10-Bromo-N,N-di-phenyl-anthracen-9-amine.

In the title compound, C26H18BrN, the dihedral angles between the anthracene ring system and the phenyl rings are 89.51 (14) and 74.03 (15)°. In the extended structure, a weak C-H⋯Br inter-action occurs, which generates [100] chains, but no significant π-π or C-H⋯π inter-actions are observed.

Design of an anticancer organoruthenium complex as the guest and polydiacetylene-coated fluorogenic nanocarrier as the host: engineering nanocarrier using ene-yne conjugation for sustained guest release, enhanced anticancer activity and reduced in vivo toxicity.

Despite the enormous efforts made over the past two decades to develop metallodrugs and nanocarriers for metallodrug delivery, there are still few precise strategies that aim to optimize the design of both metallodrugs and metallodrug carriers jointly in a concerted effort. In this work, three half-sandwich ruthenium(II) complexes with pyridylimidazo[1,5-a]pyridine ligand functionalized with polycyclic aromatic moiety (Ru(nap), Ru(ant), Ru(pyr)) are evaluated as possible anticancer candidates and polydiacetylene (PDA)-coated amino-functionalized mesoporous silica nanoparticles (AMSNs) are designed as a functional nanocarrier for drug delivery. Ru(pyr) exhibits higher cytotoxicity in HT-29 colorectal cancer cells compared to other complexes and cis-platin, but it does not exhibit better cellular uptake. Ru(pyr) is found to be preferentially accumulated in plasma, mitochondria, and ER-Golgi membrane. The complex induces cell cycle arrest in the G0/G1 phase, while higher concentrations cause programmed cell death via apoptosis. Ru(pyr) influences cancer cell adhesion property and acts as an antioxidant in HT-29 cells. In order to modulate the anticancer potency of Ru(pyr), AMSNs are used to encapsulate the complex, and then diacetylene self-assembly is allowed to deposit on the surface of the nanoparticles. Subsequently, the nanoparticles undergo topopolymerization, which results in π-conjugated PDA-Ru(pyr)@AMSNs. Owing to the ene-yne polymeric skeleton in the backbone, the non-fluorescent AMSNs turn into red-emissive particles, which are exploited for cell imaging applications. The release profile analysis reveals that such a π-conjugated polymer prevents the premature release of the complex from porous silica nanoparticles with the accelerated release of the complex in an acidic medium compared to physiological conditions. The PDA gatekeepers have also been proven to enhance the cellular internalization of Ru(pyr) with slow continuous release from the nanoformulation. Zebrafish embryo toxicity analysis suggests that the PDA-coated nanocarriers could be suitable candidates for in vivo investigations.

4-Amino-3,5-di-chloro-pyridinium 3-hy-droxy-pico-linate monohydrate.

In the title hydrated salt, C5H5Cl2N2 +·C6H4NO3 -·H2O, the pyridine N atom of the cation is protonated and an intra-molecular O-H⋯O hydrogen bond is observed in the anion, which generates an S(6) ring. The crystal packing features N-H⋯N, O-H⋯O, N-H⋯O, C-H⋯Cl and C-H⋯O hydrogen bonds, which generate a three-dimensional network.

(2,4-Di-chloro-benzyl-idene)[2-(1H-indol-3-yl)eth-yl]amine.

In the title compound, C17H14Cl2N2, the mol-ecule exists in an E configuration with respect to the C=N bond of the Schiff base fragment. The dihedral angle between the indole ring system and the benzene ring is 80.86 (12)°. In the crystal, mol-ecules are connected by N-H⋯N hydrogen bonds, generating a C(7) chain extending along the a-axis direction. No aromatic π-π stacking occurs but weak C-H⋯π inter-actions are observed.

N,N-Ru(II)-p-cymene-poly(N-vinylpyrrolidone) surface functionalized gold nanoparticles: from organoruthenium complex to nanomaterial for antiproliferative activity.

Organometallic Ru-arene complexes are promising as anticancer agents, but the lack of tumor uptake and poor solubility in the physiological medium impede their development. In order to deal with these challenges, we developed gold nanoparticles coated with Ru(arene)-functionalized PNVP-Py, where PNVP-Py is pyridine end-functionalized poly(N-vinylpyrrolidone). It is demonstrated that these particles exhibit higher anti-proliferative activity than the individual organometallic ruthenium(ii) complex of the type [Ru(η6-p-cymene)(NN)Cl]PF6, where NN is bis(4-methoxyphenylimino)acenaphthene, against colorectal adenocarcinoma cell lines. More specifically, a RuII(η6-p-cymene) complex containing a NN bidentate ligand has been prepared and characterized by spectral studies and X-ray crystallography. To tether the isolated complex onto the surface of the AuNPs, PNVP-Py, which contains a pyridine group at one end to coordinate to the Ru-complex and a suitable functional group at the other end to bind on the surface of the AuNPs, has been prepared and utilized to obtain the macromolecular complex [Ru(η6-p-cymene)(NN)(PNVP-Py)]Cl2. Next, stable Ru(p-cym)(NN)(PNVP-Py)@AuNPs were obtained via a ligand exchange reaction of citrate-stabilized AuNPs with a macromolecular complex by a direct 'grafting to' approach and characterized well. Despite the lower DNA cleavage activity, the nanoconjugate exhibits better cytotoxicity than the individual complex against HT-29 colorectal adenocarcinoma cells on account of its enhanced permeability across the cell membrane. The AO/EB staining assay revealed that the nanoconjugate is able to induce an apoptotic mode of cell death, which was further quantitatively evaluated by Annexin V-FITC/PI double assay. An immunofluorescence assay indicated the higher potency of the nanoconjugate to inhibit cyclin D1 gene expression that is required for cancer cell growth. To the best of our knowledge, this is the first report of the modification of an organometallic Ru(arene) complex into a Ru(arene)metallopolymer-gold nanoconjugate for the development of ruthenium-based nanomedicine for cancer treatment.

Internet of Things-Enabled Aggregation-Induced Emission Probe for Cu2+ Ions: Comprehensive Investigations and Three-Dimensional Printed Portable Device Design.

Herein, we have developed a novel aggregation-induced emission (AIE) probe and three-dimensional (3D) printed portable device for copper (Cu2+) sensing in an aqueous medium. A ubiquitous synthetic route has been employed to devise the anthracene-conjugated imidazo[1,5-a]pyridine (TL19) probe as a unique anchor for Cu2+ ions. The TL19 is meticulously characterized through pivotal spectroscopic techniques, and the satisfactory results were obtained. The solvatochromic analysis and density functional theory calculations cohesively reveal that the TL19 exhibits the intramolecular charge transfer transition upon photoexcitation. Intriguingly, the TL19 exhibits spherically shaped nanoaggregates and enhanced fluorescence in DMSO/water (10:90) mixtures. This fluorescent nanoaggregate instantaneously responded toward the detection of Cu2+ via a deaggregation mechanism. The detection limit is found to be 9 pM in an aqueous medium. Further, the detection of Cu2+ in the HeLa cells has also been achieved due to bright green fluorescence, photostability, and biocompatibility nature of TL19 aggregates. On the other hand, an internet of things (IoT)-embedded 3D printed portable device is constructed for the detection of Cu2+ ions in real water samples. The Cu2+ detection is achieved through an IoT device, and results were acknowledged through an android application in 3.32 s round-trip time. Thus, the IoT-enabled AIE probe could be a prospective device for Cu2+ detection in a constrained environment.

Ruthenium derivatives attenuate LPS-induced inflammatory responses and liver injury via suppressing NF-κB signaling and free radical production.

Ruthenium metal complex has been shown to exert several chemical and biological activities. A series of three novel ruthenium derivatives (TQ 1, 2 and 4) were synthesized to evaluate the anti-inflammatory and hepatoprotective activities in lipopolysaccharide (LPS)-stimulated macrophages and mice liver injury. The hydroxyl radical (OH°) scavenging activity of these derivatives has also been evaluated. The results revealed that among the tested compounds, TQ-4 effectively attenuated LPS-induced abnormal alteration in liver histoarchistructure via reducing alanine transaminase (ALT) and aspartate transaminase (AST). This compound exhibited significant inhibition of inflammatory cytokines (TNF-α and IL-1ß), inflammatory enzyme (iNOS), the component of NF-κB signaling pathway (p65) and JNK phosphorylation in LPS-induced mice liver tissues. In vitro results showed that TQ-4 had the best inhibition of NO production and iNOS expression in LPS-induced RAW 264.7 cells. Mechanistic approach indicated that TQ-4 inhibited the LPS-induced JNK phosphorylation, IκBα degradation, NF-κB p65 phosphorylation and its nuclear translocation, and hydroxyl radical (OH°) productions in RAW 264.7 cells. However, the compounds TQ-1 and 2 had no effects in this study. TQ-4 also inhibited LPS-induced OH° production. This study reveals the protective effect of TQ-4 against LPS-induced acute liver injury, inflammation, and oxidative reaction by destructing JNK/NF-κB signaling pathways. The result of this study may infer that TQ-4 might be a promising ruthenium metal derivative and/or therapeutic agent for treating liver injury.

Author Correction: A novel ruthenium (II)-derived organometallic compound, TQ-6, potently inhibits platelet aggregation: Ex vivo and in vivo studies.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

IoT-enabled dye-sensitized solar cells: an effective embedded tool for monitoring the outdoor device performance.

Herein, we have developed a tool for monitoring the outdoor performance of dye-sensitized solar cells. In this regard, a new dye consisting of an N-aryl-substituted imidazole with N-alkylated carbazole as the donor and cyanoacrylic acid as the acceptor has been designed. The overall power conversion efficiency of the designed dye reached ∼50%, with respect to that of the N719-based device (4%) under similar experimental conditions. Further, the device was interfaced with an IoT system, which measured the voltage and transmitted the device parameters to the user's mobile phone through a cloud channel. The developed IoT tool provides a resolution of 0.0315 mV and a round-trip delay time of <0.32 s for transmitting the information to the user's mobile phone.

Pyrene-Based Chemosensor for Picric Acid-Fundamentals to Smartphone Device Design.

Developing a fluorescent probe for the selective and sensitive detection of explosives is a topic of continuous research interest. Additionally, underlying the principles behind the detection mechanism is indeed providing substantial information about the design of an efficient fluorescence probe. In this context, a pyrene-tethered 1-(pyridin-2-yl)imidazo[1,5-a]pyridine-based fluorescent probe (TL18) was developed and employed as a fluorescent chemosensor for nitro explosives. The molecular structure of TL18 was well-characterized by NMR and EI-MS spectrometric techniques. UV-visible absorption, steady-state, and time-resolved fluorescence spectroscopic techniques have been employed to explicate the photophysical properties of TL18. The fluorescent nature of the TL18 probe was explored for detection of nitro explosives. Intriguingly, the TL18 probe was selectively responsive to picric acid over other explosives. The quantitative analysis of the fluorescence titration studies of TL18 with picric acid proved that the probe achieved a detection limit of 63 nM. Further, DFT and QTAIM studies were used to establish the nature of the sensing mechanism of TL18. The hydrogen-bonding interactions are the reason for the imperative sensing property of TL18 for picric acid. Thus, our experimental and theoretical studies provide an adequate and appropriate prerequisite for an efficient fluorescent probe. Furthermore, a smartphone-interfaced portable fluorimeter module is developed to facilitate sensitive and real-time sensing of picric acid. This portable module was capable of detecting picric acid down to 99 nM. Eventually, these studies will have a significant impact on development and application of a new class of chemosensors for detection of explosives.

Coordination geometry-induced optical imaging of l-cysteine in cancer cells using imidazopyridine-based copper(ii) complexes.

Overexpression of cysteine cathepsins proteases has been documented in a wide variety of cancers, and enhances the l-cysteine concentration in tumor cells. We report the synthesis and characterization of copper(ii) complexes [Cu(L1)2(H2O)](SO3CF3)2, 1, L1 = 3-phenyl-1-(pyridin-2-yl)imidazo[1,5-a]pyridine, [Cu(L2)2(SO3CF3)]SO3CF3, 2, L2 = 3-(4-methoxyphenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine, [Cu(L3)2(H2O)](SO3CF3)2, 3, L3 = 3-(3,4-dimethoxy-phenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine and [Cu(L4)2(H2O)](SO3CF3)2, 4, L4 = dimethyl-[4-(1-pyridin-2-yl-imidazo[1,5-a]pyridin-3-yl)phenyl]amine as 'turn-on' optical imaging probes for l-cysteine in cancer cells. The molecular structure of complexes adopted distorted trigonal pyramidal geometry (τ, 0.68-0.87). Cu-Npy bonds (1.964-1.989 Å) were shorter than Cu-Nimi bonds (2.024-2.074 Å) for all complexes. Geometrical distortion was strongly revealed in EPR spectra, showing g‖ (2.26-2.28) and A‖ values (139-163 × 10-4 cm-1) at 70 K. The d-d transitions appeared around 680-741 and 882-932 nm in HEPES, which supported the existence of five-coordinate geometry in solution. The Cu(ii)/Cu(i) redox potential of 1 (0.221 V vs. NHE) was almost identical to that of 2 and 3 but lower than that of 4 (0.525 V vs. NHE) in HEPES buffer. The complexes were almost non-emissive in nature, but became emissive by the interaction of l-cysteine in 100% HEPES at pH 7.34 via reduction of Cu(ii) to Cu(i). Among the probes, probe 2 showed selective and efficient turn-on fluorescence behavior towards l-cysteine over natural amino acids with a limit of detection of 9.9 × 10-8 M and binding constant of 2.3 × 105 M-1. The selectivity of 2 may have originated from a nearly perfect trigonal plane adopted around a copper(ii) center (∼120.70°), which required minimum structural change during the reduction of Cu(ii) to Cu(i) while imaging Cys. The other complexes, with their distorted trigonal planes, required more reorganizational energy, which resulted in poor selectivity. Probe 2 was employed for optical imaging of l-cysteine in HeLa cells and macrophages. It exhibited brighter fluorescent images by visualizing Cys at pH 7.34 and 37 °C. It showed relatively less toxicity for these cell lines as ascertained by the MTT assay.

Structure⁻Activity Relationship Study of Newly Synthesized Iridium-III Complexes as Potential Series for Treating Thrombotic Diseases.

Platelets play a major role in hemostatic events and are associated with various pathological events, such as arterial thrombosis and atherosclerosis. Iridium (Ir) compounds are potential alternatives to platinum compounds, since they exert promising anticancer effects without cellular toxicity. Our recent studies found that Ir compounds show potent antiplatelet properties. In this study, we evaluated the in vitro antiplatelet, in vivo antithrombotic and structure⁻activity relationship (SAR) of newly synthesized Ir complexes, Ir-1, Ir-2 and Ir-4, in agonists-induced human platelets. Among the tested compounds, Ir-1 was active in inhibiting platelet aggregation induced by collagen; however, Ir-2 and Ir-4 had no effects even at their maximum concentrations of 50 µM against collagen and 500 µM against U46619-induced aggregation. Similarly, Ir-1 was potently inhibiting of adenosine triphosphate (ATP) release, calcium mobilization ([Ca2+]i) and P-selectin expression induced by collagen-induced without cytotoxicity. Likewise, Ir-1 expressively suppressed collagen-induced Akt, PKC, p38MAPKs and JNK phosphorylation. Interestingly, Ir-2 and Ir-4 had no effect on platelet function analyzer (PFA-100) collagen-adenosine diphosphate (C-ADP) and collagen-epinephrine (C-EPI) induced closure times in mice, but Ir-1 caused a significant increase when using C-ADP stimulation. Other in vivo studies revealed that Ir-1 significantly prolonged the platelet plug formation, increased tail bleeding times and reduced the mortality of adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism in mice. Ir-1 has no substitution on its phenyl group, a water molecule (like cisplatin) can replace its chloride ion and, hence, the rate of hydrolysis might be tuned by the substituent on the ligand system. These features might have played a role for the observed effects of Ir-1. These results indicate that Ir-1 may be a lead compound to design new antiplatelet drugs for the treatment of thromboembolic diseases.

Ir-6: A Novel Iridium (III) Organometallic Derivative for Inhibition of Human Platelet Activation.

Platelet activation has been reported to play a major role in arterial thrombosis, cancer metastasis, and progression. Recently, we developed a novel Ir(III)-based compound, [Ir(Cp∗)1-(2-pyridyl)-3-(4-dimethylaminophenyl)imidazo[1,5-a]pyridine Cl]BF4 or Ir-6 and assessed its effectiveness as an antiplatelet drug. Ir-6 exhibited higher potency against human platelet aggregation stimulated by collagen. Ir-6 also inhibited ATP-release, intracellular Ca2+ mobilization, P-selectin expression, and the phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), v-Akt murine thymoma viral oncogene (Akt)/protein kinase B, and mitogen-activated protein kinases (MAPKs), in collagen-activated platelets. Neither the adenylate cyclase inhibitor SQ22536 nor the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one significantly reversed the Ir-6-mediated inhibition of collagen-induced platelet aggregation. Moreover, Ir-6 did not considerably diminish OH radical signals in collagen-activated platelets or Fenton reaction solution. At 2 mg/kg, Ir-6 markedly prolonged the bleeding time in experimental mice. In conclusion, Ir-6 plays a crucial role by inhibiting platelet activation through the inhibition of signaling pathways, such as the PLCγ2-PKC cascade and the subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore, Ir-6 is a potential therapeutic agent for preventing or treating thromboembolic disorders or disrupting the interplay between platelets and tumor cells, which contributes to tumor cell growth and progression.

Possible Molecular Targets of Novel Ruthenium Complexes in Antiplatelet Therapy.

In oncotherapy, ruthenium (Ru) complexes are reflected as potential alternatives for platinum compounds and have been proved as encouraging anticancer drugs with high efficacy and low side effects. Cardiovascular diseases (CVDs) are mutually considered as the number one killer globally, and thrombosis is liable for the majority of CVD-related deaths. Platelets, an anuclear and small circulating blood cell, play key roles in hemostasis by inhibiting unnecessary blood loss of vascular damage by making blood clot. Platelet activation also plays a role in cancer metastasis and progression. Nevertheless, abnormal activation of platelets results in thrombosis under pathological settings such as the rupture of atherosclerotic plaques. Thrombosis diminishes the blood supply to the heart and brain resulting in heart attacks and strokes, respectively. While currently used anti-platelet drugs such as aspirin and clopidogrel demonstrate efficacy in many patients, they exert undesirable side effects. Therefore, the development of effective therapeutic strategies for the prevention and treatment of thrombotic diseases is a demanding priority. Recently, precious metal drugs have conquered the subject of metal-based drugs, and several investigators have motivated their attention on the synthesis of various ruthenium (Ru) complexes due to their prospective therapeutic values. Similarly, our recent studies established that novel ruthenium-based compounds suppressed platelet aggregation via inhibiting several signaling cascades. Our study also described the structure antiplatelet-activity relationship (SAR) of three newly synthesized ruthenium-based compounds. This review summarizes the antiplatelet activity of newly synthesized ruthenium-based compounds with their potential molecular mechanisms.

Structure-Antiplatelet Activity Relationships of Novel Ruthenium (II) Complexes: Investigation of Its Molecular Targets.

The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven to be a positive approach to the prevention of thrombosis. Ruthenium complexes are fascinating for the development of new drugs, as they possess numerous chemical and biological properties. The present study aims to evaluate the structure-activity relationship (SAR) of newly synthesized ruthenium (II) complexes, TQ-1, TQ-2 and TQ-3 in agonists-induced washed human platelets. Silica gel column chromatography, aggregometry, immunoblotting, NMR, and X-ray analyses were performed in this study. Of the three tested compounds, TQ-3 showed a concentration (1-5 µM) dependent inhibitory effect on platelet aggregation induced by collagen (1 µg/mL) and thrombin (0.01 U/mL) in washed human platelets; however, TQ-1 and TQ-2 had no response even at 250 µM of collagen and thrombin-induced aggregation. TQ-3 was effective with inhibiting collagen-induced ATP release, calcium mobilization ([Ca2+]i) and P-selectin expression without cytotoxicity. Moreover, TQ-3 significantly abolished collagen-induced Lyn-Fyn-Syk, Akt-JNK and p38 mitogen-activated protein kinases (p38 MAPKs) phosphorylation. The compound TQ-3 containing an electron donating amino group with two phenyl groups of the quinoline core could be accounted for by its hydrophobicity and this nature might be the reason for the noted antiplatelet effects of TQ-3. The present results provide a molecular basis for the inhibition by TQ-3 in collagen-induced platelet aggregation, through the suppression of multiple machineries of the signaling pathway. These results may suggest that TQ-3 can be considered a potential agent for the treatment of vascular diseases.

A combined experimental and computational investigation on pyrene based D-π-A dyes.

The geometry (twist vs. planar) of a dye is one of the most pivotal factors for determining intramolecular charge transfer (ICT), light harvesting and photovoltaic properties of dye-sensitized solar cells. In order to comprehend the role of dye geometry on the above properties, we have devised the pyrene based D-π-A dyes namely 2-cyano-3-(5-pyren-1-yl-furan-2-yl)-acrylic acid (PFCC) and 2-cyano-3-(5-pyren-1-ylethynyl-furan-2-yl)-acrylic acid (PEFCC). The synthesized pyrene dyes were well characterized by NMR and EI-MS spectrometry. In both the dyes, the donor (pyrene) and acceptor (cyanoacrylic acid) segments remained the same. The varied π-spacers were furan and ethynyl furan. The influences of the ethynyl spacer on the energy levels, light absorption, dynamics of excited states and photovoltaic properties of the DSCs were systematically investigated via theoretical calculations and spectroscopic measurements. UV-visible absorption spectral measurements indicated that the introduction of the ethynyl spacer enhances the molar absorptivity of a dye (PEFCC) in the order of 2, but does not shift the absorption range, which is consistent with the results obtained from density functional theory (DFT) calculations. The theoretical analysis indicated that the charge transfer transition is mainly constituted of the HOMO to the LUMO that were found to be located on donor and acceptor segments, respectively, which is supportive for efficient charge separation and electron injection processes. TDDFT calculations highlighted that the LUMO of the PEFCC dye is more stabilized by the incorporation of the ethynyl group between the pyrene and furan moieties that aid to inject electrons efficiently into TiO2 thereby resulting in an enhanced power conversion efficiency of 2.47% when compared to the PFCC dye. Notably, the overall conversion efficiency of the PEFCC dye reached 60% with respect to that of an N719-based device (4.12%) fabricated under similar conditions. Transient absorption kinetic studies demonstrated that a slower charge recombination rate is an essential factor behind enhanced efficiencies in PEFCC based cells.

Catalytic fixation of atmospheric carbon dioxide by copper(ii) complexes of bidentate ligands.

New copper(ii) complexes, [Cu(L1)2(H2O)](ClO4)2, 1 [L1 = 2-pyridin-2-yl-quinoline], [Cu(L2)2(H2O)](ClO4)2, 2 [L2 = 2-pyridin-2-yl-quinoxaline], [Cu(L3)2(H2O)](ClO4)2, 3 [L3 = 6,7-dimethyl-2-pyridin-2-yl-quinoxaline], [Cu(L4)2(H2O)](ClO4)2, 4 [L4 = 4-phenyl-2-pyridin-2-yl-quinoline] and [Cu(L5)2(H2O)](ClO4)2, 5 [L5 = 4-phenyl-2-pyridin-2-yl-quinazoline], were synthesized and characterized as catalysts for selective fixation of atmospheric CO2. The molecular structure of 2 was determined by single-crystal X-ray studies and shown to have an unusual trigonal bipyramid geometry (τ, 0.936) around the copper(ii) center, with the coordination of two ligand units and a water molecule. The Cu-Nquin (2.040, 2.048 Å) bonds are slightly longer than the Cu-Npyr (1.987 Å) bonds but shorter than the Cu-Owater bond (2.117 Å). Well-defined Cu(ii)/Cu(i) redox potentials of around 0.352 to 0.401 V were observed for 1-5 in acetonitrile. The electronic absorption spectra of 1-5 showed ligand-based transitions at around 208-286 nm with a visible shoulder at around 342-370 nm. The d-d transitions appeared at around 750-800 and 930-955 nm in acetonitrile. The rhombic EPR spectra of 1-5 exhibited three different g values gx, 2.27-2.34; gy, 2.06-2.09; and gz, 1.95-1.98 at 70 K. Atmospheric CO2 was successfully fixed by 1-5 using Et3N as a sacrificial reducing agent, resulting in CO32--bound complexes of type [Cu(L)CO3(H2O)] that display an absorption band at around 614-673 nm and a νst at 1647 cm-1. This CO32--bound complex of 1 was crystallized from the reaction mixture and it displayed a distorted square pyramidal geometry (τ, 0.369) around the copper(ii) center via the coordination of only one ligand unit, a carbonate group, and water molecules. Furthermore, treatment of the carbonate-bound Cu(ii) complexes with one equivalent of H+ under N2 atmosphere resulted in the liberation of bicarbonate (HCO3-) and regenerated the parent complexes. These regenerated catalysts were active enough to fix CO2 in eight repeating cycles without any change in efficiency. The fixation of CO2 possibly occurs via the formation of Cu(i)-species, which is accompanied by the formation of an MLCT band at around 450-500 nm. The rates of Cu(i)-species formation, kobs, were determined and found to be 5.41-10.31 × 10-3 s-1 in the presence of Et3N in acetonitrile at 25 °C. Interestingly, the copper(i)-species of 3 has been successfully crystallized and displayed a distorted tetrahedral geometry through the coordination of two units of ligand L3.

A novel ruthenium (II)-derived organometallic compound, TQ-6, potently inhibits platelet aggregation: Ex vivo and in vivo studies.

Arterial thrombosis plays a key role in cardiovascular diseases. Hence, developing more effective antithrombotic agents is necessary. We designed a ruthenium (II)-derived complex, [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), as a new antiplatelet drug. TQ-6 (0.3 µM) exhibited extremely strong inhibitory activity against platelet aggregation, Src, and Syk phosphorylation stimulated by agonists in human platelets. In collagen-activated platelets, TQ-6 also inhibited ATP-release, [Ca+2]i, P-selectin expression, FITC-PAC-1 binding, and hydroxyl radical formation, as well as the phosphorylation of phospholipase Cγ2, protein kinase C, mitogen-activated protein kinases, and Akt. Neither FITC-JAQ1 nor FITC-triflavin binding or integrin ß3 phosphorylation stimulated by immobilized fibrinogen were diminished by TQ-6. Furthermore, TQ-6 had no effects in cyclic nucleotide formation. Moreover, TQ-6 substantially prolonged the closure time in whole blood, increased the occlusion time of thrombotic platelet plug formation and bleeding time in mice. In conclusion, TQ-6 has a novel role in inhibiting platelet activation through the inhibition of the agonist receptors-mediated inside-out signaling such as Src-Syk-PLCγ2 cascade and subsequent suppression of granule secretion, leading to disturb integrin αIIbß3-mediated outside-in signaling, and ultimately inhibiting platelet aggregation. Therefore, TQ-6 has potential to develop as a therapeutic agent for preventing or treating thromboembolic disorders.

Antiplatelet Activity of a Newly Synthesized Novel Ruthenium (II): A Potential Role for Akt/JNK Signaling.

In oncotherapy, ruthenium complexes are considered as potential alternatives for platinum compounds, and have been proved as promising anticancer drugs with high efficacy and lesser side effects. Platelet activation plays a major role in cancer metastasis and progression. Hence, this study explored the effect of a newly synthesized ruthenium complex, [Ru(η6-cymene)(L)Cl]BF4(TQ5), where L = 4-phenyl-2-pyridin-2-yl-quinazoline), on human platelet activation. TQ5 (3-5 µM) inhibited concentration-dependent collagen-induced platelet aggregation in washed human platelets. However, this compound only inhibited platelet aggregation at a maximum concentration of 500 and 100 µM against thrombin and 9,11-dideoxy-11α, 9α-epoxymethanoprostaglandin (U46619)-induced stimulation, respectively. TQ5 inhibited collagen-induced ATP release and calcium mobilization ([Ca2+]i), without inducing cell cytotoxicity. In addition, neither SQ22536, an adenylate cyclase inhibitor, nor 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor, significantly reversed the TQ5-mediated inhibition of platelet aggregation. TQ5 inhibited the collagen-induced phosphorylation of protein kinase B (Akt) and c-Jun N-terminal kinase (JNK), but did not effectively inhibit extracellular signal-regulated kinase 1/2 (ERK1/2) and p38-mitogen-activated protein kinase (p38-MAPK) in human platelets. Additionally, TQ5 significantly prolonged the closure time in whole blood and increased the occlusion time of thrombotic platelet plug formation in mice. This study demonstrates, for the first time, that a newly synthesized ruthenium complex, TQ5, exhibits potent antiplatelet activity by hindering ATP release and [Ca2+]i, and by decreasing the activation of Akt/JNK signals. Together, these results suggest that TQ5 could be developed as a therapeutic agent that helps prevent or treat thromboembolic disorders, since it is found to be potently more effective than a well-established antithrombotic aspirin.

Pyrene based D-π-A architectures: synthesis, density functional theory, photophysics and electron transfer dynamics.

Pyrene derivatives show immense potential as sensitizers for dye-sensitized solar cells (DSCs). Therefore, this work focuses on the impact of π-spacers on the photophysical, electrochemical and photovoltaic properties of pyrene based D-π-A dyes, since the insertion of π-spacers is one of the doable strategies to improve the light harvesting properties of the dye. In this respect, three new pyrene based D-π-A dyes have been synthesized and characterized by 1H, 13C NMR, and elemental analyses and EI-MS spectrometry. The selected π-spacers are benzene, thiophene and furan. Compared with a benzene spacer, the introduction of a heterocyclic ring spacer reduces the band gap of the dye and brings about the broadening of the absorption spectra to the longer wavelength region through intramolecular charge-transfer (ICT). Combined experimental and theoretical studies were performed to investigate the ICT process involved in the pyrene derivatives. The profound solvatochromism with increased nonradiative rate constants (knr) has been construed in terms of ICT from the pyrene core to rhodanine-3-acetic acid via conjugated π-spacers. Electrochemical data also reveal that the HOMO and LUMO energy levels are fine-tuned by incorporating different π-spacers between pyrene and rhodanine-3-acetic acid. On the basis of the optimized DSC test conditions, the best performance was found for PBRA, in which a benzene group is the conjugated π-spacer. The divergence in the photovoltaic behaviors of these dyes was further explicated by femtosecond fluorescence and electrochemical impedance spectroscopy.