) and C (5), briaexcavatin L (6), briaexcavatolide U (7) and briarenol K (8). The structures of briaranes 1-8 were established using spectroscopic methods. The absolute configuration of briavioid A (9), obtained in a previous study, was reported for the first time in this study by a single-crystal X-ray diffraction analysis using a copper radiation source. The anti-inflammatory activity of briaranes 1 and 2 and briaranes 4-8 was evaluated by screening their inhibitory ability against the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells.

Altered coordination between frontal delta and parietal alpha networks underlies anhedonia and depressive rumination in major depressive disorder.

BACKGROUND: A hyperactive default mode network (DMN) has been observed in people with major depressive disorder (MDD), and weak DMN suppression has been linked to depressive symptoms. However, whether dysregulation of the DMN contributes to blunted positive emotional experience in people with MDD is unclear. METHODS: We recorded 128-channel electroencephalograms (EEGs) from 24 participants with MDD and 31 healthy controls in a resting state (RS) and an emotion-induction state (ES), in which participants engaged with emotionally positive pictures. We combined Granger causality analysis and data-driven decomposition to extract latent brain networks shared among states and groups, and we further evaluated their interactions across individuals. RESULTS: We extracted 2 subnetworks. Subnetwork 1 represented a delta (δ)-band (1~4 Hz) frontal network that was activated more in the ES than the RS (i.e., task-positive). Subnetwork 2 represented an alpha (α)-band (8~13 Hz) parietal network that was suppressed more in the ES than the RS (i.e., task-negative). These subnetworks were anticorrelated in both the healthy control and MDD groups, but with different sensitivities: for participants with MDD to achieve the same level of task-positive (subnetwork 1) activation as healthy controls, more suppression of task-negative (subnetwork 2) activation was necessary. Furthermore, the anticorrelation strength in participants with MDD correlated with the severity of 2 core MDD symptoms: anhedonia and rumination. LIMITATIONS: The sample size was small. CONCLUSION: Our findings revealed altered coordination between 2 functional networks in MDD and suggest that weak suppression of the task-negative α-band parietal network contributes to blunted positive emotional responses in adults with depression. The subnetworks identified here could be used for diagnosis or targeted for treatment in the future.

Porous Supramolecular Assembly of Pentiptycene-Containing Gold(I) Complexes: Persistent Excited-State Aurophilicity and Inclusion-Induced Emission Enhancement.

We report herein a porous supramolecular framework formed by a linear mononuclear Au(I) complex (1) via the tongue-and-groove-like joinery between the pentiptycene U-cavities (grooves) and the rod-shaped π-conjugated backbone and alkyl chains (tongues) with the assistance of C-H···π and aurophilic interactions. The framework contains distorted tetrahedral Au4 units, which undergo stepwise and persistent photoinduced Au(I)-Au(I) bond shortening (excited-state aurophilicity), leading to multicolored luminescence photochromism. The one-dimensional pore channels could accommodate different solvates and guests, and the guest inclusion-induced luminescence enhancement (up to 300%) and/or vapochromism are characterized. A correlation between the aurophilic bonding and the luminescence activity is uncovered by TDDFT calculations. Isostructural derivatives 2 and 3 corroborate both the robustness of the porous supramolecular assembly and the mechanisms of the stimulation-induced luminescence properties of 1. This work demonstrates the cooperation of aurophilicity and structural porosity and adaptability in achieving novel supramolecular photochemical properties.

Ten-year trends in depression care in Taiwan.

BACKGROUND/PURPOSE: The number of psychiatrists working in community clinics in Taiwan has increased dramatically in the recent decade. This study aimed to investigate the trend of prevalence and incidence of depressive disorders and assess the quality of depression care between 2007 and 2016 in Taiwan. METHODS: We used the claims database derived from Taiwan's National Health Insurance (NHI) program, in which approximately 23.0 million individuals were enrolled, translating to a coverage rate of 99%. Patients with depressive disorders were identified based on International Classification of Diseases codes. The process indicators of depression care quality included visit, duration, and dose adequacy. The outcome indicators included the rate of psychiatric hospitalisation, emergency visit, self-harm hospitalisation, and suicide. RESULTS: The prevalence of treated depressive disorders increased from 1.61% in 2007 to 1.92% in 2016, i.e., a 25% increase, whereas the incidence of first-ever or recurrent depressive disorder did not change significantly. The number of patients treated by psychiatrists and in community clinics also increased. The quality of depression care improved, the proportion of patients receiving minimum psychiatric clinic follow-up and adequate medication increased, and the rate of emergency visits, psychiatric hospitalisation, and self-harm hospitalisation declined. CONCLUSION: The community-based psychiatric services increased and the quality indicators of depression care in Taiwan improved during 2007-2016. The causality warrants further investigations.

Chapter Open for the Excited-State Intramolecular Thiol Proton Transfer in the Room-Temperature Solution.

We report here, for the first time, the experimental observation on the excited-state intramolecular proton transfer (ESIPT) reaction of the thiol proton in room-temperature solution. This phenomenon is demonstrated by a derivative of 3-thiolflavone (3TF), namely, 2-(4-(diethylamino)phenyl)-3-mercapto-4H-chromen-4-one (3NTF), which possesses an -S-H···O═ intramolecular H-bond (denoted by the dashed line) and has an S1 absorption at 383 nm. Upon photoexcitation, 3NTF exhibits a distinctly red emission maximized at 710 nm in cyclohexane with an anomalously large Stokes shift of 12 230 cm-1. Upon methylation on the thiol group, 3MeNTF, lacking the thiol proton, exhibits a normal Stokes-shifted emission at 472 nm. These, in combination with the computational approaches, lead to the conclusion of thiol-type ESIPT unambiguously. Further time-resolved study renders an unresolvable (<180 fs) ESIPT rate for 3NTF, followed by a tautomer emission lifetime of 120 ps. In sharp contrast to 3NTF, both 3TF and 3-mercapto-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (3FTF) are non-emissive. Detailed computational approaches indicate that all studied thiols undergo thermally favorable ESIPT. However, once forming the proton-transferred tautomer, the lone-pair electrons on the sulfur atom brings non-negligible nπ* contribution to the S1' state (prime indicates the proton-transferred tautomer), for which the relaxation is dominated by the non-radiative deactivation. For 3NTF, the extension of π-electron delocalization by the diethylamino electron-donating group endows the S1' state primarily in the ππ* configuration, exhibiting the prominent tautomer emission. The results open a new chapter in the field of ESIPT, covering the non-canonical sulfur intramolecular H-bond and its associated ESIPT at ambient temperature.

Complementarity of 2,6-Dimethanolpyridine and Di(ethylene glycol) in the Complexation of Na+ Ions: Attaching Multiple Copies of [2]Catenane Branches to Isophthalaldehyde-Containing Cores.

In this study we found that 2,6-dimethanolpyridine displays good complementarity toward di(ethylene glycol) for the complexation of Na+ ions, allowing us to use this recognition system for the efficient synthesis of hetero[2]catenanes; indeed, it allowed us to attach multiple copies of [2]catenanes to branched systems presenting multiple isophthalaldehyde units. When we attempted to form a catenane from a preformed macrocycle featuring only a single di(ethylene glycol) unit, reacting it with a di(ethylene glycol) derivative presenting two amino termini, isophthalaldehyde, and templating Na+ ions [i.e., with the aim of using di(ethylene glycol)·Na+·di(ethylene glycol) recognition to template the formation of the interlocked imino macrocycle], the yields of the hetero[2]catenane and homo[2]catenane, comprising two imino macrocyclic units, were both poor (14% and 7%, respectively). In contrast, when one or two 2,6-dimethanolpyridine units were present in the preformed macrocycles, their reactions with the same diamine, dialdehyde, and Na+ ions provided the hetero[2]catenanes with high selectivity and efficiency (44% and 64% yields, respectively), with minimal formation of the competing homo[2]catenane. The high complementary of the 2,6-dimethanolpyridine·Na+·di(ethylene glycol) ligand pair allowed us to synthesize [2]catenane dimers and trimers directly from corresponding isophthalaldehyde-presenting cores, with yields, after subsequent reduction and methylation, of 42% and 31%, respectively.

[B-Cl-B]+ Cations: Chloroborane Masked Chiral Borenium Ions.

A tricoordinate borenium ion has received considerable attention in recent years for its applications in Lewis acid catalysis. Over the years, asymmetric catalysis mediated by a chiral borenium ion has also been developed. To stabilize the electron-deficient boron atom, a series of chloroborane masked borenium ions featuring the symmetrical [B-Cl-B]+ linkage are prepared and utilized as the catalyst for the enantioselective Diels-Alder cycloaddition of cyclopentadiene and 2,2,2-trifluoroethyl acrylate. The presence of a Cp* ligand is critical in realizing the cyclic diboron compounds, and the stability of the resulting [B-Cl-B]+ cation is dependent on the steric bulkiness of the oxazolidinone moiety. The stereoselectivity of the Diels-Alder cycloaddition is controlled by the substituents of the chiral oxazolidinone ligand and could be further improved via the coordination of SnCl4 at the bridging chloride of the [B-Cl-B]+ cation.

Tuning the Circular Dichroism and Circular Polarized Luminescence Intensities of Chiral 2D Hybrid Organic-Inorganic Perovskites through Halogenation of the Organic Ions.

Through the incorporation of various halogen-substituted chiral organic cations, the effects of chiral molecules on the chiroptical properties of hybrid organic-inorganic perovskites (HOIPs) are investigated. Among them, the HOIP having a Cl-substituted chiral cation exhibits the highest circular dichroism (CD) and circular polarized luminescence (CPL) intensities, indicating the existence of the largest rotatory strength, whereas the F-substituted HIOP shows the weakest intensities. The observed modulation can be correlated to the varied magnetic transition dipole of HOIPs, which is sensitive to the d-spacing between inorganic layers and the halogen-halogen interaction between organic cations and the inorganic sheets. These counteracting effects meet the optimal CD and CPL intensity with chlorine substitution, rendering the rotatory strength of HOIPs arranged in the order of (ClMBA)2 PbI4 >(BrMBA)2 PbI4 >(IMBA)2 PbI4 >(MBA)2 PbI4 >(FMBA)2 PbI4 .

Alkyl Chain Length- and Polymorph-Dependent Photomechanochromic Fluorescence of Anthracene Photodimerization in Molecular Crystals: Role of the Lattice Stiffness.

Anthracene-pentiptycene hybrid systems 1-Cn, where n refers to the number of carbon atoms in the linear alkyl chain, crystallize in three different polymorphs, denoted Y (yellow), G (green), and B (blue) forms in terms of the fluorescence color. While all Y-form crystals show the same yellow-to-blue fluorescence color response to the photomechanical stress generated by the anthracene [4+4] photodimerization reaction, the four G forms exhibit distinct photomechanofluorochromism (PMFC): from green to blue for G-1-C4, to orange for G-1-C7, to red for G-1-C8, and to red then blue for G-1-C9, and the B forms show no photochromic activity. The intriguing RGB three-color PMFC and abnormal topochemical reactivity of G-1-C9 are attributed to inherent softness of the crystal lattice.

PSb+P Ligand: Platform for a Stibenium to Transition-Metal Interaction.

The coordination chemistry of cationic divalent pnictogen ligands, such as nitrenium and phosphenium, has been well-explored in recent years. However, corresponding studies of a heavier congener, stibenium ion, are rare. To better facilitate a Sb+-metal interaction, a tridentate P-Sb+-P ligand with two phosphine buttresses was designed and synthesized, and its coordination chemistry toward late transition metals was investigated. The stibenium ligand was delivered as an activated P(SbCl)P-AgOTf complex (2) that releases AgCl and the P-Sb+-P ligand upon the treatment with transition metals. Reacting 2 with Rh(I) and Ir(I) metals yielded the anticipated stibenium-transition-metal complexes [(Rh(COD)Cl)2(µ-PSb+P)] OTf ([3][OTf]) and [(Ir(COD)Cl)2(µ-PSb+P)] OTf ([4][OTf]). The M-Sb+-M bridging structure was confirmed by single-crystal X-ray crystallography, and the bonding situation was examined computationally. Theoretical studies revealed the presence of three-center delocalized M-Sb+-M bonding interactions in [3][OTf] and [4][OTf].

Steric Engineering of Cyclometalated Pt(II) Complexes toward High-Contrast Monomer-Excimer-Based Mechanochromic and Vapochromic Luminescence.

Ligands play a crucial role in the supramolecular photoluminescence properties of Pt(II) square-planar complexes. To improve the luminescence color responses of N∧C∧N cyclometalated Pt(II) complexes to external stimuli such as mechanical stress and chemical vapors, we have conducted a steric engineering of the previous systems 1a-1d [Inorg. Chem. 2017, 56, 4978-4989] by introducing two tert-butyl groups to the tridentate ligand to form complexes 2a-2c. Unlike the "too low" or "too high" steric hindrance of the NCNPt core in 1a-1d, the combined steric effects of the tert-butyl groups at one side and the pentiptycene group at the other side of the NCNPt core in 2b are "just right" for generating as-prepared powders with pure monomer (green) emission or pure excimer (red) emission, depending on the rate of precipitation from solutions. The synergistic steric effects are also beneficial to the solid-state luminescence quantum efficiency (30-36%). As a result of the differences in steric interactions and thus in the relative monomer vs excimer emission intensity, each complex of 2a-2c performs a two-step luminescence mechanochromism and vapochromism with different color patterns. This work provides an intriguing example of steric engineering of Pt(II) complexes toward highly emissive molecular solids with high-contrast mechanochromic and vapochromic luminescence.

N-Allylation versus C-allylation of intermediates from aza-Michael adducts of arylideneisoxazol-5-ones.

Reactions of arylidene-isoxazol-5-ones with intermediates from palladium-catalysed decarboxylation of allyl carbamates proceeded through aza-Michael addition and N-allylation to give the corresponding bis-adducts, ß-amido-N-allylated products, in good yields. In similar reactions with 4-vinyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, a cyclic allyl carbamate, C-allylation took place to yield a series of spiro[isoxazole-4,3'-quinolin]-5-ones in high yields. Regio-selective N- versus C-allylation is illustrated to occur in an inter- versus intra-molecular fashion. The structure and stereochemistry of these products are determined by NMR spectroscopy and further confirmed by X-ray crystallography. This work offers an excellent method for the preparation of various substituted isoxazol-5-ones.

Synthesis of 2-arylamino-3-cyanoquinolines via a cascade reaction through a nitrilium intermediate.

A new method for the preparation of 2-amino-3-cyanoquinolines from readily available aryldiazonium salts, 2-aminoarylketones, and malononitrile via a cascade reaction is reported. This one-pot approach involves the in situ generation of an N-arylnitrilium intermediate from the direct reaction of aryldiazonium salts and malononitrile, which undergoes intermolecular amination, Knoevenagel condensation, and then aromatization to yield the desired compound in moderate to good yields. This methodology features a quick assembly of C2 and C3 functionalized quinolines.

Aqueous Palladium-Catalyzed Direct Arylation Polymerization of 2-Bromothiophene Derivatives.

Aqueous palladium-catalyzed direct arylation polymerization (DArP) of 2-bromothiophene derivatives 6-(2-(2-bromothiophen-3-yl)ethoxy)hexyl trimethylammonium bromide (T1) and 4-(2-(2-bromothien-3-yl)ethoxy)butylsulfonate (T2) is achieved. The supporting ligand, triphenylphosphine-3,3',3''-trisulfonic acid trisodium salt (m-TPPTs), facilitates DArP of both derivatives; however, its separation from the polymers by dialysis is difficult due to its strong aggregation in water and N,N-dimethylacetamide (DMAc). This is supported by dynamic light scattering, gel permeation chromatography (GPC), and single-crystal X-ray crystallography. Pyrimidine-Pd(OAc)2 is utilized in the DArP of T1 to afford PT1 without ligand contamination. Density functional theory calculations to determine the coordinating capability of the carboxylate/pivalic acid/water to palladium indicate the viability of implementing DArP in water. Finally, polyelectrolyte molecular-weight overestimation by GPC in water is attributed to the polyelectrolyte effect. Aggregation of the conjugated polyelectrolytes leads to a contracted hydrodynamic volume, and the molecular weight and dispersity assessed by GPC in DMAc significantly deviate from the actual values. An objective approach to evaluate the molecular weight for conjugated polyelectrolytes requires further development.

N-Heterocyclic Carbene Copper(I) Rotaxanes Mediate Sequential Click Ligations with All Reagents Premixed.

We have prepared NHC-CuI complexes with a rotaxane structure and used them as sterically sensitive catalysts for one-pot sequential copper-catalyzed azide/alkyne cycloadditions in solutions containing all of the coupling partners premixed in unprotected form. Most notably, a photolabile and sterically encumbered complex first catalyzed the coupling of a less bulky azide/alkyne pair; after removing the protective macrocyclic component from the rotaxane structure, through irradiation with light, the exposed dumbbell-shaped NHC-CuI complex catalyzed the second click reaction of a bulkier azide/alkyne pair. Using this approach, we obtained predominantly, from a single sealed pot, a bis-triazole product (84 %) from a mixture of two sterically distinct azides and a diyne.

Multicomponent Self-Assembly of Metallo-Supramolecular Macrocycles and Cages through Dynamic Heteroleptic Terpyridine Complexation.

Spontaneous formation of the heteroleptic cadmium(II) bis(terpyridine) complex under ambient conditions can be achieved by a combination of 6,6''-di(2,6-dimethoxylphenyl)-substituted and unsubstituted terpyridine-based ligands. Building on this dynamic heteroleptic complexation, diverse metallo-supramolecular macrocycles and cages were readily assembled in quantitative yields from the predesigned multicomponent systems. The complementary ligation reinforced self-recognition to facilitate the shape-dependent self-sorting of a four-component dynamic library into two well-defined parallelograms. In addition, the subtle lability difference between homoleptic and heteroleptic complexes led to the site-selective CdII -ZnII transmetalation in the Sierpinski triangle. Facile construction of a dodecanuclear tetrahedral metallocage was also realized by using two self-recognizable tritopic building blocks. The photophysical study of the metallo-supramolecules assembled from the d10 metal ions revealed intense ligand-based photoluminescence in solution. The self-assembly strategy described here provides an efficient methodology for building pre-programmable, sophisticated supramolecular architectures furnished with photoactivity.

[2]Catenanes Displaying Switchable Gin-Trap-Like Motion.

Sodium ion-controlled switching from "folded" to "linear" states results in significant changes in the molecular shape of a [2]catenane, such that it mimics the operation of a gin trap, with a fluorescent alarm signal appearing when pyrene side arms were present on its two macrocyclic components.